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Δευτέρα 13 Μαρτίου 2017

Plated-rich plasma for androgenetic alopecia: Does it work? Evidence from meta analysis

Summary

Introduction

The use of plated-rich plasma (PRP) has increased among different surgical specialities for the treatment of various conditions. Androgenetic alopecia is a common condition, with severe attendant psychosocial implications. PRP injections for hair restoration have become a popular practice among plastic surgeons. We performed a meta-analysis comparing local injection of plated-rich plasma versus control to evaluate this issue in order to investigate the effectiveness of PRP local injections for androgenetic alopecia.

Methods

A systematic literature search was performed. Primary outcome was the increase in number of hairs. Secondary outcomes were the increase in hair thickness and the percentage increase in hair number and thickness. We performed random-effect analysis.

Results

Six studies involving 177 patients were retrieved and included in the present analysis. A significantly locally increased hair number per cm2 was observed after PRP injections versus control (mean difference (MD) 17.90, 95%CI 5.84-29.95, P=.004). Similarly, a significantly increased hair thickness cross section per 10−4 mm2 (MD 0.22, 95%CI 0.07-0.38, P=.005) favoring PRP group. The pooled results did not show statistically significant differences in percentage increase in hair number (MD 24.12%, 95%CI −12.76-60.99, P=.20) and hair thickness (MD 32.63%, 95%CI −16.23-81.48, P=0.19) among patients treated with PRP.

Conclusions

Local injection of PRP for androgenic alopecia might be associated with an increased number of hairs and some hair thickness improvement in the treated areas with minimal morbidity. The results of this meta-analysis should be interpreted with caution as it consists of pooling many small studies. Larger randomized studies can verify this perception.



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Simvastatin-associated dermatomyositis



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Adverse effects of isotretinoin: A large, retrospective review

Abstract

Acne is a very common and disfiguring disease that affects mostly adolescents and, to some extent, adults. The objective of our study was to estimate the adverse effects after isotretinoin by treatment of 3,525 patients due to acne vulgaris in a 5-year observation. Retrospective, comparative study was carried out in Poland and Romania from January 2012 to August 2016. Inclusion criteria into this study were moderate, severe, and nodulocystic inflammatory acne vulgaris. Exclusion criteria were mild acne, pregnant, and lactating women. Statistical analysis was carried out using T test and Chi square. All patients were treated with oral isotretinoin. Patient age ranged from 13-35 years. Dry lips was the most commonly reported adverse effect, affecting 100% of users, followed by xerosis (94.97%) and facial erythema (66.21%). Of all adverse effects, psychiatric symptoms accounted for 25.16%; eye lesions accounted for 8.96%. In lab investigations an increase in the level of total cholesterol and serum triglycerides was observed. This study documents the adverse effect profile of isotretinoin in a large number of patients collected over a period of 4 years. Side effects were mild and well tolerated and did not necessitate stopping the treatment. However, it is important to educate patients about this potential consequence.



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Successful treatment to a tretinoin/clindamycin gel in a late onset of nevus comedonicus



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Therapeutic Potential, Challenges and Future Perspective of Cancer Stem Cells in Translational Oncology: A Critical Review

Stem cell research is a rapidly developing field that offers effective treatment for a variety of malignant and non-malignant diseases. Stem cell is a regenerative medicine associated with the replacement, repair, and restoration of injured tissue. Stem cell research is a promising field having maximum therapeutic potential. Cancer stem cells (CSCs) are the cells within the tumor that posses capacity of selfrenewal and have a root cause for the failure of traditional therapies leading to re-occurrence of cancer. CSCs have been identified in blood, breast, brain, and colon cancer. Traditional therapies target only fast growing tumor mass, but not slow-dividing cancer stem cells. It has been shown that embryonic pathways such as Wnt, Hedgehog and Notch, control self-renewal capacity and involved in cancer stem cell maintenance. Targeting of these pathways may be effective in eradicating cancer stem cells and preventing chemotherapy and radiotherapy resistance. Targeting CSCs has become one of the most effective approaches to improve the cancer survival by eradicating the main root cause of cancer. The present review will address, in brief, the importance of cancer stem cells in targeting cancer as better and effective treatment along with a concluding outlook on the scope and challenges in the implication of cancer stem cells in translational oncology.

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Role of Imaging in Testicular Cancer

Testicular malignancy is the most common nonhematologic malignancy in young men. Around 95% of them are germ cell tumors (GCTs), and with correct assessment of the disease and application of chemotherapy and radiotherapy survival rates of more than 90% can be achieved. Imaging studies not only aid in the diagnosis of testicular cancer but also help determine the tumor extent and site of metastatic disease, in monitoring treatment response, surgical planning and detecting sites of relapse and residual disease. Scrotal sonography combined with clinical examination has a high sensitivity for diagnosing testicular cancer and thus is often the first imaging modality to be performed on patients presenting with testicular mass. Abdominal and pelvic CT and chest CT remain the preferred techniques for staging, monitoring of treatment response, and detecting relapse and residual disease in patients with testicular cancer but MRI, PET with 18F-FDG (fluorodeoxyglucose) and sonography also show promises in certain situations. This article reviews the literatures on the role of imaging in the management of testicular germ cell cancer.

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Cancer Associated Thrombosis: Focus on Prevention and Treatment of Venous Thromboembolism

Cancer-associated thrombosis (CAT) accounts for about 20% of all thrombosis worldwide. It is the second leading cause of death in cancer patients. The risk of venous thromboembolism (VTE) is 4 -7 times higher and the risk of recurrent VTE three times higher in the cancer patients, compared to the non-cancer patients. The survival of cancer patients with VTE is lower than that of patients without VTE. In the last two decades, the incidence of CAT has risen in the ambulatory patients than in the inpatient setting. While the role of pharmacologic thromboprophylaxis (PTP) is established in the hospitalized cancer patients, ambulatory PTP is not, except in patients with multiple myeloma and myeloproliferative neoplasms. In the last decade, the low-molecular-weight heparin (LMWH) has emerged as the standard of care for the treatment of acute cancer-associated VTE. Many questions remain unanswered with regards to the optimal duration of LMWH therapy in the CAT, the role of direct oral anticoagulants (DOACs) in CAT, and the optimal anticoagulation management in thrombocytopenic cancer patients. Research trials are necessary to define a subset of ambulatory solid tumor patients who may benefit from PTP and to define the role of DOACs in the prevention and treatment of CAT.

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Review: Circulating microRNAs in Predicting the Prognosis of Gastrointestinal Cancers

Gastrointestinal cancers remain a significant health problem worldwide. Resistance to treatment in a subset of patients is a major problem and personalized treatment is expected to improve prognosis in these individuals. Assessment of biomarkers, which are generally genes, proteins, phosphoproteins and/or microRNAs (miRNAs), and their levels in tumor or blood, leads to a view of the molecular characteristics (signature) of a given patient's tumor and thus provides information that will enable personalized treatment. miRNAs are short noncoding RNAs that regulate gene expression at the post-transcriptional level. Deregulation of miRNA expression has been demonstrated in various cancers, including gastrointestinal (GI) cancers. The high stability of miRNAs in the blood circulation offers enormous advantage for prognostic applications as blood samples can be easily procured noninvasively. Circulating miRNAs have been demonstrated to be valuable instruments in prognosis of GI cancers. Additionally, serial collection of blood samples is possible for monitoring the progress of cancer, something that cannot be done reasonably with tumor tissue. We review previous reports that used circulating miRNAs as biomarkers in the prognosis of GI cancers, and also highlight the fascinating possibility of using the gathered information to identify new therapeutic targets.

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Different trajectories of decline for global form and global motion processing in ageing, Mild Cognitive Impairment and Alzheimer’s disease

Publication date: Available online 14 March 2017
Source:Neurobiology of Aging
Author(s): Gillian Porter, John Wattam-Bell, Antony Bayer, Judy Haworth, Oliver Braddick, Janette Atkinson, Andrea Tales
The visual processing of complex motion is impaired in Alzheimer's disease (AD). However, it is unclear whether these impairments are biased towards the motion stream or part of a general disruption of global visual processing, given some reports of impaired static form processing in AD. Here, for the first time, we directly compared the relative preservation of motion and form systems in AD, Mild Cognitive Impairment (MCI) and healthy ageing, by measuring coherence thresholds for well-established global rotational motion and static form stimuli known to be of equivalent complexity. Our data confirm a marked motion-processing deficit specific to some AD patients, and greater than any form-processing deficit for this group. In parallel, we identified a more gradual decline in static form recognition, with thresholds raised in MCI patients and slightly further in the AD group compared with controls. We conclude that complex motion processing is more vulnerable to decline in dementia than complex form processing, perhaps owing to greater reliance on long-range neural connections heavily targeted by AD pathology.



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Successful use of Bruton's kinase inhibitor, ibrutinib, to control paraneoplastic pemphigus in a patient with paraneoplastic autoimmune multiorgan syndrome and chronic lymphocytic leukaemia

Abstract

We present the case of a 51-year-old man who developed paraneoplastic pemphigus (PNP) in the context of chronic lymphocytic leukemia (CLL). His CLL was successfully controlled with ibrutinib. Concurrently, there was significant improvement of his PNP, suggesting that ibrutinib may be a very useful addition to the treatment options in this potentially life-threatening autoimmune disorder.



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The effect of rLH supplementation to the GnRH-antagonist protocol on endocrine dynamics in the advanced reproductive age

Abstract

Purpose

To explore serum endocrine dynamics, specifically LH levels, following rLH supplementation to rFSH following GnRH-antagonist treatment in the advance reproductive age.

Methods

Women were prospectively and similarly treated employing rFSH and the flexible GnRH-antagonist protocol, while rLH was supplemented only to the study group. Serum FSH, LH, E2, and P were evaluated throughout the follicular phase. Three strategies were a priori planned to examine endocrine dynamics among women enrolled.

Results

While serum LH drop were similar before GnRH-antagonist stimulation, it dropped more times in the control group compared to the study group. Among women receiving rFSH only, serum LH levels dropped ≤2, ≤1 and ≤0.5 mIU/mL in 71.4, 46.4, and 28.6% of cases, while this occurred only in 38.7% (P = 0.01), 6.5% (P = 0.0004) and 3.2% (P = 0.007) of women receiving combined rFSH and rLH treatment, respectively. The same trend was found when serum LH dropped in at least two occasions following the GnRH-antagonist administration. Conversely, serum LH diagrams throughout the follicular phase did not differ between the two groups. Furthermore, individual area under the curve values of LH, E2, and P was similar between the two groups following GnRH-antagonist initiation.

Conclusions

Different strategies to explore LH dynamics following the GnRH-antagonist administration have resulted in diverse results, implying the need for a consensus definition of LH threshold for adequate folliculogenesis and steroidogenesis. Such action would pave the way for understanding which groups of patients may benefit from rLH supplementation.



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Is Coronary Atherosclerosis One Disease or Many?: Setting Realistic Expectations for Precision Medicine.

Author: Khera, Amit V. MD; Kathiresan, Sekar MD
Page: 1005-1007


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The Gut Microbiome and Its Role in Cardiovascular Diseases.

Author: Tang, W. H. Wilson MD; Hazen, Stanley L. MD, PhD
Page: 1008-1010


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Releasing the Brakes on the Fibrinolytic System in Pulmonary Emboli: Unique Effects of Plasminogen Activation and [alpha]2-Antiplasmin Inactivation.

Author: Singh, Satish PhD; Houng, Aiilyan BS; Reed, Guy L. MD
Page: 1011-1020


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Thrombolytic Therapy Targeting Alpha 2-Antiplasmin.

Author: Urano, Tetsumei MD, PhD; Suzuki, Yuko MD, PhD
Page: 1021-1023


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Use of Intravenous Recombinant Tissue Plasminogen Activator in Patients With Acute Ischemic Stroke Who Take Non-Vitamin K Antagonist Oral Anticoagulants Before Stroke.

Author: Xian, Ying MD, PhD; Federspiel, Jerome J. MD, PhD; Hernandez, Adrian F. MD, MHS; Laskowitz, Daniel T. MD, MHS; Schwamm, Lee H. MD; Bhatt, Deepak L. MD, MPH; Smith, Eric E. MD, MPH; Fonarow, Gregg C. MD; Peterson, Eric D. MD, MPH
Page: 1024-1035


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Three Arterial Grafts Improve Late Survival: A Meta-Analysis of Propensity-Matched Studies.

Author: Gaudino, Mario MD; Puskas, John D. MD; Di Franco, Antonino MD; Ohmes, Lucas B. MD; Iannaccone, Mario MD; Barbero, Umberto MD; Glineur, David MD; Grau, Juan B. MD; Benedetto, Umberto MD; D'Ascenzo, Fabrizio MD; Gaita, Fiorenzo MD; Girardi, Leonard N. MD; Taggart, David P. MD
Page: 1036-1044


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Does First-Trimester Screening Modify the Natural History of Congenital Heart Disease?: Analysis of Outcome of Regional Cardiac Screening at 2 Different Time Periods.

Author: Jicinska, Hana MD, PhD; Vlasin, Pavel MD; Jicinsky, Michal MD; Grochova, Ilga MD; Tomek, Viktor MD, PhD; Volaufova, Julia PhD; Skovranek, Jan MD, PhD; Marek, Jan MD, PhD
Page: 1045-1055


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Long-Term Biased [beta]-Arrestin Signaling Improves Cardiac Structure and Function in Dilated Cardiomyopathy.

Author: Ryba, David M. BS; Li, Jieli MD, PhD; Cowan, Conrad L. PhD; Russell, Brenda PhD; Wolska, Beata M. PhD; Solaro, R. John PhD
Page: 1056-1070


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Biased Agonism at the Angiotensin Receptor: Blocker and Calcium Sensitizer at the Same Time.

Author: Woo, Anthony Yiu-Ho PhD; Komuro, Issei MD, PhD; Xiao, Rui-Ping MD, PhD
Page: 1071-1074


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Ischemia and No Obstructive Coronary Artery Disease (INOCA): Developing Evidence-Based Therapies and Research Agenda for the Next Decade.

Author: Bairey Merz, C. Noel MD; Pepine, Carl J. MD; Walsh, Mary Norine MD; Fleg, Jerome L. MD; Camici, Paolo G. MD; Chilian, William M. PhD; Clayton, Janine Austin MD; Cooper, Lawton S. MD; Crea, Filippo MD; Di Carli, Marcelo MD; Douglas, Pamela S. MD; Galis, Zorina S. PhD; Gurbel, Paul MD; Handberg, Eileen M. PhD; Hasan, Ahmed MD; Hill, Joseph A. MD; Hochman, Judith S. MD; Iturriaga, Erin BS, MSN; Kirby, Ruth BS, RN; Levine, Glenn N. MD; Libby, Peter MD; Lima, Joao MD; Mehta, Puja MD; Desvigne-Nickens, Patrice MD; Olive, Michelle PhD; Pearson, Gail D. MD; Quyyumi, Arshed A. MD; Reynolds, Harmony MD; Robinson, British MA; Sopko, George MD; Taqueti, Viviany MD; Wei, Janet MD; Wenger, Nanette MD
Page: 1075-1092


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Telemedicine in Pediatric Cardiology: A Scientific Statement From the American Heart Association.

Author: Satou, Gary M. MD, FAHA, Chair; Rheuban, Karen MD; Alverson, Dale MD; Lewin, Mark MD; Mahnke, Christopher MD; Marcin, James MD; Martin, Gerard R. MD, FAHA; Mazur, Lisa Schmitz JD; Sahn, David J. MD, FAHA; Shah, Sanket MD; Tuckson, Reed MD; Webb, Catherine L. MD, FAHA; Sable, Craig A. MD, FAHA, Vice Chair; On behalf of the American Heart Association Congenital Cardiac Disease Committee of the Council on Cardiovascular Disease in the Young and Council on Quality Care and Outcomes Research
Page: e648-e678


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Coronary Endothelial Dysfunction and the Index of Microcirculatory Resistance as a Marker of Subsequent Development of Cardiac Allograft Vasculopathy.

Author: Lee, Jang Hoon MD; Okada, Kozo MD, PhD; Khush, Kiran MD, MAS; Kobayashi, Yuhei MD; Sinha, Seema MD; Luikart, Helen RN; Valantine, Hannah MD; Yeung, Alan C. MD; Honda, Yasuhiro MD; Fearon, William F. MD
Page: 1093-1095


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Letter by Lewis and Miller Regarding Article, "Experimentally Increasing the Compliance of Titin Through RNA Binding Motif-20 (RBM20) Inhibition Improves Diastolic Function in a Mouse Model of Heart Failure With Preserved Ejection Fraction".

Author: Lewis, Gavin A. MBChB; Miller, Christopher A. MB ChB, PhD
Page: e679-e680


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Response by Methawasin and Granzier to Letter Regarding Article, "Experimentally Increasing the Compliance of Titin Through RNA Binding Motif-20 (RBM20) Inhibition Improves Diastolic Function in a Mouse Model of Heart Failure With Preserved Ejection Fraction".

Author: Methawasin, Mei MD, PhD; Granzier, Henk PhD
Page: e681-e682


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Letter by Jin-shan and Xue-bin Regarding Article, "Tachycardia-Induced Cardiomyopathy in a 43-Year-Old Man".

Author: Jin-shan, He MD; Xue-bin, Li MD
Page: e683


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Response by Zhao et al to Letter Regarding Article, "Tachycardia-Induced Cardiomyopathy in a 43-Year-Old Man".

Author: Zhao, Yun-Tao MD, PhD; Wang, Lei MD; Yi, Zhong MD, PhD
Page: e684-e685


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Helicobacter Pylori infection in Omani children



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Issue Information



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Analysis of Disease Activity Categories in Chronic Spontaneous/Idiopathic Urticaria

Abstract

Background

Measurement of disease activity guides treatment of chronic spontaneous urticaria (CSU). A weekly Urticaria Activity Score―here, the average of twice-daily patient assessment of itch and hives scores summed over 1 week (UAS7TD)―measures severity from 0 to 42. Insufficient evidence exists whether disease activity states, defined by categorical UAS7TD scores, correlate with other patient-reported outcomes and treatment response.

Objective

To evaluate and compare categorical UAS7TD scores with selected measures of disease-related quality of life and impact.

Methods

Data from three randomised clinical trials of omalizumab in CSU were pooled. Continuous UAS7TD scores were categorised into five disease activity states: urticaria-free, well-controlled, mild, moderate, and severe urticaria. Total scores from the Dermatology Life Quality Index (DLQI); the Chronic Urticaria Quality of Life questionnaire (CU-Q2oL); and questions on sleep and daily activity interference, presence of angioedema, and diphenhydramine use were compared within categorised UAS7TD disease-state scores, using one-way analyses of variance for analysis at different time points and mixed-effects regressions for analysis of all data pooled.

Results

Pooled analyses showed that categorical UAS7TD disease states accurately predicted differences among treated CSU patients with different levels of disease activity. A consistent pattern existed between categories, with higher-activity disease states associated with significantly higher impact and an increase in angioedema frequency. Results at different treatment time points were consistent.

Conclusion

Categorical UAS7TD disease states can discriminate between measures when considering the impact of urticaria activity. Using five categorical disease states could simplify clinical assessment and monitoring of treatment efficacy.

This article is protected by copyright. All rights reserved.



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Search strategies for finding systematic reviews

Abstract

I have read with interest the 2017 article by F Gómez-García and colleagues called "Systematic reviews and meta-analyses on psoriasis: role of funding sources, conflict of interest, and bibliometric indices as predictors of methodological quality" published in the BJD.

This study makes a very important point about the influence of funding sources and conflicts of interests on the methodological quality of systematic reviews.

However, I have some concerns about the search strategy used to find systematic reviews for this analysis.

This article is protected by copyright. All rights reserved.



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The C- terminal region of the Major Outer Sheath Protein (Msp) of Treponema denticola inhibits neutrophil chemotaxis

Summary

Treponema denticola is an oral spirochete strongly associated with severe periodontal disease. A prominent virulence factor, the major outer sheath protein (Msp), disorients neutrophil chemotaxis by altering the cellular phosphoinositide balance, leading to impairment of downstream chemotactic events including actin rearrangement, Rac1 activation and Akt activation in response to chemoattractant stimulation. The specific regions of Msp responsible for interactions with neutrophils remain unknown. In this study, we investigated the inhibitory effect of truncated Msp regions on neutrophil chemotaxis and associated signaling pathways. Murine neutrophils were treated with recombinant protein truncations followed by assessment of chemotaxis and associated signal pathway activation. Chemotaxis assays indicate sequences within the C-terminal region; particularly the first 130 amino acids, have the strongest inhibitory effect on neutrophil chemotaxis. Neutrophils incubated with the C-terminal region protein also demonstrated the greatest inhibition of Rac1 activation, increased phosphoinositide phosphatase activity, and decreased Akt activation; orchestrating impairment of chemotaxis. Furthermore, incubation with antibodies specific to only the C-terminal region blocked the Msp induced inhibition of chemotaxis and denaturing the protein restored Rac1 activation. Msp from the strain OTK, with numerous amino acid substitutions throughout the polypeptide, including the C-terminal region compared to strain 35405, showed increased ability to impair neutrophil chemotaxis. Collectively, these results indicate the C-terminal region of Msp is the most potent region to modulate neutrophil chemotactic signaling and that specific sequences and structure is likely required. Knowledge of how spirochetes dampen neutrophil response is limited and Msp may represent a novel therapeutic target for periodontal disease.

This article is protected by copyright. All rights reserved.



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Changes in university orthodontic care over a period of 20 years

Abstract

Aim

The aim of the present study was to analyze whether there were changes in the severity of malocclusions of patients treated at the Department of Orthodontics, University of Giessen, Germany over a period of 20 years (1992–2012) and if the implementation of the KIG system (German index of treatment need) in 2001 had any effect on the patient cohort. Furthermore, the study aimed to analyze the influence of the severity of malocclusion on treatment quality and economic efficiency (relation payment per case/treatment effort).

Materials and methods

The files of all 5385 patients admitted to the orthodontic department between 1992 and 2012 were screened and the following information was recorded: patient characteristics, treatment duration, KIG, treatment outcome, and costs.

Results

In the KIG period, patients were older, pretreatment malocclusions were more severe, treatment took longer, required more appointments, and did not achieve the same degree of perfection as in the pre-KIG period. Patients with a higher pretreatment KIG category had longer treatments and did not achieve the same degree of perfection as patients with lower KIG categories. Although total payment was slightly higher for the more severe cases, their cost-per-appointment ratio was significantly lower.

Conclusion

In the present university department, a shift of the orthodontic care task towards more complex cases has occurred over the last 20 years. Generally the quality of orthodontic treatment was good, but it has been demonstrated that the higher KIG cases did not end up at the same level of excellence as the lower KIG cases. Furthermore, KIG 5 patients had a longer treatment duration, and required more appointments than lower KIG cases.



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Thermal imaging of the pulp during residual adhesive removal

Abstract

Objective

The aim of this study was to evaluate the temperature changes of the pulpal area during different adhesive clean-up procedures.

Materials and methods

A total of 80 freshly extracted adult maxillary premolar teeth were divided into four groups. Adhesive clean-up was performed with 6- and 12-fluted tungsten carbide burs (TCB) using low- and high-speed handpieces with air or water cooling after bracket debonding. The temperature changes and cool down times were evaluated with a thermal camera. Paired t test, analysis of variance (ANOVA), and Student–Newman–Keuls multiple comparison analysis were used for statistical analysis of the data.

Results

All experimental groups, except the water cooling group, showed a significant temperature rise (p < 0.001) after residual adhesive removal. Only the 6-fluted TCB group with air cooling using a high-speed handpiece exceeded the critical 5.5 °C threshold value (5.91 ± 0.89 °C); this group also exhibited the longest cool down time to initial temperature (71.95 ± 13.68 s). The smallest temperature rise (0.48 ± 0.90 °C) and shortest cooling time value (11.90 ± 5.3 s) were measured in the 6-fluted TCB group with water cooling using a high-speed handpiece.

Conclusion

Appropriate cooling procedures and fine tungsten carbide burs should be used during the removal of remnant adhesives after bracket debonding in order to prevent adverse pulpal reactions.



http://ift.tt/2ml7HRr

From the midnight sun to the longest night: sleep in Antarctica

Sleep disturbances are the main health complaints from personnel deployed in Antarctica. The current paper presents a systematic review of research findings on sleep disturbances in Antarctica. The available sources were divided in three categories: results based on questionnaire surveys or sleep logs, studies using actigraphy, and data from polysomnography results. Other areas relevant to the issue were also examined. These included chronobiology, since the changes in photoperiod have been known to affect circadian rhythms; mood disturbances; exercise, sleep and hypoxia; countermeasure investigations in Antarctica; and other locations lacking a normal photoperiod.

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A Systematic Review of Complications Associated with Direct Implants Vs. Tissue Expanders Following Wise Pattern Skin Sparing Mastectomy

With proven oncological safety and improved aesthetic outcomes, the Type IV or "Wise Pattern" skin sparing mastectomy (SSM) is a procedure that is being performed with increasing frequency. Unfortunately, it is also associated with an increased risk of complication. The purpose of this investigation is to determine the complications associated with direct-to-implant and two-step tissue-expander breast reconstruction following Wise Pattern SSM.

http://ift.tt/2mDx2qH

Changes in university orthodontic care over a period of 20 years

Abstract

Aim

The aim of the present study was to analyze whether there were changes in the severity of malocclusions of patients treated at the Department of Orthodontics, University of Giessen, Germany over a period of 20 years (1992–2012) and if the implementation of the KIG system (German index of treatment need) in 2001 had any effect on the patient cohort. Furthermore, the study aimed to analyze the influence of the severity of malocclusion on treatment quality and economic efficiency (relation payment per case/treatment effort).

Materials and methods

The files of all 5385 patients admitted to the orthodontic department between 1992 and 2012 were screened and the following information was recorded: patient characteristics, treatment duration, KIG, treatment outcome, and costs.

Results

In the KIG period, patients were older, pretreatment malocclusions were more severe, treatment took longer, required more appointments, and did not achieve the same degree of perfection as in the pre-KIG period. Patients with a higher pretreatment KIG category had longer treatments and did not achieve the same degree of perfection as patients with lower KIG categories. Although total payment was slightly higher for the more severe cases, their cost-per-appointment ratio was significantly lower.

Conclusion

In the present university department, a shift of the orthodontic care task towards more complex cases has occurred over the last 20 years. Generally the quality of orthodontic treatment was good, but it has been demonstrated that the higher KIG cases did not end up at the same level of excellence as the lower KIG cases. Furthermore, KIG 5 patients had a longer treatment duration, and required more appointments than lower KIG cases.



http://ift.tt/2mFOlJm

Thermal imaging of the pulp during residual adhesive removal

Abstract

Objective

The aim of this study was to evaluate the temperature changes of the pulpal area during different adhesive clean-up procedures.

Materials and methods

A total of 80 freshly extracted adult maxillary premolar teeth were divided into four groups. Adhesive clean-up was performed with 6- and 12-fluted tungsten carbide burs (TCB) using low- and high-speed handpieces with air or water cooling after bracket debonding. The temperature changes and cool down times were evaluated with a thermal camera. Paired t test, analysis of variance (ANOVA), and Student–Newman–Keuls multiple comparison analysis were used for statistical analysis of the data.

Results

All experimental groups, except the water cooling group, showed a significant temperature rise (p < 0.001) after residual adhesive removal. Only the 6-fluted TCB group with air cooling using a high-speed handpiece exceeded the critical 5.5 °C threshold value (5.91 ± 0.89 °C); this group also exhibited the longest cool down time to initial temperature (71.95 ± 13.68 s). The smallest temperature rise (0.48 ± 0.90 °C) and shortest cooling time value (11.90 ± 5.3 s) were measured in the 6-fluted TCB group with water cooling using a high-speed handpiece.

Conclusion

Appropriate cooling procedures and fine tungsten carbide burs should be used during the removal of remnant adhesives after bracket debonding in order to prevent adverse pulpal reactions.



http://ift.tt/2ml7HRr

Genome-wide in vivo RNAi screen identifies ITIH5 as a metastasis suppressor in pancreatic cancer

Abstract

The overwhelming majority of pancreatic ductal adenocarcinoma (PDAC) is not diagnosed until the cancer has metastasized, leading to an abysmal average life expectancy (3–6 months post-diagnosis). Earlier detection and more effective treatments have been hampered by inadequate understanding of the underlying molecular mechanisms controlling metastasis. We hypothesized that metastasis suppressors are involved in controlling metastasis in pancreatic cancer. Using an unbiased genome-wide shRNA screen, an shRNA library was transduced into the non-metastatic PDAC line S2-028 followed by intrasplenic injection. Resulting liver metastases were individually isolated from these mice. One liver metastatic nodule contained shRNA for ITIH5 (Inter-alpha-trypsin inhibitor heavy chain 5), suggesting that ITIH5 may act as a metastasis suppressor. Consistent with this notion, metastatic PDAC cell lines had significantly lower protein expression of ITIH5 compared to immortalized pancreatic ductal epithelial cells and non-/poorly-metastatic PDAC cell lines. By manipulating expression of ITIH5 in different PDAC cell lines (over-expression in metastatic, knockdown in non-metastatic) functional and selective regulation of metastasis was observed for ITIH5. Orthotopic tumor growth of PDAC cells was not blocked following orthotopic injection. In vitro ITIH5 over-expression inhibited motility and invasion. Immunohistochemical analysis of a human PDAC tissue microarray revealed that ITIH5 expression inversely correlated with both survival and invasion/metastasis. ITIH5 is, therefore, functionally validated as a PDAC metastasis suppressor and shows promise as a prognostic biomarker.



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Temporal variability of ammonia emission potentials for six plant species in an evergreen subtropical forest in southwest China

Abstract

The temporal variability of leaf ammonia (NH3) emission potentials (the ratio of leaf tissue ammonium to proton concentration) and nitrogen (N) pools of six dominant plant species were investigated at the Tieshanping (TSP) forested catchment, southwest China. The results showed that the NH3 emission potentials and N pools presented small variations among seasons, which were mainly controlled by plant species and the leaf age. Also, high emission potential in one species did not correspond to high tissue N content. Specifically, the Chinese fir (Cunninghamia lanceolata) had higher NH3 emission potential (mean: 46.2) but lower N content (mean: 1.6% of Dw). The leaf privet (Ligustrum quihoui Carr.) was with the moderate emission potential (15) and the highest N content (2.7% of Dw) on average, which for the Masson pine (Pinus massoniana) were both low. Overall, the emission potentials of the six species were too low (<200) to build up a sufficiently high NH3 partial pressure in the leaves. Therefore, the Masson pine dominant subtropical forest at TSP acts as a sink for the atmospheric NH3, indicating that using the N flux in throughfall only may significantly underestimate the N income of the ecosystem. The results are informative for future modeling of plant-atmosphere NH3 exchange and estimating N budget in local or regional scales.



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The effect of the feeding pattern of complex industrial wastewater on activated sludge characteristics and the chemical and ecotoxicological effluent quality

Abstract

Research has demonstrated that the feeding pattern of synthetic wastewater plays an important role in sludge characteristics during biological wastewater treatment. Although considerable research has been devoted to synthetic wastewater, less attention has been paid to industrial wastewater. In this research, three different feeding strategies were applied during the treatment of tank truck cleaning (TTC) water. This industry produces highly variable wastewaters that are often loaded with hazardous chemicals, which makes them challenging to treat with activated sludge (AS). In this study, it is shown that the feeding pattern has a significant influence on the settling characteristics. Pulse feeding resulted in AS with a sludge volume index (SVI) of 68 ± 15 mL gMLSS−1. Slowly and continuously fed AS had to contend with unstable SVI values that fluctuated between 100 and 600 mL gMLSS−1. These fluctuations were clearly caused by the feeding solution. The obtained settling characteristics are being supported by the microscopic analysis, which revealed a clear floc structure for the pulse fed AS. Ecotoxicological effluent assessment with bacteria, Crustacea and algae identified algae as the most sensitive organism for all effluents from all different reactors. Variable algae growth inhibitions were measured between the different reactors. The chemical and ecotoxicological effluent quality was comparable between the reactors.



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Oxidation of indometacin by ferrate (VI): kinetics, degradation pathways, and toxicity assessment

Abstract

The oxidation of indometacin (IDM) by ferrate(VI) (Fe(VI)) was investigated to determine the reaction kinetics, transformation products, and changes in toxicity. The reaction between IDM and Fe(VI) followed first-order kinetics with respect to each reactant. The apparent second-order rate constants (k app) decreased from 9.35 to 6.52 M−1 s−1, as the pH of the solution increased from 7.0 to 10.0. The pH dependence of k app might be well explained by considering the species-specific rate constants of the reactions of IDM with Fe(VI). Detailed product studies using liquid chromatography-tandem mass spectrometry (LC-MS/MS) indicated that the oxidation products were primarily derived from the hydrolysis of amide linkages, the addition of hydroxyl groups, and electrophilic oxidation. The toxicity of the oxidation products was evaluated using the Microtox test, which indicated that transformation products exhibited less toxicity to the Vibrio fischeri bacteria. Quantitative structure-activity relationship (QSAR) analysis calculated by the ecological structure activity relationship (ECOSAR) revealed that all of the identified products exhibited lower acute and chronic toxicity than the parent pharmaceutical for fish, daphnid, and green algae. Furthermore, Fe(VI) was effective in the degradation IDM in water containing carbonate ions or fulvic acid (FA), and in lake water samples; however, higher Fe(VI) dosages would be required to completely remove IDM in lake water in contrast to deionized water.



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2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines



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Correction



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2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines



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Reply: Characteristic Left Ventricular Regional Wall Motion Abnormality Can Help Prevent Unnecessary Ischemic Workup



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Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation and Valvular Heart Disease

AbstractBackground

Valvular heart disease (VHD) and atrial fibrillation (AF) often coexist. Phase III trials comparing non–vitamin K antagonist oral anticoagulants (NOACs) with warfarin excluded patients with moderate/severe mitral stenosis or mechanical heart valves, but variably included patients with other VHD and valve surgeries.

Objectives

This study aimed to determine relative safety and efficacy of NOACs in patients with VHD.

Methods

We performed a meta-analysis of the 4 phase III AF trials of the currently available NOACs versus warfarin in patients with coexisting VHD to assess pooled estimates of relative risk (RR) and 95% confidence intervals (CIs) for stroke/systemic embolic events (SSEE), major bleeding, intracranial hemorrhage (ICH), and all-cause death.

Results

Compared with warfarin, the rate of SSEE in patients treated with higher-dose NOACs was lower and consistent among 13,585 patients with (RR: 0.70; 95% CI: 0.58 to 0.86) or 58,098 without VHD (RR: 0.84; 95% CI: 0.75 to 0.95; interaction p = 0.13). Major bleeding in patients on higher-dose NOACs versus warfarin was similar and consistent among patients with (RR: 0.93; 95% CI: 0.68 to 1.27) or without VHD (RR: 0.85; 95% CI: 0.70 to 1.02; interaction p = 0.63 for VHD/no-VHD difference). Intracranial hemorrhage was lower with higher-dose NOACs than with warfarin irrespective of VHD (RR: 0.47; 95% CI: 0.24 to 0.93, and 0.49; 95% CI: 0.41 to 059, respectively; interaction p = 0.91). No protective effect of higher-dose NOACs in preventing all-cause death seemed to be present in patients with VHD versus without VHD (RR:1.01; 95% CI: 0.90 to 1.14 vs. RR: 0.88; 95% CI: 0.82 to 0.94, respectively; interaction p = 0.03).

Conclusions

High-dose NOACs provide overall efficacy and safety similar in AF patients with or without VHD.



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Trends in U.S. Cardiovascular Care: 2016 Report From 4 ACC National Cardiovascular Data Registries

Abstract

Cardiovascular disease is a leading cause of death and disability in the United States. National programs, such as the National Cardiovascular Data Registry, facilitate assessments of the quality of care and outcomes for broad populations of patients with cardiovascular disease. This report provides data for 2014 from 4 National Cardiovascular Data Registry hospital quality programs: 1) CathPCI (Diagnostic Catheterization and Percutaneous Coronary Intervention) for coronary angiography and percutaneous coronary intervention (667,424 procedures performed in 1,612 hospitals); 2) ICD Registry for implantable cardioverter-defibrillators (158,649 procedures performed in 1,715 hospitals); 3) ACTION–GWTG (Acute Coronary Treatment and Intervention Outcomes Network–Get With The Guidelines) for acute coronary syndromes (182,903 patients admitted to 907 hospitals); and 4) IMPACT (Improving Pediatric and Adult Congenital Treatment) for cardiac catheterization and intervention for pediatric and adult congenital heart disease (20,169 procedures in 76 hospitals). The report provides perspectives on the demographic and clinical characteristics of enrolled patients, characteristics of participating centers, and selected measures of processes and outcomes of care in these programs.



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Valvular Heart Disease Patients on Edoxaban or Warfarin in the ENGAGE AF-TIMI 48 Trial

AbstractBackground

The use of non-vitamin K antagonist oral anticoagulants (NOACs) instead of vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and coexisting valvular heart disease (VHD) is of substantial interest.

Objectives

This study explored outcomes in patients with AF with and without VHD in the ENGAGE AF–TIMI 48 (Effective Anticoagulation with factor Xa Next Generation in Atrial Fibrillation-Thrombolysis In Myocardial Infarction 48) trial, comparing edoxaban with warfarin.

Methods

Valvular heart disease was defined as history or baseline echocardiography evidence of at least moderate aortic/mitral regurgitation, aortic stenosis, or prior valve surgery (bioprosthesis replacement, valve repair, valvuloplasty). Patients with moderate to severe mitral stenosis or mechanical heart valves were excluded from the trial. Comparisons were made of rates of stroke/systemic embolic event (SSEE), major bleeding, additional efficacy and safety outcomes, as well as net clinical outcomes, in patients with or without VHD treated with edoxaban or warfarin, using adjusted Cox proportional hazards.

Results

After adjustment for multiple baseline characteristics, compared with no-VHD patients (n = 18,222), VHD patients (n = 2,824) had a similar rate of SSEE but higher rates of death (hazard ratio [HR]: 1.40; 95% confidence interval [CI]:1.26 to 1.56; p <0.001), major adverse cardiovascular events (HR: 1.29; 95% CI: 1.16 to 1.43; p <0.001), and major bleeding (HR: 1.21; 95% CI: 1.03 to 1.42; p = 0.02). Higher-dose edoxaban regimen had efficacy similar to warfarin in the presence of VHD (for SSEE, HR: 0.69; 95% CI: 0.44 to 1.07, in patients with VHD, and HR: 0.91; 95% CI: 0.77 to 1.07, in patients without VHD; p interaction [pint] = 0.26; and for less major bleeding, HR: 0.74; 95% CI: 0.53 to 1.02 in patients with VHD, and HR: 0.82; 95% CI: 0.71 to 0.94, in patients with no VHD; pint = 0.57).

Conclusions

The presence of VHD increased the risk of death, major adverse cardiovascular events, and major bleeding but did not affect the relative efficacy or safety of higher-dose edoxaban versus warfarin in AF. (Global Study to Assess the Safety and Effectiveness of Edoxaban (DU-176b) vs. Standard Practice of Dosing With Warfarin in Patients With Atrial Fibrillation [ENGAGE AF-TIMI 48]; NCT00781391)



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Lipoprotein(a) Improves Cardiovascular Risk Prediction Based on Established Risk Algorithms



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NOACs for Stroke Prevention in Atrial Fibrillation With Valve Disease: Filling the Gaps



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Reply: Role of Adiponectin: Important or Null?



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Statin Intolerance and Risk of Coronary Heart Events and All-Cause Mortality Following Myocardial Infarction

AbstractBackground

Many patients report adverse reactions to, and may not tolerate, statin therapy. These patients may be at increased risk for coronary heart disease (CHD) events and mortality.

Objectives

This study evaluated the risk for recurrent myocardial infarction (MI), CHD events, and all-cause mortality in Medicare beneficiaries with statin intolerance and in those with high adherence to statin therapy.

Methods

We studied 105,329 Medicare beneficiaries who began a moderate- or high-intensity statin dosage after hospitalization for MI between 2007 and 2013. Statin intolerance was defined as down-titrating statins and initiating ezetimibe therapy, switching from statins to ezetimibe monotherapy, having International Classification of Diseases, 9th revision, diagnostic codes for rhabdomyolysis or an antihyperlipidemic adverse event, followed by statin down-titration or discontinuation, or switching between ≥3 types of statins within 1 year after initiation. High statin adherence over the year following hospital discharge was defined as proportion of days covered ≥80%. Recurrent MI, CHD events (recurrent MI or a coronary revascularization procedure), and mortality were identified from 1 year after hospital discharge through December 2014.

Results

Overall, 1,741 patients (1.65%) had statin intolerance, and 55,567 patients (52.8%) had high statin adherence. Over a median of 1.9 to 2.3 years of follow-up, there were 4,450 recurrent MIs, 6,250 CHD events, and 14,311 deaths. Compared to beneficiaries with high statin adherence, statin intolerance was associated with a 36% higher rate of recurrent MI (41.1 vs. 30.1 per 1,000 person-years, respectively), a 43% higher rate of CHD events (62.5 vs. 43.8 per 1,000 person-years, respectively), and a 15% lower rate of all-cause mortality (79.9 vs. 94.2 per 1,000 person-years, respectively). The multivariate-adjusted hazard ratios (HR) comparing beneficiaries with statin intolerance versus those with high statin adherence were 1.50 (95% confidence interval [CI]: 1.30 to 1.73) for recurrent MI, 1.51 (95% CI: 1.34 to 1.70) for CHD events, and 0.96 (95% CI: 0.87 to 1.06) for all-cause mortality.

Conclusions

Statin intolerance was associated with an increased risk for recurrent MI and CHD events but not all-cause mortality.



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JACC Instructions for Authors



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Statin Intolerance: An Elusive But Morbid Disorder



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A Test in Context: E/A and E/e' to Assess Diastolic Dysfunction and LV Filling Pressure

Abstract

Diastolic dysfunction represents a combination of impaired left ventricular (LV) relaxation, restoration forces, myocyte lengthening load, and atrial function, culminating in increased LV filling pressures. Current Doppler echocardiography guidelines recommend using early to late diastolic transmitral flow velocity (E/A) to assess diastolic function, and E to early diastolic mitral annular tissue velocity (E/e') to estimate LV filling pressures. Although both parameters have important diagnostic and prognostic implications, they should be interpreted in the context of a patient's age and the rest of the echocardiogram to describe diastolic function and guide patient management. This review discusses: 1) the physiological basis for the E/A and E/e' ratios; 2) their roles in diagnosing diastolic dysfunction; 3) prognostic implications of abnormalities in E/A and E/e'; 4) special scenarios of the E/A and E/e' ratios that are either useful or challenging when evaluating diastolic function clinically; and 5) their usefulness in guiding therapeutic decision making.



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Efficacy and Safety of Tolvaptan in Patients Hospitalized With Acute Heart Failure

AbstractBackground

The oral vasopressin-2 receptor antagonist tolvaptan causes aquaresis in patients with volume overload, potentially facilitating decongestion and improving the clinical course of patients with acute heart failure (AHF).

Objectives

The TACTICS-HF (Targeting Acute Congestion with Tolvaptan in Congestive Heart Failure) study was conducted to address the acute use of tolvaptan to improve congestion in AHF.

Methods

The TACTICS-HF study randomized patients (n = 257) within 24 h of AHF presentation in a prospective, double blind, placebo-controlled trial. Patients were eligible regardless of ejection fraction, and were randomized to either 30 mg of tolvaptan or placebo given at 0, 24, and 48 h, with a fixed-dose furosemide regimen as background therapy. The primary endpoint was the proportion of patients considered responders at 24 h. Secondary endpoints included symptom improvement, changes in renal function, and clinical events.

Results

Dyspnea relief by Likert scale was similar between groups at 8 h (25% moderately or markedly improved with tolvaptan vs. 28% placebo; p = 0.59) and at 24 h (50% tolvaptan vs. 47% placebo; p = 0.80). Need for rescue therapy was also similar at 24 h (21% tolvaptan, 18% placebo; p = 0.57). The proportion defined as responders at 24 h (primary study endpoint) was 16% for tolvaptan and 20% for placebo (p = 0.32). Tolvaptan resulted in greater weight loss and net fluid loss compared with placebo, but tolvaptan-treated patients were more likely to experience worsening renal function during treatment. There were no differences in in-hospital or post-discharge clinical outcomes.

Conclusions

In patients hospitalized with AHF, dyspnea, and congestion, the addition of tolvaptan to a standardized furosemide regimen did not improve the number of responders at 24 h, despite greater weight loss and fluid loss. (Targeting Acute Congestion With Tolvaptan in Congestive Heart Failure [TACTICS-HF]; NCT01644331)



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The Emergence of Sports Cardiology as a Specialty



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Tolvaptan in Acute Heart Failure: Time to Move On



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GRK2 Regulates {alpha}2-Adrenergic Receptor-Dependent Catecholamine Release in Human Adrenal Chromaffin Cells



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Short-Term Effects of Tolvaptan in Patients With Acute Heart Failure and Volume Overload

AbstractBackground

In patients with acute heart failure (AHF), dyspnea relief is the most immediate goal. Renal dysfunction, diuretic resistance, and hyponatremia represent treatment impediments.

Objectives

It was hypothesized that the addition of tolvaptan to a background diuretic improved dyspnea early in patients selected for an enhanced vasopressin antagonism response.

Methods

In a double-blind trial, patients were randomized to tolvaptan 30 mg/day or placebo. Study entry required hospitalization within the previous 36 h, active dyspnea, and any of the following: 1) estimated glomerular filtration rate <60 ml/min/1.73 m2; 2) hyponatremia; or 3) diuretic resistance (urine output ≤125 ml/h following intravenous furosemide ≥40 mg). The primary endpoint was a 7-point change in self-assessed dyspnea at 8 and 16 h, using a novel standardized approach.

Results

We randomized 250 patients. There was no difference in the primary endpoint of day 1 dyspnea reduction, despite significantly greater weight reduction with tolvaptan (–2.4 ± 2.1 kg vs. –0.9 ± 1.8 kg; p < 0.001). At day 3, dyspnea reduction was greater with tolvaptan (p = 0.01). There were 2 significant treatment-by-subgroup interactions: patients without elevated jugular venous pressure and those without ascites showed directional favorability of tolvaptan over placebo for the primary endpoint compared with patients with these findings.

Conclusions

Despite rapid and persistent weight loss with tolvaptan compared with placebo, in patients with AHF who were selected for greater potential benefit from vasopressin receptor inhibition, tolvaptan was not associated with greater early improvement in dyspnea. Apparent subsequent differences in dyspnea warrant further exploration of the temporal relationship between diuresis and dyspnea relief and a possible clinical role for tolvaptan. (Randomized, Double-Blind, Placebo Controlled Study of the Short Term Clinical Effects of Tolvaptan in Patients Hospitalized for Worsening Heart Failure With Challenging Volume Management [SECRET of CHF]; NCT01584557)



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Characteristic Left Ventricular Regional Wall Motion Abnormality Can Help Prevent Unnecessary Ischemic Workup



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Perianal Lesions in Children: An Updated Review

Abstract

Perianal lesions in children are common reasons for dermatology clinic visits and a well-defined approach to diagnosis and management is helpful to the practicing clinician. In this article, we review and update various etiologies of perianal lesions in the pediatric population, including infectious, papulosquamous, vascular, and neoplastic. We provide a standard initial approach to diagnosis and updates on current management. Infectious etiologies of perianal lesions discussed in this article include fungal, bacterial, parasitic, and viral. Perianal papulosquamous lesions often encountered in children, and discussed in this article, include acrodermatitis enteropathica, psoriasis, contact dermatitis, and many others. We also discuss the diagnosis and management of other entities including infantile hemangiomas, Langerhans cell histiocytosis, and fibrous hamartoma of infancy.



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IFC(EDITORIAL BOARD)

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Publication date: April 2017
Source:DNA Repair, Volume 52





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Reply: Methotrexate neurotoxicity due to drug interactions: an inadequate folinic acid effect



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Association between neuroendocrine tumors biomarkers and primary tumor site and disease type based on total 68Ga-DOTATATE-Avid tumor volume measurements

Objective

To determine the association between neuroendocrine tumor (NET) biomarker levels and the extent of disease as assessed by 68Ga DOTATATE PET/CT imaging.

Design

A retrospective analysis of a prospective database of patients with NETs.

Methods

Fasting plasma chromogranin A (CgA), neuron-specific enolase (NSE), gastrin, glucagon, vasoactive intestinal peptide (VIP) and pancreatic polypeptide (PP), and 24-h urinary 5-hydroxyindoleacetic acid (5-HIAA) levels were measured. Correlation between biomarkers and total 68Ga-DOTATATE-avid tumor volume (TV) was analyzed.

Results

The analysis included 232 patients. In patients with pancreatic NETs (n = 112), 68Ga-DOTATATE TV correlated with CgA (r = 0.6, P = 0.001, Spearman). In patients with multiple endocrine neoplasia type 1 (n = 39), 68Ga-DOTATATE TV correlated with glucagon (r = 0.5, P = 0.01) and PP levels (r = 0.5, P = 0.049). In patients with von Hippel–Lindau (n = 24), plasma VIP (r = 0.5, P = 0.02) and PP levels (r = 0.7, P < 0.001) correlated with 68Ga-DOTATATE TV. In patients with small intestine NET (SINET, n = 74), 68Ga-DOTATATE TV correlated with CgA (r = 0.5, P = 0.02) and 5-HIAA levels (r = 0.7, P < 0.001), with 5-HIAA ≥8.1 mg/24 h associated with metastatic disease with high positive (81.8%) and negative (85.7%) predictive values (P = 0.001). 68Ga-DOTATATE TV in patients with NET of unknown primary (n = 16) and those with NET of other primary location (n = 30) correlated with 5-HIAA levels (r = 0.8, P = 0.002 and r = 0.7, P = 0.02 respectively).

Conclusions

Our data supports the use of specific NET biomarkers based on the site of the primary NET and the presence of hereditary syndrome-associated NET. High urinary 5-HIAA levels indicate the presence of metastatic disease in patients with SINET.



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Steroid hormone analysis in diagnosis and treatment of DSD: position paper of EU COST Action BM 1303 'DSDnet

Disorders or differences in sex development (DSD) comprise a heterogeneous group of conditions with an atypical sex development. For optimal diagnosis, highly specialised laboratory analyses are required across European countries. Working group 3 of EU COST (European Cooperation in Science and Technology) Action BM 1303 'DSDnet' 'Harmonisation of Laboratory Assessment' has developed recommendations on laboratory assessment for DSD regarding the use of technologies and analytes to be investigated. This position paper on steroid hormone analysis in diagnosis and treatment of DSD was compiled by a group of specialists in DSD and/or hormonal analysis, either from participating European countries or international partner countries. The topics discussed comprised analytical methods (immunoassay/mass spectrometry-based methods), matrices (urine/serum/saliva) and harmonisation of laboratory tests. The following positions were agreed upon: support of the appropriate use of immunoassay- and mass spectrometry-based methods for diagnosis and monitoring of DSD. Serum/plasma and urine are established matrices for analysis. Laboratories performing analyses for DSD need to operate within a quality framework and actively engage in harmonisation processes so that results and their interpretation are the same irrespective of the laboratory they are performed in. Participation in activities of peer comparison such as sample exchange or when available subscribing to a relevant external quality assurance program should be achieved. The ultimate aim of the guidelines is the implementation of clinical standards for diagnosis and appropriate treatment of DSD to achieve the best outcome for patients, no matter where patients are investigated or managed.



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The GIP/GIPR axis is functionally linked to GH-secretion increase in a significant proportion of gsp- somatotropinomas

Objective

Glucose-dependent insulinotropic polypeptide receptor (GIPR) overexpression has been recently described in a proportion of gsp somatotropinomas and suggested to be associated with the paradoxical increase of GH (GH-PI) during an oral glucose load.

Design and methods

This study was aimed at linking the GIP/GIPR pathway to GH secretion in 25 somatotropinomas-derived primary cultures and correlating molecular with clinical features in acromegalic patients. Given the impairment of the GIP/GIPR axis in acromegaly, an additional aim was to assess the effect of GH/IGF-1 stimulation on GIP expression in the enteroendocrine cell line STC-1.

Results

Nearly 80% of GIPR-expressing somatotropinomas, all of them negative for gsp mutations, show increased GH secretion upon GIP stimulation, higher sensitivity to Forskolin but not to somatostatin analogs. Besides increased frequency of GH-PI, GIPR overexpression does not appear to affect acromegalic patients' clinical features. In STC-1 cells transfected with GIP promoter-driven luciferase vector, IGF-1 but not GH induced dose-dependent increase in luciferase activity.

Conclusions

We demonstrate that GIPR mediates the GH-PI in a significant proportion of gsp acromegalic patients. In these cases, the stimulatory effect of IGF-1 on GIP promoter support the hypothesis of a functional GH/IGF-1/GIP axis. Further studies based on larger cohorts and the development of a stable transgenic model with inducible GIPR overexpression targeted to pituitary somatotroph lineage will be mandatory to establish the real role of GIPR in the pathogenesis of somatotropinomas.



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Pembrolizumab and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma

Conditions:   Lymphocyte-Rich Classical Hodgkin Lymphoma;   Recurrent Lymphocyte-Depleted Classical Hodgkin Lymphoma;   Recurrent Mixed Cellularity Classical Hodgkin Lymphoma;   Recurrent Nodular Sclerosis Classical Hodgkin Lymphoma;   Refractory Lymphocyte-Depleted Classical Hodgkin Lymphoma;   Refractory Mixed Cellularity Classical Hodgkin Lymphoma;   Refractory Nodular Sclerosis Classical Hodgkin Lymphoma
Interventions:   Drug: Carboplatin;   Drug: Etoposide;   Drug: Ifosfamide;   Other: Laboratory Biomarker Analysis;   Biological: Pembrolizumab
Sponsors:   Northwestern University;   Merck Sharp & Dohme Corp.;   National Cancer Institute (NCI)
Not yet recruiting - verified March 2017

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Isocapnic Hyperventilation - an Alternative Method

Condition:   Oropharyngeal Neoplasms
Intervention:   Device: Isocapnic hyperventilation
Sponsor:   Sahlgrenska University Hospital, Sweden
Recruiting - verified March 2017

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IGFBP-4 regulates adult skeletal growth in a sex-specific manner

Insulin-like growth factor-1 (IGF-1) and its binding proteins are critical mediators of skeletal growth. Insulin-like growth factor-binding protein 4 (IGFBP-4) is highly expressed in osteoblasts and inhibits IGF-1 actions in vitro. Yet, in vivo studies suggest that it could potentiate IGF-1 and IGF-2 actions. In this study, we hypothesized that IGFBP-4 might potentiate the actions of IGF-1 on the skeleton. To test this, we comprehensively studied 8- and 16-week-old Igfbp4–/– mice. Both male and female adult Igfbp4–/– mice had marked growth retardation with reductions in body weight, body and femur lengths, fat proportion and lean mass at 8 and 16 weeks. Marked reductions in aBMD and aBMC were observed in 16-week-old Igfbp4–/– females, but not in males. Femoral trabecular BV/TV and thickness, cortical fraction and thickness in 16-week-old Igfbp4–/– females were significantly reduced. However, surprisingly, males had significantly more trabeculae with higher connectivity density than controls. Concordantly, histomorphometry revealed higher bone resorption and lower bone formation in Igfbp4–/– females. In contrast, Igfbp4–/– males had lower mineralized surface/bone surface. Femoral expression of Sost and circulating levels of sclerostin were reduced but only in Igfbp4–/– males. Bone marrow stromal cultures from mutants showed increased osteogenesis, whereas osteoclastogenesis was markedly increased in cells from Igfbp4–/– females but decreased in males. In sum, our results indicate that loss of Igfbp4 affects mesenchymal stromal cell differentiation, regulates osteoclastogenesis and influences both skeletal development and adult bone maintenance. Thus, IGFBP-4 modulates the skeleton in a gender-specific manner, acting as both a cell autonomous and cell non-autonomous factor.



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Pygoscelis antarcticus feathers as bioindicator of trace element risk in marine environments from Barton Peninsula, 25 de Mayo (King George) Island, Antarctica

Abstract

We report the contents of elements in feathers of Chinstrap penguin (Pygoscelis antarcticus), which had not been informed up to now, such as silver and bromine and others listed as hazardous by the United States Environmental Protection Agency as arsenic, cobalt, chromium, and mercury. Analyses of the element concentrations in feathers, adult and chicken, from Barton Peninsulas at 25 de Mayo (King George) Island, South Shetlands, were made by Instrumental Neutron Activation Analysis. Samarium, lanthanum a, thorium, and uranium concentrations in Chinstrap penguin feathers were below 0.1 mg/kg. This suggests that the elements in feather do not come from atmospheric particles surface deposition. Arsenic (0.120 ± 0.050 mg/kg) and cobalt (0.030 ± 0.020 mg/kg) concentrations were lower than the reports for other colony of Chinstrap penguins, and essential elements as iron (26 ± 12 mg/kg), zinc (78.0 ± 5.3 mg/kg), and chromium (0.51 ± 0.27 mg/kg) were in the same range while Se (2.90 ± 0.65 mg/kg) content were the lowest reported. Mercury (0.43 ± 0.21 mg/kg), chromium (0.210 ± 0.060 mg/kg), and silver (0.083 ± 0.003 mg/kg) in chicks tended to be lower than in adults. Iron, cobalt, and arsenic concentrations in feathers found in this study were the lowest compared to measurements were in several penguin species in Antarctica. These results confirm to feathers like effective indicators for the trace elements incorporated in the penguins and it provide a data set which can adds to the baseline for bioindication studies using feathers.



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Ant ( Hymenoptera, Formicidae ) diversity along a pollution gradient near the Middle Ural Copper Smelter, Russia

Abstract

Ants are considered to be suitable indicators of ecological change and are widely used in land management and environmental monitoring. However, responses of ant communities to industrial pollution are less known so far. We studied pollution-related variations of ant diversity and abundance near the Middle Ural Copper Smelter (Russia) in 2009 and 2013, with pitfall traps set up at 10 sites in Picea obovata and Abies sibirica forest. This study provided evidences for humped pollution-induced dynamics of ant diversity and abundance. Species richness and diversity peaked in the habitat intermediate between slightly damaged and fully destroyed forest ecosystems. The total abundance of ants peaked in the middle of the pollution gradient and was determined mainly by the dominant species Formica aquilonia. The abundance of other species increased towards the smelter, but was less important for total abundance than that of red wood ants. Community dominants changed with increase of exposure; F. aquilonia, a typical species of mature forests, was replaced by species of open habitats, Lasius niger and Myrmica ruginodis. Habitat variables and competition between species seem to affect local ant communities more strongly than pollution exposure. Stand basal area and cover of the field layer were the main determinants of ant diversity and abundance of individual species.



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Briquettes production for use as power source for combustion using charcoal thin waste and sanitary sewage sludge

Abstract

This study evaluated the feasibility of production of briquettes using fine charcoal, sewage sludge, and mixtures thereof for use in energy production. The briquettes of 7–8 cm diameter and 20 cm length were produced in the conical press extruder type, mixing sewage sludge to charcoal fines in different ratios: 0:100, 25:75, 50:50, 75:25, and 100:0, with the addition of a binder (glue flour) in a ratio of 8 mass% prepared for briquetting. After air drying (temperatures between 24 and 30°C) for 48 h, the mechanical, thermal, and morphological characterizations were performed. The morphological properties of the briquettes were evaluated by scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy. The briquettes produced had mechanical strength, with values between 210 and 420 kgf, and densities between 0.75 and 0.91 g cm−3. The calorific value of briquettes was in the range from 13.21 to 23.10 MJ kg−1, in which there was an increase with the increase of concentration of charcoal fines in the mixture. Thermogravimetric analysis showed mass losses that occurred in the temperature range between 150 and 740 °C. The results of the mechanical and thermal properties showed the feasibility of using fine charcoal briquettes from sewage sludge as well as mixtures thereof, for the production of energy. The fine charcoal briquette was the one with the highest calorific value, but not showed the highest resistance to mechanical shock.



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Enhanced plasma protein carbonylation in patients with myelodysplastic syndromes

Publication date: Available online 12 March 2017
Source:Free Radical Biology and Medicine
Author(s): Alžběta Hlaváčková, Jana Štikarová, Kristýna Pimková, Leona Chrastinová, Pavel Májek, Roman Kotlín, Jaroslav Čermák, Jiří Suttnar, Jan Evangelista Dyr
Myelodysplastic syndromes (MDS) represent a heterogeneous group of pre-leukemic disorders, characterized by ineffective hematopoiesis and the abnormal blood cell development of one or more lineages. Oxidative stress, as an important factor in the carcinogenesis of onco-hematological diseases, is also one of the known factors involved in the pathogenesis of MDS. An increase of reactive oxygen species (ROS) may lead to the oxidation of DNA, lipids, and proteins, thereby causing cell damage. Protein carbonylation caused by ROS is defined as an irreversible post-translational oxidative modification of amino acid side chains, and could play an important role in signaling processes. The detection of protein carbonyl groups is a specific useful marker of oxidative stress.In this study, we examined 32 patients divided into three different subtypes of MDS according to the World Health Organization (WHO) classification criteria as refractory anemia with ringed sideroblasts (RARS), refractory cytopenia with multilineage dysplasia (RCMD), refractory anemia with excess blasts-1,2 (RAEB-1,2). We found significant differences in protein carbonylation between the group of all MDS patients and healthy controls (P=0.0078). Furthermore, carbonylated protein levels were significantly elevated in RARS patients compared to healthy donors (P=0.0013) and to RCMD patients (P=0.0277). We also found a significant difference in the total iron binding capacity (TIBC) between individual subgroups of MDS patients (P=0.0263). Moreover, TIBC was decreased in RARS patients compared to RCMD patients (P=0.0203). TIBC moderately negatively correlated with carbonyl levels (r=−0.5978, P=0.0054) in the MDS patients as a whole. Additionally we observed changes in the carbonylated proteins of RARS patients in comparison with healthy controls and their negative controls. Using tandem mass spectrometry (LC-MS/MS) we identified 27 uniquely carbonylated proteins of RARS patients, which were generated by ROS and could influence the pathophysiology of low-risk MDS.These data indicate that increased protein carbonylation is related with RARS as low-risk MDS subgroup. We suggest that this type of post-translational modification in MDS disease is not "only" a consequence of oxidative stress, but also plays an active role in the pathophysiology and iron metabolism within the RARS subgroup of MDS. Measurement of plasma carbonyl levels and the isolation of carbonylated plasma proteins, followed by their identification, could serve as a potential diagnostic and prognostic tool in MDS.

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Protective effects of coffee against oxidative stress induced by the tobacco carcinogen benzo[α]pyrene

Publication date: Available online 12 March 2017
Source:Free Radical Biology and Medicine
Author(s): Sandra Kalthoff, Steffen Landerer, Julia Reich, Christian P. Strassburg
Aims:Coffee consumption has been epidemiologically associated with a lower risk for liver cirrhosis and cancer. UDP-glucuronosyltransferases (UGT1A) catalyze the detoxification of reactive metabolites thereby acting as indirect antioxidants. Aim of the study was to examine UGT1A regulation in response to Benzo[α]pyrene (BaP) to elucidate the potentially protective effects of coffee on BaP-induced oxidative stress and toxicity.Results:In cell culture (HepG2, KYSE70 cells) and in htgUGT1A-WT mice, UGT1A transcription was activated by BaP, while it was reduced or absent htgUGT1A-SNP (containing 10 commonly occurring UGT1A-SNPs) mice. siRNA-mediated knockdown identified aryl hydrocarbon receptor (AhR) and nuclear factor erythroid2-related factor-2 (Nrf2) as mediators of BaP-induced UGT1A upregulation. Exposure to coffee led to a reduction of BaP-induced production of reactive oxygen species in vitro and in htgUGT1A-WT and –SNP mice. After UGT1A silencing by UGT1A-specific siRNA in cell culture, the coffee-mediated reduction of ROS production was significantly impaired compared to UGT1A expressing cells.Conclusion:A common UGT1A haplotype, prevalent in 9% (homozygous) of the White population, significantly impairs the expression of UGT1A enzymes in response to the putative tobacco carcinogen BaP and is likely to represent a significant risk factor for reduced detoxification and increased genotoxicity. Coffee was demonstrated to inhibit BaP-induced production of oxidative stress by UGT1A activation, and is therefore an attractive candidate for chemoprotection in risk groups for HCC or other tumors.

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Ergothioneine products derived by superoxide oxidation in endothelial cells exposed to high-glucose

Publication date: Available online 12 March 2017
Source:Free Radical Biology and Medicine
Author(s): Luigi Servillo, Nunzia D'Onofrio, Rosario Casale, Domenico Cautela, Alfonso Giovane, Domenico Castaldo, Maria Luisa Balestrieri
Ergothioneine (Egt), 2-mercapto-L-histidine betaine (ESH), is a dietary component acting as antioxidant and cytoprotectant. In vitro studies demonstrated that Egt, a powerful scavenger of hydroxyl radicals, superoxide anion, hypochlorous acid and peroxynitrite, protects vascular function against oxidative damages, thus preventing endothelial dysfunction. In order to delve the peculiar oxidative behavior of Egt, firstly identified in cell free-systems, experiments were designed to identify the Egt oxidation products when endothelial cells (EC) benefit of its protection against high-glucose (hGluc). HPLC-ESI-MS/MS analyses revealed a decrease in the intracellular GSH levels and an increase in the ophthalmic acid (OPH) levels during hGluc treatment. Interestingly, in the presence of Egt, the decrease of the GSH levels was lower than in cells treated with hGluc alone, and this effect was paralleled by lower OPH levels. Egt was also effective in reducing the cytotoxicity of H2O2 and paraquat (PQT), an inducer of superoxide anion production, showing a similar time-dependent pattern of GSH and OPH levels, although with peaks occurring at different times. Importantly, Egt oxidation generated not only hercynine (EH) but also the sulfonic acid derivative (ESO3H) whose amounts were dependent on the oxidative stress employed. Furthermore, cell-free experiments confirmed the formation of both EH and ESO3H when Egt was reacted with superoxide anion. In summary, these data, by identifying the EH and ESO3H formation in EC exposed to hGluc, highlight the cellular antioxidant properties of Egt, whose peculiar redox behavior makes it an attractive candidate for the prevention of oxidative stress-associated endothelial dysfunction during hyperglicaemia.

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Exogenous and endogenous lipids of human hair

Purpose

The aim of this study was to characterize the external and internal lipids of Caucasian hair and their influence in different hair properties such as moisture content, hydrophobic character, and mechanical properties.

Methods

Lipid extraction and their analysis by thin layer chromatography with flame ionization detector were carried out. Lipid rearrangement and water sorption and desorption evaluation of these fibers with and without lipids will also be determined using different techniques such as differential scanning calorimetry, thermogravimetric analysis and dynamic vapor sorption, mainly to evaluate permeation changes of these hair fibers possibly related to the fluidity of the lipids extracted.

Results

Caucasian fibers were found to be well hydrated, and moisture diminution was observed mainly for the external lipid extracted fibers. Unexpectedly, the lipid extraction promoted an increase in the break tenacity of the Caucasian fibers. The hydrophobic character of the fiber surfaces indicates the marked hydrophobicity of all fibers. Delipidization promotes only a slight diminution of their hydrophobic properties.

Water uptake and desorption studies indicate an important water regain for Caucasian fibers. The external extracted hair fibers presented a diminution of maximum water regain, which surprisingly increases with the following internal lipid extraction. This can be due to a higher water desorption found only for external extracted fibers.

Conclusions

The relationship between fluidity of lipids extracted and hair fiber water diffusion were established. Extraction of internal lipids of Caucasian fibers, which have a higher unsaturated lipid content than external lipids of the same hair fiber, leads to a lower water permeability of the fiber. On the capillar formulations should be considered the importance of lipid fluidity to modify the permeability of the fiber.



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Skin hydration analysis by experiment and computer simulations and its implications for diapered skin

Background

Experimental work on skin hydration is technologically challenging, and mostly limited to observations where environmental conditions are constant. In some cases, like diapered baby skin, such work is practically unfeasible, yet it is important to understand potential effects of diapering on skin condition. To overcome this challenge, in part, we developed a computer simulation model of reversible transient skin hydration effects.

Methods

Skin hydration model by Li et al. (Chem Eng Sci, 138, 2015, 164) was further developed to simulate transient exposure conditions where relative humidity (RH), wind velocity, air, and skin temperature can be any function of time. Computer simulations of evaporative water loss (EWL) decay after different occlusion times were compared with experimental data to calibrate the model. Next, we used the model to investigate EWL and SC thickness in different diapering scenarios.

Results

Key results from the experimental work were: (1) For occlusions by RH=100% and free water longer than 30 minutes the absorbed amount of water is almost the same; (2) Longer occlusion times result in higher water absorption by the SC. The EWL decay and skin water content predictions were in agreement with experimental data. Simulations also revealed that skin under occlusion hydrates mainly because the outflux is blocked, not because it absorbs water from the environment. Further, simulations demonstrated that hydration level is sensitive to time, RH and/or free water on skin. In simulated diapering scenarios, skin maintained hydration content very close to the baseline conditions without a diaper for the entire duration of a 24 hours period.

Conclusion

Different diapers/diaper technologies are known to have different profiles in terms of their ability to provide wetness protection, which can result in consumer-noticeable differences in wetness. Simulation results based on published literature using data from a number of different diapers suggest that diapered skin hydrates within ranges considered reversible.



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A Contemporary Series of Renal Masses With Emphasis on Recently Recognized Entities and Tumors of Low Malignant Potential.: A Report Based on 624 Consecutive Tumors from a Single Tertiary Center

Publication date: Available online 12 March 2017
Source:Pathology - Research and Practice
Author(s): Maria Rosaria Raspollini, Ilaria Montagnani, Rodolfo Montironi, Liang Cheng, Guido Martignoni, Andrea Minervini, Sergio Serni, Giulio Nicita, Marco Carini, Antonio Lopez-Beltran
Introduction.A number of new renal tumor entities have been recognized by the 2016 World Health Organization classification of urologic tumors. The classification includes tumors with different behavior and introduces one tumor with low malignant potential, the multilocular cystic clear cell renal cell neoplasm of low malignant potential (mcCCRCNLMP).However, some categories still labeled as "carcinoma", such as clear cell papillary renal cell carcinoma (CCPRCC), renal angioleiomyomatous tumor (RAT), and tubulocystic carcinoma (TCRCC), all with a particularly good prognosis when diagnosed as low stage, show no malignant behavior: in fact, no metastases have been reported in these categories when surgically excised. Current experience is limited to supporting these neoplasms as benign entities although, recent literature data is defining these entities as "low malignant potential tumors".Material and Methods.We conducted a search through our files on a consecutive series of 624 renal tumors diagnosed over a period of 2 years to address the incidence of this category of tumors.Results.Applying strict histological criteria, the "low malignant potential" tumors, comprised 7% of renal masses that are less than 4cm in size and 3,8% of renal masses measuring 4-7cm in the series of 624 renal tumors. When benign tumors are taken into considerations, the benign and "low malignant potential tumors" represent about one third of renal masses<4cm and one sixth of renal masses between 4 and 7cm. All these cases haven't shown recurrence or metastasis at follow-up, mean follow-up of 18 months (range 6-30 months).Conclusions.This information may assist urologists in developing guidelines for counseling and proper clinical management for patients with "low malignant potential" tumors or small renal masses.



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PGE2-synthesis and signaling in malignant transformation and progression of human hepatocellular carcinoma

Publication date: Available online 12 March 2017
Source:Human Pathology
Author(s): Shengbing Zang, Xiaojie Ma, Yanbin Wu, Wenwen Liu, Haili Cheng, Jiasi Li, Jingfeng Liu, Aimin Huang
Prostaglandin E 2 (PGE2), which is the most abundant prostaglandin produced in hepatocellular carcinoma (HCC), may be involved in hepatocarcinogenesis. Here, the amount of PGE2 was significantly increased in HCC tissue and adjacent non-cancerous tissues relative to normal liver tissue (P<.001). In addition, the expression of EP2 receptor was considerably up-regulated in HCC tissue compared with the expression of EP1 (P<.05), EP3 (P<.01), and EP4 (P<.01) receptor. The expression of EP2 receptor was positively correlated with the level of PGE2 in HCC tissue (P<.001). Furthermore, PGE2 significantly increased proliferation and invasion potential of human HCC cells. However, antagonism of EP2 signaling suppressed PGE2-induced growth and invasion in human HCC cells. Taken together, upregulation of PGE2 level was associated with proliferation and invasion potential of HCC, and EP2 receptor predominately mediated the function of PGE2 in the transformation and progression of HCC.



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Clinical Significance of Spasmolytic Polypeptide-expressing Metaplasia and Intestinal Metaplasia in EBV-associated and EBV-negative Gastric Cancer

Publication date: Available online 12 March 2017
Source:Human Pathology
Author(s): Yu Zhang, Jian-ning Chen, Min Dong, Zhi-gang Zhang, Yi-wang Zhang, Jun-yan Wu, Hong Du, Hai-gang Li, Yan Huang, Chun-kui Shao
Spasmolytic polypeptide-expressing metaplasia (SPEM) and intestinal metaplasia (IM) have been recognized as neoplastic precursors in gastric carcinogenesis. We explored the relationship between SPEM and IM in Epstein–Barr virus-associated (EBVaGC) and Epstein–Barr virus-negative (EBVnGC) gastric cancer. 64 EBVaGC and 154 EBVnGC patients were included. EBV-positivity was identified using EBER-1 in situ hybridization. SPEM was sub-classified into absent, early and advanced SPEM. Acute and chronic inflammation was graded as absent, mild, moderate and marked. Univariate and multivariate logistic regression analyses were conducted to analyze the correlation between SPEM, IM and inflammation. Our study revealed that SPEM was detected in 87.5% EBVaGC and 85.1% EBVnGC patients. Distribution of patients according to the SPEM classification was significantly different between EBVaGC and EBVnGC groups (P=.038). IM was observed less frequently in EBVaGC when compared to EBVnGC patients (P<.001). No difference was observed between EBVaGC and EBVnGC in the levels of acute and chronic inflammation. A positive correlation between IM and SPEM status was observed in both EBVaGC and EBVnGC patients. Furthermore, advanced SPEM was an independent influential factor to IM in EBVnGC (P=.013). In conclusion, SPEM was associated with both EBVaGC and EBVnGC more frequently than IM. Moreover, advanced SPEM had a stronger association with IM than early SPEM in EBVnGC. These results suggest that identification of SPEM should be used as a high-risk indicator for detecting early gastric carcinoma, and should be brought to the attention of pathologists and clinicians.



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Correlation of Histological Grade of Dedifferentiation with Clinical Outcome in 55 patients with Dedifferentiated Liposarcomas

Publication date: Available online 12 March 2017
Source:Human Pathology
Author(s): Kossivi Dantey, Karen Schoedel, Oleksandr Yergiyev, David Bartlett, Uma N.M. Rao
In this study the histologic grade of dedifferentiated liposarcomas was correlated with outcome in surgically resected specimens in 55 patients over a 19-year period at the University of Pittsburgh Medical Center. The tumors were located in the retroperitoneum (N=34); the extremities and thigh (N=16), and the remainder involved the spermatic cord and head and neck. Most tumors were large (mean=21 cm.) Follow up was available in all 55 patients (median=36months). Forty-one tumors classified as high-grade dedifferentiated liposarcoma (HG-DDLPS) had mitotically active pleomorphic and spindle cells and foci of necrosis. They included tumors with foci of smooth muscle differentiation (N=12), osteosarcoma (N=4), and myxoid areas (N=9). Fourteen tumors classified as low-grade dedifferentiated liposarcoma (LG-DDLPS) displayed a predominantly bland, monomorphic, spindle cell population with few mitoses and scant necrosis. The Kaplan–Meier method and log rank test were used for statistical analysis. All tumors had unequivocal foci of well-differentiated liposarcoma (WDLPS). Fluorescence in situ hybridization (FISH) detected amplification of MDM2 in 29 cases. Twenty of 41 patients (49%) with HG-DDLPS died of tumor, and two patients died with LG-DDLPS (14%). The overall survival of patients with LG-DDLPS was significantly longer (P=.02). The median survival was 113months for the LGDDLPS and 48months for the HGDDLPS. Metastases (N=4) occurred only in the high-grade tumors and were independent of the type of heterologous differentiation. Patients with HG-DDLPS were at a greater risk of earlier death. Distinction between the two groups is important for patient selection for possible adjuvant therapy.



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Concomitant expression of ezrin and HER2 predicts distant metastasis and poor prognosis of patients with salivary gland carcinomas

Publication date: Available online 12 March 2017
Source:Human Pathology
Author(s): Kazuki Hashimoto, Ryuichi Hayashi, Takashi Mukaigawa, Manabu Yamazaki, Satoshi Fujii
Salivary gland carcinomas (SGCs) exhibit heterogeneous biological behaviors, including the formation of distant metastases, which is a critical event associated with poor prognosis. Ezrin, which is a member of the ezrin–radixin–moesin family of plasma membrane–cytoskeleton linker proteins, may provide a marker for metastasis and poor survival of patients with cancer. The aim of the present study was to investigate the relationship between ezrin expression and the expression of HER2, p53, and Ki-67 as well as clinicopathological factors in SGCs. For this purpose, we used immunohistochemistry to analyze the expression of these proteins in tissue-microarrays prepared from formalin-fixed, paraffin-embedded primary tumor tissues of 221 patients with SGCs. Using receiver operating characteristic curves, we determined cutoff values of 30% and 5.0% for high expression of ezrin and Ki-67, respectively. High ezrin expression detected in samples from 63 (28.5%) patients with SGCs significantly correlated with male sex, high-grade histopathology, high Ki-67 labeling index, HER2 overexpression, aberrant expression of p53, and distant metastasis. Multivariate analysis demonstrated that high ezrin expression was an independent prognostic factor for shorter overall survival (hazard ratio, 2.11 [1.09–4.05]; P=.027). Further, concomitant high expression of ezrin and HER2 overexpression correlated significantly with shorter disease-free survival and overall survival as well as a high incidence of distant metastasis (P<.001). These findings indicate that ezrin and HER2 expression in patients with SGCs represents a high-grade histopathological subtype that requires adjuvant therapy, including molecularly targeted therapies, to decrease the risk of subsequent metastasis.



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Tuning of bandwidth by superposition of bending and radial resonance modes in bilayer laminate composite

Publication date: 15 May 2017
Source:Materials & Design, Volume 122
Author(s): S. Dinesh Kumar, J. Magesh, V. Subramanian
Though the magnetoelectric (ME) coupling strength found to be enhanced at electromechanical resonance, the narrow bandwidth limits its device functionality. Hence, widening the resonance bandwidth without affecting the ME coupling strength is essential for practical applications. This paper explores the possibility of tuning the resonance bandwidth by superimposing radial mode over bending mode in simple asymmetric bilayer laminate structure. Such superposition of modes can be realized by varying the thickness of the ferroelectric layer in ME composite. In order to examine this, (BiScO3-PbTiO3)-NiFe2O4 bilayer ME composite with varying thickness were fabricated and characterized with direct and converse ME measurements. As expected, variation in thickness of the bilayer tunes the second bending mode to overlap with the radial mode. The direct and converse ME studies demonstrate that the resonance bandwidth is modulated due to overlapping of modes. The off-phase superposition of resonance and anti-resonance frequency of radial and bending mode is essential for bandwidth tuning.

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Designed porous microstructures for electrochemical reduction of bulk hematite ceramics

Publication date: 15 May 2017
Source:Materials & Design, Volume 122
Author(s): Yu.A. Ivanova, J.F. Monteiro, L.B. Teixeira, N. Vitorino, A.V. Kovalevsky, J.R. Frade
This work proposes a new approach for electrochemical reduction of hematite to magnetite and/or metallic iron, based on ceramic cathodes with designed microstructures. The processing method, involving emulsification of concentrated aqueous ceramic suspensions with melted paraffin, enables preparation of cellular hematite ceramics possessing open porosity and pore interconnectivity controlled by simple process parameters. The obtained porous hematite ceramics were successfully used as cathodes for in situ electrochemical reduction in aqueous alkaline electrolyte. Electrochemical reduction converts the designed ceramic microstructure to corresponding cellular Fe/Fe3O4/Fe2O3 composites with adjustable phase distributions and high prospects for applications in heterogeneous catalysis or other applications, based on unique combinations of active functionalities of metallic Fe, magnetite and hematite.

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Laves phase control of Inconel 718 alloy using quasi-continuous-wave laser additive manufacturing

Publication date: 15 May 2017
Source:Materials & Design, Volume 122
Author(s): Hui Xiao, Simeng Li, Xu Han, Jyoti Mazumder, Lijun Song
Nb segregation and Laves phase formation are known to be detrimental to mechanical properties of Inconel 718. However, effective efforts to suppress Nb segregation and Laves phase formation are still lacking. In this work, a quasi-continuous-wave (QCW) laser additive manufacturing (LAM) is used to control Nb segregation and Laves phase formation. Thermal behaviors of the molten pool, microstructural evolution and mechanical response of the fabricated samples to aging treatment were investigated. Compared to continuous wave (CW) LAM, QCW-LAM results in a refined and equiaxed dendrite microstructure, a reduced Nb segregation, and attended fine and discrete Laves phase particles, due to an improved cooling rate with one order of magnitude and a decreased solidification time of the molten pool. In addition, the QCW sample shows a good response to aging treatment with a higher hardness and more desired tensile properties due to the reduced Nb segregation, the obtained fine discrete Laves phase and the refined dendrite microstructure. The tensile strength (~1404.1MPa), the yield strength (~1120.6MPa) and the ductility (~12.4pct) of the aged QCW sample are higher than the ASTM limits of the wrought Inconel 718 alloy.

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Utilizing p-type native oxide on liquid metal microdroplets for low temperature gas sensing

Publication date: 15 May 2017
Source:Materials & Design, Volume 122
Author(s): Mahnaz Shafiei, Faegheh Hoshyargar, Nunzio Motta, Anthony P. O'Mullane
Liquid metals based on gallium oxidize under ambient conditions to form a native oxide on the surface. Here we take advantage of the semiconducting properties of this oxide layer for gas sensing applications. In particular, the development of gas sensors that operate at low temperatures is an ongoing challenge. Therefore, to address this problem, we fabricated conductometric sensors based on an oxidized liquid metal galinstan layer, and investigated their sensitivity towards NO2, NH3 and CH4 gases. The fabrication of the sensing layer was achieved via a simple approach, involving the sonication of the liquid metal in acetonitrile to produce a solution of micro/nanodroplets and dropcasting it onto a non-conducting alumina substrate at different loadings. The material properties of the developed film were extensively investigated by means of field emission scanning electron microscopy, Raman spectroscopy, X-ray diffraction and X-ray photoelectron spectroscopy. The results confirmed the presence of an amorphous oxide on the surface of the droplets. Hall effect measurements indicated that the oxide film was p-type, which influenced the sensing response towards the different gases. We demonstrated that a physisorption process occurs at 100°C, leading to a detection limit as low as 1 and 20ppm for NO2 and NH3, respectively.

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Effect of ball-milling time on mechanical and magnetic properties of carbon nanotube reinforced FeCo alloy composites

Publication date: 15 May 2017
Source:Materials & Design, Volume 122
Author(s): Amar J Albaaji, Elinor G Castle, Mike J Reece, Jeremy P Hall, Sam L Evans
Carbon nanotubes (CNTs) reinforced FeCo alloys were produced by high energy ball-milling and spark plasma sintering (SPS). CNTs distribution in the FeCo alloy was gradually improved as ball-milling time increased, with a uniform dispersion achieved after 6h ball-milling. Tensile tests demonstrated that, as the ball-milling time increased, the yield strength increased in the composites; a maximum 50% relative increase in tensile strength due to the addition of CNTs was achieved after 1h ball-milling, which then decreased with further ball-milling. The elongation to fracture was significantly increased after 1h ball-milling and then decreased with further ball-milling. SEM results show a patch of dimples in the fracture surface of the composite, indicating improved ductility due to CNTs. The coercivity was increased with increased ball-milling time, while the saturation induction showed a peak value after 1h of ball-milling and then decreased with further ball-milling. Raman spectra of the composite indicated that no serious damage had been imparted to the CNTs during ball-milling.

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Assessing new peptides that may be involved in the physiological regulation of the gonadal axis in humans: gonadotropin inhibitory hormone

Abstract

The hypothalamo-pituitary-testicular (HPT) and hypothalamo-pituitary-ovarian (HPO) axes are integrated networks that regulate androgenization or estrogenization (including embryonic, infantile, pubertal and adult sexual maturation), male or female sexual behavior, and spermatogenesis or ovulation, respectively. Dysregulation of the HPT axis, for example, results in pubertal delay, eunuchism, impaired spermatogenesis, and reduced systemic androgen exposure; and may also contribute to some of the features of male aging, impair recovery from protracted critical illness, and induce visceral adiposity, sarcopenia, osteopenia, and insulin resistance. Furthering knowledge of how the gonadal axes are regulated will thereby inform important and diverse pathophysiological processes.



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Measuring TSH receptor antibody [TRAb] to influence treatment choices in Graves’ disease

Summary

TSH receptor antibody (TRAb) plays a key role in the pathogenesis of Graves' disease (GD) and its levels correlate with the clinical course. The 2nd and 3rd generation TRAb assays have >95% sensitivity and specificity for the diagnosis of GD, and have improved the utility of TRAb to predict relapse. TRAb levels decline with antithyroid drug (ATD) therapy and after thyroidectomy. Its level increases for a year following radioactive iodine (RAI) therapy, with a gradual fall thereafter. TRAb level >12 IU/L at diagnosis of GD is associated with 60% risk of relapse at 2 years and 84% at 4 years. The prediction of risk of relapse improves further to >90% with TRAb >7.5 IU/L at 12 months or >3.85 IU/L at cessation of ATD therapy. TRAb tests are not expensive, and hence TRAb measurements at presentation, after 12 months and/or 18 months (at cessation) of ATD therapy could potentially guide treatment choices in GD. Elevated TRAb favours definitive treatment in the form of RAI or thyroidectomy, depending on the presence or absence of moderate to severe Graves ophthalmopathy (GO) and the ability to comply with radiation protection requirements. Use of ATDs in early pregnancy is associated with increased risk of congenital anomalies; early ablative treatment [RAI / surgery] should be considered in women of childbearing age at higher risk of relapse of GD. TRAb >5 IU/L in pregnant women with current or previously treated GD is associated with increased risk of foetal and neonatal thyrotoxicosis, and hence needs close monitoring. TRAb levels parallel the course of GO, and elevated TRAb is an indication for steroid prophylaxis to prevent progression of GO with RAI therapy.

This article is protected by copyright. All rights reserved.



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Discovery of three toxin peptides with Kv1.3 channel and IL-2 cytokine inhibiting activities from Non-Buthidae scorpions Chaerilus tricostatus and Chaerilus tryznai

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Publication date: Available online 12 March 2017
Source:Peptides
Author(s): Li Ding, Jing Chen, Jinbo Hao, Jiahui Zhang, Xuejun Huang, Fangfang Hu, Zheng Wu, Yaru Liu, Wenxin Li, Zhijian Cao, Yingliang Wu, Jian Li, Shan Li, Hongyan Liu, Wenlong Wu, Zongyun Chen
Non-Buthidae venomous scorpions are huge natural sources, however, only a few works have been done to understand their toxin peptides. Here, we described three new potential immunomodulating toxin peptides Ctri18, Ctry68 and Ctry2908 from two Non-Buthidae scorpions Chaerilus tricostatus and Chaerilus tryznai. Sequence alignment analyses showed that Ctri18, Ctry68 and Ctry2908 are three new members of scorpion toxin α-KTx15 subfamily. Electrophysiological experiments showed that Ctri18, Ctry68 and Ctry2908 blocked the Kv1.3 channel at micromole to nanomole levels, but had weak effects on potassium channel KCNQ1 and sodium channel Nav1.4, which indicated that Ctri18, Ctry68 and Ctry2908 might have specific inhibiting effects on the Kv1.3 channel. ELISA experiments showed that Ctri18, Ctry68 and Ctry2908 inhibited IL-2 cytokine secretions of activated T lymphocyte in human PBMCs. Excitingly, consistent with the good Kv1.3 channel inhibitory activity, Ctry2908 inhibited cytokine IL-2 secretion in nanomole level, which indicated that Ctry2908 might be a new lead drug template towards Kv1.3 channels. Together, these studies discovered three new toxin peptides Ctri18, Ctry68 and Ctry2908 with Kv1.3 channel and IL-2 cytokine inhibiting activities from two scorpions Chaerilus tricostatus and Chaerilus tryznai, and highlighted that non-Buthidae venomous scorpions are new natural toxin peptide sources.



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Semi-microbiological synthesis of an active lysinoalanine-bridged analog of glucagon-like-peptide-1

Publication date: Available online 12 March 2017
Source:Peptides
Author(s): Anneke Kuipers, Louwe de Vries, Marcel P. de Vries, Rick Rink, Tjibbe Bosma, Gert N. Moll
Some modified glucagon-like-peptide-1 (GLP-1) analogs are highly important for treating type 2 diabetes. Here we investigated whether GLP-1 analogs expressed in Lactococcus lactis could be substrates for modification and export by the nisin dehydratase and transporter enzyme. Subsequently we introduced a lysinoalanine by coupling a formed dehydroalanine with a lysine and investigated the structure and activity of the formed lysinoalanine-bridged GLP-1 analog. Our data show: i) GLP-1 fused to the nisin leader peptide is very well exported via the nisin transporter NisT, ii) production of leader-GLP-1 via NisT is higher than via the SEC system, iii) leader-GLP-1 exported via NisT was more efficiently dehydrated by the nisin dehydratase NisB than when exported via the SEC system, iv) individual serines and threonines in GLP-1 are dehydrated by NisB to a significantly different extent, v) an introduced Ser30 is well dehydrated and can be coupled to Lys34 to form a lysinoalanine-bridged GLP-1 analog, vi) a lysinoalanine(30-34) variant's conformation shifts in the presence of 25% trifluoroethanol towards a higher alpha helix content than observed for wild type GLP-1 under identical condition, vii) a lysinoalanine(30-34) GLP-1 variant has retained significant activity. Taken together the data extend knowledge on the substrate specificities of NisT and NisB and their combined activity relative to export via the Sec system, and demonstrate that introducing a lysinoalanine bridge is an option for modifying therapeutic peptides.

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