Comparison of efficacy and safety of levofloxacin-containing versus standard sequential therapy in eradication of Helicobacter pylori infection in Korea.

Abstract:
BACKGROUND
Declining of eradication rates for Helicobacter pylori in Korea may be partly from the increasing prevalence of antibiotic resistance, especially clarithromycin resistance.

AIM
To compare the efficacy and the safety of using 10-day standard sequential therapy and levofloxacin-containing sequential therapy as a first-line treatment for Helicobacter pylori eradication in Korea.

METHODS
A total of 200 patients with proven Helicobacter pylori infection randomly received 10-day standard sequential therapy (n = 100) or levofloxacin-containing sequential therapy (n = 100). The standard sequential therapy group received rabeprazole and amoxicillin for 5 days, followed by rabeprazole, clarithromycin, and metronidazole for 5 more days. The levofloxacin-containing sequential therapy group was treated with rabeprazole and amoxicillin for 5 days, followed by rabeprazole, levofloxacin, and metronidazole for 5 more days.

RESULTS
Intention-to-treat eradication rates were 79.0% and 78.0% for groups of standard sequential and levofloxacin-containing sequential therapy, respectively (P = 0.863). Per-protocol eradication rates were 84.9% and 81.3%, respectively, for these two therapies (P = 0.498). There were no significant differences between the groups in regard to the eradication rates and adverse events.

CONCLUSIONS
The 10-day levofloxacin-containing sequential regimen and the standard sequential regimen showed the similar eradication rates of Helicobacter pylori in Korea.

Lee|Hyuk|H|
Hong|Sung Noh|SN|
Min|Byung-Hoon|BH|
Lee|Jun Haeng|JH|
Rhee|Poong-Lyul|PL|
Lee|Yong Chan|YC|
Kim|Jae J|JJ|

Sequential therapy
Eradication
Helicobacter pylori
Levofloxacin


Platelet-derived growth factor β-receptor, transforming growth factor β type I receptor, and CD44 protein modulate each other's signaling and stability.

Abstract: Growth factors, such as platelet-derived growth factor BB (PDGF-BB) and transforming growth factor β (TGFβ), are key regulators of cellular functions, including proliferation, migration, and differentiation. Growth factor signaling is modulated by context-dependent cross-talk between different signaling pathways. We demonstrate in this study that PDGF-BB induces phosphorylation of Smad2, a downstream mediator of the canonical TGFβ pathway, in primary dermal fibroblasts. The PDGF-BB-mediated Smad2 phosphorylation was dependent on the kinase activities of both TGFβ type I receptor (TβRI) and PDGF β-receptor (PDGFRβ), and it was prevented by inhibitory antibodies against TGFβ. Inhibition of the activity of the TβRI kinase greatly reduced the PDGF-BB-dependent migration in dermal fibroblasts. Moreover, we demonstrate that the receptors for PDGF-BB and TGFβ interact physically in primary dermal fibroblasts and that stimulation with PDGF-BB induces internalization not only of PDGFRβ but also of TβRI. In addition, silencing of PDGFRβ by siRNA decreased the stability of TβRI and delayed TGFβ-induced signaling. We further show that the hyaluronan receptor CD44 interacts with both PDGFRβ and TβRI. Depletion of CD44 by siRNA increased signaling via PDGFRβ and TβRI by stabilizing the receptor proteins. Our data suggest that cross-talk between PDGFRβ and TβRI occurs in dermal fibroblasts and that CD44 negatively modulates signaling via these receptors.

Porsch|Helena|H| Mehić|Merima|M| Olofsson|Berit|B| Heldin|Paraskevi|P| Heldin|Carl-Henrik|CH|

D020797:Receptor, Platelet-Derived Growth Factor beta

D000077293:Receptor, Transforming Growth Factor-beta Type I

D018125:Receptors, Transforming Growth Factor beta

CD44
PDGF
Cell Signaling
Cell Surface Receptor
Cellular Regulation
Transforming Growth Factor β (TGF-β)


Experimental and computational micromechanics at the tibial cement-trabeculae interface.

Abstract: Aseptic loosening of the tibial component in cemented total knee arthroplasty remains a major concern. We hypothesize that micromotion between the cement and trabeculae leads to increased circulation of interstitial fluid which in turn causes fluid-induced resorption of the trabeculae. Another mechanism for implant loosening is trabecular strain shielding. Using a newly developed experimental setup and digital image correlation (DIC) methods we were able to measure micromotion and strains in lab-prepared cement-trabeculae interface specimens (n=4). Finite element (FE) models of these specimens were developed to determine whether differences in micromotion and strain in morphologically varying specimens could be simulated accurately. Results showed that the measured micromotion and strains correlated well with FE model predictions (r(2)=0.59-0.85; r(2)=0.66-0.90). Global specimen strains measured axially matched well with the FE model strains (r(2)=0.87). FE model cement strains showed an increasing trend with distance from the cement border. The influence of loss of trabecular connectivity at the specimen edges was studied using our FE model results. Micromotion values at the outer edge of the specimens were higher than the specimen interior when considering a very thin outer edge (0.1mm). When the outer edge thickness was increased to about one trabecular length (0.8mm), there was a drop in the median and peak values. Using the experimental and modelling approach outlined in this study, we can further study the mechanisms that lead to loss of interlock between cement and trabeculae at the tibial interface.

Srinivasan|Priyanka|P|
Miller|Mark A|MA|
Verdonschot|Nico|N|
Mann|Kenneth A|KA|
Janssen|Dennis|D|

Aseptic loosening
Micromotion
Digital image correlation
Bone-cement interface
Finite element analysis


Donor-/Acceptor-Substituted Tetrakis(arylethynyl)benzenes: The Influence of Donor Group on Optoelectronic Properties.

Abstract: We have prepared nine structural isomers of a tetrakis(arylethynyl)benzene chromophore functionalized with 4-butoxyphenyl and pyridyl units as the respective donor and acceptor units and examined their steady-state spectroscopic parameters to study how small structural variations effect the electronic absorption and emission spectra. Unlike their 4-dibutylaminophenyl congeners that exhibited dynamic hypsochromic or bathochromic shifts in response to Lewis and Brønsted acids, the current class of compounds simply showed quenched fluorescence upon protonation; only AlCl3 elicited a red-shifted fluorescence response. Computational studies of each system were also performed to provide additional insight into the energy levels and electronic transitions present.

chromophores
fluorescence
alkynes
cross-coupling
donor−acceptor compounds


Childhood Maltreatment and Relationship Quality: A Review of Type of Abuse and Mediating and Protective Factors.

Abstract: Childhood maltreatment (CM) has long been recognized as a risk factor for good intimate relationships. Research on the effects of CM on relationship functioning has focused on sexual abuse in girls. However, CM also includes emotional and physical abuse and neglect and is also common in boys. Moreover, prior research has mostly focused on individuals in isolation, ignoring that marriage is a system in which two partners mutually influence each other. Questions also remain about mediating and protective factors for healthy relationships in the context of CM. This article reviews the literature on the link between different forms of CM and one's own and one's partner relationship quality. It reviews 43 empirical studies that assessed associations between CM in any form and relationship quality. Also, mediating and protective factors and major methodological topics are examined. The review indicated that CM (neglect, sexual, emotional, or physical abuse) is associated with lower relationship quality in men and women. Psychological distress, cognitive and behavioral problems, insecure attachment, and self-dysregulation were identified as mediating factors. Protective processes involve good coping strategies, emotion regulation, parental support, and early secure attachment, but not partner characteristics. The results regarding gender are inconclusive. It is crucial to broaden the research on the dyadic effects of CM of various forms on relationship quality and study mediating and protective factors. More studies on neglect and diverse populations are needed, as well as prospective studies. This will enable the development of prevention programs for couples with a partner exposed to CM.

relationship quality
protective factors
CM
mediating factors


Developing Graphic Messages for Vaping Prevention Among Black and Latino Adolescents: Participatory Research Approach.

Abstract:
BACKGROUND
As an important transition stage in human development, adolescence is a critical window for vaping prevention. There is a substantial gap in communication research on vaping prevention among racial and ethnic minority groups. Their representation is essential to develop, implement, and disseminate innovative and effective interventions for vaping prevention.

OBJECTIVE
The aim of this study is to describe the participatory research (PR) procedures used with Black and Latino adolescents to develop culturally and linguistically appropriate graphic messages for vaping prevention.

METHODS
This PR study used a qualitative, user-centered design method. We conducted a series of focus groups with 16 Black and Latino adolescents to develop culturally and linguistically appropriate graphic messages for vaping prevention. The biobehavioral model of nicotine addiction provided a framework for the development of the graphic messages. Participants met 4 times to provide iterative feedback on the graphic messages until they reached a consensus on overall quality and content.

RESULTS
At baseline, the participants' mean age was 15.4 years (SD 1.4). Of the participants, 50% (8/16) were female, 88% (14/16) were heterosexual, 56% (9/16) were Black/African American, and 44% (7/16) were Hispanic/Latino. A total of 12 of the 16 participants (75%) chose to participate in the English sessions. Participants decided to create four types of graphic messages: (1) financial reward, (2) health reward, (3) social norms, and (4) self-efficacy. Meeting 4 times with the 4 groups provided sufficient opportunities for iterative feedback on the graphic messages to reach a consensus on overall quality and content.

CONCLUSIONS
It is feasible and practical to build PR among Black and Latino adolescents focused on vaping prevention. Adolescents added innovation and creativity to the development of culturally and linguistically appropriate graphic messages for vaping prevention. Appropriate staffing, funding, and approaches are key for successful PR efforts among Black and Latino adolescents. Future research is needed to evaluate the impact of the graphic messages on vaping prevention.

vaping
Black
Latino
adolescents
electronic cigarettes


A New Method for Assessing Masking and Residual Inhibition of Tinnitus.

Abstract: Tinnitus masking and residual inhibition (RI) are two well-known psychoacoustic measures of tinnitus. While it has long been suggested that they may provide diagnostic and prognostic information, these measures are still rarely performed in clinics, as they are too time consuming. Given this issue, the main goal of the present study was to validate a new method for assessing these measures. An acoustic sequence made of pulsed stimuli, which included a fixed stimulus duration and interstimulus interval, was applied to 68 tinnitus patients at two testing sites. First, the minimum masking level (MML) was measured by raising the stimulus intensity until the tinnitus was unheard during the stimulus presentation. Second, the level of the stimulus was further increased until the tinnitus was suppressed during the silence interval between the acoustic pulses. This level was called the minimum residual inhibition level (MRIL). The sequential measurement of MML and MRIL from the same stimulus condition offers several advantages such as time efficiency and the ability to compare results between the MRIL and MML. Our study confirms that, from this new approach, MML and MRIL can be easily and quickly obtained from a wide variety of patients displaying either normal hearing or different hearing loss configurations. Indeed, MML was obtained in all patients except one (98.5%), and some level of MRIL was found on 59 patients (86.7%). More so, this approach allows the categorization of tinnitus patients into different subgroups based on the properties of their MRIL.

Fournier|Philippe|P| Cuvillier|Anne-Flore|AF| Gallego|Stéphane|S| Paolino|Fabien|F| Paolino|Michel|M| Quemar|Anne|A| Londero|Alain|A| Norena|Arnaud|A|

masking
residual inhibition
tinnitus
psychoacoustics
minimum masking level


The feasibility of a search filter for the adverse effects of nondrug interventions in MEDLINE and Embase.

Abstract: Authors and indexers are increasingly including terms for adverse drug effects in the titles, abstracts, or indexing of records in MEDLINE and Embase. However, it is not clear if this is the same for studies with nondrug adverse effects data. We therefore assessed the feasibility of using adverse effects terms when searching MEDLINE or Embase to retrieve papers of nondrug adverse effects. A collection of papers that reported data on nondrug adverse effects was sought from included studies of systematic reviews. Each included study was analysed to ascertain whether the corresponding record in MEDLINE and Embase included adverse effects terms in the title, abstract, or indexing. From 9129 records screened from DARE, 30 reviews evaluating nondrug adverse effects met our inclusion criteria. From these, 635 unique papers were included in our analysis. Sensitive searches for adverse effects required generic and specific named adverse effects terms using the title, abstract, and indexing. Records relating to surgical interventions were more likely to contain adverse effects terms than records relating to nonsurgical interventions. Using any adverse effects terms in the title, abstract or indexing in MEDLINE and Embase would have identified an average of 94% of papers on surgical adverse effect interventions per systematic review and 72% of papers on nonsurgical adverse effects per systematic review. Hence, while a generic nondrug adverse effect search filter may not yet be feasible, a filter for the adverse effects of surgical interventions may be within reach.

D064420:Drug-Related Side Effects and Adverse Reactions

D016247:Information Storage and Retrieval

Adverse Effects
Medline
Complications
Information storage and retrieval
Literature searching


Microencapsulation of Coenzyme Q10 and bile acids using ionic gelation vibrational jet flow technology for oral delivery.

Abstract: Developing new delivery dosage forms with robust delivery and safety profiles remains a challenge to the pharmaceutical industry in terms of optimum gut absorption, consistent dosing and bioavailability; particularly for orally administered drugs that are poorly water soluble. Coenzyme Q10 is an example of a poorly water-soluble compound with low bioavailability, and significant inter-individual variation after oral administration; limiting its optimum efficacy, as a powerful antioxidant with significant promise in treating hearing disorders. Microencapsulation technology is one way to optimize drug bioavailability and absorption profile. One example is Ionic Gelation Vibrational Jet Flow techniques, using new encapsulating parameters to determine the nature of formed capsules. Bile acids are an example of an excipient that can be used to improve membrane permeability; and will be examined. This review addresses the applications of microencapsulation technology on oral delivery and efficacy profiles of poorly water-soluble drugs, focusing on Coenzyme Q10.

microencapsulation
Coenzyme Q10
bile acids
poorly water-soluble drugs
drug delivery
β-cyclodextrin


Swept-Source-Based Chromatic Confocal Microscopy.

Abstract: Chromatic confocal microscopy (CCM) has been intensively developed because it can exhibit effective focal position scanning based on the axial chromatic aberration of broadband light reflected from a target. To improve the imaging speed of three-dimensional (3D) surface profiling, we have proposed the novel concept of swept-source-based CCM (SS-CCM) and investigated the usefulness of the corresponding imaging system. Compared to conventional CCM based on a broadband light source and a spectrometer, a swept-source in the proposed SS-CCM generates light with a narrower linewidth for higher intensity, and a single photodetector employed in the system exhibits a fast and sensitive response by immediately obtaining spectrally encoded depth from a chromatic dispersive lens array. Results of the experiments conducted to test the proposed SS-CCM system indicate that the system exhibits an axial chromatic focal distance range of approximately 360 μm for the 770-820 nm swept wavelength range. Moreover, high-speed surface profiling images of a cover glass and coin were successfully obtained with a short measurement time of 5 ms at a single position.

Jeong|Dawoon|D|
Park|Se Jin|SJ|
Jang|Hansol|H|
Kim|Hyunjoo|H|
Kim|Jaesun|J|
Kim|Chang-Seok|CS|0000-0002-2811-8137

chromatic confocal microscopy
chromatic aberration
swept-source
high-speed
3D surface profile
wavelength-swept laser


Long non-coding RNA TUG1 promotes cell proliferation and metastasis by negatively regulating miR-300 in gallbladder carcinoma.

Abstract:
BACKGROUND
As we all know, long non-coding RNAs (lncRNAs) have been reported to play vital roles in various human cancers. In this study, we aimed to explore the role of lncRNA TUG1 in gallbladder carcinoma (GBC) development.

METHODS
Total RNA was extracted from the tissues of thirty GBC patients, four GBC cell lines. We detected the expression levels of TUG1 using quantitative real-time PCR. We performed CCK8, colony formation, transwell invasion and apoptosis assays to study the effects of TUG1 on GBC cell proliferation and invasion. Western blot assay was performed to assess to the expression level of epithelial-mesenchymal transition (EMT) markers in transforming growth factor-β1 (TGF-β1) treated and TUG1 knockdown GBC cell. Lastly, dual-luciferase reporter assay and quantitative real-time PCR were performed to verify the potential target microRNAs (miRNAs) of TUG1.

RESULTS
TUG1 expression was significantly overexpressed in GBC tissues. Functionally, this study demonstrated that knockdown of TUG1 significantly inhibited GBC cell proliferation, metastasis. Mechanically, we found that TUG1 is upregulated by TGF-β1, and knockdown of TUG1 inhibited GBC cell EMT. Furthermore, we identified that miR-300, which has been reported as a suppressor in other types of cancer, is negatively regulated by TUG1.

CONCLUSIONS
LncRNA TUG1 promotes GBC cell proliferation, metastasis and EMT progression by functioning as a miRNA sponge to abrogate the endogenous effect of miR-300.

Ma|Fei|F| Wang|Shou-Hua|SH| Cai|Qiang|Q| Jin|Long-Yang|LY| Zhou|Di|D| Ding|Jun|J| Quan|Zhi-Wei|ZW|

D015972:Gene Expression Regulation, Neoplastic

Long non-coding RNA
TUG1
Proliferation
Metastasis
miR-300
Gallbladder carcinoma


Removal of full-thickness vertical corneal stromal wooden foreign bodies: An innovative ab-interno technique.

Abstract: A 28-year-old male presented with three full-thickness stromal wooden foreign bodies vertically oriented in the left cornea. An innovative intracameral approach was used. Paracentesis was done and healon was injected into the anterior chamber. Iris repositor was introduced into the anterior chamber and the area of foreign bodies was pushed up to compress the stroma. The wooden foreign body projected above the corneal surface and were picked up one by one using McPherson forceps. One of the foreign bodies has penetrated through the Descemet's membrane resulting a corneal perforation. A corneal perforation was confirmed by observing egress of the irrigating solution, injected into the anterior chamber through the paracentesis opening. The corneal perforation was sealed with corneal glue. He achieved 6/9 BCVA (OS) at 8 weeks and maintained it during18 months follow-up.

wooden foreign body
Cornea
corneal perforation
N butyl cyanoacrylate tissue adhesive
corneal foreign body


Emerging evidence for speeded alphabet printing as a measure of processing speed and working memory.

Abstract: Alphabet Printing (in the forward and backward order) is a brief and highly portable test with promise as a screening measure of processing speed and simple working memory, constructs which are only minimally assessed in many of the most commonly-used cognitive screening instruments. The aim of this project was to examine the construct validity of timed Alphabet Printing in a sample of 254 Veterans with cognitive complaints and a history of possible head injury. Criterion measures included more established tests of processing speed and simple working memory, including the Trail Making Test and the Digit Span subtest from the fourth edition of the Wechsler Adult Intelligence Scales. Alphabet Printing scores moderately correlated with the criterion measures of attention, working memory, and processing speed, and demonstrated acceptable classification accuracy in discriminating between individuals with and without evidence of cognitive impairment on Trails B. These findings provide additional support for the possible utility of including Alphabet Printing during cognitive screenings or as part of a larger neuropsychological test battery.

Tolle|Kathryn|K|
Spencer|Robert J|RJ|
Montgomery|Valencia|V|
Bieliauskas|Linas A|LA|

Alphabet printing
processing speed
cognitive screen
attention
neuropsychology
psychometrics


Do we need invasive confirmation of cardiac magnetic resonance results?

Abstract:
INTRODUCTION
Coronary artery revascularization is indicated in patients with documented significant obstruction of coronary blood flow associated with a large area of myocardial ischemia and/or untreatable symptoms. There are a few invasive or noninvasive methods that can provide information about the functional results of coronary artery narrowing. The application of more than one method of ischemia detection in one patient to reevaluate the indications for revascularization is used in case of atypical or no symptoms and/or borderline stenosis.

AIM
To evaluate whether the results of cardiac magnetic resonance need to be reconfirmed by the invasive functional method.

MATERIAL AND METHODS
The hospital database revealed 25 consecutive patients with 29 stenoses who underwent cardiac magnetic resonance (CMR) and fractional flow reserve (FFR) between the end of 2010 and the end of 2014. The maximal time interval between CMR and FFR was 6 months. None of the patients experienced any clinical events or underwent procedures on coronary arteries between the studies.

RESULTS
According to the analysis, the agreement of CMR perfusion with the FFR method was at the level of 89.7%. Assuming that FFR is the gold standard in assessing the severity of stenoses, the sensitivity of CMR perfusion was 90.9%. The percentage of non-severe lesions which were correctly identified in CMR was 88.9%.

CONCLUSIONS
The study shows that CMR perfusion is a highly sensitive method to detect hemodynamically significant CAD and exclude nonsevere lesions. With FFR as the reference standard, the diagnostic accuracy of MR perfusion to detect ischemic CAD is high.

Siastała|Paweł|P|
Kądziela|Jacek|J|
Małek|Łukasz A|ŁA|
Śpiewak|Mateusz|M|
Lech|Katarzyna|K|
Witkowski|Adam|A|

magnetic resonance
fractional flow reserve
coronary artery disease
functional assessment


Anal cytology as a predictor of anal intraepithelial neoplasia in HIV-positive men and women.

Abstract: Human immunodeficiency virus (HIV)-infected individuals have increased risk of anal intraepithelial neoplasia (AIN) and squamous cell carcinoma (SCC). Cytologic screening is invaluable in the detection of cervical neoplasia, therefore many clinicians have adopted anal cytology as part of anal cancer screening in patients at high-risk for anal neoplasia. The purpose of this study is to determine whether anal cytology is a valuable screening test for identifying AIN in HIV+ patients. The cohort included 228 HIV+ patients who underwent anal cancer screening with collection of 318 anal cytology specimens between January 2006 and December 2009. Of this group, 74 (32.5%) patients had associated anal biopsies within a 6-month period, with a total of 89 comparison cases. The anal cytology samples were classified using the 2001 Bethesda System terminology. The sensitivity of anal cytology in detecting ASC-US, AIN 1-3 or SCC was 93%. Cytology was 88% sensitive for detecting low-grade AIN (AIN 1), but only 20% sensitive for detecting high-grade AIN (AIN 2-3) or SCC. Atypical squamous cells of undetermined significance cases were distributed evenly between low- and high-grade AIN, with two cases having normal histology. Only six cases had negative cytology, all of which were associated with AIN on biopsy, for a false negative rate of 7%. Anal cytology is a good predictor of AIN, as confirmed by the high degree of sensitivity. However, there is poor correlation between the cytological and histological grade of AIN. Cytology underestimates the grade of dysplasia compared to the corresponding biopsy.

Betancourt|Eve M|EM|
Wahbah|Mary M|MM|
Been|Laura C|LC|
Chiao|Elizabeth Y|EY|
Citron|Deborah R|DR|
Laucirica|Rodolfo|R|

anal intraepithelial neoplasia
human immunodeficiency virus
anal cytology and histology


Anti-CCP-positive patients with RA have a higher 10-year probability of fracture evaluated by FRAX®: a registry study of RA with osteoporosis/fracture.

Abstract:
BACKGROUND
Positive anticyclic citrullinated peptide (anti-CCP+) is associated with bone loss in patients with rheumatoid arthritis (RA). However, whether overall positivity or specific levels of anti-CCP are associated with prevalent fracture or a 10-year probability of fracture remains unclear.

METHODS
This interim analysis of an RA registry was conducted at Chang Gung Memorial Hospital in Kaohsiung (CGMHK) for RA-related osteoporosis/fracture. Consecutive patients with RA who had visited the rheumatology clinic at CGMHK since September 1, 2014, and fulfilled the classification criteria of RA were enrolled. The demographics, disease duration, Disease activity in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR), lifestyle, evidence of previous fracture, risk factors of fracture in the Fracture Risk Assessment Tool (FRAX®), and FRAX® score of each participant were collected. Anti-CCP, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and bone mineral density (BMD) were measured at enrollment. The patients were grouped by positivity or quartiles of anti-CCP level (I-IV).

RESULTS
Five hundred twenty-one patients with RA were enrolled through May 31, 2016. In total, 359 (68.9%) patients were anti-CCP+. Compared with anti-CCP- patients, anti-CCP+ patients had a significantly higher DAS28-ESR (p = 0.0001) and 10-year probability of major (15.0 [18.9] vs. 12.0 [15.3], p = 0.0461) or hip (5.0 [9.2] vs. 3.6 [8.2], p = 0.0118) fracture, but a significantly lower BMD of the FN (p = 0.0196). The rates of osteoporosis and previous fracture were comparable. There were 130, 127, 132, and 132 patients in groups I-IV, respectively. The DAS28-ESR was significantly different (p = 0.0001) among the groups and correlated to anti-CCP levels. The BMD and 10-year probability of major (p = 0.0067) and hip (p = 0.0013) fracture among the groups were also different.

CONCLUSIONS
Anti-CCP+ RA patients had a higher 10-year probability of major or hip fracture, independent of anti-CCP levels, and a lower BMD of the FN than anti-CCP- patients.

Cheng|Tien-Tsai|TT|0000-0002-8943-5056
Yu|Shan-Fu|SF|
Su|Fu-Mei|FM|
Chen|Yin-Chou|YC|
Su|Ben Yu-Jih|BY|
Chiu|Wen-Chan|WC|
Hsu|Chung-Yuan|CY|
Chen|Jia-Feng|JF|
Ko|Chi-Hua|CH|
Lai|Han-Ming|HM|

FRAX
Rheumatoid arthritis
Anti-cyclic citrullinated peptide


Neurobiological correlates of apathy in Alzheimer's disease and mild cognitive impairment: a critical review.

Abstract:
BACKGROUND
In Alzheimer's disease (AD) and mild cognitive impairment (MCI), apathy was associated with faster clinical deterioration. Studies involving neurobiological correlates such as neuroimaging and biomarkers have presented distinct results.

OBJECTIVE
This work aimed to analyze neurobiological correlates of apathy in AD and MCI based on evidence from the literature involving brain neuroimaging and classical AD biomarkers.

METHODS
This review comprised studies published from 1996 to June 2013 from the Pubmed database. The studies were divided into Part I (neuroimaging) and Part II (chemical biomarkers). The analysis included the identification of brain regions involved and assessments of apathy and cognition. We found 68 publications: 33 fulfilled the inclusion criteria; 35 were case reports or were not clear about the measurements of apathy and were excluded. From the 33 eligible studies, 26 were classified into part I, and 7 studies were included in part II. We created specific criteria to appropriately classify the quality level of each publication.

RESULTS
Prefrontal regions and the anterior cingulate were the leading brain areas associated with apathy in AD and MCI. Other regions, including cortical and subcortical structures, have also been implicated in this syndrome.

CONCLUSIONS
Abnormalities in frontal regions (associated with impairments in planning and decision making) and anterior cingulate (related to emotional blunting and loss of motivation) were the crucial structures associated with apathy in AD and MCI.

Stella|Florindo|F|
Radanovic|Márcia|M|
Aprahamian|Ivan|I|
Canineu|Paulo Renato|PR|
de Andrade|Larissa Pires|LP|
Forlenza|Orestes Vicente|OV|

neurobiological correlates
Apathy
Alzheimer's disease
mild cognitive impairment
review
neuroimaging


Human Melioidosis.

Abstract: The causative agent of melioidosis, Burkholderia pseudomallei, a tier 1 select agent, is endemic in Southeast Asia and northern Australia, with increased incidence associated with high levels of rainfall. Increasing reports of this condition have occurred worldwide, with estimates of up to 165,000 cases and 89,000 deaths per year. The ecological niche of the organism has yet to be clearly defined, although the organism is associated with soil and water. The culture of appropriate clinical material remains the mainstay of laboratory diagnosis. Identification is best done by phenotypic methods, although mass spectrometric methods have been described. Serology has a limited diagnostic role. Direct molecular and antigen detection methods have limited availability and sensitivity. Clinical presentations of melioidosis range from acute bacteremic pneumonia to disseminated visceral abscesses and localized infections. Transmission is by direct inoculation, inhalation, or ingestion. Risk factors for melioidosis include male sex, diabetes mellitus, alcohol abuse, and immunosuppression. The organism is well adapted to intracellular survival, with numerous virulence mechanisms. Immunity likely requires innate and adaptive responses. The principles of management of this condition are drainage and debridement of infected material and appropriate antimicrobial therapy. Global mortality rates vary between 9% and 70%. Research into vaccine development is ongoing.


Cardiovascular disease research activity in the Middle East: a bibliometric analysis.

Abstract:
OBJECTIVES
The Middle East has a high prevalence of noncommunicable chronic diseases. The objective of this article was to quantify the research activity in cardiovascular disease (CVD) in the Middle East over the last 10 years.

METHODS
A Medline search was conducted using medical subject headings and author affiliation to retrieve research articles published from the Middle East between 2003 and 2012 (inclusive).

RESULTS
Middle Eastern countries produced only 3% of the total number of CVD research articles in the world. However, the overall trend showed an increase in the number of articles over the years, mainly from Turkey and Iran. Within this region, the ratio of CVD to non-CVD publications was highest in Qatar (0.23). Lebanon ranked first in the number of CVD publications per million persons (PMP) averaging 194.2 publications PMP and Turkey ranked highest in the number of CVD publications per US$1000 gross domestic product (GDP) per capita averaging 954 CVD publications per US$1000 GDP per capita.

CONCLUSIONS
Although there has been a drive towards greater publication of CVD papers in the last decade, research activity in the Middle East still lags behinds developed countries. Greater productivity is anticipated to emerge to accompany the recent significant investment in research in Gulf countries.

Al-Kindi|Sadeer|S|
Al-Juhaishi|Taha|T|
Haddad|Fadi|F|
Taheri|Shahrad|S|
Abi Khalil|Charbel|C|

cardiovascular disease
Middle East
bibliometric analysis
epidemiology
global health


Effects of pomegranate juice on blood pressure: A systematic review and meta-analysis of randomized controlled trials.

Abstract: Punica granatum L. (Pomegranate) has been claimed to provide several health benefits. Pomegranate juice is a polyphenol-rich fruit juice with high antioxidant capacity. Several studies suggested that pomegranate juice can exert antiatherogenic, antioxidant, antihypertensive, and anti-inflammatory effects. Nevertheless, the potential cardioprotective benefits of pomegranate juice deserve further clinical investigation. To systematically review and meta-analyze available evidence from randomized placebo-controlled trials (RCTs) investigating the effects of pomegranate juice consumption and blood pressure (BP). A comprehensive literature search in Medline and Scopus was carried out to identify eligible RCTs. A meta-analysis of eligible studies was performed using a random-effects model. Quality assessment, sensitivity analysisand publication bias evaluations were conducted using standard methods. Quantitative data synthesis from 8 RCTs showed significant reductions in both systolic [weighed mean difference (WMD): -4.96mmHg, 95% CI: -7.67 to -2.25, p<0.001) and diastolic BP (WMD: -2.01mmHg, 95% CI: -3.71 to -0.31, p=0.021) after pomegranate juice consumption. Effects on SBP remained stable to sensitivity analyses. Pomegranate juice reduced SBP regardless of the duration (>12 wks: WMD=-4.36mmHg, 95% CI: -7.89 to -0.82, p=0.016) and <12 wks: WMD=-5.83 mmHg, 95% CI: -10.05 to -1.61, p=0.007) and dose consumed (>240cc: WMD=-3.62mmHg, 95% CI: -6.62 to -0.63, p=0.018) and <240cc: WMD=-11.01mmHg, 95% CI: -17.38 to -4.65, p=0.001, pomegranate juice per day) whereas doses >240cc provided a borderline significant effect in reducing DBP. The present meta-analysis suggests consistent benefits of pomegranate juice consumption on BP. This evidence suggests it may be prudent to include this fruit juice in a heart-healthy diet.

Sahebkar|Amirhossein|A| Ferri|Claudio|C| Giorgini|Paolo|P| Bo|Simona|S| Nachtigal|Petr|P| Grassi|Davide|D|

D016032:Randomized Controlled Trials as Topic

Pomegranate
Blood pressure
Antioxidants
Cardiovascular risk
Flavonoids


Clinical value of a [18F]-FDG PET-CT muscle-to-muscle SUV ratio for the diagnosis of active dermatomyositis.

Abstract:
OBJECTIVE
To study a muscle-to-muscle standardised uptake value (SUV) ratio with FDG-PET/CT (FDG-PET) as a marker for the detection of disease activity in dermatomyositis (DM).

METHODS
Patients with DM (n = 24) who met the European Neuro-Muscular Centre diagnostic criteria were retrospectively identified over a 3-year period through a national survey. Muscle biopsy was performed in all patients. Maximum SUV was measured in proximal muscles (SUVPROX) that had the highest radiotracer uptake on visual grading as well as in the musculus longissimus thoracis (SUVMLT), whereas mean SUV was measured for the liver (SUVLIV). Muscle-to-liver SUV ratios for either muscle group were compared and a SUVPROX/SUVMLT ratio was calculated. SUVPROX/SUVMLT of DM patients were compared with age- and sex-matched control subjects (n = 24) with melanoma who had received FDG-PET scans.

RESULTS
DM patients presented with proximal and symmetrical muscle uptake. Differences in SUVPROX/SUVLIV and SUVMLT/SUVLIV ratios in DM subjects were significant (p < 0.001). SUVPROX/SUVMLT ratios in DM and their controls also differed significantly (p = 0.0012). The SUVPROX/SUVMLT ratio threshold between DM subjects and controls was 1.73 with a sensitivity of 50% (CI95%, 29.1 to 70.9%) and specificity at 83.3% (CI95%, 62.6 to 95.3%). When amyopathic DM patients were removed from the analysis, specificity was increased to 95% (CI95%, 75.1 to 99.9%) with a likelihood ratio of 10 and an AUC of 83.4% (CI95%, 71.4 to 95.4%).

CONCLUSION
A muscle-to-muscle SUVPROX/SUVMLT ratio with a cut-off value of 1.73 in FDG-PET imaging might serve as a non-invasive marker to determine disease activity in dermatomyositis.

KEY POINTS
• [18F]-FDG PET-scanner standardised uptake value (SUV) could reflect disease activity in dermatomyositis (DM). • A ratio of SUV in proximal muscles (SUVPROX) to SUV in musculus longissimus thoracis (SUVMLT) could be used to determine active DM. • Active disease is suspected for SUV PROX /SUV MLT ratios greater than 1.73.

D000072078:Positron Emission Tomography Computed Tomography

Dermatomyositis
Amyopathic dermatomyositis
Fluorodeoxyglucose F18
Myositis
Positron-emission tomography


Effects of Clockwise and Counterclockwise Job Shift Work Rotation on Sleep and Work-Life Balance on Hospital Nurses.

Abstract: Rotational shift work is associated with sleep disturbances, increased risk of cardiovascular and psychological disorders, and may negatively impact work⁻life balance. The direction of shift rotation (Clockwise, CW or counterclockwise, CCW) and its role in these disorders are poorly understood. The aim of the study was to investigate the effect of the shift schedule direction on sleep quantity and quality, alertness and work performance, and on work⁻life balance on hospital nurses. One-hundred female nurses, working a continuous rapid shift schedule in hospitals in the north of Italy, participated in this cross-sectional study. Fifty worked on CW rotation schedule (Morning: 6 a.m.⁻2 p.m., Afternoon: 2 p.m.⁻10 p.m., Night: 10 p.m.⁻6 a.m., 2 rest days) and fifty on CCW rotation (Afternoon, Morning, Morning, Night, 3 rest days). Data were collected by ad hoc questionnaire and daily diary. During the shift cycle CW nurses slept longer (7.40 ± 2.24 h) than CCW (6.09 ± 1.73; p < 0.001). CW nurses reported less frequently than CCW awakening during sleep (40% vs. 80%; p < 0.001), attention disturbance during work (20% vs. 64%; p < 0.001), and interference with social and family life (60% vs. 96% and 20% vs. 70%, respectively; p < 0.001). CCW rotating shift schedule seems to be characterized by higher sleep disturbances and a worse work⁻life balance.

clockwise and counterclockwise shift rotation


The longitudinal association between internalizing symptoms and academic achievement among immigrant and non-immigrant children in Norway.

Abstract: The aim of this study was to explore the longitudinal relation between internalizing symptoms and academic achievement, as two processes of children and youth development, among children in Norway, and whether having an immigrant background moderated this association. Data collected from 4,458 students in Norway in four waves over three years were analyzed with multi-group latent growth curve modeling (LGM). Results showed that internalizing symptoms level remained unchanged over time both for immigrant and non-immigrant children, while levels of academic achievement increased only for children of immigrants with both parents born outside of Norway. Further analyses supported a reciprocal relation between internalizing symptoms and academic achievement and revealed that the initial level of academic achievement predicted the rate of change in internalizing symptoms over time, but not vice versa. Moreover, immigrant background did not moderate the associations in the model, however, children of immigrants with both parents born abroad initially had lower levels of academic achievement, but showed an increase in academic achievement, compared to their non-immigrant peers as well as to peers with one native-born parent after controlling for gender and their grade at the first observation. The implications for policy and practice were discussed.

Keles|Serap|S|
Olseth|Asgeir Røyrhus|AR|
Idsøe|Thormod|T|
Sørlie|Mari-Anne|MA|

internalizing symptoms
academic achievement
Children of immigrants
latent growth modeling
parallel process


Hypertension and cardiac arrhythmias: a consensus document from the European Heart Rhythm Association (EHRA) and ESC Council on Hypertension, endorsed by the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS) and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE).

Abstract: Hypertension is a common cardiovascular risk factor leading to heart failure (HF), coronary artery disease, stroke, peripheral artery disease and chronic renal insufficiency. Hypertensive heart disease can manifest as many cardiac arrhythmias, most commonly being atrial fibrillation (AF). Both supraventricular and ventricular arrhythmias may occur in hypertensive patients, especially in those with left ventricular hypertrophy (LVH) or HF. Also, some of the antihypertensive drugs commonly used to reduce blood pressure, such as thiazide diuretics, may result in electrolyte abnormalities (e.g. hypokalaemia, hypomagnesemia), further contributing to arrhythmias, whereas effective control of blood pressure may prevent the development of the arrhythmias such as AF. In recognizing this close relationship between hypertension and arrhythmias, the European Heart Rhythm Association (EHRA) and the European Society of Cardiology (ESC) Council on Hypertension convened a Task Force, with representation from the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLEACE), with the remit to comprehensively review the available evidence to publish a joint consensus document on hypertension and cardiac arrhythmias, and to provide up-to-date consensus recommendations for use in clinical practice. The ultimate judgment regarding care of a particular patient must be made by the healthcare provider and the patient in light of all of the circumstances presented by that patient.

de Oliveira Figueiredo|Márcio Jansen|MJ|

D000959:Antihypertensive Agents
D001145:Arrhythmias, Cardiac
D001794:Blood Pressure
D032921:Consensus
D003362:Cost-Benefit Analysis
D016757:Death, Sudden, Cardiac
D017048:Health Care Costs
D006329:Heart Conduction System
D006801:Humans
D006973:Hypertension
D018570:Risk Assessment
D012307:Risk Factors
D016896:Treatment Outcome

Hypertension
Arrhythmias
Atrial fibrillation
Left ventricular hypertrophy
EHRA consensus document


Long-term results after mitral valve surgery using minimally invasive versus sternotomy approach: a propensity matched comparison of a large single-center series.

Abstract:
BACKGROUND
Mitral valve (MV) surgery has traditionally been performed by conventional sternotomy (CS), but more recently minimally invasive surgery (MIS) has become another treatment option. The aim of this study is to compare short- and long-term results of MV surgery after CS and MIS.

METHODS
This study was a retrospective propensity-matched analysis of MV operations between January 2005 and December 2015.

RESULTS
Among 1357 patients, 496 underwent CS and 861 MIS. Matching resulted in 422 patients per group. The procedure time was longer with MIS than CS (192 vs. 185 min; p = 0.002) as was cardiopulmonary bypass time (133 vs. 101 min; p < 0.001) and X-clamp time (80 vs. 71 min; p < 0.001). 'Short-term' successful valve repair was higher with MIS (96.0% vs. 76.0%, p < 0.001). Length of hospital stay was shorter in MIS than CS patients (10 vs. 11 days; p = 0.001). There was no difference in the overall 30-day mortality rate. Cardiovascular death was lower after MIS (1.2%) compared with CS (3.8%; OR 0.30; 95%CI 0.11-0.84). The difference did not remain significant after adjustment for procedural differences (aOR 0.40; 95%CI 0.13-1.25). Pacemaker was required less often after MIS (3.3%) than CS (11.2%; aOR 0.31; 95%CI 0.16-0.61), and acute renal failure was less common (2.1% vs. 11.9%; aOR 0.22; 95%CI 0.10-0.48). There were no significant differences with respect to rates of stroke, myocardial infarction or repeat MV surgery. The 7-year survival rate was significantly better after MIS (88.5%) than CS (74.8%; aHR 0.44, 95%CI 0.31-0.64).

CONCLUSION
This study demonstrates that good results for MV surgery can be obtained with MIS, achieving a high MV repair rate, low peri-procedural morbidity and mortality, and improved long-term survival.

Cetinkaya|Ayse|A| Geier|Anna|A| Bramlage|Karin|K| Hein|Stefan|S| Bramlage|Peter|P|0000-0002-4121-6866 Schönburg|Markus|M| Choi|Yeong-Hoon|YH| Richter|Manfred|M|

D019060:Minimally Invasive Surgical Procedures

Mitral valve
Sternotomy
Minimally invasive mitral valve surgery
Mitral valve repair
Outcomes


Evaluation studies on the combined effect of hydrothermal treatment and octenyl succinylation on the physic-chemical, structural and digestibility characteristics of sweet potato starch.

Abstract: In order to increase the degree of substitution (DS), a combination of heat-moisture treatment (HMT) and octenyl succinylation (OSA) was used to modify sweet potato starch (SPS). The content of OSA had significant influence on the DS of starch, and DS of HMT OSA-modified SPS (HOSA-SPS) was higher than that of OSA-modified SPS (OSA-SPS), indicating that prior HMT could enhance the reaction. HOSA-SPS showed higher contents of SDS and RS in comparison with OSA-SPS as OSA concentration was beyond 6%. HMT decreased swelling power of starch while OSA modification had a contrary role (p < 0.05). Scanning electron microscopy (SEM) showed starch was destroyed by OSA modification while HMT had slight effect on the structure. X-ray diffraction (XRD) indicated that crystal type of starch was transformed from C- to A-type resulted from HMT, and remained unchanged by OSA modification. The onset, peak, and conclusion gelatinization temperatures of starch increased by HMT and decreased by OSA modification (p < 0.05).

Lv|Qing-Qing|QQ| Li|Gao-Yang|GY| Xie|Qiu-Tao|QT| Zhang|Bao|B| Li|Xiao-Min|XM| Pan|Yi|Y| Chen|Han-Qing|HQ|

Sweet potato starch
Heat-moisture treatment
Octenyl succinic anhydride


Alginic acid: A mild and renewable bifunctional heterogeneous biopolymeric organocatalyst for efficient and facile synthesis of polyhydroquinolines.

Abstract: Alginic acid, a widely used naturally occurring carbohydrate which is generally derived from brown seaweeds, can be considered as a bifunctional heterogeneous and green biopolymeric organocatalyst. Alginic acid, without any post-modification with active Bronsted or Lewis acid centers, was found to be a highly active, cost-effective, commercially-available, renewable and recoverable heterogeneous biopolymeric organocatalyst for the expeditious synthesis of polyhydroquinolines (PHQs). Polyhydroquinolines were synthesized from the four-component Hantzsch reaction of ethyl acetoacetate, different aldehydes, ammonium acetate and cyclic 1,3-diones under mild conditions in high to quantitative yields, 75-97%, using alginic acid. Furthermore, alginic acid was found to be reusable for at least 6 consecutive cycles without considerable loss of its catalytic activity.

Dekamin|Mohammad G|MG|
Karimi|Zahra|Z|
Latifidoost|Zahra|Z|
Ilkhanizadeh|Siamand|S|
Daemi|Hamed|H|
Naimi-Jamal|M Reza|MR|
Barikani|Mehdi|M|

Alginic acid
Polyhydroquinolines (PHQs)
Biopolymer
Green chemistry
Hantzsch esters
Heterocycles
Organocatalysis


Leucine-rich repeat kinase 2 regulates Sec16A at ER exit sites to allow ER-Golgi export.

Abstract: Leucine-rich repeat kinase 2 (LRRK2) has been associated with Parkinson's disease (PD) and other disorders. However, its normal physiological functions and pathogenic properties remain elusive. Here we show that LRRK2 regulates the anterograde ER-Golgi transport through anchoring Sec16A at the endoplasmic reticulum exit sites (ERES). LRRK2 interacted and co-localized with Sec16A, a key protein in the formation of ERES. Lrrk2 depletion caused a dispersion of Sec16A from ERES and impaired ER export. In neurons, LRRK2 and Sec16A showed extensive co-localization at the dendritic ERES (dERES) that locally regulate the transport of proteins to the dendritic spines. A loss of Lrrk2 affected the association of Sec16A with dERES and impaired the activity-dependent targeting of glutamate receptors onto the cell/synapse surface. Furthermore, the PD-related LRRK2 R1441C missense mutation in the GTPase domain interfered with the interaction of LRRK2 with Sec16A and also affected ER-Golgi transport, while LRRK2 kinase activity was not required for these functions. Therefore, our findings reveal a new physiological function of LRRK2 in ER-Golgi transport, suggesting ERES dysfunction may contribute to the pathogenesis of PD.

Cho|Hyun Jin|HJ|
Yu|Jia|J|
Xie|Chengsong|C|
Rudrabhatla|Parvathi|P|
Chen|Xi|X|
Wu|Junbing|J|
Parisiadou|Loukia|L|
Liu|Guoxiang|G|
Sun|Lixin|L|
Ma|Bo|B|
Ding|Jinhui|J|
Liu|Zhihua|Z|
Cai|Huaibin|H|

D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2

Sec16A
dendritic ERES (dERES)
ER exit sites (ERES)
ER–Golgi transport
Leucine‐rich repeat kinase 2 (LRRK2)


Seasonal variability in ecosystem functioning across estuarine gradients: The role of sediment communities and ecosystem processes.

Abstract: Functional trait approaches advance the understanding of biodiversity-ecosystem function (BDEF) relationships and its control by the environmental context. Application of these insights into management remains constrained due to lack of evidence from real-world ecosystems that capture the natural spatial and temporal gradients at which biodiversity and environmental conditions operate. In this study we measured macrofauna community traits, ecosystem processes and abiotic properties at 9 locations during 4 months, spanning a wide gradient in sedimentary habitats and salinity in the Scheldt estuary, and quantified the (a)biotic contribution to sediment community oxygen consumption, as a measure of ecosystem function. We found that functional attributes of the macrofauna community and its effect on bio-irrigation can predict ecosystem function, but especially during the colder period of the year. This result highlights that generalizations about BDEF relationships, and biodiversity loss on ecosystem functions, are limited whenever this temporal component is not acknowledged.

Mestdagh|Sebastiaan|S|
Fang|Xiaoyu|X|
Soetaert|Karline|K|
Ysebaert|Tom|T|
Moens|Tom|T|
Van Colen|Carl|C|

Ecosystem functioning
Ecosystem processes
Macrofauna
Estuaries
Sediment biogeochemistry
Soft sediments


Pluralistic Ignorance as a Contributing Factor to Concussion Underreporting.

Abstract:
BACKGROUND
Concussion underreporting is endemic, and social norms are an established predictor of concussion reporting behavior. However, pluralistic ignorance-a situation in which most individuals in a group hold the belief that their peers' views differ from their own, despite views actually being similar-has not been studied in this context.

AIM
To assess whether pluralistic ignorance contributes to concussion underreporting.

METHOD
We surveyed 2,504 military service academy cadets. Each cadet was presented with a survey asking about their willingness to self-report a concussion, their perception of other cadets' willingness to report a concussion, and personal and demographic factors.

RESULTS
Most cadets viewed themselves as more willing to report a concussion than others (mean difference = 1.12, 95% CI [1.02, 1.21]), a belief consistent with pluralistic ignorance. Demographic characteristics were associated with holding this belief. For example, female cadets and upper-class cadets were more likely to show this disparity than male or under-class cadets, respectively. Collegiate athletes not only showed similar willingness to report concussion as nonathletes but also perceived other cadets as less likely to report concussions. Meanwhile, future pilots showed less self-report willingness and perceived that others were similarly unwilling to report concussions.

DISCUSSION
A majority of this economically and geographically diverse population displays characteristics of pluralistic ignorance: They largely share proconcussion reporting sentiments but incorrectly perceive that others do not. This belief is not held uniformly in all subpopulations, which may inform how these beliefs are developed and maintained.

CONCLUSIONS
Pluralistic ignorance is an important consideration in concussion education efforts.

pluralistic ignorance
concussion
social norms
concussion reporting
disclosure
young adult


Implementing collective leadership in healthcare organisations.

Abstract: Effective leadership is essential in healthcare organisations, with several high-profile reports on suboptimal care in the NHS demonstrating a link between ineffective leadership and compromised patient safety. Therefore, it is important that nurses understand how leadership is defined and what effective leadership entails in practice. Various types of leadership are described in the literature, such as transactional, transformational and contingency leadership. One approach that could be beneficial in NHS organisations is collective leadership, which involves developing a leadership culture where formal and informal leaders work together to generate actions. This article explores the implementation of collective leadership in healthcare organisations, the potential benefits of this approach, and the behaviours and qualities that nurses require to be collective leaders.

leadership
patient safety
patients
leadership development
leadership frameworks
leadership models
leadership skills
professional development
professional issues
shared leadership


Growth differentiation factor 15 neutralization does not impact anorexia or survival in lipopolysaccharide-induced inflammation.

Abstract: Growth differentiation factor 15 (GDF15) causes anorexia and weight loss in animal models, and higher circulating levels are associated with cachexia and reduced survival in cancer and other chronic diseases such as sepsis. To investigate the role of sepsis-induced GDF15, we examined whether GDF15 neutralization via a validated and highly potent monoclonal antibody, mAB2, modulates lipopolysaccharide (LPS)-induced anorexia, weight loss, and mortality in rodents. LPS injection transiently increased circulating GDF15 in wild-type mice, decreased food intake and body weight, and increased illness behavior and mortality at a high dose. GDF15 neutralization with mAB2 did not prevent or exacerbate any of the effects of LPS. Similarly, in GDF15 knockout mice, the LPS effect on appetite and survival was comparable with that observed in wild-type controls. Therefore, effective inhibition of circulating active GDF15 via an antibody or via gene knockout demonstrated that survival in the LPS acute inflammation model was independent of GDF15.

Breen|Danna M|DM|
Jagarlapudi|Srinath|S|
Patel|Anita|A|
Zou|Chang|C|
Joaquim|Stephanie|S|
Li|Xiangping|X|
Kang|Liya|L|
Pang|Jincheng|J|
Hales|Katherine|K|
Ziso-Qejvanaj|Enida|E|
Vera|Nicholas B|NB|
Bennett|Donald|D|
He|Tao|T|
Lambert|Matthew|M|
Kelleher|Kerry|K|
Wu|Zhidan|Z|
Zhang|Bei B|BB|
Lin|Laura|L|
Seeley|Randy J|RJ|
Bezy|Olivier|O|


Immunomodulatory activities of zinc(II)phthalocyanine on the mammalian macrophages through p38 pathway: Potential ex vivo immunomodulatory PDT reagents.

Abstract: A series of zinc phthalocyanine having imidazolyl moieties was synthesized. These compounds' immunostimulatory and immunomodulatory activities were tested on the mammalian macrophages in vitro. In the absence of photo induction neither dmso soluble nor the water soluble imidazole Pc had any immunostimulatory or immunomodulatory effect on the macrophage activity based on the differences in the pro-inflammatory cytokine secretion levels compared to the control groups. Upon photo induction, especially, at 5 min exposure time both derivatives lead to an increased pro-inflammatory cytokine secretion level by LPS activated macrophages. Whereas, this effect was completely reversed after 10 min of light treatment and both derivatives gained stark anti-inflammatory potential. Our molecules were cell penetrating and exerted their effects by regulating the phosphorylation levels of p38. This study is one of its first examples suggesting differential immunomodulatory photo dynamic therapy applications of phthalocyanine derivatives depending on light exposure time as well as their possible route of modulating the intracellular signaling pathways.

Macrophages
PDT
Phthalocyanines
Anti-inflammatory molecules
Immunomodulation


An updated review of pharmacokinetic drug interactions and pharmacogenetics of statins.

Abstract:
INTRODUCTION
Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) lower cholesterol synthesis in patients with hypercholesterolemia. Increased statin exposure is an important risk factor for skeletal muscle toxicity. Potent inhibitors of cytochrome P450 (CYP) 3A4 significantly increase plasma concentrations of the active forms of simvastatin, lovastatin, and atorvastatin. Fluvastatin is metabolized by CYP2C9, whereas pravastatin, rosuvastatin, and pitavastatin are unaffected by inhibition by either CYP. Statins also have different affinities for membrane transporters involved in processes such as intestinal absorption, hepatic absorption, biliary excretion, and renal excretion.

AREAS COVERED
In this review, the pharmacokinetic aspects of drug-drug interactions with statins and genetic polymorphisms of CYPs and drug transporters involved in the pharmacokinetics of statins are discussed.

EXPERT OPINION
Understanding the mechanisms underlying statin interactions can help minimize drug interactions and reduce the adverse side effects caused by statins. Since recent studies have shown the involvement of drug transporters such as OATP and BCRP as well as CYPs in statin pharmacokinetics, further clinical studies focusing on the drug transporters are necessary. The establishment of biomarkers based on novel mechanisms, such as the leakage of microRNAs into the peripheral blood associated with the muscle toxicity, is important for the early detection of statin side effects.


Effectiveness of training patients using DVD in the accurate use of inhalers for the treatment of bronchial asthma.

Abstract:
BACKGROUND
Inhalants are the standard treatment for patients with bronchial asthma. Inaccurate inhaler use leads to inadequate therapeutic effects and unnecessary dosage increases. However, it is a challenge for practitioners to master the various devices available and train patients on the accurate use of inhalers. Thus, establishing a system to instruct patients on how to accurately use inhalers is essential. We prepared a DVD and accompanying user manual explaining the operation of each inhaler device used in Japan. This pilot study aimed to examine the efficacy of these materials.

METHODS
The subjects were 33 outpatients with bronchial asthma who received treatment in our facility for asthma and had already received conventional inhalant training. The oral medication and inhalants used by the patients were not changed. The patients were randomly assigned to a DVD viewing group or non-viewing group; various parameters were comparatively examined after 4 weeks.

RESULTS
Significant improvements in Asthma Control Test scores, inhalation technique, forced vital capacity, forced expiratory volume in 1 s, impulse oscillometry resonant frequency, and induced sputum eosinophil count were observed in the DVD viewing group at 4 weeks post training.

CONCLUSIONS
Pulmonary function and inflammatory parameters improved significantly in the DVD viewing group. These findings suggest that unnecessary step-up of asthma treatment can be avoided, leading to treatment cost reduction. Training patients with asthma in accurate inhaler use improves quality of life and therefore has great clinical significance. Hence, this method should be used more extensively in Japan and worldwide.

Training
Inhaler
Asthma
Corticosteroids
Inhalation therapy


NTRK Fusions in Central Nervous System Tumors: A Rare, but Worthy Target.

Abstract: The neurotrophic tropomyosin receptor kinase (NTRK) genes (NTRK1, NTRK2, and NTRK3) code for three transmembrane high-affinity tyrosine-kinase receptors for nerve growth factors (TRK-A, TRK-B, and TRK-C) which are mainly involved in nervous system development. Loss of function alterations in these genes can lead to nervous system development problems; conversely, activating alterations harbor oncogenic potential, promoting cell proliferation/survival and tumorigenesis. Chromosomal rearrangements are the most clinically relevant alterations of pathological NTRK activation, leading to constitutionally active chimeric receptors. NTRK fusions have been detected with extremely variable frequencies in many pediatric and adult cancer types, including central nervous system (CNS) tumors. These alterations can be detected by different laboratory assays (e.g., immunohistochemistry, FISH, sequencing), but each of these approaches has specific advantages and limitations which must be taken into account for an appropriate use in diagnostics or research. Moreover, therapeutic targeting of this molecular marker recently showed extreme efficacy. Considering the overall lack of effective treatments for brain neoplasms, it is expected that detection of NTRK fusions will soon become a mainstay in the diagnostic assessment of CNS tumors, and thus in-depth knowledge regarding this topic is warranted.

Gambella|Alessandro|A|
Senetta|Rebecca|R|
Collemi|Giammarco|G|
Vallero|Stefano Gabriele|SG|
Monticelli|Matteo|M|
Cofano|Fabio|F|
Zeppa|Pietro|P|
Garbossa|Diego|D|
Pellerino|Alessia|A|
Rudà|Roberta|R|
Soffietti|Riccardo|R|
Fagioli|Franca|F|
Papotti|Mauro|M|
Cassoni|Paola|P|
Bertero|Luca|L|

D016543:Central Nervous System Neoplasms

NTRK
central nervous system
gene fusion
glioma
molecular pathology
pediatric tumors
precision medicine
targeted therapies


Studies on the alkaloid composition of the Hawaiian Baby Woodrose Argyreia nervosa, a common legal high.

Abstract: Seeds from the Hawaiian Baby Woodrose Argyreia nervosa of different origin and labelling and with allegedly high levels of ergot alkaloids were analysed using high performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS/MS) technique. Lysergic acid amide (LSA), ergometrine, lysergol/elymoclavine/setoclavine, chanoclavine, lysergic acid and their respective stereoisomers were identified as well as penniclavine and lysergic acid α-hydroxyethylamide. In addition, methylergometrine, methysergide, and lysergylalanine were detected, some high molecular weight ergot alkaloid derivatives and hydroxyalanine derived ergopeptide fragments were detected indicating the presence of ergopeptides in the seeds. The results of the study demonstrate that the content of ergot alkaloids in Argyreia nervosa seeds depends on the quality of the material. For a consumer the quality of the seeds is unforeseeable. For the toxicological expert it is essential to investigate not only the identity of such a confiscated seed material, but also the various ergot alkaloid constituents to assess the hazardous nature and the toxic potential of the material.

Paulke|Alexander|A|
Kremer|Christian|C|
Wunder|Cora|C|
Wurglics|Mario|M|
Schubert-Zsilavecz|Manfred|M|
Toennes|Stefan W|SW|

D002851:Chromatography, High Pressure Liquid

Argyreia nervosa
Legal highs
Ergot alkaloids
Lysergic acid amide
Ergometrine
Ergopeptides
Peptide alkaloids


Association of occupational exposure with features of systemic sclerosis.

Abstract:
BACKGROUND
Occupational exposure is reported as playing a substantial causative role in systemic sclerosis (SSc).

OBJECTIVE
We sought to compare the characteristics of SSc in patients with and without occupational exposure to crystalline silica/solvents.

METHODS
In all, 142 patients with SSc were enrolled in this prospective study. An expert committee performed blind evaluation of occupational exposure to crystalline silica/solvents.

RESULTS
Patients exposed to crystalline silica more often exhibited: diffuse cutaneous SSc (P = .02), digital ulcers (P = .05), interstitial lung disease (P = .0004), myocardial dysfunction (P = .006), and cancer (P = .06). Patients exposed to solvents more frequently developed: diffuse cutaneous SSc (P = .001), digital ulcers (P = .01), interstitial lung disease (P = .02), myocardial dysfunction (P = .04), and cancer (P = .003); in addition, these patients were more frequently anti-Scl 70 positive and anticentromere negative. Under multivariate analysis, significant factors for SSc associated with exposure to silica/solvents were: male gender (odds ratio 19.31, 95% confidence interval 15.34-69.86), cancer (odds ratio 5.97, 95% confidence interval 1.55-23.01), and digital ulcers (odds ratio 2.42, 95% confidence interval 1.05-5.56).

LIMITATIONS
The cohort originated from a single geographic region.

CONCLUSION
Occupational exposure to crystalline silica/solvents is correlated with more severe forms of SSc characterized by: diffuse cutaneous involvement, interstitial lung disease, general microangiopathy (digital ulcers and myocardial dysfunction), and association with cancer. Occupational exposure should be systematically checked in all patients with SSc, as exposed patients seem to develop more severe forms of SSc.

Marie|Isabelle|I| Menard|Jean-François|JF| Duval-Modeste|Anne-Bénédicte|AB| Joly|Pascal|P| Dominique|Stéphane|S| Bravard|Pierre|P| Noël|David|D| Gehanno|Jean-François|JF| Bubenheim|Michael|M| Benichou|Jacques|J| Levesque|Hervé|H|

systemic sclerosis
crystalline silica
solvents
digital ulcers
interstitial lung disease
cancer
occupational factors


Evaluation of Leishmania (Leishmania) infantum excreted-secreted antigens for detection of canine leishmaniasis.

Abstract: The efficacy of tests with L. (L.) infantum excreted-secreted antigens (ESA) to detect canine leishmaniasis (CanL) was evaluated using immunoblotting (ESA-blot), ELISA (ESA-ELISA) and ELISA with alkaline extract from promastigotes (PAE). Of one hundred fifty-five domestic dogs tested, 100 were suspected of CanL, 23 had other diseases and 32 were healthy. Sera from the dogs suspected of CanL were tested by immunohistochemistry (IHC), and 54% were confirmed to be infected by L. (L.) infantum (38 symptomatic and 16 asymptomatic). Of these, 100% were positive by ESA-blot, ESA-ELISA and PAE-ELISA. In the ESA-blot their sera recognized polypeptides in the 26.5-31.5kDa region. Of the 46% of dogs with negative IHC, 44-53% tested positive in all three tests irrespective of clinical status. The twenty-three dogs with other diseases were negative by ESA-blot, but sera from 9% and 26% of them reacted with ESA-ELISA and PAE-ELISA, respectively. The 32 healthy dogs were negative in all the tests. ESA-blot showed good correlation with IHC in the detection of CanL and a high specificity index.

Pinedo-Cancino|Viviana|V|
Laurenti|Márcia Dalastra|MD|
Kesper|Norival|N|
Umezawa|Eufrosina Setsu|ES|

Canine leishmaniasis
Immunoblotting
ELISA
Excreted antigens
Leishmania infantum
Secreted antigens


First comprehensive analysis of lysine acetylation in Alvinocaris longirostris from the deep-sea hydrothermal vents.

Abstract:
BACKGROUND
Deep-sea hydrothermal vents are unique chemoautotrophic ecosystems with harsh conditions. Alvinocaris longirostris is one of the dominant crustacean species inhabiting in these extreme environments. It is significant to clarify mechanisms in their adaptation to the vents. Lysine acetylation has been known to play critical roles in the regulation of many cellular processes. However, its function in A. longirostris and even marine invertebrates remains elusive. Our study is the first, to our knowledge, to comprehensively investigate lysine acetylome in A. longirostris.

RESULTS
In total, 501 unique acetylation sites from 206 proteins were identified by combination of affinity enrichment and high-sensitive-massspectrometer. It was revealed that Arg, His and Lys occurred most frequently at the + 1 position downstream of the acetylation sites, which were all alkaline amino acids and positively charged. Functional analysis revealed that the protein acetylation was involved in diverse cellular processes, such as biosynthesis of amino acids, citrate cycle, fatty acid degradation and oxidative phosphorylation. Acetylated proteins were found enriched in mitochondrion and peroxisome, and many stress response related proteins were also discovered to be acetylated, like arginine kinases, heat shock protein 70, and hemocyanins. In the two hemocyanins, nine acetylation sites were identified, among which one acetylation site was unique in A. longirostris when compared with other shallow water shrimps. Further studies are warranted to verify its function.

CONCLUSION
The lysine acetylome of A. longirostris is investigated for the first time and brings new insights into the regulation function of the lysine acetylation. The results supply abundant resources for exploring the functions of acetylation in A. longirostris and other shrimps.

Lysine acetylation
Hydrothermal vent
Hemocyanins
Alvinocarididae
Post-translational modification


Task Performance Changes the Amplitude and Timing of the BOLD Signal.

Abstract: Translational studies comparing imaging data of animals and humans have gained increasing scientific interests. With this upcoming translational approach, however, identifying harmonized statistical analysis as well as shared data acquisition protocols and/or combined statistical approaches is necessary. Following this idea, we applied Bayesian Adaptive Regression Splines (BARS), which have until now mainly been used to model neural responses of electrophysiological recordings from rodent data, on human hemodynamic responses as measured via fMRI. Forty-seven healthy subjects were investigated while performing the Attention Network Task in the MRI scanner. Fluctuations in the amplitude and timing of the BOLD response were determined and validated externally with brain activation using GLM and also ecologically with the influence of task performance (i.e. good vs. bad performers). In terms of brain activation, bad performers presented reduced activation bilaterally in the parietal lobules, right prefrontal cortex (PFC) and striatum. This was accompanied by an enhanced left PFC recruitment. With regard to the amplitude of the BOLD-signal, bad performers showed enhanced values in the left PFC. In addition, in the regions of reduced activation such as the parietal and striatal regions, the temporal dynamics were higher in bad performers. Based on the relation between BOLD response and neural firing with the amplitude of the BOLD signal reflecting gamma power and timing dynamics beta power, we argue that in bad performers, an enhanced left PFC recruitment hints towards an enhanced functioning of gamma-band activity in a compensatory manner. This was accompanied by reduced parieto-striatal activity, associated with increased and potentially conflicting beta-band activity.

Akhrif|Atae|A|
Geiger|Maximilian J|MJ|
Romanos|Marcel|M|
Domschke|Katharina|K|
Neufang|Susanne|S|

Bayesian Adaptive Regression Spline
attention
Functional Neuroimaging
fMRI time courses


Extrapulmonary sequestration with a left internal thoracic arterial feeding vessel in an infant treated with video-assisted Thoracoscopic resection: a case report.

Abstract:
BACKGROUND
Congenital lung malformations exist along a spectrum of pathogenesis and disease severity. Extrapulmonary sequestration (EPS), in which nonfunctional lung tissue develops without connection to the tracheobronchial tree, is one rare manifestation of this disease. Atypical vascular anatomy with a systemic feeding vessel characterizes these lesions.

CASE PRESENTATION
A 3 day old, 37 week gestation infant underwent chest X-ray for confirmation of umbilical catheter placement and was found to have an elevated left hemidiaphragm consistent with eventration versus congenital diaphragmatic hernia. He remained asymptomatic and was evaluated as an outpatient at the age of 9 months, where CT angiogram demonstrated extrapulmonary versus intrapulmonary sequestration with a systemic feeding vessel from the left internal mammary artery.

CONCLUSIONS
It is exceedingly rare for the feeding artery to arise from the internal mammary; two such cases have been reported to date, both in adult patients. Here we present a third case of EPS with arterial supply from the internal mammary successfully treated with video-assisted thoracoscopic resection in a 9 month old infant.

Extrapulmonary sequestration
Internal thoracic artery
Pediatric
Video-assisted thoracoscopic surgery


Corrigendum: Fomenting Sickness: Nocebo Priming of Residents about Wind Farm Health Harms.

Abstract: [This corrects the article on p. 279 in vol. 2, PMID: 25566521.].

nocebo
wind farms
news media
psychogenic illness
wind energy
wind farm noise


Silica exposure and disease in semi-precious stone craftsmen, Minas Gerais, Brazil.

Abstract:
BACKGROUND
Brazil is an exporter of precious stones and craftsmen often work in poor conditions. We assessed silica-related diseases among crystal craftsmen and the complexity of its control.

METHODS
Case-series including 118 subjects evaluated from 2006 to 2015, based on medical interviews, chest X-rays, spirometry, and respirable silica samples.

RESULTS
Median age and length of exposure were 32 and 13 years, respectively. Silicosis, with 1/0 as a threshold, was diagnosed radiologically in 57 individuals (48.3%). Respirable silica concentrations were 0.9-29.3 times greater than the Brazilian occupational exposure limit. A Receiver Operating Characteristic (ROC) curve with the same diagnosis threshold showed best discrimination at a cut point of 12.5 years of exposure, corresponding to 4.85 mg-y/m3 of cumulative silica exposure. There was a significant decline in FEV1 across radiological and cumulative silica exposure categories. Eleven individuals (9.3%) had mycobacterial diseases at baseline or follow-up.

CONCLUSION
Crystal craftsmen continue to suffer from silicosis, lung function impairment, comorbidity, and death due to silicosis. To date collective protection in some work sheds has not diminished silica levels. Long-term follow-up is needed to evaluate further improvements in preventive measures. Am. J. Ind. Med. 60:239-247, 2017. © 2017 Wiley Periodicals, Inc.

Carneiro|Ana Paula S|AP|
Braz|Nayara F T|NF|
Algranti|Eduardo|E|
Bezerra|Olivia M P A|OM|
Araujo|Natália P S|NP|
Amaral Eng Hyg|Lênio S|LS|
Edmé|Jean L|JL|
Sobaszek|Annie|A|
Chérot-Kornobis|Nathalie|N|

stone craftsmen
spirometry
silicosis
occupational exposure
tuberculosis


Amifampridine phosphate (Firdapse(®)) is effective and safe in a phase 3 clinical trial in LEMS.

Abstract:
OBJECTIVE
We evaluated the efficacy and safety of amifampridine phosphate (Firdapse(®)) for symptomatic treatment in Lambert-Eaton myasthenic syndrome (LEMS).

METHODS
Phase 3, randomized, double-blind, study. Patients were treated initially with amifampridine phosphate for 7-91 days, followed by randomization to continue amifampridine phosphate for 14 days or placebo (7-day taper, 7-day placebo). The primary efficacy endpoints were changes from baseline at day 14 in Quantitative Myasthenia Gravis and Subject Global Impression scores.

RESULTS
The coprimary efficacy end points and 1 of the secondary efficacy end points were met, showing a significant benefit of aminfampridine phosphate over placebo at Day 14. All 5 primary, secondary, and tertiary endpoints achieved statistical significance at Day 8. Amifampridine phosphate was well tolerated; the most common adverse events were oral and digital paresthesias, nausea, and headache.

CONCLUSIONS
This study provides Class I evidence of efficacy of amifampridine phosphate as a symptomatic treatment for LEMS.

Oh|Shin J|SJ|
Shcherbakova|Natalya|N|
Kostera-Pruszczyk|Anna|A|
Alsharabati|Mohammad|M|
Dimachkie|Mazen|M|
Blanco|Jose Munoz|JM|
Brannagan|Thomas|T|
Lavrnić|Dragana|D|
Shieh|Perry B|PB|
Vial|Christophe|C|
Meisel|Andreas|A|
Komoly|Samuel|S|
Schoser|Benedikt|B|
Sivakumar|Kumaraswamy|K|
So|Yuen|Y|
|||

Amifampridine phosphate
LEMS
Lambert-Eaton myasthenic syndrome
3,4-DAP
3,4-diaminopyridine
Potassium channel blockers
Small cell lung cancer (SCLC)


Unrecognized and delayed to diagnose of adolescence tuberculosis case in a boarding school in West Java, Indonesia.

Abstract: Adolescent is a high-risk population for developing tuberculosis (TB) disease, unfortunately adolescence TB remains to be neglected. Clinical manifestations of TB are usually chronic and nonspecific that could be mimicking other disease. Unrecognized TB disease will lead to misdiagnosis, delayed, and inappropriate management. A 15-year-old female adolescent, admitted to the hospital due to severe anemia, loss of body weight accompanied with recurrent fever and tend to be easily tired. She was through investigation for hematology disorder with normal results. She was studying in a Muslim boarding school with overcrowded environment. History of contact with TB patient was unclear. Tuberculosis diagnosed based on positive genXpert result, detected sensitive to rifampicin Mycobacterium tuberculosis although acid-fast bacilli sputum smear and culture yielded results were negative. Worsening of the chest X-ray were obtained, initially showed infiltrate of the lung and then revealed bronchogenic spread. Lymph nodes enlargement of the neck-proven TB from fine-needle aspiration biopsy. Anti-TB drugs were started, and after the treatment, there were clinical improvement. TB among adolescents against many unique challenges such as difficulty in case detection, wider potential transmissions and problem on adherence; hence, this age group should be identified as a primary issue in the community.

Daulay|Rini Savitri|RS|
Majeda|Allisa|A|
Nataprawira|Heda Melinda|HM|

Adolescence
tuberculosis
boarding school
anemia
unrecognized tuberculosis


Assessing a doctor you've rarely worked with: The use of workplace-based assessments in a busy inner city emergency department.

Abstract:
OBJECTIVE
Historically, end-of-term assessments for Junior Medical Officers in our ED have been completed by nominated Consultants based on varying amounts of observation in addition to feedback from other health professionals. Our hypothesis is that this system of assessment is both inconsistent and unreliable. Our objective was to increase the validity of our assessment process using workplace-based assessments linked specifically to the domains set out in the Australian Medical Council intern assessment form.

METHODS
Current practice was established using an online survey. Workplace-based assessments were then performed on each junior doctor throughout the course of a term. A repeat survey at the end of term was used to audit the use of the workplace-based assessments and their effect on the adequacy of the assessments.

RESULTS
Almost three quarters of our Consultants used workplace-based assessments as part of their end-of-term assessment. Overall, 80% of Consultants agreed that the Junior Medical Officers assessment process was improved when using workplace-based assessments as an adjunct.

CONCLUSION
Workplace-based assessments improve the validity of end-of-term assessments for junior doctors in an ED as perceived by those performing the assessment.

D001315:Australia
D002983:Clinical Competence
D004521:Educational Measurement
D004635:Emergency Medicine
D004636:Emergency Service, Hospital
D006786:Hospitals, Urban
D006801:Humans
D007396:Internship and Residency
D008505:Medical Staff, Hospital
D017132:Workplace

workplace-based assessment
clinical competence
emergency medicine
hospital
medical staff


Assessment of exposure to oak wood dust using gallic acid as a chemical marker.

Abstract:
OBJECTIVES
The American Conference of Governmental Industrial Hygienists (ACGIH) has classified oak dust as a human carcinogen (A1), based on increased sinus and nasal cancer rates among exposed workers. The aims of this study were to investigate the use of gallic acid (GA) as a chemical marker of occupational exposure to oak dusts, to develop a high-performance liquid chromatography-diode array detector method to quantify GA and to apply the method in the analysis of oak dust samples collected in several factories.

METHODS
A high-performance liquid chromatography method was developed to detect GA in oak wood dust. The method was tested in the field, and GA was extracted from inhalable oak wood dust collected using the Institute of Occupational Medicine inhalable dust sampler in the air of five woodworking plants where only oak wood is used.

RESULTS
A total of 57 samples with dust concentrations in the range of 0.27-11.14 mg/m(3) were collected. Five of these samples exceeded the Italian threshold limit value of 5 mg/m(3), and 30 samples exceeded the ACGIH TLV of 1 mg/m(3). The GA concentrations were in the range 0.02-4.18 µg/m(3). The total oak dust sampled was correlated with the GA content with a correlation coefficient (r) of 0.95.

CONCLUSIONS
The GA in the tannic extracts of oak wood may be considered a good marker for this type of wood, and its concentration in wood dust sampled in the work environment is useful in assessing the true exposure to carcinogenic oak dust.

Wood dust
Gallic acid
Chemical marker
Occupational exposure
Oak dust exposure


Extraction, purification, methylation and GC-MS analysis of short-chain carboxylic acids for metabolic flux analysis.

Abstract: Dynamic metabolic flux analysis requires efficient and effective methods for extraction, purification and analysis of a plethora of naturally-occurring compounds. One area of metabolism that would be highly informative to study using metabolic flux analysis is the tricarboxylic acid (TCA) cycle, which consists of short-chain carboxylic acids. Here, we describe a newly-developed method for extraction, purification, derivatization and analysis of short-chain carboxylic acids involved in the TCA cycle. The method consists of snap-freezing the plant material, followed by maceration and a 12-15h extraction at -80 °C. The extracts are then subject to reduction (to stabilize β-keto acids), purified by strong anion exchange solid phase extraction and methylated with methanolic HCl. This method could also be readily adapted to quantify many other short-chain carboxylic acids.

Tivendale|Nathan D|ND|
Jewett|Erin M|EM|
Hegeman|Adrian D|AD|
Cohen|Jerry D|JD|

Methylation
Carboxylic acid
Metabolic flux
Gas chromatography-mass spectrometry
Polar metabolites
Tricarboxylic acid cycle


Dapagliflozin attenuates diabetic cardiomyopathy through erythropoietin up-regulation of AKT/JAK/MAPK pathways in streptozotocin-induced diabetic rats.

Abstract:
PURPOSE
This study was designed to investigate the mechanism of Dapagliflozin (Dapa) cardioprotection against diabetic cardiomyopathy (DCM). Structural and functional changes in the heart as well as decrease of erythropoietin (EPO) levels were reported in DCM. EPO simultaneously activates three pathways: the Janus-activated kinase-signal transducer and activator of transcription (JAK2/STAT5), phosphatidylinositol-3-kinase-Akt (PI3K/Akt), and extracellular signal-related kinase (ERK/MAPK) cascades, that result in proliferation and differentiation of cardiac cells.

METHODS AND RESULTS
DCM was induced by a high fat diet for 10 weeks followed by administration of streptozotocin. After confirmation of diabetes, rats were divided randomly to 5 groups: Group 1; normal control group, Group 2; untreated diabetic group and Groups (3-5); diabetic groups received Dapa daily (0.75 mg, 1.5 or 3 mg/Kg, p.o) respectively for a month. At the end of the experiment, full anaesthesia was induced in all rats using ether inhalation and ECG was recorded. Blood samples were collected then rats were sacrificed and their heart were dissected out and processed for biochemical and histopathological studies. Untreated diabetic rats showed abnormal ECG pattern, elevation of serum cardiac enzymes, decrease EPO levels, downregulation of P-Akt, P-JAK2 and pMAPK pathways, abnormal histological structure of the heart and increase immunostaining intensity of P53 and TNF α in the cardiomyocytes. Dapa in a dose dependent manner attenuated the alterations in the previously mentioned parameters.

CONCLUSION
The cardioprotective effect of Dapa could be mediated by increasing EPO levels and activation of P-Akt, P-JAK2 and pMAPK signalling cascades which in turn decrease apoptosis.

El-Sayed|Nora|N|
Mostafa|Yasser M|YM|
AboGresha|Noha M|NM|
Ahmed|Amal A M|AAM|
Mahmoud|Islam Z|IZ|
El-Sayed|Norhan M|NM|

Dapagliflozin
Diabetic cardiomyopathy
Erythropoietin
AKT/JAK/MAPK pathways


Namib Desert edaphic bacterial, fungal and archaeal communities assemble through deterministic processes but are influenced by different abiotic parameters.

Abstract: The central Namib Desert is hyperarid, where limited plant growth ensures that biogeochemical processes are largely driven by microbial populations. Recent research has shown that niche partitioning is critically involved in the assembly of Namib Desert edaphic communities. However, these studies have mainly focussed on the Domain Bacteria. Using microbial community fingerprinting, we compared the assembly of the bacterial, fungal and archaeal populations of microbial communities across nine soil niches from four Namib Desert soil habitats (riverbed, dune, gravel plain and salt pan). Permutational multivariate analysis of variance indicated that the nine soil niches presented significantly different physicochemistries (R 2 = 0.8306, P ≤ 0.0001) and that bacterial, fungal and archaeal populations were soil niche specific (R 2 ≥ 0.64, P ≤ 0.001). However, the abiotic drivers of community structure were Domain-specific (P < 0.05), with P, clay and sand fraction, and NH4 influencing bacterial, fungal and archaeal communities, respectively. Soil physicochemistry and soil niche explained over 50% of the variation in community structure, and communities displayed strong non-random patterns of co-occurrence. Taken together, these results demonstrate that in central Namib Desert soil microbial communities, assembly is principally driven by deterministic processes.

Johnson|Riegardt M|RM|
Ramond|Jean-Baptiste|JB|
Gunnigle|Eoin|E|
Seely|Mary|M|
Cowan|Don A|DA|

Desert ecology
Deterministic drivers
Microbial community assembly
Soil environments


Function of lipid droplet-organelle interactions in lipid homeostasis.

Abstract: Storage of non-polar lipids in ubiquitous eukaryotic organelles, lipid droplets (LDs), prevents the toxic consequences of unesterified fatty acids and provides a lipid reservoir that can be promptly used to satisfy cellular needs under multiple metabolic and physiological conditions. Tight temporal and spatial control of LD biogenesis and mobilization of neutral lipids is essential for the correct channelling of lipid intermediates to their various cellular destinations and the maintenance of cellular homeostasis. These functions are mediated by multiple interactions between LDs and other intracellular organelles that are required for the delivery of stored lipids. Here we review recent advances in the interactions of LDs with the endoplasmic reticulum (ER), mitochondria and vacuole/lysosome. This article is part of a Special Issue entitled: Membrane Contact Sites edited by Christian Ungermann and Benoit Kornmann.

D000070136:Lipid Droplet Associated Proteins

Lipid droplet
Vacuole
Contact site
Endoplasmic reticulum membrane
Triacylglycerol
Yeast


Ribosome Display: A Potent Display Technology used for Selecting and Evolving Specific Binders with Desired Properties.

Abstract: Ribosome display is a powerful engineering research tool for the high-throughput selection of peptides or proteins, which results in the generation of high-performance binders against nearly any antigen of interest. As a cell-free display system, ribosome display has been well developed with many outstanding achievements for over 20 years. Compared with other related display techniques, ribosome display shows unique advantages and development prospects. This tool has been successfully exploited for the selection of functional and specific binders in vitro. This review provides a comprehensive survey of the applications of ribosome display in screening or evolving functional proteins as well as in diagnostics and therapeutics. Previous papers on ribosome display failed to comprehensively review evolutionary strategies for proteins. In the present paper, we review all existing evolutionary strategies that have been combined with ribosome display. We also discuss shortcomings, improvement strategies, and research tendency.

Li|Ruowei|R| Kang|Guangbo|G| Hu|Min|M| Huang|He|H|

Ribosome display
Display technologies
Diagnostics
Therapeutics
Evolutionary strategies
Affinity maturation
Stability optimization


Flow visualisation study of spiral flow in the aorta-renal bifurcation.

Abstract: The aim of this study was to analyse the flow dynamics in an idealised model of the aorta-renal bifurcation using flow visualisation, with a particular focus on the effect of aorta-to-renal flow ratio and flow spirality. The recirculation length was longest when there was low flow in the renal artery and smaller in the presence of spiral flow. The results also indicate that patients without spiral flow or who have low flow in the renal artery due to the presence of stenosis may be susceptible to heightened development of atherosclerotic lesions.

Fulker|David|D| Javadzadegan|Ashkan|A| Li|Zuming|Z| Barber|Tracie|T|


Complete remission in metastatic primary malignant melanoma of the esophagus with nivolumab: a case report.

Abstract:
BACKGROUND
Primary malignant melanoma of the esophagus is a rare form of mucosal melanoma with a poor prognosis. While immune checkpoint inhibitors have recently extended overall survival in metastatic melanoma, data on their effects on primary malignant melanoma of the esophagus are limited because of its rarity. Here, we report the first case of long-term complete remission of metastatic primary malignant melanoma of the esophagus after nivolumab monotherapy.

CASE PRESENTATION
A 79-year-old Asian man with a history of prostate cancer, gallbladder cancer, deep vein thrombosis, hypertension, and diabetes mellitus presented with gross hematuria. Cystoscopy revealed a solitary tumor on the right posterior wall of the bladder, and transurethral resection of bladder tumor was performed. Pathology was consistent with metastatic melanoma. A pigmented submucosal tumor-like growth in the esophagus was discovered on esophagogastroduodenoscopy. Computed tomography showed widespread metastases. The patient was diagnosed as having primary malignant melanoma of the esophagus with metastases to the stomach, subcutaneous tissue, lung, bladder, pleura, and peritoneum. Complete remission was achieved after seven cycles of triweekly nivolumab monotherapy. While nivolumab was discontinued because of kidney injury, the patient has remained tumor-free for over 4 years without further treatment.

CONCLUSION
Immune checkpoint inhibitors may have astonishing curative effects in selected populations. More research is warranted to identify factors that increase the likelihood of achieving complete remission in primary malignant melanoma of the esophagus as well as in other melanomas.


Performance of gimbal-based dynamic tumor tracking for treating liver carcinoma.

Abstract:
BACKGROUND
Since the introduction of tumor tracking in radiotherapy, it is possible to ensure a precise irradiation of moving targets. To follow the tumor movement, most systems rely on the detection of implanted markers and correlation models between the internal and external patient movement. This study reports the clinical workflow and first results of the dynamic tumor tracking (DTT) performance for patients with liver carcinoma at the Vero SBRT system of the University Hospital Erlangen regarding the detection of the internal marker and the changes of the determined correlation models.

METHODS
So far 13 liver patients were treated with DTT. For each patient, two fiducial markers (FM), which are monitored with X-rays during treatment, were implanted in the vicinity of the tumor. All patients received a fraction dose of 4-6 Gy with 8 to 12 fractions. Treatment and patient data is evaluated by processing the acquired log-files of the DTT treatment. Based on this, the marker detection and the changes of the correlation model between the internal and external movement is investigated.

RESULTS
The median treatment time was 19:42 min. During treatment a median of 173 X-ray stereoscopic images were acquired. The marker detection was successful in 64.6% of the images. The FM detection is independent of the relative angle between the marker and the imager, but shows a dependency on the average intensity surrounding the FM position within the kV images. The number of correlation models needed during treatment increases in the presence of baseline shifts. The comparison of the correlation models shows large differences in the internal-external correlation between the different models acquired for one patient.

CONCLUSION
Thirteen liver patients were treated with DTT at the Vero SBRT system and the marker detection was analyzed. Furthermore, the importance of regularly monitoring the internal target motion could be shown, since the correlation between the internal and external motion changes considerably over the course of the treatment.

Ziegler|Marc|M| Brandt|Tobias|T| Lettmaier|Sebastian|S| Fietkau|Rainer|R| Bert|Christoph|C|

Tumor tracking - stereotactic body radiation therapy - liver cancer - real-time monitoring


COVID-19 and the Otolaryngologist: Preliminary Evidence-Based Review.

Abstract: The SARS-CoV-2 virus, which causes coronavirus disease 2019 (COVID-19), has rapidly swept across the world since its identification in December 2019. Otolaryngologists are at unique risk due to the close contact with mucus membranes of the upper respiratory tract and have been among the most affected healthcare workers in Wuhan, China. We present information on COVID-19 management relevant to otolaryngologists on the frontlines of this pandemic and provide preliminary guidance based on practices implemented in China and other countries and practical strategies deployed at Stanford University. Laryngoscope, 130:2537-2543, 2020.


Rates of Anovulation in Adolescents and Young Adults with Moderate to Severe Primary Dysmenorrhea and Those without Primary Dysmenorrhea.

Abstract:
STUDY OBJECTIVE
To evaluate rates of presumptive anovulation in eumenorrheic adolescents and young adults with moderate to severe primary dysmenorrhea and those without primary dysmenorrhea.

DESIGN
Participants completed luteinizing hormone surge ovulation predictor test kits. Anovulatory cycles were defined by never receiving a positive result before the next menstrual period; participants were grouped as anovulatory if they experienced at least 1 anovulatory cycle during study participation. Participants rated daily level of menstrual pain on a 0-10 numeric rating scale.

SETTING
A university-based clinical research laboratory.

PARTICIPANTS
Thirty-nine adolescents and young adults (ages 16-24) with primary dysmenorrhea and 52 age-matched control girls.

INTERVENTIONS AND MAIN OUTCOME MEASURES
Rates of presumptive anovulation.

RESULTS
One hundred sixty-eight cycles were monitored, 29.8% (N = 50) of which were anovulatory (37.1% [39/105] vs 17.5% [11/63] of cycles in control and dysmenorrhea groups, respectively). During study participation, control girls were significantly more likely to have had at least 1 anovulatory cycle than were girls with primary dysmenorrhea (44.2% [23/52] vs 17.9% [7/39] of participants, respectively; P < .01). Cycle length and number of bleeding days between ovulatory and anovulatory cycles were similar. The primary dysmenorrhea group's maximum menstrual pain ratings did not differ between ovulatory and anovulatory cycles (4.77 and 4.36, respectively; P > .05).

CONCLUSION
Our data support previous findings of increased rates of ovulation in primary dysmenorrhea. However, menstruation after anovulatory cycles can be as painful as menstruation after ovulatory cycles. These data support the idea that regular menses do not necessarily indicate that a normal ovulatory cycle has occurred. Previous implications that ovulation is necessary for the development of substantial menstrual pain are incomplete.

Seidman|Laura C|LC|
Brennan|Kathleen M|KM|
Rapkin|Andrea J|AJ|
Payne|Laura A|LA|

Anovulation
Adolescent
Young adult
Dysmenorrhea