bluuebunny/crossref_metadata_2025 huggingface dataset:
Anticholinergic drugs and risk of dementia: case-control study
Authors: Richardson Kathryn , Fox Chris , Maidment Ian , Steel Nicholas , Loke Yoon K , Arthur Antony , Myint Phyo K , Grossi Carlota M , Mattishent Katharina , Bennett Kathleen , Campbell Noll L , Boustani Malaz , Robinson Louise , Brayne Carol , Matthews Fiona E , Savva George M
Published: April 2018

Objectives

To estimate the association between the duration and level of exposure to different classes of anticholinergic drugs and subsequent incident dementia.

Design

Case-control study.

Setting

General practices in the UK contributing to the Clinical Practice Research Datalink.

Participants

40 770 patients aged 65-99 with a diagnosis of dementia between April 2006 and July 2015, and 283 933 controls without dementia.

Interventions

Daily defined doses of anticholinergic drugs coded using the Anticholinergic Cognitive Burden (ACB) scale, in total and grouped by subclass, prescribed 4-20 years before a diagnosis of dementia.

Main outcome measures

Odds ratios for incident dementia, adjusted for a range of demographic and health related covariates.

Results

14 453 (35%) cases and 86 403 (30%) controls were prescribed at least one anticholinergic drug with an ACB score of 3 (definite anticholinergic activity) during the exposure period. The adjusted odds ratio for any anticholinergic drug with an ACB score of 3 was 1.11 (95% confidence interval 1.08 to 1.14). Dementia was associated with an increasing average ACB score. When considered by drug class, gastrointestinal drugs with an ACB score of 3 were not distinctively linked to dementia. The risk of dementia increased with greater exposure for antidepressant, urological, and antiparkinson drugs with an ACB score of 3. This result was also observed for exposure 15-20 years before a diagnosis.

Conclusions

A robust association between some classes of anticholinergic drugs and future dementia incidence was observed. This could be caused by a class specific effect, or by drugs being used for very early symptoms of dementia. Future research should examine anticholinergic drug classes as opposed to anticholinergic effects intrinsically or summing scales for anticholinergic exposure.

Trial registration

Registered to the European Union electronic Register of Post-Authorisation Studies EUPAS8705.
A narrative review on cervical interventions in adults with chronic whiplash-associated disorder
Authors: Anderson Charlotte , Yeung Euson , Tong Tiffany , Reed Nick
Published: April 2018

Introduction

Whiplash injuries are common in society, but clinical interventions are inconclusive on the most effective treatment. Research and reviews have been completed with the goal of determining clinical interventions that are effective for whiplash injuries and disorders, but literature has not recently been summarised on best practices for cervical spine interventions for adults with chronic whiplash.

Purpose

The objective of this narrative review is to update and expand on previous works, to provide recommendations for clinical interventions and future research in the area of cervical spine rehabilitation for adults with chronic whiplash-associated disorder.

Method

The Arskey and O’Malley methodology was used for this narrative review. CINHAL, EMBASE, Medline, PsychInfo, Scopus, Web of Science, as well as grey literature, were searched from 2003 to April 2017. Two reviewers screened titles and abstracts for relevance to the review, and content analysis summarised the study findings. A total of 14 citations were included in the final review.

Findings

Exercise-based interventions targeted at the cervical spine appear most beneficial for adults with chronic whiplash-associated disorder (WAD). Invasive interventions still require more rigorous studies to deem their effectiveness for this population.

Conclusion

Further research is required to investigate and determine clinically relevant results for cervical spine intervention in patients with chronic WAD.
Effect of short and long moderate-intensity exercises in modifying cardiometabolic markers in sedentary Kenyans aged 50 years and above
Authors: Magutah Karani , Meiring Rebecca , Patel Nilesh B , Thairu Kihumbu
Published: April 2018

Objectives

We compared effects of shorter moderate-intensity exercise time (<10 min bouts) on cardiometabolic parameters with the current recommendations among elderly adults.

Methods

Fifty-three sedentary individuals aged ≥50 years were divided into exercise groups1: male and2 female short-duration bouts (MSand FS, respectively), and3 male and4 female long-duration bouts (MLand FL, respectively). Short-duration bouts consisted three 5–10 min moderate-intensity jogging sessions daily, and long-duration bouts consisted 30–60 min sessions 3–5 days weekly. Cumulative exercise times were equivalent. Physical activity (PA) was measured by log and activity monitors. Fasting venous blood at baseline and 8 weekly intervals was used for blood chemistry.

Results

After 24 weeks, MSand FSwith total cholesterol (TC) of >5.2 mmol/L and >5.3 mmol/L decreased from 22.2% to 14.8% and from 30.9% to 11.5%, respectively. For ML, this decreased from 25.9% to 3.7%, while FLhad 0% change. In MSand ML, TC/high-density lipoproteins (HDLs) of >5.0 mmol/L dropped from 22.2% to 7.4% and from 22.2% to 15.4%, respectively. In FSand FL, TC/HDL of >4.5 mmol/L declined from 19.2% to 7.7% and from 19.2% to 3.8%, respectively. MSand MLwith fasting blood glucose of ≥5.5 mmol/L declined from 40.7% to 11.1% and from 33.3% to 3.7%, respectively. Similarly, it declined from 46.2% to 0% and 42.3% to 11.5% for FSand FL, respectively. There were no differences in the changes between regimes throughout the study.

Conclusion

Bouts lasting <10 min per session are as good as those lasting ;≥30 min in improving cardiometabolic profiles of sedentary adults aged ≥50 years.
Baseline patient characteristics associated with response to biologic therapy in patients with psoriatic arthritis enrolled in the Corrona Psoriatic Arthritis/Spondyloarthritis Registry
Authors: Mease Philip J , Karki Chitra , Liu Mei , Kavanaugh Arthur , Ritchlin Christopher T , Huynh Doquyen Hoa , Palmer Jacqueline B , Greenberg Jeffrey D
Published: April 2018

Objectives

To compare baseline characteristics between patients with psoriatic arthritis (PsA) who achieved and did not achieve minimal disease activity (MDA) with biologic therapy in the US-based Corrona Psoriatic Arthritis/Spondyloarthritis Registry.

Methods

Patients with PsA aged ≥18 years enrolled between March 2013 and March 2016 who were receiving biologics at enrolment (baseline), not in MDA and had ≥2 follow-up visits were included. Patients were classified as those who remained on their index biologic and achieved MDA at the second follow-up visit (MDA achievers (MDA-A)) and those who did not (MDA non-achievers (MDA-NA)). Demographics, clinical characteristics, patient-reported outcomes and medication history were compared between groups.

Results

Of 148 patients with PsA who met the inclusion criteria, 34 (23.0%) and 114 (77.0%) were classified as MDA-A and MDA-NA, respectively. At baseline, most patients (96.6%) were receiving tumour necrosis factor inhibitors, and both groups were similar in age, sex, race, medication history, enthesitis and dactylitis counts, disease duration and comorbidities. Compared with MDA-A, MDA-NA had significantly worse mean tender joint count (7.2 vs 3.4), patient-reported pain (51.2 vs 35.7), patient-reported fatigue (54.1 vs 42.4), physical function (Health Assessment Questionnaire, 1.0 vs 0.6), Bath Ankylosing Disease Activity Index (5.0 vs 3.4) and Bath Ankylosing Spondylitis Functional Index (4.0 vs 2.0) scores (all p<0.05).

Conclusions

Approximately one in four patients achieved MDA with their index biologic at the time of the second follow-up visit. Both groups were similar in several baseline demographic and clinical features; however, patients who did not achieve MDA generally had worse tender joint counts and patient-reported outcomes.
The Impact of Income and Taxation in a Price-Tiered Cigarette Market: findings from the ITC Bangladesh Surveys
Authors: Huq Iftekharul , Nargis Nigar , Lkhagvasuren Damba , Hussain AKM Ghulam , Fong Geoffrey T
Published: April 2018

Background

Taxing tobacco is among the most effective measures of tobacco control. However, in a tiered market structure where multiple tiers of taxes coexist, the anticipated impact of tobacco taxes on consumption is complex. This paper investigates changing smoking behaviour in lieu of changing prices and changing income. The objective of the paper is to evaluate the effectiveness of change in prices (through taxes) and change in income in a price-tiered cigarette market.

Method

A panel dataset from the International Tobacco Control Bangladesh surveys is used for analysis. For preliminary analysis transition matrices are developed. Next, probit and multinomial logit regression models are used to identify the effects of changes in prices and changes in income along with other control variables.

Findings

Transition matrices show significant movement of smokers across price tiers from one wave to another. Regression results show that higher income raises the probability to up-trade and decreases the probability to down-trade. Results also show that higher prices raises the probability to up-trade and reduces the probability to down-trade. Although not significant, there exists a negative relationship between the probability to down-trade and the probability to intend to quit.

Conclusion

It is evident from the results that a price-tiered market provides smokers more opportunities to accommodate their smoking behaviour when faced with price and income change. Therefore, tiered structure of the tax system should be replaced with uniform taxes. Moreover, overall cigarette taxes need to be raised to an extent so that it off-sets any positive effects of income growth.
Influences of spawning timing, water temperature, and climatic warming on early life history phenology in western Alaska sockeye salmon
Authors: Sparks Morgan M. , Falke Jeffrey A. , Quinn Thomas P. , Adkison Milo D. , Schindler Daniel E. , Bartz Krista , Young Dan , Westley Peter A.H.
Published: April 2018

We applied an empirical model to predict hatching and emergence timing for 25 western Alaska sockeye salmon (Oncorhynchus nerka) populations in four lake-nursery systems to explore current patterns and potential responses of early life history phenology to warming water temperatures. Given the temperature regimes sockeye salmon experienced during development, we predicted hatching to occur in as few as 58 days to as many as 260 days depending on spawning timing and temperature. For a focal lake spawning population, our climate–lake temperature model predicted a water temperature increase of 0.7 to 1.4 °C from 2015 to 2099 during the incubation period, which translated to a hatching timing that was 16 to 30 days earlier. The most extreme warming scenarios shifted development to approximately 1 week earlier than historical minima and thus climatic warming may lead to only modest shifts in phenology during the early life history stage of this population. The marked variation in the predicted timing of hatching and emergence among populations in close proximity on the landscape may serve to buffer this metapopulation from climate change.
Protective Effects of Ginsenoside Rb1 against Blood–Brain Barrier Damage Induced by Human Immunodeficiency Virus-1 Tat Protein and Methamphetamine in Sprague-Dawley Rats
Authors: Li Juan , Zeng Bairui , Hu Xiao , Li Zhen , Zhang Dongxian , Yang Genmeng , Dai Jiejie , Zeng Xiaofeng
Published: April 2018

Although antiretroviral therapy has helped to improve the lives of individuals infected with human immunodeficiency virus 1 (HIV-1), these patients are often still afflicted with HIV-1-associated neurocognitive disorders, which can lead to neurocognitive impairment and even dementia, and continue to hamper their quality of life. Methamphetamine abuse in HIV-1 patients poses a potential risk for HIV-associated neurocognitive disorders, because methamphetamine and HIV-1 proteins such as transactivator of transcription can synergistically damage the blood–brain barrier (BBB). In this study, we aimed to examine the effects of methamphetamine and HIV-1 Tat protein on the blood–brain barrier function and to determine whether ginsenoside Rb1 (GsRb1) plays a role in protecting the BBB. Sprague-Dawley rats were divided into four groups. The experimental groups received methamphetamine and HIV-1 Tat protein or both and the control group received saline or GsRb1 pretreatment. Oxidative stress-related factors, tight junction (TJ) proteins, blood–brain barrier permeability, and morphological changes were recorded in each group. The results showed that the group treated with Methamphetamine[Formula: see text]Tat showed a significant change at the ultrastructural level and in the levels of oxidative stress-related factors, TJ proteins, and BBB permeability, suggesting that the BBB function was severely damaged by HIV-1 Tat and methamphetamine synergistically. However, malondialdehyde levels and BBB permeability were lower and the oxidative stress-related factors superoxide dismutase and glutathione were higher in the GsRb1-treated group than in the Methamphetamine[Formula: see text]Tat-treated group, indicating that GsRb1 can protect the BBB against the toxic effects of HIV-1 Tat and methamphetamine. These results show that GsRb1 may offer a potential therapeutic option for patients with HIV-associated neurocognitive disorders or other neurodegenerative diseases.
Design of narrow band multi-channel optical filters using zero index medium
Authors: Anusha N. P. , Sharan Alok
Published: April 2018

We propose a design of narrow-band multi-channel optical filter using multiple stacks of unit cell consisting of trilayer of Doubly positive medium (DPS)–Doubly negative medium (DNG)–Epsilon negative medium (ENG). Finite Difference Time Domain (FDTD) technique is used to numerically simulate the effect of optical thickness of DPS, DNG and ENG media on tunability of the transmission spectrum of such a medium. We also demonstrate the control on the number of channels at different frequencies that can be transmitted through such medium.
Analytical Global Median Filtering Forensics Based on Moment Histograms
Authors: Gupta Abhinav , Singhal Divya
Published: April 2018

Median filtering forensics in images has gained wide attention from researchers in recent years because of its inherent nature of preserving visual traces. Although many forensic methods are developed for median filtering detection, probability of detection reduces under JPEG compression at low-quality factors and for low-resolution images. The feature set reduction is also a challenging issue among existing detectors. In this article, a 19-dimensional feature set is analytically derived from image skewness and kurtosis histograms. This new feature set is exploited for the purpose of global median filtering forensics and verified with exhaustive experimental results. The efficacy of the method is tested on six popular databases (UCID, BOWS2, BOSSBase, NRCS, RAISE, and DID) and found that the new feature set uncovers filtering traces for moderate, low JPEG post-compression and low-resolution operation. Our proposed method yields lowest probability of error and largest area under the ROC curve for most of the test cases in comparison with previous approaches. Some novel test cases are introduced to thoroughly assess the benefits and limitations of the proposed method. The obtained results indicate that the proposed method would provide an important tool to the field of passive image forensics.
QoE-Aware OTT-ISP Collaboration in Service Management
Authors: Floris Alessandro , Ahmad Arslan , Atzori Luigi
Published: April 2018

It is a matter of fact that quality of experience (QoE) has become one of the key factors determining whether a new multimedia service will be successfully accepted by the final users. Accordingly, several QoE models have been developed with the aim of capturing the perception of the user by considering as many influencing factors as possible. However, when it comes to adopting these models in the management of the services and networks, it frequently happens that no single provider has access to all of the tools to either measure all influencing factors parameters or control over the delivered quality. In particular, it often happens to the over-the-top (OTT) and Internet service providers (ISPs), which act with complementary roles in the service delivery over the Internet. On the basis of this consideration, in this article we first highlight the importance of a possible OTT-ISP collaboration for a joint service management in terms of technical and economic aspects. Then we propose a general reference architecture for a possible collaboration and information exchange among them. Finally, we define three different approaches, namely joint venture, customer lifetime value based, and QoE fairness based. The first aims to maximize the revenue by providing better QoE to customers paying more. The second aims to maximize the profit by providing better QoE to the most profitable customers (MPCs). The third aims to maximize QoE fairness among all customers. Finally, we conduct simulations to compare the three approaches in terms of QoE provided to the users, profit generated for the providers, and QoE fairness.
Data Musicalization
Authors: Tulilaulu Aurora , Nelimarkka Matti , Paalasmaa Joonas , Johnson Daniel , Ventura Dan , Myllys Petri , Toivonen Hannu
Published: April 2018

Data musicalization is the process of automatically composing music based on given data as an approach to perceptualizing information artistically. The aim of data musicalization is to evoke subjective experiences in relation to the information rather than merely to convey unemotional information objectively. This article is written as a tutorial for readers interested in data musicalization. We start by providing a systematic characterization of musicalization approaches, based on their inputs, methods, and outputs. We then illustrate data musicalization techniques with examples from several applications: one that perceptualizes physical sleep data as music, several that artistically compose music inspired by the sleep data, one that musicalizes on-line chat conversations to provide a perceptualization of liveliness of a discussion, and one that uses musicalization in a gamelike mobile application that allows its users to produce music. We additionally provide a number of electronic samples of music produced by the different musicalization applications.
Improved Audio Steganalytic Feature and Its Applications in Audio Forensics
Authors: Luo Weiqi , Li Haodong , Yan Qi , Yang Rui , Huang Jiwu
Published: April 2018

Digital multimedia steganalysis has attracted wide attention over the past decade. Currently, there are many algorithms for detecting image steganography. However, little research has been devoted to audio steganalysis. Since the statistical properties of image and audio files are quite different, features that are effective in image steganalysis may not be effective for audio. In this article, we design an improved audio steganalytic feature set derived from both the time and Mel-frequency domains for detecting some typical steganography in the time domain, including LSB matching, Hide4PGP, and Steghide. The experiment results, evaluated on different audio sources, including various music and speech clips of different complexity, have shown that the proposed features significantly outperform the existing ones. Moreover, we use the proposed features to detect and further identify some typical audio operations that would probably be used in audio tampering. The extensive experiment results have shown that the proposed features also outperform the related forensic methods, especially when the length of the audio clip is small, such as audio clips with 800 samples. This is very important in real forensic situations.
The impact of preserved Klotho gene expression on antioxidative stress activity in healthy kidney
Authors: Kimura Takaaki , Shiizaki Kazuhiro , Akimoto Tetsu , Shinzato Takahiro , Shimizu Toshihiro , Kurosawa Akira , Kubo Taro , Nanmoku Koji , Kuro-o Makoto , Yagisawa Takashi
Published: April 2018

Klotho, which was originally identified as an antiaging gene, forms a complex with fibroblast growth factor 23 receptor in the kidney, with subsequent signaling that regulates mineral metabolism. Other biological activities of Klotho, including antiaging effects such as protection from various types of cellular stress, have been shown; however, the precise mechanism of these effects of Klotho gene in the healthy human kidney is not well understood. In this study, we examined the relationships of Klotho and antioxidative stress gene expression levels in zero-hour biopsy specimens from 44 donors in kidney transplantation and verified them in animal models whose Klotho gene expression levels were varied. The nitrotyrosine expression level in the kidney was evaluated in these animal models. Expression levels of Klotho gene were positively correlated with the p53 gene and antioxidant enzyme genes such as catalase, superoxide dismutase 1 (SOD1), SOD2, peroxiredoxin 3 (PRDX3), and glutathione peroxidase 1 (GPX1) but not clinical parameters such as age and renal function or pathological features such as glomerulosclerosis and interstitial fibrosis tubular atrophy. The expression levels of all genes were significantly higher in mice with Klotho overexpression than in wild-type mice, and those except for catalase, PRDX3, and GPX1 were significantly lower in Klotho-deficient mice than in wild-type littermate mice. Nitrotyrosine-positive bands of various sizes were observed in kidney from Klotho-deficient mice only. The preservation of Klotho gene expression might induce the antioxidative stress mechanism for homeostasis of healthy human kidney independently of its general condition, including age, renal function, and histological findings.
Association between Nonsteroidal Anti-Inflammatory Drugs and Colorectal Cancer: A Population-Based Case–Control Study
Authors: Kuo Chun-Nan , Pan Jen-Jung , Huang Ya-Wen , Tsai Hui-Ju , Chang Wei-Chiao
Published: April 2018

Background: COX-2 overexpression may contribute to colorectal cancer occurrence. Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce colorectal cancer recurrence, but the efficacy of primary prevention in Asian populations is still elusive. Thus, we examined the primary preventive efficacy of aspirin and NSAIDs on colorectal cancer incidence in Taiwan.

Methods: A nested case–control study was conducted using the National Health Insurance Research Database (NHIRD) in Taiwan. We identified patients with diagnosis of colorectal cancer from 2005 to 2013 in the Registry of Catastrophic Illness Patient Database. We selected patients without colorectal cancer from the Longitudinal Health Insurance Database as the controls and matched them with cases. NSAID exposure was defined as at least two prescriptions 13 to 48 months prior to the index date. Conditional logistic regression models were performed to evaluate the association between NSAID use and colorectal cancer.

Results: A total of 65,208 colorectal cancer cases and 65,208 matched controls were identified. Patients with aspirin use had a lower risk of colorectal cancer compared with nonusers [adjusted OR (AOR) = 0.94, 95% confidence interval (CI) = 0.90–0.99]. NSAID use was associated with lower incidence of colorectal cancer (AOR = 0.96; 95% CI = 0.92–1.00). When examining colon or rectal cancer, similar decreased risks were observed. Patients taking more cumulative days of NSAIDs use tended to experience a more protective effect on colorectal cancer, but no dose–response effects were noted.

Conclusions: Aspirin and NSAIDs were associated with a reduced risk of colorectal cancer development among a study cohort in an Asian population.

Impact: This study provided a possible chemoprevention for colorectal cancer in an Asian population. Cancer Epidemiol Biomarkers Prev; 27(7); 737–45. ©2018 AACR.
A High-Content Screening of Anticancer Compounds Suggests the Multiple Tyrosine Kinase Inhibitor Ponatinib for Repurposing in Neuroblastoma Therapy
Authors: Sidarovich Viktoryia , De Mariano Marilena , Aveic Sanja , Pancher Michael , Adami Valentina , Gatto Pamela , Pizzini Silvia , Pasini Luigi , Croce Michela , Parodi Federica , Cimmino Flora , Avitabile Marianna , Emionite Laura , Cilli Michele , Ferrini Silvano , Pagano Aldo , Capasso Mario , Quattrone Alessandro , Tonini Gian Paolo , Longo Luca
Published: April 2018

Novel druggable targets have been discovered in neuroblastoma (NB), paving the way for more effective treatments. However, children with high-risk NB still show high mortality rates prompting for a search of novel therapeutic options. Here, we aimed at repurposing FDA-approved drugs for NB treatment by performing a high-content screening of a 349 anticancer compounds library. In the primary screening, we employed three NB cell lines, grown as three-dimensional (3D) multicellular spheroids, which were treated with 10 μmol/L of the library compounds for 72 hours. The viability of 3D spheroids was evaluated using a high-content imaging approach, resulting in a primary hit list of 193 compounds. We selected 60 FDA-approved molecules and prioritized drugs with multi-target activity, discarding those already in use for NB treatment or enrolled in NB clinical trials. Hence, 20 drugs were further tested for their efficacy in inhibiting NB cell viability, both in two-dimensional and 3D models. Dose-response curves were then supplemented with the data on side effects, therapeutic index, and molecular targets, suggesting two multiple tyrosine kinase inhibitors, ponatinib and axitinib, as promising candidates for repositioning in NB. Indeed, both drugs showed induction of cell-cycle block and apoptosis, as well as inhibition of colony formation. However, only ponatinib consistently affected migration and inhibited invasion of NB cells. Finally, ponatinib also proved effective inhibition of tumor growth in orthotopic NB mice, providing the rationale for its repurposing in NB therapy. Mol Cancer Ther; 17(7); 1405–15. ©2018 AACR.
Tumor-Independent Host Secretomes Induced By Angiogenesis and Immune-Checkpoint Inhibitors
Authors: Mastri Michalis , Lee Christina R. , Tracz Amanda , Kerbel Robert S. , Dolan Melissa , Shi Yuhao , Ebos John M.L.
Published: April 2018

The levels of various circulating blood proteins can change in response to cancer therapy. Monitoring therapy-induced secretomes (TIS) may have use as biomarkers for establishing optimal biological effect (such as dosing) or identifying sources of toxicity and drug resistance. Although TIS can derive from tumor cells directly, nontumor “host” treatment responses can also impact systemic secretory programs. For targeted inhibitors of the tumor microenvironment, including antiangiogenic and immune-checkpoint therapies, host TIS could explain unexpected collateral “side effects” of treatment. Here, we describe a comparative transcriptomic and proteomic analysis of host TIS in tissues and plasma from cancer-free mice treated with antibody and receptor tyrosine kinase inhibitors (RTKI) of the VEGF, cMet/ALK, and PD-1 pathways. We found that all cancer therapies elicit TIS independent of tumor growth, with systemic secretory gene change intensity higher in RTKIs compared with antibodies. Our results show that host TIS signatures differ between drug target, drug class, and dose. Notably, protein and gene host TIS signatures were not always predictive for each other, suggesting limitations to transcriptomic-only approaches to clinical biomarker development for circulating proteins. Together, these are the first studies to assess and compare “off-target” host secretory effects of VEGF and PD-1 pathway inhibition that occur independent of tumor stage or tumor response to therapy. Testing treatment impact on normal tissues to establish host-mediated TIS signatures (or “therasomes”) may be important for identifying disease agnostic biomarkers to predict benefits (or limitations) of drug combinatory approaches. Mol Cancer Ther; 17(7); 1602–12. ©2018 AACR.
A Rare Cause of Juvenile Stroke: Extracranial Carotid Artery Aneurysm with Venous Complete Reconstruction of the Carotid Bifurcation
Authors: Domanin Maurizio , Lanfranconi Silvia , Romagnoli Silvia , Runza Letterio , Cortini Francesca , Comi Giacomo Piero , Gabrielli Livio
Published: April 2018

Extracranial carotid artery aneurysms (ECAA) are a rare cause of embolic stroke. The underlying etiology is variable, with atherosclerosis being the most common entity in older subjects. Several treatments have been developed over the last 20 years, but the preferred method remains unknown. Notwithstanding the widespread use of endovascular techniques, surgical reconstruction by means of a bifurcated venous bypass graft should be applied in younger patients. In this way, it is possible to avoid major concerns about the development of long-term intrastent restenosis, and also to spare the external carotid artery which represents the main branch for the ipsilateral cerebral and facial perfusion. We propose ECAA resection and interposition of the inverted great saphenous vein to both the internal and external carotid artery by means the use of a tributary, i.e., the Giacomini vein.
IL-33 and Its Receptor ST2 after Inhaled Allergen Challenge in Allergic Asthmatics
Authors: Mitchell Patrick D. , Salter Brittany M. , Oliveria John Paul , El-Gammal Amani , Tworek Damian , Smith Steve G. , Sehmi Roma , Gauvreau Gail M. , O'Byrne Paul M.
Published: April 2018

Background: Previous murine models have demonstrated interleukin (IL)-33 to be an important mediator of type-2 inflammation and to promote airway hyperresponsiveness in allergic asthma. A number of inflammatory cells produce IL-33 and eosinophils express ST2 mRNA. The relationship between IL-33 and eosinophils in allergic asthma, however, remains unclear. Objective: The aim of this work was to evaluate in vitro the effect of allergen inhalation on IL-33 levels and expression of its receptor (ST2L) on eosinophils in allergic asthmatics, and the effect of IL-33 stimulation on eosinophil activity. Methods: Plasma and sputum IL-33, soluble ST2 (sST2) levels, and ST2L expression on eosinophils were measured in 10 healthy controls and 10 allergic asthmatics. Asthmatics underwent allergen and diluent inhalation challenges. Blood and sputum samples were collected to measure IL-33, sST2, and ST2L eosinophil expression before and 24 h after allergen inhalation. Purified blood eosinophils from allergic asthmatics were incubated overnight with IL-33 to assess ST2 and intracellular IL-5 expression. Results: Baseline levels of IL-33 in sputum and sST2 in plasma and sputum were similar in allergic asthmatics compared to healthy controls. In addition, there was no difference in blood or sputum eosinophil ST2L expression in healthy controls versus allergic asthmatics. Eosinophil ST2L expression was significantly increased 24 h postallergen inhalation in allergic asthmatics. In vitro stimulation of human eosinophils with IL-33 and LPS significantly increased eosinophil ST2L expression and IL-33 stimulation increased intracellular IL-5 expression, which was attenuated by treatment with sST2 and ST2 blockade. Conclusion and Clinical Relevance: In mild asthmatics, there was a significant upregulation of ST2 surface expression on eosinophils from blood and sputum following allergen inhalation challenge. In vitro, IL-33 stimulation of eosinophils increases both ST2 membrane expression and IL-5 production. These results support a role for IL-33 in causing allergen-induced eosinophilia. Blockade of IL-33 and ST2 signaling may present a novel therapeutic avenue for asthma treatment.
Multiples of Median-Transformed, Normalized Reference Ranges of Steroid Profiling Data Independent of Age, Sex, and Units
Authors: Zalas Dominika , Reinehr Thomas , Niedziela Marek , Borzikowsky Christoph , Flader Maciej , Simic-Schleicher Gunter , Akkurt Halit Ilker , Heger Sabine , Hornig Nadine , Holterhus Paul-Martin , Kulle Alexandra E.
Published: April 2018

Background/Aims: The high complexity of pediatric reference ranges across age, sex, and units impairs clinical application and comparability of steroid hormone data, e.g., in congenital adrenal hyperplasia (CAH). We developed a multiples-of-median (MoM) normalization tool to overcome this major drawback in pediatric endocrinology. Methods: Liquid chromatography tandem mass spectrometry data comprising 10 steroid hormones representing 905 controls (555 males, 350 females, 0 to > 16 years) from 2 previous datasets were MoM transformed across age and sex. Twenty-three genetically proven CAH patients were included (21-hydroxylase deficiency [21OHD], n = 19; 11β-hydroxylase deficiency [11OHD], n = 4). MoM cutoffs for single steroids predicting 21OHD and 11OHD were computed and validated through new, independent patients (21OHD, n = 8; adrenal cortical carcinoma, n = 6; obesity, n = 40). Results: 21OHD and 11OHD patients showed disease-typical, easily recognizable MoM patterns independent of age, sex, and concentration units. Two single-steroid cutoffs indicated 21OHD: 3.87 MoM for 17-hydroxyprogesterone (100% sensitivity and 98.83% specificity) and 12.28 MoM for 21-deoxycortisol (94.74% sensitivity and 100% specificity). A cutoff of 13.18 MoM for 11-deoxycortisol indicated 11OHD (100% sensitivity and 100% specificity). Conclusions: Age- and sex-independent MoMs are straightforward for a clinically relevant display of multi-steroid patterns. In addition, defined single-steroid MoMs can serve alone as predictors of 21OHD and 11OHD. Finally, MoM transformation offers substantial enhancement of routine and scientific steroid hormone data exchange due to improved comparability.
Repetitive Negative Thinking and Its Role in Perinatal Mental Health
Authors: Moulds Michelle L. , Black Melissa J. , Newby Jill M. , Hirsch Colette R.
Published: April 2018

Background: There is evidence that anxiety is common, perhaps even more prevalent than depression, in the post-partum period. In this review we propose adopting a transdiagnostic approach to perinatal mental health: to delineate psychopathology and identify potential underlying cognitive mechanisms such as repetitive negative thinking (RNT). Sampling and Methods: We provide an overview of key studies of RNT in perinatal mental health and suggest directions for future work. We propose the value of examining post-partum depression and anxiety, and their co-occurrence, and of testing whether the psychological mechanisms that predict and maintain depression and anxiety also play a role in these conditions in the post-partum period. Further, given that psychological distress often first emerges in the antenatal phase, we make a case for investigating RNT across the perinatal period – i.e., in antenatal and postnatal women. Results and Conclusions: RNT may be a modifiable risk factor which can be targeted in pregnancy to prevent depression and anxiety in new mothers.
Effect of Antenatal Pelvic Floor Muscle Exercise on Mode of Delivery: A Randomized Controlled Trial
Authors: El-Shamy Fayiz F. , Abd El Fatah Eman
Published: April 2018

Background: Vaginal delivery is the best end of the pregnancy for the mother and the newborn. Aim: To evaluate the impacts of short-term antenatal pelvic floor muscle (PFM) exercises on a woman’s mode of delivery. Methods: This is a randomized controlled trial that recruited 20 healthy pregnant women aged between 20 and 25 years and able to contract the PFMs. The participants were included in the study at 20 weeks of gestation (WG) and were randomly allocated to one of two groups: the intervention group (n = 10) or the control group (n = 10). PFM strength was measured by vaginal squeeze pressure at 20 and 36 WG, and delivery outcomes were evaluated by a blinded searcher from the birth registry after labor. Results: There were no statistically significant changes between both groups at baseline regarding gestational age, type of labor, previous pregnancy complications, and PFM strength (p > 0.05). There was a significant change between both groups in mean PFM strength at 36 WG (p < 0.05). A significant correlation was observed between PFM strength at 36 WG and mode of delivery (vaginal delivery: r = 0.58, p < 0.05; caesarean delivery: r = –0.49, p < 0.05). Conclusions: PFM exercise is recommended for healthy pregnant women as a safe and inexpensive strategy for increasing the vaginal delivery rate.
АНАЛІЗ ВІТЧИЗНЯНОГО ФАРМАЦЕВТИЧНОГО РИНКУ РЕКТАЛЬНИХ ЛІКАРСЬКИХ ЗАСОБІВ, ЩО ЗАСТОСОВУЮТЬСЯ ДЛЯ ЛІКУВАННЯ ПРОКТОЛОГІЧНИХ ЗАХВОРЮВАНЬ
Authors: Oliynyk I. M. , Fedenko S. М. , Fedorovska М. І.
Published: April 2018

Мета роботи. Вивчення номенклатури зареєстрованих в Україні ректальних лікарських засобів (ЛЗ) для лікування таких проктологічних захворювань, як геморой, анальна тріщина, проктити. Матеріали і методи. Застосовано маркетинговий, статистичний та графічний аналізи.Результати й обговорення. У ході досліджень встановлено, що на вітчизняному ринку представлено 34 найменування ректальних ЛЗ різних форм випуску, з яких 71 % − супозиторії, 26 % − мазі та 3 % − креми; частка ЛЗ українського виробництва становить 35 %, а іноземного − 65 %. Результати проведеного маркетингового аналізу свідчать, що актуальним і перспективним є створення нових вітчизняних ректальних лікарських засобів для застосування в проктології.Висновки. Проведено маркетингове дослідження вітчизняного ринку ректальних лікарських препаратів, які застосовують у терапії проктологічних захворювань. Ректальні лікарські засоби були проаналізовані за країною виробником, формою випуску, вмістом діючих компонентів та ціновою політикою. В результаті проведеного дослідження зроблено висновок, що асортимент вітчизняних ректальних лікарських препаратів, які застосовують в проктології, є недостатнім, тому актуальною є розробка нових, ефективних форм ректальних лікарських засобів для лікування проктологічних захворювань.
ПОРІВНЯЛЬНИЙ АНАЛІЗ РЕЗУЛЬТАТІВ IN VIVO СКРИНІНГУ ТА IN SILICO ПРОГНОЗУВАННЯ ПСИХО- ТА НЕЙРОТРОПНИХ ВЛАСТИВОСТЕЙ 3-(N-R,R′-АМІНОМЕТИЛ)-2-МЕТИЛ-1Н-ХІНОЛІН-4-ОНІВ
Authors: Podolsky I. M. , Shtrygol' S. Yu. , Tsyvunin V. V.
Published: April 2018

Мета роботи. Провести аналіз результатів скринінгових in vivo досліджень та ретроспективного in silico прогнозування психо- та нейротропних властивостей 3-(N-R,R′-амінометил)-2-метил-1Н-хінолін-4-онів за допомогою програми PASS.Матеріали і методи. Аналіз результатів попередніх скринінгових in vivo досліджень психо- та нейротропних властивостей 3-(N-R,R′-амінометил)-2-метил-1Н-хінолін-4-онів ґрунтувався на опублікованих нами даних. Комп’ютерне прогнозування спектра біологічних властивостей 3-(N-R,R′-амінометил)-2-метил-1Н-хінолін-4-онів проведено ретроспективно за допомогою системи PASS Online.Результати й обговорення. Систематизація та аналіз результатів проведених раніше експериментальних фармакологічних досліджень показали, що більшість 3-(N-R,R′-амінометил)-2-метил-1Н-хінолін-4-онів має виразні ноотропні властивості, які у деяких похідних поєднуються з високою антидепресивною активністю, протитривожним ефектом, седативними або, навпаки, стимулювальними властивостями. Аналіз результатів для окремих підгруп 3-(N-R,R′-амінометил)-2-метил-1Н-хінолін-4-онів дозволив виявити певні зв’язки між хімічною будовою та характером біологічної дії сполук.Результати PASS-прогнозу показали, що найбільш імовірними біологічними ефектами 3-(N-R,R′-амінометил)-2-метил-1Н-хінолін-4-онів є здатність виступати інгібіторами убіхінол-цитохром с редуктази, глюконат 2-дегідрогенази, пластохінол-пластоціанін редуктази, кінази рецепторів тромбоцитарного фактора росту та енхансерами експресії 3-гідрокси-3-метилглутарил-КоА синтази 2. Показники для ефектів, які хоча б опосередковано можуть впливати на функції ЦНС (активатори потенціалзалежних кальцієвих каналів та інгібітори вивільнення серотоніну), мають значно нижчі значення.Висновки. За умови використання комп’ютерного прогнозування спектра фармакологічної активності 3-(N-R,R′-амінометил)-2-метил-1Н-хінолін-4-онів за допомогою програми PASS як основного підґрунтя для подальших скринінгових досліджень цей клас сполук було б втрачено як перспективний в аспекті пошуку нових речовин, здатних впливати на функції ЦНС.
МОРФОЛОГО-АНАТОМІЧНІ ОЗНАКИ ТРАВИ МАРУНИ ДІВОЧОЇ (TANACETUM PARTHENIUM (L.) SСHULTZ. BIP.)
Authors: Hordiei K. R. , Gontova T. N. , Zolotaikina M. Yu. , Sira L. M.
Published: April 2018

Мета роботи. Провести ідентифікацію трави Tanacetum parthenium за макро- та мікроскопічними ознаками згідно з ДФУ 2.0. Встановити основні діагностичні ознаки стебла, листя, кошиків та квіток.Матеріали і методи. Об’єктом дослідження були зразки трави маруни дівочої, зібрані у період із початку до масового цвітіння у 7 областях України. Для макроскопічного опису використовували цільну, різану, свіжу та висушену сировину. Мікроскопічні дослідження проводили на сировині фіксованій у суміші спирт-гліцерин-вода (1:1:1). В роботі використовували фотоапарат OLYMPUS Lens FE-140, мікроскоп МБИ-6, мікроскоп БИОЛАМ - М.Результати й обговорення. Визначено основні морфолого-анатомічні ознаки у вітчизняних серіях трави маруни дівочої згідно з ДФУ 2.0. Виявлено додаткові діагностичні ознаки: 4–6-клітинні головчасті волоски; стебло ребристе, в ребрах субепідермально розташована 5–6-шарова кутова коленхіма; склеренхіма розташована над пучками і між ними; судини ксилеми спіральні та пористі; схізо-лізигенні вмістища з брунатним вмістом в паренхімі ложа кошика; сосочкоподібна епідерма несправжньоязичкових квіток; паренхімні, прямостінні клітини епідерми трубчастих квіток; кристали кальцію оксалату в листочках обгортки представлено друзами.Висновки Проведено ідентифікацію трави Tanacetum parthenium за макро- та мікроскопічними ознаками згідно з ДФУ 2.0. Визначено основні діагностичні ознаки стебла, листя, кошиків та квіток. Встановлено додаткові діагностичні ознаки, які запропоновано додати при розробці національної частини монографії «Маруни дівочої трава» для ДФУ.
ФОКУС НА ВАКЦИНАЦІЮ: ПОГЛЯД ЛІКАРІВ ТА БАТЬКІВ І АНАЛІЗ ЇЇ ФАРМАЦЕВТИЧНОГО ЗАБЕЗПЕЧЕННЯ ЩОДО КЕРОВАНИХ ДИТЯЧИХ БАКТЕРІЙНИХ ІНФЕКЦІЙ
Authors: Fedyak I. O. , Bilyk I. P. , Mateyko G. B.
Published: April 2018

Мета. Висвітлення результатів опитування лікарів та батьків щодо проблем подолання в Україні вакцинокерованих дитячих бактерійних інфекцій (кашлюку та менінгококової інфекції) насамперед шляхом вакцинації, а також вивчення стану фізичної та соціально-економічної доступності вакцин для проведення імунопрофілактики за кошти батьків.Методи і матеріали. У роботі використані методи анонімного анкетування, маркетингового аналізу, графічного представлення результатів.Результати дослідження. 50 % опитаних лікарів вважають, що основна причина відмови батьків від вакцинації – негативна суспільна думка, сформована ЗМІ. Водночас батьки-респонденти заперечують значний вплив ЗМІ на їхній вибір щодо імунопрофілактики, бо в основу відмови вакцинувати дітей ставлять сумніви щодо безпеки (38 %) та якості (32 %) вакцин. Загалом 96 % батьків дали згоду на вакцинацію, а 58 % – за власний кошт. Разом з тим, вітчизняний фармацевтичний ринок виявився неготовим до цього, бо показав недостатню фізичну доступність при умовно фінансовій доступності вакцин проти кашлюку та повну відсутність вакцин для попередження менінгококової інфекції.Висновки. Установлено, що у 2015 і 2017 роках вакцина проти менінгококової інфекції Менактра (США) та вакцини для первинної імунізації від кашлюку АКДП–Біолік (Україна), Інфанрикс (Великобританія) демонстрували незадовільну присутність на українському фармацевтичному ринку. Водночас моніторинг ринку виявив, що присутні на ньому вакцини мали позитивні тенденції їх соціально-економічної доступності при умові матеріального забезпечення сімей, не нижче середньонаціонального рівня.
КОРОТКИЙ НАРИС ЖИТТЄВОГО ТА ТВОРЧОГО ШЛЯХУ ПРОФЕСОРА РОМАНА МИХАЙЛОВИЧА ПІНЯЖКА (до 90-річчя від дня народження)
Authors: Hromovyk B. P. , Datsko A. Yo. , Kalynyuk T. H.
Published: April 2018

Стаття присвячена висвітленню історії життя і творчого шляху доктора фармацевтичних наук і професора Романа Піняжка – одного із найвидатніших представників української фармацевтичної науки й практики другої половини ХХ століття.
Endovascular Therapy in Ischemic Stroke With Acute Large‐Vessel Occlusion: Recovery by Endovascular Salvage for Cerebral Ultra‐Acute Embolism Japan Registry 2
Authors: Yoshimura Shinichi , Sakai Nobuyuki , Uchida Kazutaka , Yamagami Hiroshi , Ezura Masayuki , Okada Yasushi , Kitagawa Kazuo , Kimura Kazumi , Sasaki Makoto , Tanahashi Norio , Toyoda Kazunori , Furui Eisuke , Matsumaru Yuji , Minematsu Kazuo , Morimoto Takeshi , Kuwayama Naoya , Ogasawara Kuniaki , Iihara Koji , Takeuchi Masataka , Morimoto Masafumi , Onda Toshiyuki , Shibata Masunari , Ohta Takahiro , Imai Keisuke , Itabashi Ryo , Yamashita Taro , Fukawa Norihito , Kimura Naoto , Doijiri Ryosuke , Ohta Hajime , Enomoto Yukiko , Kanbayashi Chisaku , Yamaura Ikuya , Ishihara Hideyuki , Kamiya Yuki , Hayase Makoto , Nii Kouhei , Kobayashi Junya , Yasuda Hiroaki , Kondo Ryushi , Yamamoto Daisuke , Sakaguchi Manabu , Satomi Junichiro , Yagita Yoshiki , Handa Akira , Shindo Atsushi , Hiyama Nagayasu , Toma Naoki , Tsumoto Tomoyuki , Tsuruta Wataro , Matsumoto Keigo , Kiura Yoshihiro , Yamazaki Takaaki , Hatano Taketo , Matsumoto Yoshihisa , Kojima Takao , Ikeda Norio , Sakamoto Shigeyuki , Ohnishi Hiroyuki , Haraguchi Koichi , Uchiyama Naoyuki
Published: April 2018

Background

Endovascular therapy has been shown to be effective in patients with acute cerebral large‐vessel occlusion, but real‐world efficacies are unknown.

Methods and Results

We conducted a prospective registry at 46 centers between October 2014 and January 2017. Eligible patients were those who were aged 20 years or older, with acute cerebral large‐vessel occlusion, and who were hospitalized within 24 hours of the onset. We enrolled both consecutive patients who were treated with or without endovascular therapy. Endovascular therapy included thrombectomy, balloon angioplasty, stenting, local fibrinolysis, and piercing. The primary outcome was a favorable outcome as defined by a modified Rankin Scale of 0 to 2 at 90 days after onset. Secondary outcomes were modified Rankin Scale of 0 to 1 and mortality. Safety outcomes were intracerebral hemorrhage or a recurrence of ischemic stroke. We constructed the 2242 (1121 each) propensity score–matched patients cohort based on a propensity score for endovascular therapy and estimated the adjusted odds ratio, followed by sensitivity analyses on original 2399 (1278 in endovascular therapy versus 1121 in no endovascular therapy) patients. In the propensity score–matched cohort, favorable outcomes were observed in 35.3% and 30.7% of patients in the endovascular therapy and no endovascular therapy groups, respectively (
P=
0.02). The adjusted odds ratio for the favorable outcome was 1.44 (95% confidence interval, 1.10–1.86,
P
=0.007). The efficacy of endovascular therapy in achieving favorable outcomes did not differ between our subgroups and in the sensitivity analyses.

Conclusions

Endovascular therapy decreased disabilities at 90 days in real‐world patients with acute cerebral large‐vessel occlusion.

Clinical Trial Registration

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT02419794.