Re: Heat generation and drill wear during dental implant site preparation: systematic review

Publication date: Available online 7 October 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): Stephan Christian Möhlhenrich, Ali Modabber, Timm Steiner, David A. Mitchell, Frank Hölzle




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Re: Heat generation and drill wear during dental implant site preparation

Publication date: Available online 7 October 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): M. Koopaie, S. Kolahdouz




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Chronic recurrent dislocation of the temporomandibular joint secondary to a complex facial tic disorder

Publication date: Available online 7 October 2017
Source:British Journal of Oral and Maxillofacial Surgery
Author(s): K.E. French, M.H. Wilson, P.J. Revington




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Macrophage Polarization and Allergic Asthma

Publication date: Available online 7 October 2017
Source:Translational Research
Author(s): Arjun Saradna, Danh C. Do, Shruthi Kumar, Qing-Ling Fu, Peisong Gao
Allergic asthma is associated with airway inflammation and airway hyper-responsiveness. Macrophage polarization has been shown to have a profound impact on asthma pathogenesis. Upon exposure to local micro-environments, recruited macrophages can be polarized into either classically activated (or M1) or alternatively activated (or M2) phenotypes. Macrophage polarization has been heavily associated with development of asthma. The process of regulation of macrophage polarization involves an intricate interplay between various cytokines, chemokines, transcriptional factors, and immune-regulatory cells. Different signals from the microenvironment are controlled by different receptors on the macrophages to initiate various macrophage polarization pathways. Most importantly, there is an increased attention on the epigenetic changes (e.g., microRNAs, DNA methylation and histone modification) that impact macrophage functional responses and M1/M2 polarization through modulating cellular signaling and signature gene expression. Thus, modulation of macrophage phenotypes through molecular intervention by targeting some of those potential macrophage regulators may have therapeutic potential in the treatment of allergic asthma and other allergic diseases. In this review, we will discuss the origin of macrophages, characterization of macrophages, macrophage polarization in asthma, and the underlying mechanisms regarding allergen-induced macrophage polarization with emphasis on the regulation of epigenetics, which will provide new insights into the therapeutic strategy for asthma.



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Compassion as the reunion of feminine and masculine virtues in medicine

The central role of the virtue of compassion in the shaping of the professional character of healthcare providers is a well-emphasized fact. On the other hand, the utmost obligation of physicians is to alleviate or eliminate human suffering. Traditionally, according to the Aristotelian understanding of virtues and virtue ethics, human virtues have been associated with masculinity. In recent decades, the founders of the ethics of care have introduced a set of virtues with feminine nature. This paper analyzes the notion of compassion as a common virtue between the traditional/masculine and care/feminine sets of virtues and shows that compassion is a reunion and merging point of both sets of human virtues. This role can be actualized through the development and promotion of compassion as an important part of the character of an ideal physician/healthcare provider. In addition, this paper argues that the notion of compassion can shed light on some important aspects of the contemporary debates on healthcare provider-patient relationship and medical futility. Despite the recent technological and scientific transformations in medicine, the interpersonal relationship between healthcare providers and patients still plays a vital role in pursuing the goals of healthcare. The virtue of compassion plays a central role in the establishment of a trust-based physician-patient relationship. This central role is discernible in the debate of medical futility in which making difficult decisions, depends largely on trust and rapport which are achievable by compassion in the physician and the recognition of this compassion by the patients and their surrogate decision makers.

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Sorry, but you really should be wearing a retainer for the rest of your life

Remember ages ago when you finally had your train tracks removed and were sent home with strict instructions to wear your retainer every night? Yeah, that was a mistake. And if you haven't been wearing your retainer every night for the last few years, that mistake could have repercussions.

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Insecticidal effect of several essential oils against Musca domestica

Abstract

This study aimed to evaluate for the first time the insecticidal effects of essential oils of bergamot (Citrus bergamia), palmarosa grass (Cymbopogon martini), vetiver grass (Vetiveria zizanioides), and red cedar (Juniperus virginiana) against the house fly (Musca domestica). The in vitro study was performed in captured adult flies, which were separated on testing cages (n = 20). Subsequently, the essential oils cited above were used in the concentrations of 1, 5, and 10%, and a control group was maintained for test validation. All flies were monitored for 8 h after treatment. All four oils showed insecticidal effect against the fly species studied in vitro and after 8 h of treatment, an efficacy of 73% was observed for the essential oil of bergamot, 55% for palmarosa grass, 75% for vetiver grass, and 89% for red cedar. We conclude that the essential oils tested showed insecticidal effect against house fly, acting as an environmentally sustainable alternative to be applied in human habitats, especially against flies' resistant to chemical insecticides. In addition, the use of such oils may decrease the doses of synthetic drugs routinely used.

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Astronomers Identify Rare Comet-like Binary Asteroid

Astronomers Identify Rare Comet-like Binary Asteroid Aadil Islam '21 Spotting a shooting star in the sky is an infrequent spectacle in itself, yet a German-led group of astronomers appears to have doubled their fortune this past year. In September of 2016, NASA's Hubble Space Telescope was used to spot 288P, […]

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Sequential versus concomitant therapy for treatment of Helicobacter pylori infection: an updated systematic review and meta-analysis

Abstract

Background

Sequential and concomitant therapies are two innovative therapies for Helicobacter pylori (H. pylori) eradication. However, the comparative efficacy and safety of these treatments are controversial. Therefore, we aimed to conduct an updated systematic review and meta-analysis of studies that compared these two treatments.

Methods

A search of PubMed, Embase, the Cochrane Library, and Web of Science was carried out. Randomized controlled trials (RCTs) that compared sequential with concomitant therapies were selected for meta-analysis.

Results

Twenty RCTs were included in the analysis. The eradication rate of 10-day sequential therapy was superior to that of 5-day concomitant therapy (82.09 versus 77.79%, relative risk (RR) 1.052 (95% confidence interval (CI) 1.004–1.103), P = 0.035)), similar to that of 7-day concomitant therapy (82.40 versus 86.99%, RR 0.959 (95% CI 0.874–1.053), P = 0.382), and inferior to that of 10-day concomitant therapy (78.39 versus 83.32%, RR 0.945 (95% CI 0.907–0.984, P = 0.006); the occurrence of diarrhea was higher in 10-day concomitant therapy than that in 10-day sequential therapy. Compared with the eradication rate of sequential therapy, that of concomitant therapy was higher in metronidazole-resistant strains (RR 0.912 (95% CI 0.844–0.986, P = 0.020)) and strains resistant to metronidazole and clarithromycin (RR 0.542 (95% CI 0.308–0.956, P = 0.035)).

Conclusion

The efficacy of concomitant therapy was duration dependent, and 10-day concomitant therapy was superior to 10-day sequential therapy. Compared to sequential therapy, concomitant therapy was more efficacious for metronidazole-resistant strains and metronidazole plus clarithromycin-resistant strains. However, diarrhea was more frequent with concomitant therapy than with sequential therapy.

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Feasibility of coronary angiography and percutaneous coronary intervention after transcatheter aortic valve replacement using a Medtronic™ self-expandable bioprosthetic valve

Abstract

Background and Objective

With aging, the progression of atherosclerosis in the coronary arteries is expected. The Medtronic™ self-expandable aortic bioprosthetic valve is deployed in the supra-annular position, and it has been challenging to selectively engage coronary arteries post-transcatheter aortic valve replacement (TAVR) even though there are diamond-shaped spaces in the mesh frame within the valve. Given the scarcity of data, we analyzed angiographic and clinical data from all patients requiring coronary angiography (CA) or intervention post-TAVR.

Methods

From January 2012 to December 2016, 403 patients were treated for severe aortic stenosis with TAVR at our center using the Medtronic™ self-expandable valve. This study included patients who underwent CA with or without percutaneous coronary intervention (PCI) after TAVR.

Results

Twenty-eight patients underwent 43 CAs after TAVR at our institution. Eleven patients (39%) were women. More than 90% of the procedures were performed for acute coronary syndrome. Thirty-six cases were performed using the transfemoral approach (83%). Forty-two of 43 (97%) left coronary arteries were selectively engaged, and 29 of 32 (90%) right coronary arteries were selectively engaged. We were able to engage 11 saphenous vein grafts and two left internal mammary artery grafts selectively (100%). The mean fluoroscopy time for diagnostic CA was 11.5 min, and for PCI, instantaneous wave-free ratio, or intravascular ultrasound (IVUS) interrogation, it was 19 minutes. The mean amount of contrast used for diagnostic CA was 102 cc per case, and for PCI, iFR, or IVUS, it was 146 cc per case. No periprocedural complication was noted.

Conclusions

CA with or without PCI after TAVR is feasible with supra-annular self-expandable valves. With the proper technique in experienced hands, it can be conducted safely.

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Self-apposing stent-assisted coil embolization for the treatment of coronary artery aneurysm

Abstract

Coronary artery aneurysms (CAA) represent an uncommon disease with yet unclear standards of treatment. Clinical and anatomic characteristics determine choice of treatment. Stent-assisted coil embolization has been described as a valuable option for management of patients with wide-neck coronary aneurysms. Choice of appropriate stent sizing can be challenging particularly when there is a large difference between proximal and distal diameters. We report a case of stent-assisted coil embolization of a coronary aneurysm using a self-expandable stent. This type of stent can be helpful to treat CAA involving coronary sites where marked tapering of vessel diameter is often present.

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The safety and effectiveness of adenosine diphosphate receptor inhibitor pretreatment among acute myocardial infarction patients treated with percutaneous coronary intervention in community practice: Insights from the TRANSLATE-ACS study

Objectives

To understand the optimal timing of adenosine diphosphate (ADP) receptor inhibitor pretreatment prior to percutaneous coronary intervention (PCI) among acute myocardial infarction (MI) patients.

Background

The role of ADP receptor inhibitor pretreatment in this population is unclear.

Methods

A total of 9,251 ADP receptor inhibitor-naïve MI patients undergoing PCI at 229 TRANSLATE-ACS sites were evaluated. Adjusted risks of in-hospital major adverse cardiovascular events (MACE) and major bleeding were compared among patients with and without pretreatment using inverse probability-weighted propensity adjustment.

Results

Of 9,251 patients treated with either prasugrel or clopidogrel during the index MI hospitalization, 4,056 (44%) received pretreatment (ST-segment elevation MI [STEMI] 54.9%, non-STEMI 45.1%); pretreatment was used more commonly among those receiving clopidogrel than prasugrel (52% vs. 20%, P < 0.0001). MACE risks were not significantly different between patients with and without pretreatment (clopidogrel 2.1% vs. 2.2%, adjusted hazard ratio [HR] 1.00, 95% confidence interval [CI] 0.70–1.43; prasugrel 2.1% vs. 2.3%, adjusted odds ratio [OR] 0.82, 95% CI 0.42–1.60). No differences in major bleeding were observed among those receiving versus not receiving pretreatment (clopidogrel 3.1% vs. 3.5%, adjusted HR 0.94, 95% CI 0.65–1.36; prasugrel 2.5% vs. 2.7%, adjusted OR 0.93, 95% CI 0.42–2.02); results were similar when stratified by MI type.

Conclusions

ADP receptor inhibitor pretreatment (44%) is commonly used among acute MI patients undergoing PCI in contemporary practice, but no significant differences were found in in-hospital MACE and/or bleeding risks between patients receiving versus not receiving pretreatment, regardless of ADP receptor inhibitor type.

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Impact of flow, gradient, and left ventricular function on outcomes after transcatheter aortic valve replacement

Abstract

Objectives

To assess the impact of low flow with and without preserved left ventricular ejection fraction (LVEF) on outcomes after transcatheter aortic valve replacement (TAVR).

Background

Prior studies have shown that patients with low flow, AVG, and LVEF have worse outcomes after TAVR. It is unclear whether low AVG and LVEF remain prognostic after adjusting for flow, and how the outcomes of patients with low flow with and without preserved LVEF compare after TAVR. The goal of this study was to provide insight into these open questions.

Methods

Data from 340 TAVR patients at Brigham and Women's Hospital from 2011 through 2015 were analyzed. Low flow was defined as stroke volume index (SVI) ≤35 mL/m², low AVG as mean gradient < 40 mmHg, and reduced LVEF as < 50%.

Results

Low flow was present in 96 (28.2%) patients, 48 (50.0%) of whom also had reduced LVEF. At 1 year, low flow was associated with increased mortality (21.9 vs 7.4%; P = 0.0002) and heart failure (HF) (20.8 vs 5.3%; P = 0.0113). Among patients with low flow, those with preserved LVEF had increased mortality (HR 5.17, 95% CI 2.73-9.80; P < 0.001) and HF (HR 7.69, 95% CI 3.86-15.31; P < 0.001). After adjusting for clinical factors, patients with low flow had increased mortality (HR 6.51, 95% CI 2.98-14.22; P < 0.001) and HF (HR 5.52, 95% CI 2.34-12.98; P < 0.001), while neither low AVG nor low LVEF were associated with increases in mortality or HF.

Conclusions

In patients undergoing TAVR, low flow was an independent predictor of 1-year mortality and HF, and a stronger predictor than either low AVG or LVEF. Patients with low flow and preserved EF had increased mortality and HF at 1-year, while those with low flow and reduced EF had outcomes similar to patients with normal flow.

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Maintenance of valvular integrity with Impella left heart support: Results from the multicenter PROTECT II randomized study

Abstract

Background

The Impella 2.5 axial flow pump, which is positioned across the aortic valve, is widely employed for hemodynamic support. The present study compared structural and functional integrity of the left heart valves in patients undergoing Impella vs intra-aortic balloon pump in the randomized PROTECT II trial.

Methods and Results

Transthoracic echocardiograms were performed at baseline, 1 and 3 months in 445 patients in the PROTECT II trial. Serial studies were analyzed by an independent echocardiography core laboratory for aortic and mitral valve structure and function, and left ventricular ejection fraction (LVEF). During Impella support there was no appreciable change in the degree of baseline valvular regurgitation. There were no cases of structural derangement of the mitral or aortic valve after use of the Impella device. At 90-day follow-up, there was an average 22% relative increase in LVEF from baseline (27% ± 9 vs. 33% ± 11, P < 0.001).

Conclusions

The present echocardiographic analysis of the PROTECT II study confirms prior observations regarding the safety of the Impella 2.5 device with respect to mitral and aortic valve function.

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Soil aggregate and organic carbon distribution at dry land soil and paddy soil: the role of different straws returning

Abstract

Agriculture wastes returning to soil is one of common ways to reuse crop straws in China. The returned straws are expected to improve the fertility and structural stability of soil during the degradation of straw it selves. The in situ effect of different straw (wheat, rice, maize, rape, and broad bean) applications for soil aggregate stability and soil organic carbon (SOC) distribution were studied at both dry land soil and paddy soil in this study. Wet sieving procedures were used to separate soil aggregate sizes. Aggregate stability indicators including mean weight diameter, geometric mean diameter, mean weight of specific surface area, and the fractal dimension were used to evaluate soil aggregate stability after the incubation of straws returning. Meanwhile, the variation and distribution of SOC in different-sized aggregates were further studied. Results showed that the application of straws, especially rape straw at dry land soil and rice straw at paddy soil, increased the fractions of macro-aggregate (> 0.25 mm) and micro-aggregate (0.25–0.053 mm). Suggesting the nutrients released from straw degradation promotes the growing of soil aggregates directly and indirectly. The application of different straws increased the SOC content at both soils and the SOC mainly distributed at < 0.53 mm aggregates. However, the contribution of SOC in macro- and micro-aggregates increased. Straw-applied paddy soil have a higher total SOC content but lower SOC contents at > 0.25 and 0.25–0.053 mm aggregates with dry land soil. Rape straw in dry land and rice straw in paddy field could stabilize soil aggregates and increasing SOC contents best.

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Responses of growth, malformation, and thyroid hormone-dependent genes expression in Bufo gargarizans embryos following chronic exposure to Pb 2+

Abstract

The aim of this study was to examine the adverse effects of lead (Pb) exposure on Bufo gargarizans embryos. The 96 h-LC₅₀ of Pb²⁺ for B. gargarizans embryos was determined to be 26.6 mg L⁻¹ after an acute test. In the chronic test, B. gargarizans embryos at Gosner stage 3 were exposed to 10~2000 μg Pb²⁺ L⁻¹ during embryogenesis. Total length, weight, developmental stage, and malformation were monitored. In addition, the transcript levels of type II and type III iodothyronine deiodinase (Dio2 and Dio3) and thyroid hormone receptors (TRα and TRβ) were determined to assess the thyroid-disrupting effects of Pb²⁺. Slightly increased growth and development of B. gargarizans embryos were observed at low concentrations of Pb²⁺ (10, 50, and 100 μg L⁻¹), while retarded growth and development were found at high concentrations of Pb²⁺ (1000 and 2000 μg L⁻¹). In addition, Pb²⁺ exposure induced morphological abnormalities, which were characterized by edema at tail, wavy fin, abdominal edema, stunted growth, hyperplasia, and axial flexures in B. gargarizans embryos. Furthermore, our results showed that exposure to 2000 μg Pb²⁺ L⁻¹ decreased the transcript levels of Dio2, TRα, and TRβ, but it increased Dio3 mRNA level. In contrast, exposure to 50 μg Pb²⁺ L⁻¹ increased TRα mRNA level and decreased Dio3 mRNA level. These results suggested that Pb²⁺ might have thyroid-disrupting effects, leading to the disruption of growth and development in B. gargarizans embryos.

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Human biomonitoring of eight trace elements in urine of residents living in rural areas along the Yangtze River, China

Abstract

The rapid economic development and industrialization have made heavy metal contamination a great public concern, especially in China. However, the levels of heavy metals in human body, especially those susceptible to the effect of industrial progression, are rarely explored. In this study, eight elements in 2643 urinary samples of individuals living in rural areas along the Yangtze River were determined through inductively coupled plasma optical emission spectrometry (As, Cr, Cu, Fe, Mn, Pb, and Zn) and TAS-990 atomic absorption spectrophotometry (Cd). Two-level regression model was applied to explore the potential factors associated with the level of the eight trace elements. After adjusting for urinary creatinine, the geometric means were 77.5, 10.98, 14.39, 13.00, 0.59, 1.51, 489.62, and 1.80 μg/g for As, Cr, Cu, Fe, Mn, Pb, Zn, and Cd, respectively. The level of eight elements varied among individual and familial characteristics. Compared with domestic and international results, the rural residents living in riverside areas had higher level of As, Cd, Cr, Fe, and Zn. Therefore, industrial progression followed by economic development has resulted in high body burden of heavy metals. Targeted public health policies should be made to improve the local environment and the recognition of potential risk factors.

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A randomised trial comparing three Delphi feedback strategies found no evidence of a difference in a setting with high initial agreement

Publication date: Available online 7 October 2017
Source:Journal of Clinical Epidemiology
Author(s): Steven MacLennan, Jamie Kirkham, Thomas B.L. Lam, Paula R. Williamson
ObjectiveTo explore the impact of different feedback strategies on 1) subsequent agreement and 2) variability in Delphi studies.Study Design and SettingA two-round Delphi survey, with a list of outcomes generated from the results of a systematic review and interviews, was undertaken whilst developing a core outcomes set for prostate cancer including two stakeholder groups (health professionals and patients). Seventy-nine outcomes were scored on a scale of one (not important) to nine (critically important). Participants were randomised in round two to receive round one feedback from: peers only, multiple stakeholders separately, or multiple stakeholders combined.ResultsAgreement on outcomes retained for all feedback groups was high (peer: 92%, multiple separate: 90%, multiple combined: 84%). There were no statistically significant reduction in variability for peer versus multiple-separate (0.016 (-0.035, 0.067); p=0.529), or multiple-separate versus multiple-combined feedback (0.063 (-0.003, 0.129); p=0.062). Peer feedback statistically significantly reduced variability compared to multiple-combined feedback (0.079 (0.001, 0.157); p=0.046).ConclusionsWe found no evidence of a difference between different feedback strategies in terms of the number of outcomes retained or reduction in variability of opinion. However, this may be explained by the high level of existing agreement in round one. Further methodological studies nested within Delphi surveys will help clarify the best strategy.



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Genetic Risk Factors for Development of Atopic Dermatitis: a Systematic Review

Abstract

Purpose of Review

The purpose of this study is to systematically review studies conducted between April 2015 and April 2017 for the genetic risks for the development of atopic dermatitis (AD). We sought to identify (1) specific loci and genes associated with AD, (2) the proportion of studies for each gene, and (3) genetic risks that need further investigation.

Recent Findings

Studies have found that genetic predisposition and environmental triggers are involved in the pathogenesis of AD. Thirty-four loci and 46 genes have been identified as genetic risk factors, of which filaggrin gene null mutations and genes in the type 2 T-helper lymphocyte (Th2) signaling pathway have been the most extensively studied.

Summary

Our systematic review found that in the last 2 years, 46 loci and 53 genes have been studied in the development of AD. Genes involved in epidermal barrier, immune regulation, and intracellular functions were identified. We suggest that future research should investigate the intricate interaction of these genes as well as the complex interplay of genetic and environmental factors in the development of AD.

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William (Barry) Inabnet appointed Editor-in-Chief of VideoEndocrinology

Mary Ann Liebert, Inc., publishers and the American Thyroid Association (ATA) are pleased to announce that Dr. William B. Inabnet, III, Chairman of the Department of Surgery at Mount Sinai Beth Israel (New York) and The Eugene W. Friedman, MD, Professor of Surgery and the Surgical Director of the Diabetes, Obesity and Metabolism Institute at the Icahn School of Medicine at Mount Sinai has been appointed incoming Editor-in-Chief of VideoEndocrinology effective in 2018. Dr. Inabnet is also the inaugural Director of Endocrine Surgery Quality for the Mount Sinai Health System.

Gerard M. Doherty, MD, Surgeon-in-Chief, Brigham and Women's Hospital, Harvard University, has provided strong leadership for VideoEndocrinology since its inception in 2014. We are very grateful for his invaluable work and guidance in founding the first broad-based videojournal in endocrinology. Dr. Doherty will be stepping down from his role at the end of 2017.

"Dr. Inabnet was selected as Editor-in-Chief by an ATA search committee from a pool of very strong candidates because of his experience with audiovisual production and presentation, his vision, and his prominent position in the field of Endocrine Surgery. The interest of this outstanding field of candidates in the position speaks to the importance of VideoEndocrinology, especially to surgeons performing thyroid, parathyroid, and adrenal procedures," says, John C. Morris, III, MD, President of the ATA, and Professor of Medicine, Mayo Clinic, Rochester, MN. "With Barry's leadership we look forward to continued growth and stature of this groundbreaking videojournal, continuing the trajectory established by its inaugural Editor-in-Chief, Dr. Gerard Doherty."

Dr. Inabnet attended the University of North Carolina at Chapel Hill where he received his undergraduate and medical school education. He completed his residency in general surgery at Rush Medical College and Rush-Presbyterian-St Luke's Medical Center in Chicago. Dr. Inabnet then completed a fellowship in endocrine surgery at Cochin Hospital in Paris, where he trained under Professor Yves Chapuis, a world leader in the field of endocrine surgery and targeted parathyroidectomy.

An international authority in the field of minimally invasive endocrine surgery, Dr. Inabnet has pioneered new techniques in minimal access endocrine neck surgery as well as adrenal and pancreatic surgery. In 1998, he helped perform the first endoscopic thyroid resection in the United States (2nd in the world), and has since helped advance the field of video-endoscopic neck surgery. Dr. Inabnet was among the first surgeons in the United States to introduce remote access thyroid surgery and is one of the few surgeons in the world who performs transaxillary, bilateral axillo-breast approach (BABA), and transoral endoscopic thyroid surgery.

Dr. Inabnet is also a leader in the field of minimally invasive metabolic surgery with an interest in disorders of the endocrine system in obese patients, especially type 2 diabetes and malignancy.  Dr. Inabnet has participated in national and international clinical trials evaluating the role of gastrointestinal surgery in treating diabetes. He holds numerous leadership positions in the American Association of Endocrine Surgeons, American Association of Metabolic and Bariatric Surgery, the American College of Surgeons, and the American Thyroid Association.

Dr. Inabnet has authored more than 180 peer-reviewed articles and book chapters, and five textbooks. He lectures throughout the world and was inducted into the Southern Surgical Association, the American Surgical Association, the French National Academy of Surgery, and the French Academy of Medicine.

"I am truly delighted that Dr. Barry Inabnet has agreed to be at the helm of VideoEndocrinology, which fills a unique niche among the many endocrinology-focused publications," says Peter A. Kopp, MD, Editor-in-Chief of the flagship journal Thyroid and Professor of Medicine, Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago. "His broad surgical expertise combined with extensive experience in the production of audiovisual materials and a dynamic vision make him ideally suited for this position. I also wish to thank Dr. Gerard Doherty for serving as the inaugural Editor-in-Chief of VideoEndocrinology and for establishing it as an important element of the Thyroid Journal Program."

Mary Ann Liebert, Inc., publishers and the American Thyroid Association look forward to the strong continuing commitment of our editorial board, reviewers, and authors.

About the ATA
The American Thyroid Association (ATA) is the leading worldwide organization dedicated to the advancement, understanding, prevention, diagnosis and treatment of thyroid disorders and thyroid cancer. ATA is an international individual membership organization for over 1,700 clinicians and researchers from 43 countries around the world, representing a broad diversity of medical disciplines. It also serves the public, patients and their family through education and awareness efforts.

Celebrating its 94th anniversary, ATA delivers its mission through several key endeavors: the publication of highly regarded monthly journals, Thyroid, Clinical Thyroidology, VideoEndocrinology and Clinical Thyroidology for the Public; annual scientific meetings; biennial clinical and research symposia; research grant programs for young investigators, support of online professional, public and patient educational programs; and the development of guidelines for clinical management of thyroid disease.

More information about ATA is found here.

The post William (Barry) Inabnet appointed Editor-in-Chief of VideoEndocrinology appeared first on American Thyroid Association.

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Radical espontânea

Radical espontânea

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Strategy Quantification using Body Worn Inertial Sensors in a Reactive Agility Task

Publication date: Available online 7 October 2017
Source:Journal of Biomechanics
Author(s): Chika U. Eke, Stephen M. Cain, Leia A. Stirling
Agility performance is often evaluated using time-based metrics, which provide little information about which factors aid or limit success. The objective of this study was to better understand agility strategy by identifying biomechanical metrics that were sensitive to performance speed, which were calculated with data from an array of body-worn inertial sensors. Five metrics were defined (normalized number of foot contacts, stride length variance, arm swing variance, mean normalized stride frequency, and number of body rotations) that corresponded to agility terms defined by experts working in athletic, clinical, and military environments. Eighteen participants donned 13 sensors to complete a reactive agility task, which involved navigating a set of cones in response to a vocal cue. Participants were grouped into fast, medium, and slow performance based on their completion time. Participants in the fast group had the smallest number of foot contacts (normalizing by height), highest stride length variance (normalizing by height), highest forearm angular velocity variance, and highest stride frequency (normalizing by height). The number of body rotations was not sensitive to speed and may have been determined by hand and foot dominance while completing the agility task. The results of this study have the potential to inform the development of a composite agility score constructed from the list of significant metrics. By quantifying the agility terms previously defined by expert evaluators through an agility score, this study can assist in strategy development for training and rehabilitation across athletic, clinical, and military domains.



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Integrated Geometric and Mechanical Analysis of an Image-Based Lymphatic Valve. (Second Revision)

Publication date: Available online 7 October 2017
Source:Journal of Biomechanics
Author(s): Daniel J. Watson, Igor Sazonov, David C. Zawieja, James E. Moore Jr., Raoul Loon
Lymphatic valves facilitate the lymphatic system's role in maintaining fluid homeostasis. Malformed valves are found in several forms of primary lymphœdema, resulting in incurable swelling of the tissues and immune dysfunction. Their experimental study is complicated by their small size and operation in low pressure and low Reynolds number environments. Mathematical models of these structures can give insight and complement experimentation. In this work, we present the first valve geometry reconstructed from confocal imagery and used in the construction of a subject-specific model in a closing mode. A framework is proposed whereby an image is converted into a valve model. An FEA study was performed to identify the significance of the shear modulus, the consequences of smoothing the leaflet surface and the effect of wall motion on valve behaviour. Smoothing is inherent to any analysis from imagery. The nature of the image, segmentation and meshing all cause attenuation of high-frequency features. Smoothing not only causes loss of surface area but also the loss of high-frequency geometric features which may reduce stiffness. This work aimed to consider these effects and inform studies by taking a manual reconstruction and through manifold harmonic analysis, attenuating higher frequency features to replicate lower resolution images or lower degree-of-freedom reconstructions. In conclusion, two metrics were considered: trans-valvular pressure required to close the valve, ΔPc, and the retrograde volume displacement after closure. The higher ΔPc, the greater the volume of lymph that will pass through the valve during closure. Retrograde volume displacement after closure gives a metric of compliance of the valve and for the quality of the valve seal. In the case of the image-specific reconstructed valve, removing features with a wavelength longer than four μm caused changes in ΔPc. Varying the shear modulus from 10kPa to 60kPa caused a 3.85 fold increase in the retrograde volume displaced. The inclusion of a non-rigid wall caused ΔPc to increase from 1.56 to 2.52 cmH2O



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A “Sweet-Spot” for Fluid-Induced Oscillations in the Conditioning of Stem Cell-Based Engineered Heart Valve Tissues

Publication date: Available online 7 October 2017
Source:Journal of Biomechanics
Author(s): Alexander Williams, Sana Nasim, Manuel Salinas, Arash Moshkforoush, Nikolaos Tsoukias, Sharan Ramaswamy
Fluid-induced shear stresses are involved in the development of cardiovascular tissues. In a tissue engineering framework, this stimulus has also been considered as a mechanical regulator of stem cell differentiation. We recently demonstrated that the fluid-oscillating effect in combination with a physiologically-relevant shear stress magnitude contributes to the formation of stem cell-derived de novo heart valve tissues. However, the range of oscillations necessary to induce favorable gene expression and engineered tissue formation is unknown. In this study, we took a computational approach to establish a range of oscillatory shear stresses that may optimize in vitro valvular tissue growth. Taking a biomimetic approach, three physiologically-relevant flow waveforms from the human: (i) aorta, (ii) pulmonary artery and (iii) superior vena cava were utilized to simulate pulsatile flow conditions within a bioreactor that housed 3 tissue specimens. Results were compared to non-physiological pulsatile flow (NPPF) and cyclic flexure-steady flow (Flex-Flow) conditions. The oscillatory shear index (OSI) was used to quantify the fluid-induced oscillations occurring on the specimen surfaces. The range of mean OSI under the physiological conditions investigated was found to be 0.18 ≤ OSI ≤ 0.23. On the other hand, NPPF and Flex-Flow environments yielded a mean OSI of 0.37 and 0.11 respectively, which were 46% higher and 45% lower than physiological conditions. Moreover, we subsequently conducted OSI-based human bone marrow stem cell (HBMSC) culture experiments which resulted in preferential valvular gene expression and phenotype (significant upregulation of BMP, KLF2A, CD31 and α-SMA using an OSI of 0.23 in comparison to a lower OSI of 0.10 or a higher OSI of 0.38; p < 0.05). These findings suggest that a distinct range or a "sweet-spot" for physiological OSI exists in the mechanical conditioning of tissue engineered heart valves grown from stem cell sources. We conclude that in vitro heart valve matrix development could be further enhanced by simultaneous exposure of the engineered tissues to physiologically-relevant magnitudes of both fluid-induced oscillations and shear stresses.



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Wearable technology for spine movement assessment: A systematic review

Publication date: Available online 7 October 2017
Source:Journal of Biomechanics
Author(s): Enrica Papi, Woon Senn Koh, Alison H McGregor
Continuous monitoring of spine movement function could enhance our understanding of low back pain development. Wearable technologies have gained popularity as promising alternative to laboratory systems in allowing ambulatory movement analysis. This paper aims to review the state of art of current use of wearable technology to assess spine kinematics and kinetics.Four electronic databases and reference lists of relevant articles were searched to find studies employing wearable technologies to assess the spine in adults performing dynamic movements. Two reviewers independently identified relevant papers. Customised data extraction and quality appraisal form were developed to extrapolate key details and identify risk of biases of each study. Twenty-two articles were retrieved that met the inclusion criteria: 12 were deemed of medium quality (score 33.4-66.7%), and 10 of high quality (score> 66.8%). The majority of articles (19/22) reported validation type studies. Only 6 reported data collection in real-life environments. Multiple sensors type were used: electrogoniometers (3/22), strain gauges based sensors (3/22), textile piezoresistive sensor (1/22) and accelerometers often used with gyroscopes and magnetometers (15/22). Two sensors units were mainly used and placing was commonly reported on the spine lumbar and sacral regions. The sensors were often wired to data transmitter/logger resulting in cumbersome systems. Outcomes were mostly reported relative to the lumbar segment and in the sagittal plane, including angles, range of motion, angular velocity, joint moments and forces.This review demonstrates the applicability of wearable technology to assess the spine, although this technique is still at an early stage of development.



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Red blood cell motion and deformation in a curved microvessel

Publication date: Available online 7 October 2017
Source:Journal of Biomechanics
Author(s): Ting Ye, Nhan Phan-Thien, Chwee Teck Lim, Yu Li
The flow of cells through curved vessels is often encountered in various biomedical and bioengineering applications, such as red blood cells (RBCs) passing through the curved arteries in circulation, and cells sorting through a shear-induced migration in a curved channels. Most of past numerical studies focused on the cell deformation in small straight microvessels, or on the flow pattern in large curved vessels without considering the cell deformation. However, there have been few attempts to study the cell deformation and the associated flow pattern in a curved microvessel. In this work, a particle-based method, smoothed dissipative particle dynamics (SDPD), is used to simulate the motion and deformation of a RBC in a curved microvessel of diameter comparable to the RBC diameter. The emphasis is on the effects of the curvature, the type and the size of the curved microvessel on the RBC deformation and the flow pattern. The simulation results show that a small curved shape of the microvessel has negligible effect on the RBC behavior and the flow pattern which are similar to those in a straight microvessel. When the microvessel is high in curvature, the secondary flow comes into being with a pair of Dean vortices, and the velocity profile of the primary flow is skewed toward the inner wall of the microvessel. The RBC also loses the axisymmetric deformation, and it is stretched first and then shrinks when passing through the curved part of the microvessel with the large curvature. It is also found that a pair of Dean vortices arise only under the condition of De>1 (De is the Dean number, a ratio of centrifugal to viscous competition). The Dean vortices are more easily observed in the larger or more curved microvessels. Finally, it is observed that the velocity profile of primary flow is skewed toward the inner wall of curved microvessel, i.e., the fluid close to the inner wall flows faster than that close to the outer wall. This is contrary to the common sense in large curved vessels. This velocity skewness was found to depend on the curvature of the microvessel, as well as the viscous and inertial forces.



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Chiral behavior in rat tail tendon fascicles

Publication date: Available online 7 October 2017
Source:Journal of Biomechanics
Author(s): Kimberly A. Buchanan, Roderic S. Lakes, Ray Vanderby
Ex vivo tendon mechanical behavior has been well described under rotationally constrained uniaxial tensile testing. During standard loading of rat tail tendon (RTT) fascicles, apparent axial twist has been observed. To quantify this behavior, we designed a custom testing setup, utilizing magnetic suspension, to allow unconstrained axial rotation during tensile loading. We characterized the rotational behavior of single and paired RTT fascicles under cyclic loading. We also measured stress relaxation across loading cycles as well as "rotational relaxation". Single fascicle nonlinear stretch-twist coupling is well described by the asymptotic function Δθ=A(1-e-Bε) in which fascicles rotated a mean ± 51.1° within about 1% applied axial strain. On average, paired fascicles rotated just over 10°. less. Specimen cross-sectional diameter had a noticeable effect on the measured mechanical properties, particularly effective elastic modulus. Such stretch-twist couplg and size dependence cannot be understood via classical elasticity but is predicted by Cosserat (micropolar) elasticity. The current study demonstrates RTT fascicles are chiral based on observed axial load-induced twist. Additionally, our findings support existing research that suggests a helical fascicle structure. Potential consequences of helical substructures, mechanical and biological, merit further investigation.



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New Parameters Describing How Knee Ligaments Carry Force In Situ Predict Interspecimen Variations in Laxity during Simulated Clinical Exams

Publication date: Available online 7 October 2017
Source:Journal of Biomechanics
Author(s): Carl W. Imhauser, Robert N. Kent, James Boorman-Padgett, Ran Thein, Thomas L. Wickiewicz, Andrew D. Pearle
Knee laxity, defined as the net translation or rotation of the tibia relative to the femur in a given direction in response to an applied load, is highly variable from person to person. High levels of knee laxity as assessed during routine clinical exams are associated with first-time ligament injury and graft reinjury following reconstruction. During laxity exams, ligaments carry force to resist the applied load; however, relationships between intersubject variations in knee laxity and variations in how ligaments carry force as the knee moves through its passive envelope of motion, which we refer to as ligament engagement, are not well established. Thus, the objectives of this study were, first, to define parameters describing ligament engagement and, then, to link variations in ligament engagement and variations in laxity across a group of knees. We used a robotic manipulator in a cadaveric knee model (n = 20) to quantify how important knee stabilizers, namely the anterior and posterior cruciate ligaments (ACL and PCL, respectively), as well as the medial collateral ligament (MCL) engage during respective tests of anterior, posterior, and valgus laxity. Ligament engagement was quantified using three parameters: 1) anatomic slack, defined as the relative tibiofemoral motion from the neutral position of the joint to the position where the ligament began to carry force; 2) anatomic stiffness, defined as the slope of the linear portion of the ligament force–tibial motion response; and 3) ligament force at the peak applied load. Knee laxity was related to parameters of ligament engagement using univariate and multivariate regression models. Variations in the anatomic slack of the ACL and PCL predicted anterior and posterior laxity, while variations in both anatomic slack and anatomic stiffness of the MCL predicted valgus laxity. Parameters of ligament engagement may be useful to further characterize the in situ biomechanical function of ligaments and ligament grafts.



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A computational framework for estimating statistical power and planning hypothesis-driven experiments involving one-dimensional biomechanical continua

Publication date: Available online 7 October 2017
Source:Journal of Biomechanics
Author(s): Todd C. Pataky, Mark A. Robinson, Jos Vanrenterghem
Statistical power assessment is an important component of hypothesis-driven research but until relatively recently (mid-1990s) no methods were available for assessing power in experiments involving continuum data and in particular those involving one-dimensional (1D) time series. The purpose of this study was to describe how continuum-level power analyses can be used to plan hypothesis-driven biomechanics experiments involving 1D data. In particular, we demonstrate how theory- and pilot-driven 1D effect modeling can be used for sample-size calculations for both single- and multi-subject experiments. For theory-driven power analysis we use the minimum jerk hypothesis and single-subject experiments involving straight-line, planar reaching. For pilot-driven power analysis we use a previously published knee kinematics dataset as a pilot dataset. Results show that powers on the order of 0.8 could be achieved with relatively small sample sizes, five and ten for within-subject minimum jerk analysis and between-subject knee kinematics, respectively. However, the appropriate sample size depends on a priori justifications of biomechanical meaning and effect size. The main advantage of the proposed technique is that it encourages a priori justification regarding the clinical and/or scientific meaning of particular 1D effects, thereby robustly structuring subsequent experimental inquiry. In short, it shifts focus from a search for significance to a search for non-rejectable hypotheses.



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Gait Biomechanics of Skipping Are Substantially Different than Those of Running

Publication date: Available online 7 October 2017
Source:Journal of Biomechanics
Author(s): Jessica McDonnell, John Willson, Kevin A. Zwetsloot, Joseph Houmard, Paul DeVita
The inherit injury risk associated with high-impact exercises calls for alternative ways to achieve the benefits of aerobic exercise while minimizing excessive stresses to body tissues. Skipping presents such an alternative, incorporating double support, flight, and single support phases. We used ground reaction forces (GRFs), lower extremity joint torques and powers to compare skipping and running in 20 healthy adults. The two consecutive skipping steps on each limb differed significantly from each other, and from running. Running had the longest step length, the highest peak vertical GRF, peak knee extensor torque, and peak knee negative and positive power and negative and positive work. Skipping had the greater cadence, peak horizontal GRF, peak hip and ankle extensor torques, peak ankle negative power and work, and peak ankle positive power. The second vs first skipping step had the shorter step length, higher cadence, peak horizontal GRF, peak ankle extensor torque, and peak ankle negative power, negative work, and positive power and positive work. The first skipping step utilized predominately net negative joint work (eccentric muscle action) while the second utilized predominately net positive joint work (concentric muscle action). The skipping data further highlight the persistence of net negative work performed at the knee and net positive work performed at the ankle across locomotion gaits. Evidence of step segregation was seen in distribution of the braking and propelling impulses and net work produced across the hip, knee, and ankle joints. CONCLUSIONS: Skipping was substantially different than running and was temporally and spatially asymmetrical with successive foot falls partitioned into a dominant function, either braking or propelling whereas running had a single, repeated step in which both braking and propelling actions were performed equally.



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Reliability of assessing postural control during seated balancing using a physical human-robot interaction

Publication date: Available online 7 October 2017
Source:Journal of Biomechanics
Author(s): Ahmed Ramadan, Jacek Cholewicki, Clark J. Radcliffe, John M. Popovich, N. Peter Reeves, Jongeun Choi
This study evaluated the within- and between-visit reliability of a seated balance test for quantifying trunk motor control using input-output data. Thirty healthy subjects performed a seated balance test under three conditions: eyes open (EO), eyes closed (EC) and eyes closed with vibration to the lumbar muscles (VIB). Each subject performed three trials of each condition on three different visits. The seated balance test utilized a torque-controlled robotic seat, which together with a sitting subject resulted in a physical human-robot interaction (pHRI) (two degrees-of-freedom with upper and lower body rotations). Subjects balanced the pHRI by controlling trunk rotation in response to pseudorandom torque perturbations applied to the seat in the coronal plane. Performance error was expressed as the root mean square (RMSE) of deviations from the upright position in the time domain and as the mean bandpass signal energy (Emb) in the frequency domain. Intra-class correlation coefficients (ICC) quantified the between-visit reliability of both RMSE and Emb. The empirical transfer function estimates (ETFE) from the perturbation input to each of the two rotational outputs were calculated. Coefficients of multiple correlation (CMC) quantified the within- and between-visit reliability of the averaged ETFE. ICCs of RMSE and Emb for all conditions were ≥0.84. The mean within- and between-visit CMCs were all ≥0.96 for the lower body rotation and ≥0.89 for the upper body rotation. Therefore, our seated balance test consisting of pHRI to assess coronal plane trunk motor control is reliable.



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The outcome of patients in traumatic cardiac arrest presenting to deployed military medical treatment facilities: data from the UK Joint Theatre Trauma Registry

Background

The UK military was continuously engaged in armed conflict in Iraq and Afghanistan between 2003 and 2014, resulting in 629 UK fatalities. Traumatic cardiac arrest (TCA) is a precursor to traumatic death, but data on military outcomes are limited. In order to better inform military treatment protocols, the aim of this study was to define the epidemiology of TCA in the military population with a particular focus on survival rates and injury patterns.

Methods

A retrospective database analysis of the UK Joint Theatre Trauma Registry was undertaken. Patients who were transported to a UK deployed hospital between 2003 and 2014 and suffered TCA were included. Those patients injured by asphyxiation, electrocution, burns without other significant trauma and drowning were excluded. Data included mechanism of injury, Injury Severity Score (ISS), Abbreviated Injury Scale (AIS) for each body region and survival to deployed (Role 3) field hospital discharge.

Results

424 TCA patients were identified during the study period; median age was 23 years, with a median ISS of 45. The most common mechanism of injury was explosive (55.7%), followed by gunshot wound (38.9%), road traffic collision (3.5%), crush (1.7%) and fall (0.2%). 45 patients (10.6% (95% CI 8.0% to 13.9%)) survived to deployed (Role 3) hospital discharge. The most prevalent body region with a severe to maximum AIS injury was the head, followed by the lower limbs, thorax and abdomen. Haemorrhage secondary to abdominal and lower limb injury was associated with survival; traumatic brain injury was associated with death.

Conclusions

This study has shown that short-term survival from TCA in a military population is 10.6%. With appropriate and aggressive early management, although unlikely, survival is still potentially possible in military patients who suffer traumatic cardiac arrest.

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Over 40 children accidentally treated with drain cleaner instead of dental fluid

More than 40 children suffered burning sensations and blistering in their mouths after being accidentally given dental solution containing drain-cleaning fluid. http://ift.tt/2kuORuH http://ift.tt/2gl62dE More than 40 children suffered burning sensations and blistering in their mouths after being accidentally given dental solution containing drain-cleaning fluid.

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Response to the Letter to the Editor Regarding “Kinetics of Radiological Response of Thoracic Invasive Fungal Disease in Chronic Granulomatous Disease”

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The effects of diosmin on aflatoxin-induced liver and kidney damage

Abstract

Aflatoxin is among the natural toxins that cause serious side effects on living things. Diosmin is also one of the compounds with broad pharmacological effects. In this study, the effects on the oxidant/antioxidant system of 50 mg/kg body weight/day dose of diosmin, aflatoxin (500 μg/kg body weight/day), and combined aflatoxin (500 μg/kg body weight/day) plus diosmin (50 mg/kg body weight/day) given to the stomach via catheter female adult Wistar Albino rats is examined. Forty rats were used in the experiment, and these animals were randomly allocated to four equal groups. The test phase lasted 21 days, and blood samples and tissue (liver and kidney) samples were taken after this period was over. Some biochemical parameters (glucose, triglyceride, cholesterol, blood urea nitrogen, creatinine, uric acid, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total protein, albumin) and levels of malondialdehyde, nitric oxide, and 4-hydroxynonenal and activities of superoxide dismutase, catalase, and glutathione peroxidase were analyzed in the samples. The aflatoxin administered over the period indicated a significant increase in levels of malondialdehyde (MDA), nitric oxide (NO), and 4-hydroxynonenal (4-HNE) in all tissues and blood samples. Therewithal, the activity of antioxidant enzymes showed a change in the decreasing direction. Biochemical parameters of the group in which aflatoxin were administered alone changed unfavorably. Parallel effects were also observed in the histopathological findings of this group. The results showed that aflatoxin changed antioxidant/oxidant balance in favor of oxidant and eventually led to lipid peroxidation. Diosmin administration to aflatoxin-treated animals resulted in positive changes in antioxidant enzyme activities while the levels of MDA, NO, and 4-HNE were reduced in all tissues and blood samples examined. Diosmin alleviates the oxidative stress caused by aflatoxin. Similar improvement was observed in biochemical parameters of this group as well as in liver and kidney histopathology. No significant change was observed in the group treated with diosmin alone in terms of the parameters examined and histologic findings. As a result, diosmin may be included in compounds that can be used as a therapeutic and prophylactic agent in the event of the formation of aflatoxin exposure and poisoning in animals.

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Assessing Frailty and Vulnerability in Older Adults with Cancer

Abstract

Purpose of Review

Aging is associated with decreased physiologic reserve, and older adults are more susceptible to cancer treatment toxicity. In this review, we discuss the implications of frailty and vulnerability in older patients with cancer. We also review a number of instruments that can be used to assess frailty and vulnerability and propose a practical approach to incorporate these tools in a general oncology or geriatric clinic.

Recent Findings

In older patients with cancer, frailty and vulnerability are associated with all-cause mortality, postoperative complications, and treatment intolerance/toxicities. If feasible, a comprehensive geriatric assessment should be used to assess of frailty and vulnerability. If a full geriatric assessment cannot be performed, screening tools such as the Balducci's criteria, Vulnerable Elders Survey-13, Triage Risk Screening Tool, Groningen Frailty Index, and Geriatric 8 may be used.

Summary

Future studies should evaluate geriatric assessment domains that have the greatest predictive value for toxicity for each cancer type and treatment.

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Bounded Subsets of Classes of Holomorphic Functions

Some characterizations of boundedness in will be described, where are -algebras which consist of holomorphic functions defined by maximal functions.

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Recent Advances in Nanoparticles Enhanced Oil Recovery: Rheology, Interfacial Tension, Oil Recovery, and Wettability Alteration

Chemically enhanced oil recovery methods are utilized to increase the oil recovery by improving the mobility ratio, altering the wettability, and/or lowering the interfacial tension between water and oil. Surfactants and polymers have been used for this purpose for the last few decades. Recently, nanoparticles have attracted the attention due to their unique properties. A large number of nanoparticles have been investigated for enhanced oil recovery applications either alone or in combination with surfactants and/or polymers. This review discusses the various types of nanoparticles that have been utilized in enhanced oil recovery. The review highlights the impact of nanoparticles on wettability alteration, interfacial tension, and rheology. The review also covers the factors affecting the oil recovery using nanoparticles and current challenges in field implementation.

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In Vitro Evaluation of Essential Oils Derived from Piper nigrum (Piperaceae) and Citrus limonum (Rutaceae) against the Tick Rhipicephalus (Boophilus) microplus (Acari: Ixodidae)

The present research aimed to study the chemical composition and acaricidal activity of Citrus limonum and Piper nigrum essential oils against the cattle tick Rhipicephalus microplus. GC-MS analysis of C. limonum essential oil showed limonene (50.3%), β-pinene (14.4%), and γ-terpinene (11.7%) as the major components; P. nigrum oil was mainly composed of β-caryophyllene (26.2%), σ-ocymene (5.8%), and α-pinene (5.5%). Acaricide activity was evaluated at concentrations of 2.5, 5.0, and 10.0% (v/v) of each plant oil, as well as 1 : 1 combination of both oils (5% : 5%, 2.5% : 2.5%, and 1.25% : 1.25% each), by immersing engorged R. microplus females for one minute. The LC90 of oils from C. limonum, P. nigrum, and the combination were 4.9%, 14.8%, and 5.1%, respectively. C. limonum essential oil caused 100% mortality of engorged females at the highest concentration (10%). P. nigrum essential oil inhibited egg-laying by up to 96% in a concentration-dependent manner, suggesting it reduces tick fecundity. When combined, the oils presented toxicity as to C. limonum oil alone, but with stronger inhibition of oviposition (5% : 5%), indicating a possible additive effect against R. microplus. The present data provide support for further investigation of novel natural products to control bovine tick infestations.

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Output Feedback Finite-Time Stabilization of Systems Subject to Hölder Disturbances via Continuous Fractional Sliding Modes

The problem of designing a continuous control to guarantee finite-time tracking based on output feedback for a system subject to a Hölder disturbance has remained elusive. The main difficulty stems from the fact that such disturbance stands for a function that is continuous but not necessarily differentiable in any integer-order sense, yet it is fractional-order differentiable. This problem imposes a formidable challenge of practical interest in engineering because (i) it is common that only partial access to the state is available and, then, output feedback is needed; (ii) such disturbances are present in more realistic applications, suggesting a fractional-order controller; and (iii) continuous robust control is a must in several control applications. Consequently, these stringent requirements demand a sound mathematical framework for designing a solution to this control problem. To estimate the full state in finite-time, a high-order sliding mode-based differentiator is considered. Then, a continuous fractional differintegral sliding mode is proposed to reject Hölder disturbances, as well as for uncertainties and unmodeled dynamics. Finally, a homogeneous closed-loop system is enforced by means of a continuous nominal control, assuring finite-time convergence. Numerical simulations are presented to show the reliability of the proposed method.

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Redox Regulation of Inflammatory Processes Is Enzymatically Controlled

Redox regulation depends on the enzymatically controlled production and decay of redox active molecules. NADPH oxidases, superoxide dismutases, nitric oxide synthases, and others produce the redox active molecules superoxide, hydrogen peroxide, nitric oxide, and hydrogen sulfide. These react with target proteins inducing spatiotemporal modifications of cysteine residues within different signaling cascades. Thioredoxin family proteins are key regulators of the redox state of proteins. They regulate the formation and removal of oxidative modifications by specific thiol reduction and oxidation. All of these redox enzymes affect inflammatory processes and the innate and adaptive immune response. Interestingly, this regulation involves different mechanisms in different biological compartments and specialized cell types. The localization and activity of distinct proteins including, for instance, the transcription factor NFκB and the immune mediator HMGB1 are redox-regulated. The transmembrane protein ADAM17 releases proinflammatory mediators, such as TNFα, and is itself regulated by a thiol switch. Moreover, extracellular redox enzymes were shown to modulate the activity and migration behavior of various types of immune cells by acting as cytokines and/or chemokines. Within this review article, we will address the concept of redox signaling and the functions of both redox enzymes and redox active molecules in innate and adaptive immune responses.

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Response to the letter to the editor regarding “The outcomes of overlay myringoplasty: Endoscopic versus microscopic approach”

We would like to thank Prof. Zheng-Cai Lou [1] for his interest in our study entitled "The outcomes of overlay myringoplasty: Endoscopic versus microscopic approach" [2] and we appreciate the useful comments. His main concerns will be discussed below.

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Occlusal loading during biting from an experimental and simulation point of view

Publication date: Available online 7 October 2017
Source:Dental Materials
Author(s): Oliver Röhrle, Harnoor Saini, David C. Ackland
ObjectivesOcclusal loading during clenching and biting is achieved by the action of the masticatory system, and forms the basis for the evaluation of the functional performance of prosthodontic and maxillofacial components. This review provides an overview of (i) current bite force measurement techniques and their limitations and (ii) the use of computational modelling to predict bite force. A brief simulation study highlighting the challenges of current computational dental models is also presented.MethodsAppropriate studies were used to highlight the development and current bite force measurement methodologies and state-of-the-art simulation for computing bite forces using biomechanical models.ResultsWhile a number of strategies have been developed to measure occlusal forces in three-dimensions, the use of strain-gauges, piezo-electric sensors and pressure sheets remain the most widespread. In addition to experimental-based measurement techniques, bite force may be also estimated using computational models of the masticatory system. Simulations of different bite force models clearly show that the use of three-dimensional force measurements enriches the evaluation of masticatory functional performance.SignificanceHence, combining computational modelling with three-dimensional force measurement techniques can significantly improve the evaluation of masticatory system and the functional performance of prosthodontic components.



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Mixed-mode fracture toughness of texturized LS2 glass-ceramics using the three-point bending with eccentric notch test

Publication date: Available online 7 October 2017
Source:Dental Materials
Author(s): Renan Belli, Michael Wendler, Anselm Petschelt, Ulrich Lohbauer
Here we use the 3-point bending with eccentric notch test (3-PBEN) to investigate the fracture behavior of a pressable and a CAD/CAM lithium disilicate (LS2) glass-ceramics under combined mode-I and mode-II loading. The effect of the bulk texturization in the beams of the pressable LS2 is made visible through the fracture trajectory following the most energetically favorable path dictated by the crystallite alignment. The CAD/CAM LS2 shows an isotropic fracture mode but increasing fracture energy with mode-II contribution, similar to the pressable variant.



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Differential cytotoxic effects on odontoblastic cells induced by self-adhesive resin cements as a function of the activation protocol

Publication date: Available online 7 October 2017
Source:Dental Materials
Author(s): Paulo Henrique Perlatti D'Alpino, Gioconda Emanuella Diniz de Dantas Moura, Silvana Coelho de Arruda Barbosa, Lygia de Azevedo Marques, Marcos Nogueira Eberlin, Fábio Dupart Nascimento, Ivarne Luis dos Santos Tersariol
ObjectivesTo evaluate the cytotoxic effects of exposing odontoblast cells to a variety of commercial self-adhesive cements polymerized using different activation modes.MethodsFive cements: MaxCem Elite (MAX), Bifix SE (BSE), G-Cem LinkAce (GCE), Clearfil SA Luting (CAS), and RelyX U200 (U200) were mixed, dispensed into molds, and distributed in groups, according to polymerization protocols: immediate photoactivation; delayed photoactivation (10min self-curing plus light-activation); and chemical activation (no light exposure). Immortalized rat odontoblast cells (MDPC-23) were cultured. Cell viability was assessed by Trypan Blue staining and total cell death was assessed by annexin V-APC/7-AAD double staining and flow cytometry. Volatilized compounds from polymerized specimens of cements were evaluated by gas chromatography/mass spectrometry (GC–MS). Data was analyzed with 2-way ANOVA/Tukey tests (α=0.05).ResultsExposure to all of the cements tested significantly reduced the cell viability, irrespective of the activation protocol (p<0.05). The least harmful cements were CSA and U200. Total death of cells significantly increased when exposed to BSE, GCE, and MAX, especially when chemically activated (p<0.05). Characteristic apoptotic cells increased after exposure to cements, mainly for MAX, regardless of the activation mode. Chemical activation of MAX also induced necrosis. Moreover, GCE and MAX exhibited higher percentages of late apoptotic/dead cells. Chromatograms revealed 28 compounds released from the cements tested, some of them with known carcinogenic effects. Selection of self-adhesive cements and polymerization protocols affect the cytotoxicity and cell viability of odontoblastic cells.Clinical significanceDespite the simplified cementation protocol, care is needed when cementing indirect restorations with self-adhesive cements, especially on recently exposed dentin. This category of material may cause differential cytotoxic effects and should be considered when selecting a cement. This is particularly true in clinical cases of light attenuation, where the polymerization depends on chemical activation, inducing higher cytotoxic damages when using some of the cements tested.



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ADM guidance-ceramics: Fatigue principles and testing

Publication date: Available online 7 October 2017
Source:Dental Materials
Author(s): J.R. Kelly, P.F. Cesar, S.S. Scherrer, A. Della Bona, R. van Noort, M. Tholey, A. Vichi, U. Lohbauer
BackgroundClinical failure of dental ceramics is usually reported as partial fracture of the restoration (chipping) or as catastrophic fracture of the whole structure. In contrast to metals, ceramics are linear-elastic, brittle materials exhibiting extremely low damage tolerance to failure. Well documented clinical and lab reports have shown this fracture event often occurs at loads far below their fracture strength due to intrinsic fatigue degradation via slow crack growth or cyclic fatigue mechanisms. The presence and development of surface flaws have a dominant role in damage accumulation and lifetime reduction of ceramic structures.AimsThis ADM guidance document aims to summarize the aspects related to fatigue degradation of dental ceramics, reviewing the concepts of fatigue testing and furthermore aims to provide practical guidance to young scientists entering into fatigue related research. The description of fatigue strength is always accompanied by a clear understanding of the underlying fracture mechanisms.



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Response to the letter to the editor regarding “The outcomes of overlay myringoplasty: Endoscopic versus microscopic approach”

We would like to thank Prof. Zheng-Cai Lou [1] for his interest in our study entitled "The outcomes of overlay myringoplasty: Endoscopic versus microscopic approach" [2] and we appreciate the useful comments. His main concerns will be discussed below.

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The use of natural compounds for the targeting and chemoprevention of ovarian cancer

Among gynaecological cancers, ovarian cancer represents the leading cause of death in women. Current treatment for ovarian cancer entails surgery followed by combined chemotherapy with platinum and taxane, which are associated, particularly cisplatin, with severe side effects. While this treatment approach appears to be initially effective in a high number of patients, nearly 70% of them suffer a relapse within a few months after initial treatment. Therefore, more effective and better-tolerated treatment options are clearly needed.

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Direct tracheobronchopexy via left lateral thoracotomy for severe tracheobronchomalacia

An infant with pulmonary atresia/ventricular septal defect/major aortopulmonary collateral arteries underwent unifocalization, ventriculoseptal defect closure and placement of a right ventricle to pulmonary artery conduit via median sternotomy. Aortopexy and pulmonary arteriopexy via redo sternotomy were insufficient to allow weaning of continuous positive airway pressure and he required direct tracheobronchopexy via left lateral thoracotomy to alleviate posterior trachealis intrusion along the length of the trachea and left main bronchus.

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Pain control following tonsillectomy in children: A survey of patients

This prospective study aimed to survey pediatric patients and their parents after tonsillectomy to assess their pain management utilization and satisfaction.

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Supraglottoplasty for laryngomalacia: The experience from Concepcion, Chile

To review the clinical manifestations and outcomes of supraglottoplasty in patients with moderate to severe laryngomalacia at Guillermo Grant Benavente Hospital between January 2015 and January 2017.

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Direct tracheobronchopexy via left lateral thoracotomy for severe tracheobronchomalacia

An infant with pulmonary atresia/ventricular septal defect/major aortopulmonary collateral arteries underwent unifocalization, ventriculoseptal defect closure and placement of a right ventricle to pulmonary artery conduit via median sternotomy. Aortopexy and pulmonary arteriopexy via redo sternotomy were insufficient to allow weaning of continuous positive airway pressure and he required direct tracheobronchopexy via left lateral thoracotomy to alleviate posterior trachealis intrusion along the length of the trachea and left main bronchus.

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Pain control following tonsillectomy in children: A survey of patients

This prospective study aimed to survey pediatric patients and their parents after tonsillectomy to assess their pain management utilization and satisfaction.

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Supraglottoplasty for laryngomalacia: The experience from Concepcion, Chile

To review the clinical manifestations and outcomes of supraglottoplasty in patients with moderate to severe laryngomalacia at Guillermo Grant Benavente Hospital between January 2015 and January 2017.

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Cancer associated fibroblasts (CAFs) are activated in cutaneous basal cell carcinoma and in the peritumoural skin

Cutaneous basal cell carcinoma (BCC) is the commonest cancer worldwide. BCC is locally invasive and the surrounding stromal microenvironment is pivotal for tumourigenesis. Cancer associated fibroblasts (CAFs) ...

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Estimation of cresyl and xylyl contents in phosphate esters-based fire resistance hydraulic fluids by nuclear magnetic resonance spectroscopy

Abstract

In this work, a new analytical approach based on proton nuclear magnetic resonance spectroscopy has been optimized for the direct estimation of different phenolic components in a phosphate ester sample. In high resonance proton nuclear magnetic resonance spectrum of fire resistance hydraulic fluids, methyl protons of cresyl, xylyl, and other phosphates (ethyl, propyl, and butyl) are unambiguously distinguished by their different chemical shift and used for quantitative estimation. The developed methodology was validated by analyzing different synthetic blends prepared in lab and few fully formulated fire resistance hydraulic fluids. The methodology is fast, nondestructive, and useful for development of new products and troubleshooting.

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Re: Heat generation and drill wear during dental implant site preparation

We studied with interest the paper "Heat generation and drill wear during dental implant site preparation: systematic review" by Möhlhenrich et al, which provides valuable data about drilling bone. They describe "drill material" as "zirconium coated with steel", whereas because of the mechanical and thermal stresses at the interface of the drill and the bone, the material's resistance to wear must be a coating for the drill.1

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Re: Heat generation and drill wear during dental implant site preparation: systematic review

We thank you for your interest in our study as well as your valuable comments. You are of course right that "zirconium coated with steel" does not make sense and, furthermore, that the material of the drills used by Harder et al.1 was zirconium oxide and not zirconium. We apologise for any inconvenience caused.

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Chronic recurrent dislocation of the temporomandibular joint secondary to a complex facial tic disorder

We report the case of a 14-year-old boy who presented to the emergency department with bilateral dislocation of the temporomandibular joint (TMJ) of unusual aetiology. He had recently developed a repetitive action that involved thrusting the jaw forwards, which involved maximal mouth opening. This had preceded the dislocation of the TMJ two hours previously.

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Anatomy of the vasculature of the lower leg and harvest of a fibular flap: a systematic review

The fibular free flap (FFF) is based on the peroneal artery, which has a consistent anatomy and makes a minimal contribution to the pedal circulation. However, certain anatomical variations in the vasculature of the leg might leave the peroneal artery with a major role in the perfusion of the foot, and to raise a FFF could lead to ischaemic complications. Our aim was to review the implications of anatomical variants on planning and harvest of a FFF. We systematically reviewed all relevant publications, and included 28 cases that described a dominant peroneal artery and FFF.

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Prevalence of sleep apnea at the acute phase of ischemic stroke with or without thrombolysis

The aim of the study was to compare the prevalence, type, and severity of sleep apnea during the acute phase of ischemic stroke among patients either receiving or not receiving thrombolysis.

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Sleep Characteristics Associated With Drowsy Driving

The aim of this study was to evaluate sleep characteristics associated with drowsy driving in an adult population.

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Effect of sodium oxybate, modafinil, and their combination on disrupted nighttime sleep in narcolepsy

To assess the effects of three narcolepsy treatment modalities on sleep stage shifts associated with disrupted nighttime sleep (DNS) using data from a clinical trial.

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Specific motor patterns of arousal disorders in adults: A video-polysomnographic analysis of 184 episodes

To compile an objective accurate description of the motor patterns of adult arousal disorders (ADs).

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Antibiotics prescribed by dentists may contribute to serious C. diff infections

Antibiotics prescribed by dentists may contribute to the growing problem of Clostridium difficile , a serious and potentially deadly infection that causes severe diarrhea, suggests research presented at IDWeek 2017. And many of those antibiotics are likely unnecessary, researchers note.

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The use of natural compounds for the targeting and chemoprevention of ovarian cancer

Among gynaecological cancers, ovarian cancer represents the leading cause of death in women. Current treatment for ovarian cancer entails surgery followed by combined chemotherapy with platinum and taxane, which are associated, particularly cisplatin, with severe side effects. While this treatment approach appears to be initially effective in a high number of patients, nearly 70% of them suffer a relapse within a few months after initial treatment. Therefore, more effective and better-tolerated treatment options are clearly needed.

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A randomised trial comparing three Delphi feedback strategies found no evidence of a difference in a setting with high initial agreement

To explore the impact of different feedback strategies on 1) subsequent agreement and 2) variability in Delphi studies.

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Etiology of community-onset monomicrobial bacteremic pneumonia and its clinical presentation and outcome: Klebsiella and Pseudomonas matters

Publication date: Available online 7 October 2017
Source:Journal of Infection and Chemotherapy
Author(s): Chao-Yung Yang, Chung-Hsun Lee, Chih-Chia Hsieh, Wen-Chien Ko, Ching-Chi Lee
To describe the difference of the clinical features, bacteremia severity, and outcome of patient with community-onset bacteremic pneumonia between Pseudomonas, Klebsiella, and other causative microorganisms, the total 278 adults with community-onset monomicrobial bacteremic pneumonia were studied in a retrospective cohort. Klebsiella (61 patients, 21.9%) and Pseudomonas (22, 7.9%) species was the leading and the fifth common pathogen, respectively. More patients having initial presentation with critical illness (a Pitt bacteremia score ≥ 4) and a fatal comorbidity (McCabe classification) as well as a higher short- (30-day) or long-term (90-day) mortality rate was evidenced in patients infected with Klebsiella or Pseudomonas species, compared to other causative microorganisms. Compared to patients in the Klebsiella group, more frequencies of recent chemotherapy and an initial presentation of febrile neutropenia, and less proportions of diabetes mellitus were disclosed among those in the Pseudomonas group. Of importance, a significantly differential survival curve between Klebsiella or Pseudomonas species and other species during 30-day or 90-day period after bacteremia onset but a similarity of Pseudomonas and Klebsiella species was evidenced, using the Cox-regression after adjusting the independent predictors of 30-day mortality. Conclusively, of pathogens causing community-onset bacteremic pneumonia, Klebsiella and Pseudomonas species should be recognized as the highly virulent pathogens and resulted in poor short- and long-term prognoses.



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Nanoscale wide-band semiconductors for photocatalytic remediation of aquatic pollution

Abstract

Water pollution is a serious challenge to the public health. Among different forms of aquatic pollutants, chemical and biological agents create paramount threat to water quality when the safety standards are surpassed. There are many conventional remediatory strategies that are practiced such as resin-based exchanger and activated charcoal/carbon andreverse osmosis. Newer technologies using plants, microorganisms, genetic engineering, and enzyme-based approaches are also proposed for aquatic pollution management. However, the conventional technologies have shown impending inadequacies. On the other hand, new bio-based techniques have failed to exhibit reproducibility, wide specificity, and fidelity in field conditions. Hence, to solve these shortcomings, nanotechnology ushered a ray of hope by applying nanoscale zinc oxide (ZnO), titanium dioxide (TiO₂), and tungsten oxide (WO₃) particles for the remediation of water pollution. These nanophotocatalysts are active, cost-effective, quicker in action, and can be implemented at a larger scale. These nanoparticles are climate-independent, assist in complete mineralization of pollutants, and can act non-specifically against chemically and biologically based aquatic pollutants. Photocatalysis for environmental remediation depends on the availability of solar light. The mechanism of photocatalysis involves the formation of electron-hole pairs upon light irradiations at intensities higher than their band gap energies. In the present review, different methods of synthesis of nanoscale ZnO, TiO₂, and WO₃ as well as their structural characterizations have been discussed. Photodegradation of organic pollutants through mentioned nanoparticles has been reviewed with recent advancements. Enhancing the efficacy of photocatalysis through doping of TiO₂ and ZnO nanoparticles with non-metals, metals, and metal ions has also been documented in this report.

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NUDT21 regulates 3′-UTR length and microRNA-mediated gene silencing in hepatocellular carcinoma

Publication date: 1 December 2017
Source:Cancer Letters, Volume 410
Author(s): Meng Sun, Junyao Ding, Dali Li, Guoping Yang, Zeneng Cheng, Qubo Zhu
Recent studies have shown that several microRNAs (miRNAs) are involved in hepatocellular carcinoma (HCC) tumorigenesis and metastasis; however, the mechanisms responsible for the differences in the functions of these miRNAs in liver cancer remain a mystery. In our previous study, we identified NUDT21 as an interaction partner of argonaute 2 (AGO2). NUDT21 has been reported to be involved in alternative polyadenylation (APA); thus, the interaction between NUDT21 and AGO2 may be a key component of the crosstalk between APA and miRNA-mediated gene silencing in HCC. Our data showed that NUDT21 expression was decreased in HCC. Moreover, our results showed that NUDT21 co-localized with AGO2 in P/GW bodies in normal liver cells; however, this co-localization was diminished in cancer cells. Functional studies showed that NUDT21 elongated the 3′-UTR of mRNA and enhanced the efficiency of miRNA-mediated gene silencing by increasing the efficiency of AGO2-mRNA binding, which played an important role in cell proliferation. In summary, loss of NUDT21 shortened the 3′-UTR of various oncogenes in HCC cells. The shorter 3′-UTR contained less miRNA binding sites, which enabled the oncogenes to evade miRNA regulation and become overexpressed in HCC, leading to unregulated cancer cell proliferation.



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Future Horizons in Allergy

Publication date: Available online 7 October 2017
Source:Otolaryngologic Clinics of North America
Author(s): Michael J. Marino, Amber U. Luong

Teaser

There are several advances in diagnosis and management for the otolaryngologist treating allergy. These include new technologies and the refinement of current techniques, and reflect overall trends in health care toward personalized medicine. Local immunoglobulin, urinary leukotriene E4, lipidomics, microRNA within extracellular vesicles, and optical rhinometry all offer to improve the diagnostic accuracy of allergy and related nonallergic conditions. New delivery systems for intranasal steroids and antihistamines, recombinant allergens, advances in allergen immunotherapy delivery, and biologics will improve current management options. These developments will aid the otolaryngologist in diagnosing and treating allergy and related diseases.


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The Role of Allergy in Otologic Disease

Publication date: Available online 7 October 2017
Source:Otolaryngologic Clinics of North America
Author(s): Betty Yang, Christopher D. Brook

Teaser

Allergy is commonly associated with conditions such as rhinitis, sinusitis, and asthma, but the relationship between allergy and otologic diseases is less clear. This article examines the evidence for a relationship between allergic disease and several common otologic conditions, including otitis media with effusion, eosinophilic otitis media, and Ménière's disease.


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Genetic parameters for growth performance, fillet traits, and fat percentage of male Nile tilapia ( Oreochromis niloticus )

Abstract

Improvement of fillet traits and flesh quality attributes are of great interest in farmed tilapia and other aquaculture species. The main objective of this study was to estimate genetic parameters for fillet traits (fillet weight and fillet yield) and the fat content of fillets from 1136 males combined with 2585 data records on growth traits (body weight at 290 days, weight at slaughter, and daily weight gain) of 1485 males and 1100 females from a third generation of the Aquaamerica tilapia strain. Different models were tested for each trait, and the best models were used to estimate genetic parameters for the fat content, fillet, and growth traits. Genetic and phenotypic correlations were estimated using two-trait animal models. The heritability estimates were moderate for the fat content of fillets and fillet yield (0.2–0.32) and slightly higher for body weight at slaughter (0.41). The genetic correlation between fillet yield and fat was significant (0.6), but the genetic correlations were not significant between body weight and fillet yield, body weight and fat content, daily weight gain and fillet yield, and daily weight gain and fat content (− 0.032, − 0.1, − 0.09, and − 0.4, respectively). Based on the genetic correlation estimates, it is unlikely that changes in fillet yield and fat content will occur when using growth performance as a selection criterion, but indirect changes may be expected in fat content if selecting for higher fillet yield.

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Impact of a Pharmacist-Driven Care Package on Staphylococcus aureus Bacteremia Management in a Large Community Healthcare Network: A Propensity Score Matched, Quasi-Experimental Study

Publication date: Available online 7 October 2017
Source:Diagnostic Microbiology and Infectious Disease
Author(s): Jordan R. Smith, Jeremy J. Frens, Cynthia B. Snider, Kimberly C. Claeys
ObjectivesStaphylococcus aureus bacteremia (SAB) is an important cause of morbidity and mortality. Suboptimal treatment has been associated with poor patient outcomes. Our antimicrobial stewardship program (ASP) evaluated SAB management based on predefined performance measures both prior to and after instituting a "care package" intervention led by clinical pharmacists and infectious diseases physicians. The primary outcome included a 4-point "optimal care score" (OCS) consisting of targeted antibiotic therapy within 24hours, repeating blood cultures, antibiotic duration assessment, and appropriate duration of therapy. The presence of an ID consult, SAB readmission and mortality were also assessed.MethodsThis was a quasi-experimental, propensity score matched study of SAB management. Adult patients were retrospectively evaluated from October 2011 – October 2012, and intervention took place from November 2013 – December 2015. Intervention consisted of a clinical pharmacist contacting the primary team after identification of SAB to recommend 1) appropriate antibiotics within 24hours, 2) repeat blood cultures to document clearance, 3) assessment for metastatic infection, 4) and appropriate duration of therapy. These constituted the 4-point OCS. ID consult was also recommended. Patients were propensity score matched 1:2 based on age, diabetes, presence of hardware, methicillin-resistant S. aureus (MRSA) isolate, and stratified infectious source. Patients ≥18 with SAB were included.ResultsIntervention was associated with improved adherence to each metric within the OCS, and more patients in the intervention cohort achieved a perfect OCS of 4. Intervention was associated with a lower rate of readmission and mortality.ConclusionA pharmacist-driven, ASP intervention on SAB therapy was associated with increased adherence to core SAB care metrics and reduced relapse and mortality.



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PAK4 crystal structures suggest unusual kinase conformational movements

Publication date: Available online 7 October 2017
Source:Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
Author(s): Eric Y. Zhang, Byung Hak Ha, Titus J. Boggon
In order for protein kinases to exchange nucleotide they must open and close their catalytic cleft. These motions are associated with rotations of the N-lobe, predominantly around the 'hinge region'. We conducted an analysis of 28 crystal structures of the serine-threonine kinase, p21-activated kinase 4 (PAK4), including three newly determined structures in complex with staurosporine, FRAX486, and fasudil (HA-1077). We find an unusual motion between the N-lobe and C-lobe of PAK4 that manifests as a partial unwinding of helix αC. Principal component analysis of the crystal structures rationalizes these movements into three major states, and analysis of the kinase hydrophobic spines indicates concerted movements that create an accessible back pocket cavity. The conformational changes that we observe for PAK4 differ from previous descriptions of kinase motions, and although we observe these differences in crystal structures there is the possibility that the movements observed may suggest a diversity of kinase conformational changes associated with regulation.Author summaryProtein kinases are key signaling proteins, and are important drug targets, therefore understanding their regulation is important for both basic research and clinical points of view. In this study, we observe unusual conformational 'hinging' for protein kinases. Hinging, the opening and closing of the kinase sub-domains to allow nucleotide binding and release, is critical for proper kinase regulation and for targeted drug discovery. We determine new crystal structures of PAK4, an important Rho-effector kinase, and conduct analyses of these and previously determined structures. We find that PAK4 crystal structures can be classified into specific conformational groups, and that these groups are associated with previously unobserved hinging motions and an unusual conformation for the kinase hydrophobic core. Our findings therefore indicate that there may be a diversity of kinase hinging motions, and that these may indicate different mechanisms of regulation.

Graphical abstract

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