Mechanisms, Diagnosis and Treatment of Bone Metastases.

Abstract: Bone and bone marrow are among the most frequent metastatic sites of cancer. The occurrence of bone metastasis is frequently associated with a dismal disease outcome. The prevention and therapy of bone metastases is a priority in the treatment of cancer patients. However, current therapeutic options for patients with bone metastatic disease are limited in efficacy and associated with increased morbidity. Therefore, most current therapies are mainly palliative in nature. A better understanding of the underlying molecular pathways of the bone metastatic process is warranted to develop novel, well-tolerated and more successful treatments for a significant improvement of patients' quality of life and disease outcome. In this review, we provide comparative mechanistic insights into the bone metastatic process of various solid tumors, including pediatric cancers. We also highlight current and innovative approaches to biologically targeted therapy and immunotherapy. In particular, we discuss the role of the bone marrow microenvironment in the attraction, homing, dormancy and outgrowth of metastatic tumor cells and the ensuing therapeutic implications. Multiple signaling pathways have been described to contribute to metastatic spread to the bone of specific cancer entities, with most knowledge derived from the study of breast and prostate cancer. However, it is likely that similar mechanisms are involved in different types of cancer, including multiple myeloma, primary bone sarcomas and neuroblastoma. The metastatic rate-limiting interaction of tumor cells with the various cellular and noncellular components of the bone-marrow niche provides attractive therapeutic targets, which are already partially exploited by novel promising immunotherapies.

Ban|Jozef|J|
Fock|Valerie|V|
Aryee|Dave N T|DNT|
Kovar|Heinrich|H|0000-0001-6873-9109

bone metastasis
EMT
bone colonization
bone reconstruction
metastasis targeted therapy
metastatic dormancy
metastatic niche
tumor microenvironment interactions


Rare ovarian tumours. Other treatments for ovarian cancer.

Abstract:
Aim
The description of rare malignant ovarian tumours and the most suitable treatments. Alternative therapies different from intravenous chemotherapy are also explained.

Methods
Literature review and ongoing trial information have been used to elaborate this guide.

Results
Each ovarian cancer type must be identified and treated properly from diagnostic to surgery, adjuvant treatment and metastatic disease. Hormonotherapy can be useful as an alternative treatment, especially in low-grade ovarian cancer and endometrioid subtype. Tumour characterisation is appropriated for treatment selection when targeted therapy is indicated. MEK inhibitors, tyrosine-kinase inhibitors, EGFR inhibitors, therapies against integrins, antibody-drug conjugates and other strategies are described. Antiangiogenics, PARP inhibitors and immunotherapy are discussed in other parts of this publication.

Conclusion
Different ovarian cancer types must receive the appropriated treatment. Alternative therapies may be evaluated beyond the standard therapy, frequently in a clinical trial, and an individualised molecular study may help to find the best treatment.

Rare malignant ovarian tumours
Hormonotherapy
Targeted therapy


Expression, purification and substrate specificities of 3-nitrotoluene dioxygenase from Diaphorobacter sp. strain DS2.

Abstract: 3-Nitotoluene dioxygenase (3-NTDO) is the first enzyme in the degradation pathway of 3-nitrotoluene (3-NT) by Diaphorobacter sp. strain DS2. The complete gene sequences of 3-NTDO were PCR amplified from genomic DNA of Diaphorobacter sp., cloned, sequenced and expressed. The 3-NTDO gene revealed a multi component structure having a reductase, a ferredoxin and two oxygenase subunits. Clones expressing the different subunits were constructed in pET21a expression vector system and overexpressed in E. coli BL21(DE3) host. Each subunit was individually purified separately to homogeneity. The active recombinant enzyme was reconstituted in vitro by mixing all three purified subunits. The reconstituted recombinant enzyme could catalyse biotransformations on a variety of organic aromatics.

Singh|Deepak|D| Kumari|Archana|A| Ramaswamy|S|S| Ramanathan|Gurunath|G|

D015964:Gene Expression Regulation, Bacterial

D015971:Gene Expression Regulation, Enzymologic

Diaphorobacter
3-Nitotoluene dioxygenase (3-NTDO)
Biodegradation
Nitrotoluene (NT)
Rieske dioxygenase


How to best handle vaccine decliners: scientific facts and psychological approach.

Abstract: There is currently no curative drug therapy for COVID-19. The spread of the virus seems relentless despite the unprecedented epidemiological measures. Prevention remains the only feasible option to stop the pandemic; without population-level vaccination, we are unlikely to regain the quality of social life and the unrestricted economy/commerce we enjoyed before. Anti-vaxxers and conspiracy theorists are seemingly oblivious to the detrimental effect of COVID-19 both at an individual and societal level. These groups have (and probably will) continue to attempt to undermine efforts to eradicate the virus despite the fact that the major reduction in morbidity/and mortality of infectious diseases of the past century was achieved through the development of vaccines and improved hygiene. Conspiracy theories are directly associated with reduced vaccine uptake and unfortunately neither anti-vaxxers nor vaccine hesitants cannot be persuaded (debunked) with logical arguments; hence, prescribers must not only be aware of the truth underlying the dense web of misinformation but must fully understand the psychological aspects as well to be able to efficiently counsel about the potential benefits and harms. Such knowledge is pivotal to help the lay public to make informed decisions about SARS CoV-2 in general and vaccination in particular; as the COVID-19 situation can probably be best controlled with mass inoculation and novel immune therapies. The lessons learnt regarding the importance of efficient communication and the adherence to the proven epidemiological measures hopefully would be leaving us better prepared for the future if challenged by novel communicable diseases of pandemic potential.


Arabidopsis AZG2 transports cytokinins in vivo and regulates lateral root emergence.

Abstract: Cytokinin and auxin are key regulators of plant growth and development. During the last decade transport mechanisms have turned out to be the key for the control of local and long-distance hormone distributions. In contrast with auxin, cytokinin transport is poorly understood. Here, we show that Arabidopsis thaliana AZG2, a member of the AZG purine transporter family, acts as cytokinin transporter involved in root system architecture determination. Even though purines are substrates for both AZG1 and AZG2, we found distinct transport mechanisms. The expression of AZG2 is restricted to a small group of cells surrounding the lateral root (LR) primordia and induced by auxins. Compared to the wild-type (WT), mutants carrying loss-of-function alleles of AZG2 have higher LR density, suggesting that AZG2 is part of a regulatory pathway in LR emergence. Moreover, azg2 is partially insensitive to exogenous cytokinin, which is consistent with the observation that the cytokinin reporter TCSnpro :GFP showed lower fluorescence signal in the roots of azg2 compared to the WT. These results indicate a defective cytokinin signalling pathway in the region of LR primordia. The integration of AZG2 subcellular localization and cytokinin transport capacity data allowed us to propose a local cytokinin : auxin signalling model for the regulation of LR emergence.

D018506:Gene Expression Regulation, Plant

lateral root
auxin
development
cytokinin transport
AZG
lateral root overlying tissues
lateral root primordia
phytohormone


Effect of educational counseling alone on people with tinnitus: Meta-analysis of randomized controlled trials.

Abstract:
OBJECTIVE
To review and meta-analyze the efficacy of educational counseling alone in tinnitus.

METHODS
We collected randomized controlled trials (RCTs) adhered to PRISMA guidelines. Analyzed the effect of educational counseling alone versus other forms of therapy (psychological or combination) with RevMan 5.3.

RESULTS
In nine trials, 582 patients receiving educational counseling alone and 759 patients receiving other psychological or combination therapies. During the 3-6 months follow-up, there was no significant difference in the tinnitus recovery rate between these two groups (OR 0.62, 95% CI 0.34-1.16, P = 0.14; I2 = 71%, P = 0.00, random-effects model). The tinnitus symptom severity rates were also similar during 1-12 months follow-up (mean difference, 3.59, 95% CI -0.56-7.74, P = 0.09) with heterogeneity among studies (I2 = 74%, P = 0.00; random-effects model). Sensitivity analysis indicated that a single trial containing almost 40% of the patients was the cause of heterogeneity. There was no significant change in tinnitus loudness at the 3 months follow-up (OR 0.84, 95% CI 0.42-1.66, P = 0.61), with no significant heterogeneity (I2 = 0%, P = 0.60).

CONCLUSION
Educational counseling alone helps to improve tinnitus and related problems, and has the same effect as other psychological or combination therapies.

PRACTICE IMPLICATIONS
The results of the current analysis may help to develop evidence-based cost-effective treatment(s) for tinnitus, which will be minimally burdensome for the patients.

Xiang|Tao|T| Zhong|Juan|J| Lu|Tao|T| Pu|Jun-Mei|JM| Liu|Lu|L| Xiao|Yan|Y| Lai|Dan|D|

D016032:Randomized Controlled Trials as Topic

Education Counseling Tinnitus Review Psychotherapy


Outcomes Using a Postoperative Protocol in Pediatric Single-Stage Laryngotracheal Reconstruction.

Abstract:
OBJECTIVES
The aim of this study was to evaluate single-stage laryngotracheal reconstruction (ssLTR) outcomes before and after the implementation of a postoperative care protocol in pediatric patients.

METHODS
A case-control study with chart review was conducted at 2 tertiary academic centers from 2010 to 2016. Pediatric patients who underwent ssLTR with a postoperative care protocol were compared with those who did not receive care under this protocol. Data regarding perioperative management were collected and compared using χ2 and Wilcoxon rank tests. Planned extubation, length of intubation in the intensive care unit, and complications were examined.

RESULTS
Nineteen patients completed ssLTR after the protocol was initiated, and 26 prior patients were used as control subjects. Planned extubation failed in 9 patients (35%) in the control group compared with 1 patient (5%) in the protocol group (P < .05). Using a structured protocol demonstrated a decrease in delayed extubation and intensive care unit stay (P < .05). Despite more postprotocol patients' requiring posterior graft placement, preprotocol patients were less likely to be extubated within 7 days (P < .05).

CONCLUSIONS
The authors propose an intensive care unit protocol that uses a combination of pharmacologic agents to optimally reduce the risk for adverse events that delay time to extubation and thus decannulation. Timely extubation was more likely with the use of this postoperative care protocol using a multidisciplinary approach involving otolaryngologists, pharmacists, intensivists, and anesthesiologists.

intensive care
airway reconstruction
child
laryngeal stenosis
pediatric airway
treatment outcomes


Loss of H3K27me3 in meningiomas.

Abstract:
BACKGROUND
There is a critical need for objective and reliable biomarkers of outcome in meningiomas beyond WHO classification. Loss of H3K27me3 has been reported as a prognostically unfavorable alteration in meningiomas. We sought to independently evaluate the reproducibility and prognostic value of H3K27me3 loss by immunohistochemistry (IHC) in a multicenter study.

METHODS
IHC staining for H3K27me3 and analyses of whole slides from 181 meningiomas across three centers was performed. Staining was analyzed by dichotomization into loss and retained immunoreactivity, and using a 3-tiered scoring system in 151 cases with clear staining. Associations of grouping with outcome were performed using Kaplan-Meier survival estimates.

RESULTS
A total of 21 of 151 tumors (13.9%) demonstrated complete loss of H3K27me3 staining in tumor with retained endothelial staining. Overall, loss of H3K27me3 portended a worse outcome with shorter times to recurrence in our cohort, particularly for WHO grade 2 tumors which were enriched in our study. There were no differences in recurrence-free survival (RFS) for WHO grade 3 patients with retained vs loss of H3K27me3. Scoring by a 3-tiered system did not add further insights into the prognostic value of this H3K27me3 loss. Overall, loss of H3K27me3 was not independently associated with RFS after controlling for WHO grade, extent of resection, sex, age, and recurrence status of tumor on multivariable Cox regression analysis.

CONCLUSIONS
Loss of H3K27me3 identifies a subset of WHO grade 2 and possibly WHO grade 1 meningiomas with increased recurrence risk. Pooled analyses of a larger cohort of samples with standardized reporting of clinical definitions and staining patterns are warranted.

Nassiri|Farshad|F|
Wang|Justin Z|JZ|
Singh|Olivia|O|
Karimi|Shirin|S|
Dalcourt|Tatyana|T|
Ijad|Nazanin|N|
Pirouzmand|Neda|N|
Ng|Ho-Keung|HK|
Saladino|Andrea|A|
Pollo|Bianca|B|
Dimeco|Francesco|F|
Yip|Stephen|S|
Gao|Andrew|A|
Aldape|Kenneth D|KD|
Zadeh|Gelareh|G|
|||

meningioma immunohistochemistry H3K27 trimethylation


Functional analysis of StDWF4 gene in response to salt stress in potato.

Abstract: The DWARF4 (DWF4) gene encodes a C-22 hydroxylase which is pivotal for brassinosteroids (BRs) biosynthesis. In this research, aimed to understand the molecular mechanism of DWF4 on regulation of potatoes tolerance to salt stress, DWF4 was cloned from potato, named as StDWF4. Its 1476 bp open reading frame encodes a protein of 491 amino acids. The StDWF4-overexpressing (OE) and interference-expressing (RNAi) transgenic potato plants were acquired using Agrobacterium-mediated transformation, respectively. Tissue specific analysis using Quantitative real-time polymerase chain reaction (qRT-PCR) demonstrated that the StDWF4 gene expressed in the leaves, stems and roots of the transgenic and un-transgenic (NT) plants, with specially increased (StDWF4-OE)/reduced (StDWF4-RNAi) expression in the roots. The content of malondialdehyde (MDA) in StDWF4-OE potato plants was lower than that of NT, and proline content was higher than that of NT. MDA and proline content in StDWF4-OE and NT under salt-stress was significantly higher than that of the control and was increased at different sampling times. The content of soluble protein, soluble sugar and the activities of superoxide dismutase (SOD), peroxidase (POD) and ascorbate peroxidase (APX) was higher in the StDWF4-OE plantlets at varied salt treatment time than in the NT potatoes. Reduction of H2O2 content in the StDWF4-OE plants was observed. All above plant physiology indicators in the StDWF4-RNAi potatoes showed opposite variation trends. The results proved that the overexpressing of StDWF4 in potato plantlets can enhance the salt resistance by alleviating the negative effects of salt-stress. However, its interference expression in potato plants depresses the salt resistance. The results lay the groundwork for intensive study of BRs regulation in potato growth and development, and will help us to reveal the molecular mechanisms of how the BRs signaling regulate potato salt tolerance.

Zhou|Xiangyan|X| Zhang|Ning|N| Yang|Jiangwei|J| Tang|Xun|X| Wen|Yikai|Y| Si|Huaijun|H|

D010940:Plant Proteins
D055049:Salt Tolerance
D012965:Sodium Chloride
D011198:Solanum tuberosum
D013312:Stress, Physiological

StDWF4 gene
Brassinosteroids
Salt-stress
Antioxidant enzymes
Potato (Solanum tuberosum L.)


Number of teeth, denture wearing and cognitive function in relation to nutritional status in residents of nursing homes.

Abstract:
BACKGROUND
Although statistical associations between tooth loss and cognitive decline have been reported, there are few previous studies on denture wearing. Additionally, it remains unclear whether nutritional status mediates this association.

OBJECTIVE
Our purpose was to test for the hypothesis that the association between the number of teeth and denture wearing with cognitive function is mediated by nutritional status in residents of nursing homes.

MATERIALS AND METHODS
We enrolled 162 participants who required long-term care (mean age: 87.7 ± 7.5 years, 26 men and 136 women) and were admitted to eight nursing homes in Fukuoka city, from September 2013 to March 2014. A trained dentist conducted dental and swallowing examinations, and the care-staff assessed nutritional status, comorbid conditions and cognitive function using the Clinical Dementia Rating (CDR).

RESULTS
Poisson regression analysis showed that 0-19 teeth without dentures were associated with severe cognitive impairment (CDR 3) (prevalence ratio = 2.00; 95% confidence interval: 1.13-3.55) after adjustment for sex, age, suspected swallowing dysfunction and comorbid conditions. Mediation analysis confirmed that the nutritional status as a mediator of this association (the percentage mediated effect through nutritional status was 23.1%).

CONCLUSION
There is an association between dental status and cognitive impairment in elder individuals, and dentures and poor nutrition are involved in this association. However, due to the cross-sectional design of this study, there is a possibility that this association is bidirectional.

denture wearing
cognitive function
nutritional status
elders requiring long-term care


Nimesulide induced leukocytoclastic vasculitis and hepatitis: a case report.

Abstract:
BACKGROUND
Nimesulide is a non-steroidal anti-inflammatory drug with antipyretic and analgesic properties, which is still used in many countries despite its known hepatotoxicity. Along with hepatotoxicity it has also been associated with several other Adverse Drug Reactions (ADRs) including leukocytoclastic vasculitis (LCV).

CASE DESCRIPTION
A 38 year-old female presented with history of acute onset fever for which she took tablet nimesulide and paracetamol combination (100 mg Nimesulide + 500 mg paracetamol tablet), 1 tab three times daily for 4 days, following which she developed rash all over the body. She also had clinical and biochemical evidence of acute hepatitis. Histopathological examination of the skin rash documented the presence of LCV. She was managed symptomatically with anti-inflammatory and supportive therapy and was not further exposed to nimesulide.

DISCUSSION AND EVALUATION
Our case demonstrates occurrence of acute hepatitis and LCV associated with nimesulide intake. The case meets the defining criteria for the diagnosis of LCV preceded by history of nimesulide intake. There was also clinical and biochemical evidence of hepato-cellular damage which supports the concurrent development of hepatitis along with the development of LCV following nimesulide use. To the best of our knowledge there is no previous published report of LCV and hepatitis occurring concurrently in the same patient following nimesulide intake. Nimesulide should be added to the list of agents associated with these serious adverse drug reactions.

CONCLUSIONS
Nimesulide has been a contentious drug over many years. Under such evidence of serious ADRs the scientific community should consider ensuring strict pharmacovigilance with respect to its use especially in the developing countries where such monitoring systems are inadequate.

Nimesulide
Leukocytoclastic vasculitis
Hepatitis
Adverse drug reaction
Pharmacovigilence


Multiple comparisons for survival data with propensity score adjustment.

Abstract: This article considers the practical problem in clinical and observational studies where multiple treatment or prognostic groups are compared and the observed survival data are subject to right censoring. Two possible formulations of multiple comparisons are suggested. Multiple Comparisons with a Control (MCC) compare every other group to a control group with respect to survival outcomes, for determining which groups are associated with lower risk than the control. Multiple Comparisons with the Best (MCB) compare each group to the truly minimum risk group and identify the groups that are either with the minimum risk or the practically minimum risk. To make a causal statement, potential confounding effects need to be adjusted in the comparisons. Propensity score based adjustment is popular in causal inference and can effectively reduce the confounding bias. Based on a propensity-score-stratified Cox proportional hazards model, the approaches of MCC test and MCB simultaneous confidence intervals for general linear models with normal error outcome are extended to survival outcome. This paper specifies the assumptions for causal inference on survival outcomes within a potential outcome framework, develops testing procedures for multiple comparisons and provides simultaneous confidence intervals. The proposed methods are applied to two real data sets from cancer studies for illustration, and a simulation study is also presented.

Multiple comparisons
Causal inference
Simultaneous confidence intervals
Propensity score stratification


DnaG Primase-A Target for the Development of Novel Antibacterial Agents.

Abstract: The bacterial primase-an essential component in the replisome-is a promising but underexploited target for novel antibiotic drugs. Bacterial primases have a markedly different structure than the human primase. Inhibition of primase activity is expected to selectively halt bacterial DNA replication. Evidence is growing that halting DNA replication has a bacteriocidal effect. Therefore, inhibitors of DNA primase could provide antibiotic agents. Compounds that inhibit bacterial DnaG primase have been developed using different approaches. In this paper, we provide an overview of the current literature on DNA primases as novel drug targets and the methods used to find their inhibitors. Although few inhibitors have been identified, there are still challenges to develop inhibitors that can efficiently halt DNA replication and may be applied in a clinical setting.

Ilic|Stefan|S| Cohen|Shira|S| Singh|Meenakshi|M| Tam|Benjamin|B| Dayan|Adi|A| Akabayov|Barak|B|0000-0002-3882-2742

antibacterial agents
antibiotics
DNA replication
DnaG primase
bacterial inhibitors


In-depth assessment of health-related quality of life after in-hospital cardiac arrest.

Abstract:
INTRODUCTION
Evidence on physical and psychological well-being of in-hospital cardiac arrest (IHCA) survivors is scarce. The aim of this study is to describe long-term health-related quality of life (HRQoL), functional independence and psychological distress 3 and 12 months post-IHCA.

METHODS
A multicenter prospective cohort study in 25 hospitals between January 2017 - May 2018. Adult IHCA survivors were included. HRQoL (EQ-5D-5L, SF-12), psychological distress (HADS, CSI) and functional independence (mRS) were assessed at 3 and 12 months post-IHCA.

RESULTS
At 3-month follow-up 136 of 212 survivors responded to the questionnaire and at 12 months 110 of 198 responded. The median (IQR) EQ-utility Index score was 0.77 (0.65-0.87) at 3 months and 0.81 (0.70-0.91) at 12 months. At 3 months, patients reported a median SF-12 (IQR) physical component scale (PCS) of 38.9 (32.8-46.5) and mental component scale (MCS) of 43.5 (34.0-39.7) and at 12 months a PCS of 43.1 (34.6-52.3) and MCS 46.9 (38.5-54.5).

DISCUSSION
Using various tools most IHCA survivors report an acceptable HRQoL and a substantial part experiences lower HRQoL compared to population norms. Our data suggest that younger (male) patients and those with poor functional status prior to admission are at highest risk of impaired HRQoL.

Schluep|M|M|
Endeman|H|H|
Gravesteijn|B Y|BY|
Kuijs|C|C|
Blans|M J|MJ|
van den Bogaard|B|B|
Van Gemert|A W M M Koopman|AWMMK|
Hukshorn|C J|CJ|
van der Meer|B J M|BJM|
Knook|A H M|AHM|
van Melsen|T|T|
Peters|R|R|
Simons|K S|KS|
Spijkers|G|G|
Vermeijden|J W|JW|
Wils|E-J|EJ|
Stolker|R J|RJ|
Hoeks|S E|SE|

Health-related quality of life
In-hospital cardiac arrest
Patient-reported outcome measures
Psychological wellbeing


The CTGF gene -945 G/C polymorphism is associated with target lesion revascularization for in-stent restenosis.

Abstract:
BACKGROUND AND AIMS
Previous studies have shown that transforming growth factor β (TGF-β) and vascular endothelial growth factor A (VEGF-A) pathways are involved in the in-stent restenosis (ISR) process. The present study aimed to assess the relationship between single-nucleotide polymorphisms (SNPs) in genes encoding downstream proteins of TGF-β and VEGF-A pathways and the risk of target lesion revascularization (TLR) for in-stent restenosis.

METHODS
A total of 657 patients (with 781 treated lesions) who underwent percutaneous coronary intervention (PCI) with stent implantation at our center between 2007 and 2012 and completed a 4-year follow-up for clinically-driven TLR, were included. SNPs in CTGF (rs6918698), TGFBR2 (rs2228048), SMAD3 (rs17293632), KDR (rs2071559), CCL2 (rs1024610) were genotyped using TaqMan assay.

RESULTS
Major allele carriers of CTGF gene -945 G/C polymorphism (rs6918698) were significantly less likely to underwent clinically-driven TLR during follow-up than minor allele carriers. After adjustment for clinical, angiographic, and procedural covariates, CTGF polymorphism was significantly associated with TLR, and minor allele (C) carriers had nearly two times higher risk of developing ISR requiring TLR (HR of 1.93, 95%CI 1.15-3.24) compared to patients with major (GG) genotype. No significant relationship was found between other analyzed polymorphisms and cumulative incidence of TLR at 4-years.

CONCLUSIONS
Our results suggest that functional -945 G/C polymorphism in the gene encoding connective tissue growth factor is associated with the need for TLR in patients who underwent PCI for stable coronary artery disease.

Bujak|Kamil|K| Lejawa|Mateusz|M| Gąsior|Mariusz|M| Osadnik|Tadeusz|T|


pH-dependent anticancer drug release from silk nanoparticles.

Abstract: Silk has traditionally been used as a suture material because of its excellent mechanical properties and biocompatibility. These properties have led to the development of different silk-based material formats for tissue engineering and regenerative medicine. Although there have been a small number of studies about the use of silk particles for drug delivery, none of these studies have assessed the potential of silk to act as a stimulus-responsive anticancer nanomedicine. This report demonstrates that an acetone precipitation of silk allows the formation of uniform silk nanoparticles (98 nm diameter, polydispersity index 0.109), with an overall negative surface charge (-33.6 ± 5.8 mV), in a single step. Silk nanoparticles are readily loaded with doxorubicin (40 ng doxorubicin/μg silk) and show pH-dependent release (pH 4.5≫ 6.0 > 7.4). In vitro studies with human breast cancer cell lines demonstrates that the silk nanoparticles are not cytotoxic (IC50 > 120 μg mL(-1) ) and that doxorubicin-loaded silk nanoparticles are able to overcome drug resistance mechanisms. Live cell fluorescence microscopy studies show endocytic uptake and lysosomal accumulation of silk nanoparticles. In summary, the pH-dependent drug release and lysosomal accumulation of silk nanoparticles demonstrate the ability of drug-loaded silk nanoparticles to serve as a lysosomotropic anticancer nanomedicine.

Seib|F Philipp|FP|
Jones|Gregory T|GT|
Rnjak-Kovacina|Jelena|J|
Lin|Yinan|Y|
Kaplan|David L|DL|

nanomedicine
adriamycin
bombyx mori
fibroin


Diagnostic, clinical, and personality correlates of food anxiety during a food exposure in patients diagnosed with an eating disorder.

Abstract:
BACKGROUND
Eating disorders are characterized by high levels of anxiety, especially while eating. However, little is known about anxiety experienced during meals and specifically what other variables may impact such anxiety.

OBJECTIVE
We sought to further quantify and understand the relationship between food anxiety, eating disorders, and related correlates (e.g., comorbid diagnoses, personality).

METHODS
In the current study [N = 42 participants diagnosed with an eating disorder (n = 36 participants with anorexia nervosa)], we quantified anxiety before, during, and after a meal using data from a food exposure session in a partial hospital eating disorder center. We examined diagnostic, personality, and clinical factors as correlates of food anxiety.

RESULTS
Participants were more likely to experience higher food anxiety if they had a current diagnosis of major depression, obsessive-compulsive disorder, or post-traumatic stress disorder (PTSD). Concern over mistakes was the strongest and most consistent correlate of food anxiety regardless of time during the meal that anxiety was assessed. Other significant correlates were fear of positive evaluation, social appearance anxiety, BMI, and trust.

CONCLUSIONS
These findings show how diagnoses, perfectionism (concern over mistakes), and other correlates relate to anxiety during meals. Food exposure interventions may benefit from personalizations that address these factors.

LEVEL OF EVIDENCE
IV Evidence from a randomized control trial, but from the first session before effects of the design would be present.

Anorexia nervosa
Social appearance anxiety
Perfectionism
Exposure therapy
Fear of food


Teacher Online Informal Learning as a Means to Innovative Teaching During Home Quarantine in the COVID-19 Pandemic.

Abstract: The home quarantine in the COVID-19 pandemic has created challenges for teaching across the world and called for innovative teaching, as well as teachers' learning. Given the rapid development of teachers' online learning and teaching, identifying effective ways to facilitate innovative teaching under such challenging conditions is a critical issue. Although researchers have realized that workplace informal learning (IL) increasingly reveals its potential value to individual development, the relationship between IL and innovation has been under-explored. The purpose of this study was to evaluate the impact of IL on innovative teaching, through the mediating roles of three types of teaching-related efficacy, with a particular focus on college teachers and online context. A sample of 479 Chinese college teachers was randomly selected to participate in the survey. The results showed that teachers' online IL in pandemic improved their personal teaching efficacy and ICT efficacy (information and communication technology efficacy), and then facilitated their innovative teaching without differences of gender and teaching-age effect. Whereas, general teaching efficacy was not a mediator between online IL and innovative teaching. Hence, we proposed a can-do motivating model of teacher efficacy in fostering innovative teaching through informal learning. It implies three properties of teachers' online IL: social interaction, autonomous learning and novelty-seeking. It also revealed that innovative teaching can be driven in COVID-19 pandemic, mainly by learning domain-specific knowledge and skills, thus enhancing personal teaching efficacy and ICT efficacy in online teaching context.

Yu|Haiqin|H| Liu|Ping|P| Huang|Xiaoqing|X| Cao|Yuxi|Y|

informal learning
innovative teaching
personal teaching efficacy
ICT efficacy
general teaching efficacy
faculty
online teaching and learning


Can yoga have any effect on shoulder and arm pain and quality of life in patients with breast cancer? A randomized, controlled, single-blind trial.

Abstract:
OBJECTIVE
To examine the effects of yoga on shoulder and arm pain, quality of life (QOL), depression, and physical performance in patients with breast cancer.

METHODS
This prospective, randomized study included 42 patients. The patients in Group 1 underwent a 10-week Hatha yoga exercise program. The patients in Group 2 were included in a 10-week follow-up program. Our primary endpoint was arm and shoulder pain intensity.

RESULTS
The group receiving yoga showed a significant improvement in their pain severity from baseline to post-treatment, and these benefits were maintained at 2.5 months post-treatment. When compared to the control group, there were no statistically significant differences between the 2 groups with respect to the parameters assessed at the end of week 10.

CONCLUSION
Yoga was an effective and safe exercise for alleviating shoulder and arm pain, which is a complication with a high prevalence in patients with breast cancer.

Eyigor|Sibel|S| Uslu|Ruchan|R| Apaydın|Sebnem|S| Caramat|Ismail|I| Yesil|Hilal|H|

Yoga
Pain
Quality of life
Breast cancer
Exercise


Ecological quality and its relationships with human activities in China-Laos railway economic belt.

Abstract: Regional ecological quality is largely affected by human activities, which restricts the sustainable development of regional economy. Taking the China-Laos railway economic belt as an example, we investigated the effects of human activities on ecological quality. The remote sensing images of 1999, 2009 and 2019 were selected to calculate remote sensing ecological index (RSEI). Spatial autocorrelation statistics and local G statistics were used to explore the spatial-temporal variations of ecological quality in the study area. Combined with the population density in the same period, a geographically weighted regression model was constructed to quantitatively analyze the ecological effects of different human activity intensities in the study area. The results showed that the ecological quality in the study area presented a trend of increasing firstly and then decreasing later from 1999 to 2019, and that the mean value of RSEI varied from 0.645 (1999) to 0.738 (2009) and then decreasing to 0.721 in 2019. Specially, the ecological quality fluctuated more apparently in the midlands. The results of fitting population density and ecological quality based on geographical weighted regression model (GWR) were significantly better than that of least square method. R2 of different periods based on GWR was higher than 0.7 and the fitting effect was stable. The fitting degree of GWR in 2019 was the best (R2 was 0.785), and R2 in 1999 and 2009 were 0.726 and 0.754, respectively. The ecological quality along the China-Laos railway south area (such as Vientiane) was more sensitive to human activities, with most of these places belonged to moderately sensitive regions. For the highly, moderately and lowly ecological sensitive regions, every 10, 100, 1000-fold increases in population density would lead to a decrease of 0.2, 0.4 and 0.6 to the mean value of RSEI in turn. The development of economic belt would increase population density. During the planning and layout of economic belt, human activities should be controlled to avoid the deterioration of ecological quality in the potential and current sensitive regions.

Xue|Chen-Li|CL| Zhang|Hui-Qiong|HQ| Zou|Tao|T| Sun|Zi-Jian|ZJ| Cheng|Xi-Yin|XY|

remote sensing-based ecological index (RSEI)


Contrast-enhanced ultrasonography.

Abstract: Review summarizes state of the art of contrast-enhanced ultrasonography (CEUS), pinpoints technical basics and also economical comparison with other imaging methods. Most often indications of CEUS in different anatomical regions with differential diagnosis are discussed.

Mechl|Marek|M| Šprláková-Puková|Andrea|A| Foukal|Jakub|J| Šmajerová|Miriam|M| Bohatá|Šárka|Š| Válek|Vlastimil|V|

D003287:Contrast Media
D003937:Diagnosis, Differential
D014463:Ultrasonography

contrast agent imaging methods.
ultrasound


Journal subscription expenditure of UK higher education institutions.

Abstract: The academic libraries of higher education institutions (HEIs) pay significant amounts of money each year for access to academic journals. The amounts paid are often not transparent especially when it comes to knowing how much is paid to specific publishers. Therefore data on journal subscription expenditure were obtained for UK HEIs using a series of Freedom of Information requests. Data were obtained for 139 HEIs' expenditure with seven publishers over a five-year period. The majority of institutions have provided figures but some are still outstanding. The data will be of interest to those who wish to understand the economics of scholarly communication and see the scale of payments flowing within the system. Further research could replicate the data collection in other jurisdictions.

Journals
subscription
higher education institution


Identification of a five-gene signature of the RGS gene family with prognostic value in ovarian cancer.

Abstract: The RGS (regulator of G protein signaling) gene family, which includes negative regulators of G protein-coupled receptors, comprises important drug targets for malignant tumors. It is thus of great significance to explore the value of RGS family genes for diagnostic and prognostic prediction in ovarian cancer. The RNA-seq, immunophenotype, and stem cell index data of pan-cancer, The Cancer Genome Atlas (TCGA) data, and GTEx data of ovarian cancer were downloaded from the UCSC Xena database. In the pan-cancer database, the expression level of RGS1, RGS18, RGS19, and RGS13 was positively correlated with stromal and immune cell scores. Cancer patients with high RGS18 expression were more sensitive to cyclophosphamide and nelarabine, whereas those with high RGS19 expression were more sensitive to cladribine and nelarabine. The relationship between RGS family gene expression and overall survival (OS) and progression-free survival (PFS) of ovarian cancer patients was analyzed using the KM-plotter database, RGS17, RGS16, RGS1, and RGS8 could be used as diagnostic biomarkers of the immune subtype of ovarian cancer, and RGS10 and RGS16 could be used as biomarkers to predict the clinical stage of this disease. Further, Lasso cox analysis identified a five-gene risk score (RGS11, RGS10, RGS13, RGS4, and RGS3). Multivariate COX analysis showed that the risk score was an independent prognostic factor for patients with ovarian cancer. Immunohistochemistry and the HPA protein database confirmed that the five-gene signature is overexpressed in ovarian cancer. GSEA showed that it is mainly involved in the ECM-receptor interaction, TGF-beta signaling pathway, Wnt signaling pathway, and chemokine signaling pathway, which promote the occurrence and development of ovarian cancer. The prediction model of ovarian cancer constructed using RGS family genes is of great significance for clinical decision making and the personalized treatment of patients with ovarian cancer.

Hu|Yuexin|Y| Zheng|Mingjun|M| Wang|Shuang|S| Gao|Lingling|L| Gou|Rui|R| Liu|Ouxuan|O| Dong|Hui|H| Li|Xiao|X| Lin|Bei|B|


The accuracy of mean corpuscular volume guided anaemia classification in primary care.

Abstract:
BACKGROUND
Anemia can be categorized into micro-, normo- or macrocytic anemia based on the mean corpuscular volume (MCV). This categorization might help to define the etiology of anemia.

METHODS
The cohort consisted of patients newly diagnosed with anaemia in primary care. Seven aetiologies of anaemia were defined, based on an extensive laboratory protocol. Two assumptions were tested: (i) MCV <80 fl (microcytic) excludes vitamin B12 deficiency, folic acid deficiency, suspected haemolysis and suspected bone marrow disease as anaemia aetiology. (ii) MCV >100 fl (macrocytic) excludes iron deficiency anaemia, anaemia of chronic disease and renal anaemia as anaemia aetiology.

RESULTS
Data of 4129 patients were analysed. One anaemia aetiology could be assigned to 2422 (59%) patients, more than one anaemia aetiology to 888 (22%) patients and uncertainty regarding the aetiology remained in 819 (20%) patients. MCV values were within the normal range in 3505 patients (85%). In 59 of 365 microcytic patients (16%), the anaemia aetiology was not in accordance with the first assumption. In 233 of 259 macrocytic patients (90%), the anaemia aetiology was not in accordance with the second assumption.

CONCLUSIONS
Anaemia aetiologies might be ruled out incorrectly if MCV guided classification is used as a first step in the diagnostic work-up of anaemia. We recommend using a broader set of laboratory tests, independent of MCV.

Schop|Annemarie|A|0000-0002-9786-2672
Stouten|Karlijn|K|
Riedl|Jürgen A|JA|
van Houten|Ron J|RJ|
Leening|Maarten J G|MJG|
Bindels|Patrick J E|PJE|
Levin|Mark-David|MD|

Anaemia
primary care
blood chemical analysis
clinical pathology
erythrocyte indices
practice guideline


Assessment of patient understanding of their medicines: interviews with community dwelling older Australians.

Abstract:
OBJECTIVE
To identify patterns of medication load, client's care team, coordination of healthcare and clients' understanding of their medications.

METHODS
Face-to-face interviews were conducted with community-dwelling older Australians between June and August 2017 in three community pharmacies in Adelaide, South Australia.

KEY FINDINGS
Forty interviews were conducted. On average, participants were taking 7.53 medicines with 77.5% using five or more regularly. Lack of collaboration between healthcare professionals, need for increased communication between prescribers and increased patient education on medicines, were highlighted. This study demonstrates that polypharmacy and inappropriate prescribing are occurring within the community pharmacy setting, but shows insight into how these concerns can be overcome, by implementing pharmacist-led services such as non-dispensing pharmacists in community pharmacies.

CONCLUSION
Careful consideration when prescribing and effective communication are required to minimise risks associated with polypharmacy in this population.

D007722:Health Knowledge, Attitudes, Practice

community dwelling
older Australians
polypharmacy
medication use


The value of powered mobility scooters from the perspective of elderly spouses of the users - a qualitative study.

Abstract:
PURPOSE
To explore spouses' experiences of the value of mobility scooters prescribed to their partner.

MATERIAL AND METHODS
A descriptive design with a qualitative approach was used. Thirteen spouses (11 females) aged 65-86 years participated. Semi-structured interviews were conducted when the spouse's partner had had the mobility scooter for 4-6 months. The interviews were analysed using qualitative content analysis.

RESULTS
The interviews showed primarily that the spouses experienced that their everyday lives and life situation had improved since their partner had received a mobility scooter. They reported that they could engage in activities of their own choice to a greater extent. The prescription of a mobility scooter to their partner had also yielded a sense of freedom related to shared activities. On the other hand, the spouses described some of the scooter's limitations. Three categories emerged: a sense of freedom related to the spouse's own activities, a sense of freedom related to shared activities and a somewhat restricted freedom.

CONCLUSION
Prescription of a powered mobility scooter was of value to the users' spouses because it facilitated independent and shared activities and participation in the community. The value was mainly expressed as a sense of freedom when doing things on their own or together with their partner. Spouses are key persons in the rehabilitation of people with mobility restrictions. Their views on the assistive device may influence the rehabilitation process. Knowledge of spouses' experiences is thus crucial, as this may influence the future rehabilitation outcome.IMPLICATIONS FOR REHABILITATIONA powered mobility scooter prescribed to one partner eases everyday life and increases activity and participation for the spouse, which in turn may further improve the quality of life for the scooter user.The spouses' perspectives on their partners' mobility scooter use could be helpful in developing the design of the mobility device and in the prescription process.A mobility scooter has an added value by giving a sense of freedom and freedom to choose for the spouse as well as the scooter user.

Fredriksson|Carin|C| Pettersson|Ingvor|I| Hagberg|Lars|L| Hermansson|Liselotte|L|

aged
Assistive technology
ICF
mobility limitation
powered mobility devices


Effects of working memory on naturally occurring cravings.

Abstract: Elaborated Intrusion (EI) theory posits a key role for visuospatial working memory (WM) in craving. In line with the predictions of EI theory, several studies have found that WM and craving show mutually interfering effects - for example, performance of visuospatial WM tasks has been found to attenuate naturally occurring cravings. However, the extent to which these effects are driven specifically by visuospatial processing remains unclear. We conducted two experiments to investigate the effects of WM on naturally occurring cravings in more detail. In experiment 1, we examined whether such effects are driven specifically by visuospatial WM processes or can also be induced by a verbal WM task. Subjective craving ratings were attenuated equally by performance of visuospatial and verbal WM tasks, suggesting that craving is not dependent specifically on visuospatial processing. In experiment 2, we examined whether effects of visuospatial WM on craving could be driven by simple distraction. Naturally occurring cravings were attenuated in a control condition with minimal WM demands (watching a video). However, the magnitude of attenuation was significantly greater in a visuospatial WM condition. Taken together, these findings highlight a key role for WM in the attenuation of naturally occurring craving, but do not support the hypothesis that such effects are dependent specifically on visuospatial processing.

Dodds|Chris M|CM|
Magner|Bella|B|
Cooper|Emily|E|
Chesterman|Tara|T|
Findlay|Sophie|S|

Working memory
Craving
Addiction
Obesity


Antimicrobial potential of phylogenetically unique actinomycete, Streptomyces sp. JRG-04 from marine origin.

Abstract: Due to the emergence of severe infectious diseases and thriving antibiotic resistance, there is a need to explore microbial-derived bioactive secondary metabolites from unexplored regions. Present study deals with a mangrove estuary derived strain of Streptomyces sp. with potent antimicrobial activity against various pathogens, including methicillin resistant Staphylococcus aureus. Bioactive compound was effective even at low MIC level, damages the membrane of methicillin resistant S. aureus and causes cell death, however it has no cytotoxic effect on H9C2 cells. 16S rRNA shared 99.5% sequence similarity to Streptomyces longispororuber. Optimum biomass and antimicrobial compound production were observed in production medium supplemented with 1.0% maltose and 0.5% yeast extract. The active compound purified from the chloroform extract of the cell-free supernatant was studied by FT-IR, 1H NMR, 13C NMR and LC ESI-MS and identified as aromatic polyketide. β-ketosynthase (KS) domain of the Streptomyces strain revealed 93.2% sequence similarity to the benzoisochromanequinone, an actinorhodin biosynthetic gene cluster of Streptomyces coelicolor A3(2). However, the region synthesizing the secondary metabolite produced by the S. longispororuber was not related to the KS domain of the strain, due to the phenomenon of horizontal gene transfer over the period of evolutionary process, thus generating metabolic compound diversity.

Govindarajan|Ganesan|G|
Satheeja Santhi|Velayudhan|V|
Jebakumar|Solomon Robinson David|SR|

D021241:Spectrometry, Mass, Electrospray Ionization

D017550:Spectroscopy, Fourier Transform Infrared

Streptomyces
Mangrove
16S rRNA
Polyketide
Benzoisochromanequinone


Adolescents with a history of specific language impairment (SLI): strengths and difficulties in social, emotional and behavioral functioning.

Abstract: Adolescents with specific language impairment (SLI) are at a greater risk of emotional and behavioral problems compared to their typically developing (TD) peers, but little is known about their self-perceived strengths and difficulties. In this study, the self-reported social, emotional and behavioral functioning of 139 adolescents with a history of SLI and 124 TD individuals at age 16 was examined. The self-report version of the Strengths and Difficulties Questionnaire (SDQ) was used to assess their prosocial behavior and levels of peer, emotional and behavioral difficulties. Associations of these areas of functioning with gender, verbal and non-verbal skills were also investigated. Adolescents with a history of SLI were more likely than their TD peers to report higher levels of peer problems, emotional symptoms, hyperactivity and conduct problems. The majority of adolescents in both groups (87% SLI and 96% TD), however, reported prosocial behavior within the typical range. Difficulty with peer relations was the strongest differentiator between the groups, with the odds of reporting borderline or abnormally high levels of peer problems being 12 times higher for individuals with a history of SLI. Adolescents with poorer receptive language skills were also more likely to report higher levels of emotional and behavioral difficulties. The findings of this study identify likely traits that may lead to referral to services.

Conti-Ramsden|Gina|G|
Mok|Pearl L H|PL|
Pickles|Andrew|A|
Durkin|Kevin|K|

D000293:Adolescent
D000294:Adolescent Behavior
D000342:Affective Symptoms
D016022:Case-Control Studies
D019955:Conduct Disorder
D004644:Emotions
D006801:Humans
D007398:Interpersonal Relations
D007805:Language Development Disorders
D010379:Peer Group
D012649:Self Concept
D057566:Self Report
D012919:Social Behavior
D011795:Surveys and Questionnaires

Child and Adolescent Mental Health Services


A Review of New Medications and Future Directions of Medical Therapies in Glaucoma.

Abstract:
BACKGROUND
Glaucoma is one of the leading causes of blindness worldwide. Treatment is still largely targeted at lowering intraocular pressure. Intraocular pressures can be lowered through a variety of topical medications, lasers and incisional surgeries. There are currently several classes of topical medications available in the US that are aimed at lowering intraocular pressure through a variety of different mechanisms. Additionally, there have been numerous different formulations and fixed-dose combination medications that offer greatly expanded treatment options over the last several years. The wide variety of topical medications aim to address the issues with compliance, effectiveness and side effect profile that vary among each individual patient and disease.  Purpose: Three new topical medications, netarsudil 0.02%, latanoprostene bunod 0.24% and fixed-dose combination netarsudil 0.02% - latanoprost 0.005% have been approved in the US market to treat glaucoma. This review article will summarize the studies looking at their effectiveness and side effect profiles and discuss their utilization in the treatment of glaucoma. Additionally, we will briefly discuss future directions of research in topical glaucoma medications.

CONCLUSION
Three new topical glaucoma medications offer additional treatment options for patient with glaucoma. Further research is needed to better understand the utility of sustained release formulations in the treatment of glaucoma.

D000959:Antihypertensive Agents
D004338:Drug Combinations
D005901:Glaucoma
D006801:Humans
D007429:Intraocular Pressure
D009883:Ophthalmic Solutions
D017410:Practice Guidelines as Topic

Glaucoma
netarsudil
glaucoma drops
glaucoma therapy
new ocular medications


The first visually-guided bronchoscopy in European bison (Bison bonasus) - An additional tool in the diagnosis of bovine tuberculosis?

Abstract: The European bison (Bison bonasus, EB) is an endangered species, and as about 1/3 of its global population is found in Poland, it is particularly important that Polish herds should be monitored. One particular concern is tuberculosis, which is not a marginal problem in wildlife in Poland, and has been microbiologically confirmed in EB, wolves (Canis lupus) and wild boar (Sus scrofa). However, ante mortem diagnosis of tuberculosis in EB is troublesome. Therefore, the present paper evaluates the potential of bronchoscopy as a diagnostic tool. Seven EB were studied, four of which were found to be naturally infected with M. caprae; in two of these, endoscopy identified abnormalities in the respiratory tract ante mortem. Therefore, despite some limitations, endoscopy can be an additional tool for diagnosing tuberculosis in EB, especially in highly valuable animals, and to assess the stage of the disease.

Didkowska|Anna|A| Dziekan|Przemysław|P| Czujkowska|Agnieszka|A| Bereznowski|Andrzej|A| Witkowski|Lucjan|L| Orłowska|Blanka|B| Wiśniewski|Jan|J| Krzysiak|Michał|M| Krajewska-Wędzina|Monika|M| Bruczyńska|Małgorzata|M| Żychska|Monika|M| Olech|Wanda|W| Anusz|Krzysztof|K|

European bison
Bovine tuberculosis
Endoscopy
Ante-mortem diagnosis
Mycobacterium caprae


Biomarkers and Algorithms for the Diagnosis of Vitamin B12 Deficiency.

Abstract: Vitamin B12 (cobalamin, Cbl, B12) is an indispensable water-soluble micronutrient that serves as a coenzyme for cytosolic methionine synthase (MS) and mitochondrial methylmalonyl-CoA mutase (MCM). Deficiency of Cbl, whether nutritional or due to inborn errors of Cbl metabolism, inactivate MS and MCM leading to the accumulation of homocysteine (Hcy) and methylmalonic acid (MMA), respectively. In conjunction with total B12 and its bioactive protein-bound form, holo-transcobalamin (holo-TC), Hcy, and MMA are the preferred serum biomarkers utilized to determine B12 status. Clinically, vitamin B12 deficiency leads to neurological deterioration and megaloblastic anemia, and, if left untreated, to death. Subclinical vitamin B12 deficiency (usually defined as a total serum B12 of <200 pmol/L) presents asymptomatically or with rather subtle generic symptoms that oftentimes are mistakenly ascribed to unrelated disorders. Numerous studies have now established that serum vitamin B12 has limited diagnostic value as a stand-alone marker. Low serum levels of vitamin B12 not always represent deficiency, and likewise, severe functional deficiency of the micronutrient has been documented in the presence of normal and even high levels of serum vitamin B12. This review discusses the usefulness and limitations of current biomarkers of B12 status in newborn screening, infant and adult diagnostics, the algorithms utilized to diagnose B12 deficiency and unusual findings of vitamin B12 status in various human disorders.

Hannibal|Luciana|L|
Lysne|Vegard|V|
Bjørke-Monsen|Anne-Lise|AL|
Behringer|Sidney|S|
Grünert|Sarah C|SC|
Spiekerkoetter|Ute|U|
Jacobsen|Donald W|DW|
Blom|Henk J|HJ|

vitamin B12
cobalamin
homocysteine
methylmalonic acid
holo-transcobalamin
diagnostic algorithm
functional deficiency of B12


Association of depression with improper use of inhaler devices by patients with obstructive disease.

Abstract:
INTRODUCTION
Obstructive pulmonary disease may cause some psychiatric disorders such as depression, similar to other chronic diseases. Patients with chronic obstructive pulmonary disease or asthma are especially susceptible to inhaler technique errors. The aim of this study was to evaluate the depression that can affect improper use of inhaler devices and to show the contribution of age, sex, and education to correct usage.

MATERIALS AND METHODS
In this study, trained health care workers in the presence of Chest specialist requested patients to demonstrate their inhaler technique and assessed it according to the checklist. If any of the steps were missing or done incorrectly, it was marked as an incorrect technique.

RESULTS
We included 188 participants, mean age of 58.3 ± 12.7 years. Significant variables of individual risk were having comorbidities, age, sex, smoking status, and educational level. There was an inverse relationship between education level and incorrect inhaler technique. Even after controlling for age, gender, and education, depressive symptoms were a significant and independent predictor of improper use of inhaler devices. High levels of depressive symptoms were associated with a 22-fold increase (95% confidence interval, 8.9 to 53.5) in the odds of improper use of inhaler devices after adjustment for potential confounders.

CONCLUSIONS
As a result, the presence of depression symptoms may increase the improper use of inhaler devices. Further research is needed to determine if screening for and treating depression improves improper use of inhaler devices and obstructive disease outcomes in this population.

D029424:Pulmonary Disease, Chronic Obstructive

depression
obstructive pulmonary disease
inhaler technique
age


MRI-LINAC beam profile measurements using a plastic scintillation dosimeter.

Abstract: Plastic scintillation dosimeters (PSDs) possess many desirable qualities for dosimetry with LINACs. These qualities are expected to make PSDs effective for MRI-LINAC dosimetry, however little research has been conducted investigating their dosimetric performance with MRI-LINACs. In this work, an in-house PSD was used to measure 8 beam profiles with an in-line MRI-LINAC, compared with film measurements. One dimensional global gamma indices (γ) and corresponding γ pass rates were calculated to compare PSD and film profiles for the 1%/1 mm, 2%/2 mm and 3%/3 mm criterion. The mean global pass rates were 85.8%, 97.5% and 99.4% for the 1%/1 mm, 2%/2 mm and 3%/3 mm criteria, respectively. The majority of the γ failures occurred in the penumbral regions. Penumbra widths were measured to be slightly narrower with the PSD compared to film, however, the uncertainties in the measured penumbra widths brought the PSD and film penumbra widths into agreement. Differences in dose were calculated between the PSD and film, and remained within 2.2% global agreement for the central regions and 1.5% global agreement for out of field regions. These values for range of agreement were similar to the those reported in the literature for other dosimeters which are trusted for relative MRI-LINAC dosimetry.

Madden|Levi|L| Archer|James|J| Li|Enbang|E| Jelen|Urszula|U| Dong|Bin|B| Holloway|Lois|L| Rosenfeld|Anatoly|A|

D008279:Magnetic Resonance Imaging
D010315:Particle Accelerators
D010969:Plastics
D000072232:Radiation Dosimeters
D012588:Scintillation Counting

MRI-LINAC
Plastic scintillator
dosimetry
Fibre optic dosimeter


Action of trichostatin A on Alzheimer's disease-like pathological changes in SH-SY5Y neuroblastoma cells.

Abstract: The histone deacetylase inhibitor, trichostatin A, is used to treat Alzheimer's disease and can improve learning and memory but its underlying mechanism of action is unknown. To determine whether the therapeutic effect of trichostatin A on Alzheimer's disease is associated with the nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like epichlorohydrin-related protein-1 (Keap1) signaling pathway, amyloid β-peptide 25-35 (Aβ25-35) was used to induce Alzheimer's disease-like pathological changes in SH-SY5Y neuroblastoma cells. Cells were then treated with trichostatin A. The effects of trichostatin A on the expression of Keap1 and Nrf2 were detected by real-time quantitative polymerase chain reaction, western blot assays and immunofluorescence. Total antioxidant capacity and autophagy activity were evaluated by total antioxidant capacity assay kit and light chain 3-I/II levels, respectively. We found that trichostatin A increased cell viability and Nrf2 expression, and decreased Keap1 expression in SH-SY5Y cells. Furthermore, trichostatin A increased the expression of Nrf2-related target genes, such as superoxide dismutase, NAD(P)H quinone dehydrogenase 1 and glutathione S-transferase, thereby increasing the total antioxidant capacity of SH-SY5Y cells and inhibiting amyloid β-peptide-induced autophagy. Knockdown of Keap1 in SH-SY5Y cells further increased trichostatin A-induced Nrf2 expression. These results indicate that the therapeutic effect of trichostatin A on Alzheimer's disease is associated with the Keap1-Nrf2 pathway. The mechanism for this action may be that trichostatin A increases cell viability and the antioxidant capacity of SH-SY5Y cells by alleviating Keap1-mediated inhibition Nrf2 signaling, thereby alleviating amyloid β-peptide-induced cell damage.

Li|Li-Hua|LH| Peng|Wen-Na|WN| Deng|Yu|Y| Li|Jing-Jing|JJ| Tian|Xiang-Rong|XR|

total antioxidant capacity
autophagy
SH-SY5Y cells
Alzheimer’s disease
Keap1 signal
TSA
amyloid-βpeptide
neurocytotoxicity
oxidative stress damage
transcription factor Nrf2


Dorsal Cortical Breaks in Volar Barton Distal Radius Fractures.

Abstract: Background: Volar Barton fractures involve the volar articular margin of the distal radius with proximal and volar subluxation of the carpus. Although traditionally conceptualized as partial articular, some volar Barton fractures are complete articular injuries due to a dorsal cortical break in the distal radial metaphysis. While dorsal cortical breaks can affect surgical strategy, they may be difficult to identify on plain radiographs and their epidemiology remains poorly characterized. Some authors have hypothesized an association with osteoporosis; however, this hypothesis remains untested. To better characterize volar Barton fractures, we analyzed fracture geometry on pre-operative computed tomography (CT) scans to: (1) determine the frequency of a dorsal cortical break; and (2) test the null hypothesis that a dorsal cortical break is not associated with age or gender. Methods: We retrospectively reviewed adults with a volar Barton distal radius fracture and an available pre-operative CT who underwent surgical fixation. Using multivariable logistic regression, we assessed whether age or gender was an independent predictor of a dorsal cortical break. Results: Forty patients (mean age 52 years, 57% female) were identified. Including the shaft as a fragment, 32 (80%) had 3 or more discrete fracture fragments. Thirty patients (75%) had a dorsal cortical break. Dorsal cortical breaks were not associated with either age or gender (P > 0.05). Conclusions: Most (75%) patients with volar Barton distal radius fractures had a dorsal cortical break. Dorsal cortical breaks were not statistically associated with age or gender, suggesting these fracture patterns may not be associated with osteoporosis as previously hypothesized.

dorsal cortical break
Volar Barton
distal radius fracture
computed tomography
volar rim fracture
volar shearing fracture


Development of a combined in vitro cell culture--quantitative PCR assay for evaluating the disinfection performance of pulsed light for treating the waterborne enteroparasite Giardia lamblia.

Abstract: Giardia lamblia is a flagellated protozoan parasite that is recognised as a frequent cause of water-borne disease in humans and animals. We report for the first time on the use of a combined in vitro HCT-8 cell culture-quantitative PCR assay for evaluating the efficacy of using pulsed UV light for treating G. lamblia parasites. Findings showed that current methods that are limited to using vital stains before and after cyst excystation are not appropriate for monitoring or evaluating cyst destruction post PUV-treatments. Use of the human ileocecal HCT-8 cell line was superior to that of the human colon Caco-2 cell line for in vitro culture and determining PUV sensitivity of treated cysts. G. lamblia cysts were also shown to be more resistant to PUV irradiation compared to treating similar numbers of Cryptosporidium parvum oocysts. These observations also show that the use of this HCT-8 cell culture assay may replace use of animal models for determining disinfection performances of PUV for treating both C. parvum and G. lamblia.

D060888:Real-Time Polymerase Chain Reaction

In vitro
Giardia lamblia
Cell culture
Pulsed UV inactivation
Real time PCR


Operation Mechanism in Hybrid Mg-Li Batteries with TiNb2O7 Allowing Stable High-Rate Cycling.

Abstract: We studied the structural evolution and cycling behavior of TiNb2O7 (TNO) as a cathode in a nonaqueous hybrid dual-salt Mg-Li battery. A very high fraction of pseudocapacitive contribution to the overall specific capacity makes the material suitable for ultrafast operation in a hybrid battery, composed of a Mg-metal anode, and a dual-salt APC-LiCl electrolyte with Li and Mg cations. Theoretical calculations show that Li intercalation is predominant over Mg intercalation into the TNO in a dual-salt electrolyte with Mg2+ and Li+, while experimentally up to 20% Mg cointercalation was observed after battery discharge. In hybrid Mg-Li batteries, TNO shows capacities which are about 40 mA h g-1 lower than in single-ion Li batteries at current densities of up to 1.2 A g-1. This is likely due to a partial Mg cointercalation or/and location of Li cations on alternative crystallographic sites in the TNO structure in comparison to the Li-intercalation process in Li batteries. Generally, hybrid Mg-Li cells show a markedly superior applicability for a very prolonged operation (above 1000 cycles) with 100% Coulombic efficiency and a capacity retention higher than 95% in comparison to conventional Li batteries with TNO after being cycled either under a low (7.75 mA g-1) or high (1.55 A g-1) current density. The better long-term behavior of the hybrid Mg-Li batteries with TNO is especially pronounced at 60 °C. The reasons for this are an appropriate cathode electrolyte interface containing MgCl2 species and a superior performance of the Mg anode in APC-LiCl electrolytes with a dendrite-free, fast Mg deposition/stripping. This stable interface stands in contrast to the anode electrolyte interface in Li batteries with a Li anode in conventional carbonate-containing electrolytes, which is prone to dendrite formation, thus leading to a battery shortcut.

cathode electrolyte interface
fast Mg deposition/stripping
Li,Mg cointercalation
Wadsley-Roth phase
beyond lithium batteries concept
dual-salt batteries
pseudocapacitive storage


Evidence of validity for the Norwegian version of the interprofessional collaborative competency attainment survey (ICCAS).

Abstract: This was a validation study of the Norwegian version of The Interprofessional Collaborative Competency Attainment Survey (ICCAS). ICCAS consists of 20 retrospective pre- and post-questions, where respondents rate their agreement with regard to self-assessed competencies after participating in interprofessional education courses. It has been validated across various settings. The questionnaire was translated using the back-translation technique. We investigated evidence of validity regarding content, response process, and internal structure. Data were obtained from health and social care students (n = 1440, response rate 42.8%) participating in 12 different interprofessional courses in seven education institutions in Norway using a cross-sectional design. Exploratory factor analysis indicated one retracted factor for pre-scores and one retracted factor for post-scores. High McDonald's omega values indicated good internal consistency. Item deletion did not improve the scale's overall consistency on pre- or post-scores. We observed higher mean post-scores than pre-scores with moderate-to-large effect sizes, indicating a positive change in self-assessed interprofessional capabilities after training. Our findings indicate that the Norwegian version of ICCAS is a valid tool that may be implemented across a wide range of interprofessional education courses. Finally, our findings support earlier recommendations that ICCAS should be analyzed at an overall level to address change in interprofessional capabilities.

D003430:Cross-Sectional Studies
D005163:Factor Analysis, Statistical
D006801:Humans
D007400:Interprofessional Relations
D012189:Retrospective Studies
D011795:Surveys and Questionnaires

ICCAS
Interprofessional education
instrument validation
student assessment


Elevated levels of peripheral blood CD14(bright) CD16+ and CD14(dim) CD16+ monocytes may contribute to the development of retinopathy in patients with juvenile onset type 1 diabetes.

Abstract: The study aimed to analyze the CD14(bright) CD16(+) and CD14(dim) CD16(+) monocyte subsets in juvenile-onset complication-free diabetes mellitus type 1 in the context of their association with microvascular complications. 61 children with type 1 diabetes and 30 healthy individuals were enrolled in a study. CD14(bright) CD16(+) and CD14(dim) CD16(+) monocytes were quantified in peripheral blood by means of flow cytometry. At the time of sampling blood glucose concentration was taken along with biochemical measurement of renal function, CRP and glycosylated hemoglobin. The Spearman's correlations were used to compare the relationship between CD16(+) monocyte subsets and the clinical parameters that can predict the development of microangiopathies. The flow cytometric analysis of monocyte subsets in peripheral blood of analyzed subjects revealed that the numbers of CD14(bright) CD16(+) and CD14(dim) CD16(+) monocytes were significantly higher in patients with type 1 diabetes than in the healthy individuals. As to the relationship between CD16(+) monocyte subsets and the clinical parameters that can predict development of microangiopathies, it was shown that both CD16(+) subsets were associated with increased risk of retinopathy development, defined as retinopathy development value. Elevated levels of intermediate CD14(bright) CD16(+) and non-classical CD14(dim) CD16(+) monocytes predict development of diabetic retinopathy in patients with type 1 diabetes.

Ryba-Stanisławowska|Monika|M| Myśliwska|Jolanta|J| Juhas|Ulana|U| Myśliwiec|Małgorzata|M|

retinopathy
diabetes mellitus type 1
CD16+ monocyte subsets
intermediate subset
non-classical subset


Microscopic abnormality classification of cardiac murmurs using ANFIS and HMM.

Abstract: Auscultation of heart dispenses identification of the cardiac valves. An electronic stethoscope is used for the acquisition of heart murmurs that is further classified into normal or abnormal murmurs. The process of heart sound segmentation involves discrete wavelet transform to obtain individual components of the heart signal and its separation into systole and diastole intervals. This research presents a novel scheme to develop a semi-automatic cardiac valve disorder diagnosis system. Accordingly, features are extracted using wavelet transform and spectral analysis of input signals. The proposed classification scheme is the fusion of adaptive-neuro fuzzy inference system (ANFIS) and HMM. Both classifiers are trained using the extracted features to correctly identify normal and abnormal heart murmurs. Experimental results thus achieved exhibit that proposed system furnishes promising classification accuracy with excellent specificity and sensitivity. However, the proposed system has fewer classification errors, fewer computations, and lower dimensional feature set to build an intelligent system for detection and classification of heart murmurs.

cardiac murmurs
wavelet transform
fuzzy inference system
quantitative morphology


Effects of Physical Activity and Ginkgo Biloba on Cognitive Function and Oxidative Stress Modulation in Ischemic Rats.

Abstract: Either exercise or Ginkgo biloba is reported to improve cognitive functioning. The aim of this study is to compare the protective effects of forced exercise and Ginkgo biloba on oxidative stress as well as memory impairments induced by transient cerebral ischemia. Adult male Wistar rats were treated with treadmill running or Ginkgo biloba extract for 2 weeks before cerebral ischemia. Memory was assessed using a Morris water maze (MWM) task. At the end of the behavioral testing, oxidative stress biomarkers were evaluated in the hippocampus tissue. As expected, the cerebral ischemia induced memory impairment in the MWM task, and oxidative stress in the hippocampus. These effects were significantly prevented by treadmill running. Indeed, it ameliorated oxidative stress and memory deficits induced by ischemia. In contrast, Ginkgo biloba was not as effective as exercise in preventing ischemia-induced memory impairments. The results confirmed the neuroprotective effects of treadmill running on hippocampus-dependent memory.

physical activity
Ginkgo biloba
oxidative stress
rat
transient cerebral ischemia
hippocampus
spatial memory


The reproductive response to the male effect of 7- or 10-month-old female goats is improved when photostimulated males are used.

Abstract: The exposure of adult, female, Mediterranean goats during anoestrus to males with induced sexual activity via photostimulation, induces a very high percentage of ovulations. The present work examines the ability of photostimulated bucks to improve the male effect-induced reproductive response of young does over that induced by non-stimulated bucks. A 2×2 factorial experiment was designed, consisting of doe age and buck photoperiod treatments. During seasonal anoestrus, 41 does aged 7 (n=19) or 10 (n=22) months were subjected to the male effect on 10 April; half of each group was exposed to males rendered sexually active by prior exposure to 3 months of long days (16 h of light/day) from 31 October (PHOTO bucks), and half to males maintained under the natural photoperiod (CONTROL bucks). Oestrous activity was recorded daily by direct visual observation of the marks left by male-worn marking harnesses over the 32 days following the bringing of the sexes together (introduction). Doe body weight and body condition were determined weekly. Ovulation was detected by measuring plasma progesterone concentrations twice per week over the 3 weeks after introduction. The ovulation rate was assessed by transrectal ultrasonography. Fecundity, fertility, prolificacy and productivity were also determined. The interaction doe age × buck photoperiod treatment had no effect on any outcome. The percentage of females showing ovulation or oestrus was higher in the does exposed to PHOTO bucks (85% v. 43% for those exposed to CONTROL bucks) they also showed higher fertility (75% v. 43%) and productivity (1.05±0.17 v. 0.57±0.16 kids born per doe serviced) (all P values at least P<0.05). The 10-month-old group showed higher percentage of females showing ovulation, oestrus, fertility and productivity than the 7-month-old does after the male effect (females showing ovulation: 82% v. 42%; showing oestrus: 73% v. 42%; fertility: 73% v. 42% and productivity: 1.09±0.17 v. 0.47±0.14 goat kids born per doe serviced; respectively, all P values at least P<0.05). The present results show that the use of photostimulated males improves the reproductive performance of 7- and 10-month-old does, and may contribute towards increasing their productivity and lifetime reproductive performance.

male effect
fecundity
fertility
productivity
puberty


Rough set based rule induction in decision making using credible classification and preference from medical application perspective.

Abstract: This paper presents a new heuristic algorithm for reduct selection based on credible index in the rough set theory (RST) applications. This algorithm is efficient and effective in selecting the decision rules particularly the problem to be solved in a large scale. This algorithm is capable to derive the rules with multi-outcomes and identify the most significant features simultaneously, which is unique and useful in solving predictive medical problems. The end results of the proposed approach are a set of decision rules that illustrates the causes for solitary pulmonary nodule and results of the long term treatment.

Tseng|Tzu-Liang Bill|TL|
Huang|Chun-Che|CC|
Fraser|Kym|K|
Ting|Hsien-Wei|HW|

Rule induction
Credible index
Rough set theory
Medical prediction


Prediction of 3- to 5-Month Outcomes from Signs of Acute Bilirubin Toxicity in Newborn Infants.

Abstract:
OBJECTIVE
To evaluate the ability of the bilirubin-induced neurologic dysfunction (BIND) score to predict residual neurologic and auditory disability and to document the relationship of BIND score to total serum bilirubin (TSB) concentration.

STUDY DESIGN
The BIND score (assessing mental status, muscle tone, and cry patterns) was obtained serially at 6- to 8-hour intervals in 220 near-term and full-term infants with severe hyperbilirubinemia. Neurologic and/or auditory outcomes at 3-5 months of age were correlated with the highest calculated BIND score. The BIND score was also correlated with TSB.

RESULTS
Follow-up neurologic and auditory examinations were performed for 145/202 (72%) surviving infants. All infants with severe acute bilirubin encephalopathy (BIND scores 7-9) either died or suffered residual neurologic and auditory impairment. Of 24 cases with moderate encephalopathy (BIND 4-6), 15 (62.5%) resolved following aggressive intervention and were normal at follow-up. Three of 73 infants with mild encephalopathy (BIND scores 1-3) but severe jaundice (TSB ranging 33.5-38 mg/dL; 573-650 µmol/L) had residual neurologic and/or auditory impairment. A BIND score ≥4 had a specificity of 87.3% and a sensitivity of 97.4% for predicting poor neurologic outcomes (receiver operating characteristic analysis). BIND scores trended higher with severe hyperbilirubinemia (r2 = 0.54, P < .005), but 5/39 (13%) infants with TSB ≥36.5 mg/dL (624 µmol/L) had BIND scores ≤3, and normal outcomes at 3-5 months.

CONCLUSIONS
The BIND score can be used to evaluate the severity of acute bilirubin encephalopathy and predict residual neurologic and hearing dysfunction.

El Houchi|Salma Z|SZ|
Iskander|Iman|I|
Gamaleldin|Rasha|R|
El Shenawy|Amira|A|
Seoud|Iman|I|
Abou-Youssef|Hazem|H|
Wennberg|Richard P|RP|

D000208:Acute Disease
D001663:Bilirubin
D015331:Cohort Studies
D002658:Developmental Disabilities
D005260:Female
D005500:Follow-Up Studies
D005865:Gestational Age
D006801:Humans
D015994:Incidence
D007223:Infant
D007231:Infant, Newborn
D007234:Infant, Premature
D007567:Jaundice, Neonatal
D007647:Kernicterus
D008297:Male
D009460:Neurologic Examination
D011237:Predictive Value of Tests
D012372:ROC Curve
D012189:Retrospective Studies
D018570:Risk Assessment
D012680:Sensitivity and Specificity
D012720:Severity of Illness Index
D013997:Time Factors

bilirubin induced neurologic dysfunction


Changes in physical activity during a weight loss intervention and follow-up: a randomized controlled trial.

Abstract: Physical activity is an important component in weight loss treatment and weight maintenance. We evaluated the physical activity component of two weight loss programmes, either standard care (SC) as defined by national guidelines, or a commercial programme (CP; Weight Watchers) over the period of weight loss and follow-up. 772 adults (mean body mass index: 31.4 ± 2.6 kg m(-2)) were recruited by primary care practices in Australia, the United Kingdom, and Germany, and randomly assigned to 12 months SC, or the CP. They were then followed up at 24 months. Change in physical activity levels were assessed by the International Physical Activity Questionnaire (IPAQ)-short form, and pedometer recordings. Both groups reported increases in physical activity using the IPAQ from baseline to 12 months and 24 months (within groups P < 0.0001) and in pedometer steps from baseline to 12 months only (within groups P < 0.0001). Differences between groups with both methods of assessment were not significant. There was a significant difference in weight loss between the groups at 12 months favouring the CP group; however, this statistical difference was not maintained at 24 months. In conclusion, despite similar increases in reported activity, there were significant differences in weight loss and regain between groups. Therefore, greater weight loss seen with the CP is unlikely to be due to increases in physical activity. Trends in pedometer steps mirrored changes in weight over time more closely than the IPAQ; however, both assessment tools have limitations. Better activity assessment measures are needed to more accurately gauge changes in physical activity during weight loss interventions.

Fuller|N R|NR|
Williams|K|K|
Shrestha|R|R|
Ahern|A L|AL|
Holzapfel|C|C|
Hauner|H|H|
Jebb|S A|SA|
Caterson|I D|ID|

Commercial programme
IPAQ
obesity, pedometer


Temporary intravascular shunt use improves early limb salvage after extremity vascular injury.

Abstract:
OBJECTIVE
The use of temporary intravascular shunts (TIVSs) allow for restoration of distal perfusion and reduce ischemic time in the setting of arterial injury. As a damage control method, adjunct shunts restore perfusion during treatment of life-threatening injuries, or when patients require evacuation to a higher level of care. Single-center reports and case series have demonstrate that TIVS use can extend the opportunity for limb salvage. However, few multi-institutional studies on the topic have been reported. The objective of the present study was to characterize TIVS use through a multi-institutional registry and define its effects on early limb salvage.

METHODS
Data from the Prospective Observation Vascular Injury Treatment registry was analyzed. Civilian patients aged ≥18 years who had sustained an extremity vascular injury from September 2012 to November 2018 were included. Patients who had a TIVS used in the management of vascular injury were included in the TIVS group and those who had received treatment without a TIVS served as the control group. An unadjusted comparison of the groups was conducted to evaluate the differences in the baseline and outcome characteristics. Double robust estimation combining logistic regression with propensity score matching was used to evaluate the effect of TIVS usage on the primary end point of limb salvage.

RESULTS
TIVS use was identified in 78 patients from 24 trauma centers. The control group included 613 patients. Unmatched analysis demonstrated that the TIVS group was more severely injured (mean ± standard deviation injury severity score, 18.83 ± 11.76 for TIVS vs 14.93 ± 10.46 for control; P = .002) and had more severely mangled extremities (mean ± standard deviation abbreviated injury scale, extremity, score 3.23 ± 0.80 for TIVS vs 2.95 ± 0.87 for control; P = .008). Logistic regression demonstrated that propensity-matched control patients had a three times greater likelihood of amputation compared with the TIVS patients (odds ratio, 3.6; 95% confidence interval, 1.2-11.1; P = .026). Concomitant nerve injury and orthopedic fracture were associated with a greater risk of amputation. The median follow-up for the TIVS group was 12 days (interquartile range, 4-25 days) compared with 9 days (interquartile range, 4-18 days) for the control group.

CONCLUSIONS
To the best of our knowledge, the present study is the first multicenter, matched-cohort study to characterize early limb salvage as a function of TIVS use in the setting of extremity vascular injury. Shunts expedite limb perfusion and resulted in lower rates of amputation during the early phase of care. The use of TIVS should be one part of a more aggressive approach to restore perfusion in the most injured patients and ischemic limbs.

Polcz|Jeanette E|JE|
White|Joseph M|JM|
Ronaldi|Alley E|AE|
Dubose|Joseph J|JJ|
Grey|Scott|S|
Bell|Devin|D|
White|Paul W|PW|
Rasmussen|Todd E|TE|

Limb salvage
Vascular injury
Temporary shunts
Vascular shunts
Vascular trauma


Novel BCR-ABL1 fusion identified by targeted next-generation sequencing in a patient with an atypical myeloproliferative neoplasm.

Abstract: An unusual case of a BCR-ABL1-positive myeloproliferative neoplasm is presented with discordant molecular and cytogenetic characterization at diagnosis. More extensive molecular characterization of the fusion messenger RNA transcript using a next-generation sequencing approach identified a novel BCR-calcineurin-binding protein 1-ABL1 variant, which has not been described previously. This case highlights the potential utility of next-generation sequencing for a single-target application to resolve rare and unusual tumor genetic variants when standard molecular diagnostic methods are inconclusive. Although the relationship of this novel BCR-ABL1 fusion to the atypical pathologic features and initially suboptimal therapeutic response profile remains speculative, this case indicates that accurate molecular characterization of rare variants has diagnostic and potentially prognostic relevance.

Frederick|Lori|L|
Beardell|Frank|F|
Viswanatha|David S|DS|

D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive

BCR-ABL1
Next-generation sequencing
Myeloproliferative neoplasm
Chronic myeloid leukemia


Efficacy and safety of adjunctive modafinil treatment on residual excessive daytime sleepiness among nasal continuous positive airway pressure-treated japanese patients with obstructive sleep apnea syndrome: a double-blind placebo-controlled study.

Abstract:
STUDY OBJECTIVES
This double-blind study evaluated the efficacy and safety of modafinil for treating excessive daytime sleepiness in Japanese patients with obstructive sleep apnea syndrome (OSAS).

METHODS
Patients with residual excessive sleepiness (Epworth Sleepiness Scale [ESS] ≥ 11) on optimal nasal continuous positive airway pressure (nCPAP) therapy (apnea-hypopnea index ≤ 10) were randomized to either 200 mg modafinil (n = 52) or placebo (n = 62) once daily for 4 weeks. Outcomes included baseline-week 4 changes in ESS total score, sleep latency on maintenance of wakefulness test (SL-MWT), nocturnal polysomnography, Pittsburgh Sleep Quality Index (PSQI), and safety.

RESULTS
All 114 randomized patients completed the study. Mean change in ESS total score (-6.6 vs -2.4, p < 0.001) and SL-MWT (+2.8 vs -0.4 minutes, p = 0.009) were significantly greater with modafinil than with placebo. ESS total score decreased from > 11 to < 11 at the final assessment in 69.2% of modafinil-treated patients and 30.6% of placebo-treated patients (p < 0.001). Corresponding rates at week 1 were 57.7% and 33.9% (p = 0.014). Changes in nocturnal polysomnography, PSQI, and apnea-hypopnea index from baseline to the final assessment were similar in both groups. Adverse drug reactions occurred in 36.5% and 22.6% of patients in the modafinil and placebo groups, respectively (p = 0.146).

CONCLUSIONS
Once-daily modafinil was effective and well tolerated for managing residual daytime sleepiness in Japanese OSAS patients with residual excessive daytime sleepiness on optimal nCPAP therapy.

D045422:Continuous Positive Airway Pressure

D006970:Disorders of Excessive Somnolence

D064420:Drug-Related Side Effects and Adverse Reactions


Narrative exposure therapy: an evidence-based treatment for multiple and complex trauma.

Abstract: Narrative exposure therapy (NET) is a recently developed, short-term treatment for patients with a posttraumatic stress disorder (PTSD) as a result of multiple trauma. NET can be applied very successfully in patients with complex trauma complaints (Jongedijk, 2014; Schauer, Neuner, & Elbert, 2011). An important feature of NET is that trauma processing is never an isolated event but is always embedded in the context of a traumatic event and in the life history as a whole. At the start, the lifeline is laid. The lifeline is made up of a rope, with flowers (happy events), stones (traumatic events), sometimes candles (grief), or recently also sticks for aggressive acts (NET for offenders; see Stenmark, Cuneyt Guzey, Elbert, & Holen, 2014). These symbols are laid down along the rope, in chronological order. Subsequently, in the subsequent therapy sessions the lifeline is processed in chronological order, giving attention to all the important events a person has experienced in his or her life, both the adverse as well as the pleasurable ones. The narration ends with a written testimony. To date, there is good evidence NET is effective in the treatment of PTSD patients, with support from 18 RCTs (N=950). For culturally diverse populations, NET is recommended as the most evidence-based trauma treatment, besides culturally adapted CBT. NET has been investigated in different populations in Africa, Europe, and Asia. In Asia, research has been carried out in Sri Lanka as well as in China. In China, NET was conducted and investigated with survivors of the Sichuan earthquake (Zang, Hunt, & Cox, 2013, 2014). NET is understandable, even appealing and also supportive for patients with multiple trauma. In this presentation, the treatment principles and the practice of NET will be explained.

narratives
exposure
evidence-based treatment
complex trauma
NET
PTSD
refugees


Risk of cardiac arrhythmias in patients with chronic hepatitis B and C infections - A 13-year nationwide population-based study.

Abstract:
BACKGROUND
Chronic hepatitis C virus (HCV) infection is associated with higher risk of cardiovascular events than chronic hepatitis B virus (HBV). We aimed to investigate whether there is higher risk of arrhythmia in HCV infection.

METHODS
Electronic medical records from National Health Institute Research Database during 2000-2012 were retrieved for patients with HBV or HCV. Patients with missing information, aged <18 years, diagnosed with HBV or HCV before year 2000, concomitant HBV and HCV, coagulopathy or organ transplant, history of arrhythmia, device implantation, congenital heart disease, rheumatic heart disease, hypertrophic cardiomyopathy, thyroid disease, alcohol or drug abuse, valvular heart disease, or follow-up <6 months were excluded. Primary outcomes were cardiac arrhythmias and all-cause mortality.

RESULTS
After 1:1 propensity score matching, 5480 patients with HBV and 5480 patients with HCV were included for study. During a mean follow-up of 6.5 years, the risk of all-cause mortality was higher in the HCV patients than in HBV patients [hazard ratio (HR) 1.35, 95% confidence interval (CI) 1.16-1.58]. There was also a trend toward higher incidence of atrial fibrillation (HR 1.25, 95% 0.98-1.59, p=0.070) and a significantly higher incidence of sick sinus syndrome (HR 1.77, 95% CI 1.07-2.91) in HCV patients. In addition, among patients with all-cause mortality, arrhythmia death was significantly higher with chronic HCV infection.

CONCLUSIONS
In patients with chronic viral hepatitis, patients with HCV were associated with significantly increased risks of sick sinus syndrome, and all-cause mortality compared to patients with HBV.

Wu|Victor Chien-Chia|VC|
Chen|Tien-Hsing|TH|
Wu|Michael|M|
Huang|Chien-Hao|CH|
Chen|Shao-Wei|SW|
Cheng|Chun-Wen|CW|
Lin|Yu-Sheng|YS|
Chang|Po-Cheng|PC|
Hsieh|Ming-Jer|MJ|
Wang|Chao-Yung|CY|
Chang|Shang-Hung|SH|
Wang|Chun-Li|CL|
Chu|Pao-Hsien|PH|
Wu|Cheng-Shyong|CS|

Cardiac arrhythmia
Outcome
Viral hepatitis


N-glycosylation of serum proteins for the assessment of patients with IgD multiple myeloma.

Abstract:
BACKGROUND
Because glycosylation is one of the most common post-translational modifications of proteins and because changes in glycosylation have been shown to have a significant correlation with the development of many cancer types, we investigated the serum N-glycome used to diagnose, stage and evaluate the pathological outcomes in IgD multiple myeloma.

METHODS
Serum samples were available for 20 patients with IgD multiple myeloma, 41 patients with light chain multiple myeloma and 42 healthy control subjects. Serum N-glycans were released and analysed using DNA sequencer-assisted fluorophore-assisted capillary electrophoresis.

RESULTS
Characteristic changes were revealed in the serum N-glycome of IgD myeloma. In particular, three N-glycans (NG1(6)A2F, Peak3; NG1(3)A2F, Peak4; NA2FB, Peak7) showed increased clinical value. The best area under the ROC curve of NG1(6)A2F to diagnose IgD myeloma was 0.981, with a 95.0% sensitivity and 95.2% specificity, and that of NG1(3)A2F was 0.936, with a 95.0% sensitivity and 78.6% specificity. The best area under the ROC curve of NA2FB/NG1(3)A2F to differentially diagnose IgD myeloma versus light chain myeloma was 0.744, with a 95.3% sensitivity and 50.0% specificity. The level of NG1(3)A2F was correlated with the international staging system, while the higher abundance of NA2FB presented in IgD myeloma was predictive of a shorter progression-free survival.

CONCLUSIONS
The advent of serum N-glycan signatures may play a role in the diagnosis, staging and prognosis of IgD myeloma and will serve as the foundation for a precision medicine approach to this rare subtype of multiple myeloma.

Chen|Jie|J| Fang|Meng|M| Chen|Xiaoling|X| Yi|Changhong|C| Ji|Jun|J| Cheng|Cheng|C| Wang|Mengmeng|M| Gu|Xing|X| Sun|Quansheng|Q| Gao|Chunfang|C|

IgD multiple myeloma
Glycosylation
Diagnosis
Prognosis
Biomarker
N-glycan profiling


p62/SQSTM1 but not LC3 is accumulated in sarcopenic muscle of mice.

Abstract:
AIM
We investigated the pathway of autophagy signaling linked to sarcopenia of mice.

METHODS
Young adult (3-month) and aged (24- month) C57BL/6J mice were used. Using real-time PCR, Western blotting, and immunohistochemical microscopy, we evaluated the amounts of p62/SQSTM1, LC3, and Beclin-1 in the quadriceps muscle change with aging in mice.

RESULTS
Marked fiber atrophy (30%) and many fibers with central nuclei were observed in the aged mice. Western blotting using homogenate of the cytosolic fraction clearly showed that the amounts of p62/SQSTM1 and Beclin-1 proteins were significantly increased in the aged skeletal muscle. The amounts of these proteins in both nuclear and membrane fractions did not change significantly with age. Immunofluorescence labeling indicated that aged mice more frequently possessed p62/SQSTM1-positive fibers in the cytosol in quadriceps muscle than young ones (aged: 14% vs. young: 1%). In aged muscle, p62/SQSTM1-positive fibers were significantly smaller than the surrounding p62/SQSTM1-negative fibers. Aging did not elicit significant changes in the mRNA levels of p62/SQSTM1 and Beclin-1, but decreased LC3 mRNA level. In aged muscle, the location of p62/SQSTM1 immunoreactivity was similar to that of Beclin-1 protein, but not LC3.

CONCLUSION
Sarcopenia in mice appears to include a marked defect of autophagy signaling.

Sakuma|Kunihiro|K| Kinoshita|Masakazu|M| Ito|Yoshinori|Y| Aizawa|Miki|M| Aoi|Wataru|W| Yamaguchi|Akihiko|A|

p62/SQSTM1
Sarcopenia
Atrophy
Skeletal muscle
LC3, Beclin‐1


Improving surgical site infection prevention in Asia-Pacific through appropriate surveillance programs: Challenges and recommendation.

Abstract:
BACKGROUND
Surgical site infections (SSIs) represent a substantial clinical and economic burden on patients and the healthcare system. The prevention of SSIs entails surveillance activities which lead to effective mitigation strategies, which are lacking across Asia Pacific (APAC). This manuscript aims to document gaps and challenges across APAC that affect the undertaking of a successful SSI surveillance activities and to provide recommendations on overcoming such challenges.

METHODS
A targeted literature review with relevance to APAC identified a series of salient points pertaining to SSI prevention guidelines, implementation, surveillance and outcomes, which was discussed in July 2019 at the APAC Surgical Site Infection Prevention Symposium. An expert panel, comprising eight multidisciplinary experts from APAC and the USA, subsequently amalgamated the key discussion points from the Symposium and their clinical experiences in developing this article.

RESULTS
The barriers to implementing a successful and effective APAC SSI surveillance program were identified as: (a) lack of standardized definitions, reporting methodology and accountability, (b) lack of fiscal resources, (c) reporting variability and under-reporting, and (d) lack of safety culture. Implementing an effective surveillance program in APAC will require countries to develop a well-designed and robust surveillance plan and ensure adequate training for staffs involved.

CONCLUSION
To improve SSI prevention in the region, it is imperative to encourage implementation of national programs with standardized methodologies and accountabilities. An ongoing APAC information exchange, including data and methodologies, will enable continuous learning within the APAC region.

Russo|P L|PL|
Saguil|E|E|
Chakravarthy|M|M|
Lee|K Y|KY|
Ling|M L|ML|
Morikane|K|K|
Spencer|M|M|
Danker|W|W|
Yu|N Y C|NYC|
Edmiston|C E|CE|

Surgical site infection
Infection prevention
Asia Pacific
SSI surveillance


Shoot Multiplication and Callus Induction of Labisia pumila var. alata as Influenced by Different Plant Growth Regulators Treatments and Its Polyphenolic Activities Compared with the Wild Plant.

Abstract: This study aims to investigate whether the in vitro-cultured L. pumila var. alata has higher antioxidant activity than its wild plant. An 8-week-old L. pumila var. alata nodal segment and leaf explants were cultured onto Murashige and Skoog (MS) medium supplemented with various cytokinins (zeatin, kinetin, and 6-benzylaminopurine (BAP)) for shoot multiplication and auxins (2,4-dichlorophenoxyacetic acid (2,4-D) and picloram) for callus induction, respectively. The results showed that 2 mg/L zeatin produced the optimal results for shoot and leaf development, and 0.5 mg/L 2,4-D produced the highest callus induction results (60%). After this, 0.5 mg/L 2,4-D was combined with 0.25 mg/L cytokinins and supplemented to the MS medium. The optimal results for callus induction (100%) with yellowish to greenish and compact texture were obtained using 0.5 mg/L 2,4-D combined with 0.25 mg/L zeatin. Leaves obtained from in vitro plantlets and wild plants as well as callus were extracted and analyzed for their antioxidant activities (DPPH and FRAP methods) and polyphenolic properties (total flavonoid and total phenolic content). When compared with leaf extracts of in vitro plantlets and wild plants of L. pumila var. alata, the callus extract displayed significantly higher antioxidant activities and total phenolic and flavonoid content. Hence, callus culture potentially can be adapted for antioxidant and polyphenolic production to satisfy pharmaceutical and nutraceutical needs while conserving wild L. pumila var. alata.

Najhah|Mat Yunus|MY|
Jaafar|Hawa Z E|HZE|
Nakasha|Jaafar Juju|JJ|
Hakiman|Mansor|M|0000-0001-6074-8625

shoot multiplication
callus induction
Labisia pumila var. alata
plant growth regulator
polyphenolic activities
antioxidant activities