The Role of Beclin 1-Dependent Autophagy in Cancer.

Abstract: Autophagy (self-eating) is an intracellular degradation process used by cells to keep a "clean house"; as it degrades abnormal or damaged proteins and organelles, it helps to fight infections and also provides energy in times of fasting or exercising. Autophagy also plays a role in cancer, although its precise function in each cancer type is still obscure, and whether autophagy plays a protecting (through the clearing of damaged organelles and protein aggregates and preventing DNA damage) or a promoting (by fueling the already stablished tumor) role in cancer remains to be fully characterized. Beclin 1, the mammalian ortholog of yeast Atg6/Vps30, is an essential autophagy protein and has been shown to play a role in tumor suppression. Here, an update of the tumorigenesis regulation by Beclin 1-dependent autophagy is provided.


Identifying indicators sensitive to primary healthcare nurse practitioner practice: a review of systematic reviews protocol.

Abstract:
INTRODUCTION
Primary healthcare nurse practitioners (PHCNPs) practice in a wide range of clinical settings and with diverse patient populations. Several systematic reviews have examined outcomes of PHCNP roles. However, there is a lack of consistency in the definitions used for the PHCNP role across the reviews. The identification of indicators sensitive to PHCNP practice from the perspective of patients, providers and the healthcare system will allow researchers, clinicians and decision-makers to understand how these providers contribute to outcomes of care.

METHODS AND ANALYSIS
A review of systematic reviews is proposed to describe the current state of knowledge about indicators sensitive to PHCNP practice using recognised role definitions. Outcomes of interest include any outcome indicator measuring the effectiveness of PHCNPs. We will limit our search to 2010 onwards to capture the most up-to-date trends. The following electronic databases will be searched: Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library Database of Systematic Reviews and Controlled Trials Register, Database of Abstracts of Reviews of Effects, EMBASE, Global Health, Health Economics Evaluation Database, Health Evidence, HealthStar, Health Systems Evidence, Joanna Briggs Institute, Medline, PDQ-Evidence, PubMed and Web of Science. The search strategies will be reviewed by an academic librarian. Reference lists of all relevant publications will be reviewed. Grey literature will be searched from 2010 onwards, and will include: CADTH Information Services, CADTH's Grey Matters tool, OpenGrey, Organisation for Economic Co-operation and Development, ProQuest Dissertation and Theses and WHO. The PROSPERO International Prospective Register of Systematic Reviews will be searched to identify registered review protocols. The review protocol was developed using Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols recommendations. A narrative synthesis will be used to summarise study findings.

ETHICS AND DISSEMINATION
No ethical approval is required for the study. The data used in the study will be abstracted from published systematic reviews. Dissemination strategies will include peer-reviewed publication, conference presentations and presentations to key stakeholders.

PROSPERO REGISTRATION NUMBER
CRD42020198182.

D003362:Cost-Benefit Analysis
D003695:Delivery of Health Care
D006801:Humans
D015201:Meta-Analysis as Topic
D009722:Nurse Practitioners
D011320:Primary Health Care
D012107:Research Design
D012196:Review Literature as Topic
D000078202:Systematic Reviews as Topic

primary care
quality in health care
statistics & research methods


Endovascular versus medical therapy for uncomplicated type B aortic dissection: a qualitative review.

Abstract:
BACKGROUND
Uncomplicated type B dissections have been traditionally managed with antihypertensive therapy. In the endovascular era, this dictum has been revisited. This review pooled the available studies to compare the outcomes of best medical therapy (BMT) to thoracic endovascular aortic repair (TEVAR) for uncomplicated type B dissections.

METHODS
A literature search was performed to identify studies on uncomplicated type B dissections managed with BMT with and without TEVAR. The primary outcome measures were mortality rates at 30 days and at 2 years following intervention.

RESULTS
A total of 6 studies included 123 patients who underwent TEVAR/BMT, and 566 patients who had BMT alone. The mortality rates at 30 days (6.5% TEVAR/BMT vs 4.8% BMT, P = .21) and at 2 years (9.7% vs 11.9%, P = .32) were similar. Renal failure was greater in TEVAR/BMT (15.4% vs 2.1%, P < .01). Rates of surgical reintervention/intervention were similar (17.6% vs 20.1%, P = .31).

CONCLUSION
The TEVAR with BMT does not provide survival benefit compared to BMT alone, 2 years following uncomplicated type B aortic dissection.

Merola|Jonathan|J|
Garg|Karan|K|
Adelman|Mark A|MA|
Maldonado|Thomas S|TS|
Cayne|Neal S|NS|
Mussa|Firas F|FF|

D019917:Blood Vessel Prosthesis Implantation

uncomplicated
aortic dissection
endovascular repair


Endoscopic Full-Thickness Resection of Colorectal Lesions with the New FTRD System: Single-Center Experience.

Abstract:
Background and Aims
Endoscopic full-thickness resection (EFTR) is an emerging technique for the treatment of various conditions for which classic endoscopic resection techniques have failed or were considered to be at high risk for perforation. The full-thickness resection device (FTRD) is an over-the-scope system which allows a single-step EFTR. The aim of our study is to describe our experience in EFTR of colorectal lesions using the FTRD.

Methods
Nine patients (10 colorectal lesions) were proposed for EFTR. Safety, R0 resection and endoscopic treatment success were evaluated.

Results
Reasons for referral included nonlifting adenomas (n = 4), nonlifting adenoma recurrence (n = 5), and submucosal lesion (n = 1). EFTR was technically successful in all patients. The mean duration of the procedure was 55 min. R0 resection was obtained in all patients. No major complications were detected. All lesions were successfully treated by the endoscopic technique and no patient was referred for surgery. In patients with available follow-up (n = 6), no recurrence was detected.

Conclusions
EFTR is a feasible, reasonable time-consuming, safe, and promising endoscopic resection technique.

Key Messages
FTRD is an additional tool for difficult-to-treat colorectal lesions.

Mão de-Ferro|Susana|S|
Castela|Joana|J|
Pereira|Daniela|D|
Chaves|Paula|P|
Dias Pereira|António|A|

Full-thickness resection
Colorectal adenomas
Nonlifting lesions


Evidence-based recommendations to assist adults with depression to become lifelong movers.

Abstract: Depression is the most common and prevalent mental disorder today, affecting an estimated 1 in 4 Canadians at some point in their lifetime. Physical activity is recommended as a primary treatment for mild to moderate depression and a secondary treatment for moderate to severe depression. Despite this, specific guidelines are still lacking on how to best promote physical activity in this population. Accordingly, this policy brief provides evidence-based recommendations for primary care providers and allied health professionals to promote lifelong physical activity in individuals with depression. Recommendations include asking for permission to discuss physical activity with the individual; framing physical activity as something that they have control over in order to feel better; clarifying that incorporating even a few more minutes of weekly physical activity is better than nothing and that mild forms are enough to achieve mental health benefits; and providing choices of activities to try and accompanying them on their first few sessions. Moreover, this article highlights the importance of promoting physical activity enjoyment for this population, which can be done by guiding the individual to slowly build up the frequency, duration and intensity of activity; encouraging them to be self-compassionate toward physical activity; suggesting they engage in outdoor activity, listen to music, and/or participate with a buddy or group; and incorporate self-monitoring or journalling to solidify the link between physical activity and improved mood. Practitioners are encouraged to use these evidence-informed recommendations-especially maximizing choices, enhancing physical activity enjoyment and emphasizing personal preferences-to help individuals with depression move, recover and flourish. These recommendations may also be used to tailor future interventions and inform policy guidelines to reduce depression rates in Canada.

depression
physical activity
promotion
policy
public health


Low-cost nanoparticles sorbent from modified rice husk and a copolymer for efficient removal of Pb(II) and crystal violet from water.

Abstract: In this work, preparation of adsorbent nanoparticles based on treated low-value agricultural by-product rice husk (TARH), and poly(methylmethacrylate-co-maleic anhydride), poly(MMA-co-MA), is reported for the removal of Pb(II) ion and Crystal violet dye from water. The prepared adsorbent was characterized by FT-IR, SEM, AFM, DLS, BET and Zeta potential. The metal ion adsorption capability was determined for rice husk (RH), TARH, crosslinked poly(MMA-co-MA) (CNR), and CNR@TARH nanoparticles. Different factors affecting the adsorption of Pb(II) such as pH, contact time, initial metal ion concentration and also temperature were studied to investigate adsorption isotherms, kinetics and thermodynamics. For the four tested adsorption isotherm models, the equilibrium sorption data for CNR@TARH nanoparticles obeyed the Langmuir isotherm equation with maximum sorption capacity of 93.45 mg g(-1). The kinetic adsorption data fitted best the Lagergren pseudo-second order model. Regeneration of adsorbent was easily performed by adsorption/desorption experiments followed for 4 cycles. Finally, the ability of the nanoparticles to remove Crystal violet dye from aqueous solution was also investigated by varying the initial dye concentration, pH and immersion time and the adsorption mechanism followed the second-order kinetic model.

D017550:Spectroscopy, Fourier Transform Infrared

Nanoparticles
Rice husk
Crystal violet
Adsorption
Regeneration


Comparing morphological, chemical and anti-diabetic characteristics of Puerariae Lobatae Radix and Puerariae Thomsonii Radix.

Abstract:
ETHNOPHARMACOLOGICAL RELEVANCE
Puerariae Lobatae Radix (PLR) and Puerariae Thomsonii Radix (PTR) are traditional Chinese medicines used for the treatment of diabetes and cardiovascular diseases. These two herbs are used interchangeably in clinical practice, even though they possess significantly different chemical profiles. In the case of Pueraria species, the misidentification is related to the multiple Chinese common names in clinical practice and variable pharmaceutical Latin names in different versions of the Pharmacopoeia of the People's Republic of China. In addition, there is lack of evidence demonstrating how the differences in the chemical profile would impact on the pharmacological activity of the two herbs. Therefore, the aim of this study was to compare the microscopic, phytochemical profiles and anti-diabetic activity of PLR and PTR so that the two species can be differentiated.

MATERIALS AND METHODS
The microscopic characteristics of the PLR and PTR were observed and measured by an optical microscope. The major compounds were quantified by ultra-performance liquid chromatography (UPLC) and total flavonoid content (TFC) colorimetric assay. The free radical scavenging capacity was assessed by 2,2-diphenyl-2-picrylhydrazyl (DPPH) antioxidant assays. Anti-diabetic activity was determined by the inhibition of porcine pancreatic α-amylase and rat intestinal α-glucosidase activities.

RESULTS
Microscopic results illustrated that the size of xylem vessels (PLR: 0.1390 ± 0.0184 mm; PTR: 0.0471 ± 0.0109 mm), number of fibre per bundle (PLR: 32.6800 ± 2.8780; PTR: 16.5900 ± 0.9982) and the size of fibre (PLR: 0.0075 ± 0.0003 mm(2); PTR: 0.0025 ± 0.0002 mm(2)) in PLR were significantly greater than that in PTR (p<0.01). PLR possessed a significantly lower total starch content (PLR: 0.5288 ± 1.2559 mg starch/g DM; PTR: 76.7954 ± 2.9905 mg starch/g DM) and total dietary fibre content (PLR: 4.2886 ± 0.3466 g/100g DM; PTR: 12.4148 ± 0.4541 g/100g DM) as compared to PTR. Isoflavonoids including puerarin, daidzin, genistin and daidzein were the major chemical constituents in both species. However, the average content of puerarin in PLR was found to be eleven times greater than that in PTR. Furthermore, the TFC, DPPH free radical scavenging capacity, anti-α-amylase and anti-α-glucosidase in the PLR extracts were 4.42, 4.91, 3.10 and 4.22 times greater than in the PTR extracts.

CONCLUSIONS
This study provides a comprehensive investigation on the two medicinal valuable Pueraria species and allows differences to be ascertained. This information can be used to update monographs which will help practitioners and dispensers differentiate the herbs. Further study on the interchangeable use of PLR and PTR in clinical practice is urgently warranted.

Wong|Ka H|KH|
Razmovski-Naumovski|Valentina|V|
Li|Kong M|KM|
Li|George Q|GQ|
Chan|Kelvin|K|

Morphological
Anti-diabetic
Pueraria lobata
Puerariae Lobata Radix
Pueraria thomsonii
Puerariae Thomsonii Radix


Association of miR-499 Polymorphism and Its Regulatory Networks with Hashimoto Thyroiditis Susceptibility: A Population-Based Case-Control Study.

Abstract: Hashimoto thyroiditis (HT) is a common autoimmune disorder with a strong genetic background. Several genetic factors have been suggested, yet numerous genetic contributors remain to be fully understood in HT pathogenesis. MicroRNAs (miRs) are gene expression regulators critically involved in biological processes, of which polymorphisms can alter their function, leading to pathologic conditions, including autoimmune diseases. We examined whether miR-499 rs3746444 polymorphism is associated with susceptibility to HT in an Iranian subpopulation. Furthermore, we investigated the potential interacting regulatory network of the miR-499. This case-control study included 150 HT patients and 152 healthy subjects. Genotyping of rs3746444 was performed by the PCR-RFLP method. Also, target genomic sites of the polymorphism were predicted using bioinformatics. Our results showed that miR-499 rs3746444 was positively associated with HT risk in heterozygous (OR = 3.32, 95%CI = 2.00-5.53, p < 0.001, CT vs. TT), homozygous (OR = 2.81, 95%CI = 1.30-6.10, p = 0.014, CC vs. TT), dominant (OR = 3.22, 95%CI = 1.97-5.25, p < 0.001, CT + CC vs. TT), overdominant (OR = 2.57, 95%CI = 1.62-4.09, p < 0.001, CC + TT vs. CT), and allelic (OR = 1.92, 95%CI = 1.37-2.69, p < 0.001, C vs. T) models. Mapping predicted target genes of miR-499 on tissue-specific-, co-expression-, and miR-TF networks indicated that main hub-driver nodes are implicated in regulating immune system functions, including immunorecognition and complement activity. We demonstrated that miR-499 rs3746444 is linked to HT susceptibility in our population. However, predicted regulatory networks revealed that this polymorphism is contributing to the regulation of immune system pathways.

D020022:Genetic Predisposition to Disease

mir-499
regulatory network
Hashimoto thyroiditis
autoimmune thyroid disease (AITD)
single nucleotide polymorphism (SNP)


Visuospatial Organization and Recall in Cerebellar Ataxia.

Abstract: Poor visuospatial skills can disrupt activities of daily living. The cerebellum has been implicated in visuospatial processing, and patients with cerebellar injury often exhibit poor visuospatial skills, as measured by impaired memory for the figure within the Rey-Osterrieth complex figure task (ROCF). Visuospatial skills are an inherent aspect of the ROCF; however, figure organization (i.e., the order in which the figure is reconstructed by the participant) can influence recall ability. The objective of this study was to examine and compare visuospatial and organization skills in people with cerebellar ataxia. We administered the ROCF to patients diagnosed with cerebellar ataxia and healthy controls. The cerebellar ataxia group included patients that carried a diagnosis of spinocerebellar ataxia (any subtype), autosomal dominant cerebellar ataxia, or cerebellar ataxia with unknown etiology. Primary outcome measures were organization and recall performance on the ROCF, with supplemental information derived from cognitive tests of visuospatial perception, working memory, processing speed, and motor function. Cerebellar ataxia patients revealed impaired figure organization relative to that of controls. Figure copy was impaired in the patients, but their subsequent recall performance was normal, suggesting compensation from initial organization and copying strategies. In controls, figure organization predicted recall performance, but this relationship was not observed in the patients. Instead, processing speed predicted patients' recall accuracy. Supplemental tasks indicated that visual perception was intact in the cerebellar ataxia group and that performance deficits were more closely tied to organization strategies than with visuospatial skills.

Visuospatial Organization Ataxia Cerebellum Memory Cognition


Cathelicidin a potential therapeutic peptide for gastrointestinal inflammation and cancer.

Abstract: Cathelicidins, are host defense peptides synthesized and stored in circulating leukocytes and numerous types of epithelial tissues in particular the gastrointestinal (GI) tract and skin. They have been known for their antimicrobial activities against a variety of microbes. Recently it was discovered that they have other significant biological functions and produce appealing pharmacological actions against inflammation and cancer in the GI tract through defined mechanisms. Experimental evidence shows that these actions could be tissue and disease specific and concentration dependent. This article reviews some of the physiological functions of cathelicidins and also their therapeutic potential in the treatment of inflammation and cancer and also the delivery system for this peptide as targeted therapy for various disorders in the GI tract both in animals and humans.

Chow|Jimmy Yip Chuen|JY|
Li|Zhi Jie|ZJ|
Wu|William Ka Kei|WK|
Cho|Chi Hin|CH|

D000818:Animals
D000893:Anti-Inflammatory Agents
D023181:Antimicrobial Cationic Peptides
D000970:Antineoplastic Agents
D005759:Gastroenteritis
D005765:Gastrointestinal Agents
D005770:Gastrointestinal Neoplasms
D041981:Gastrointestinal Tract
D006801:Humans

Cathelicidin
Inflammation
Cancer
Gastrointestinal tract
Ulcer repair


New Targets in Non-Small Cell Lung Cancer.

Abstract: With the implementation of genomic technologies into clinical practice, we have examples of the predictive benefit of targeted therapy for oncogene-addicted cancer and identified molecular dependencies in non-small cell lung cancer. The clinical success of tyrosine kinase inhibitors against epidermal growth factor receptor and anaplastic lymphoma kinase activation has shifted treatment emphasize the separation of subsets of lung cancer and genotype-directed therapy. Advances have validated oncogenic driver genes and led to the development of targeted agents. This review highlights treatment options, including clinical trials for ROS1 rearrangement, RET fusions, NTRK1 fusions, MET exon skipping, BRAF mutations, and KRAS mutations.

Park|Soo J|SJ|
More|Soham|S|
Murtuza|Ayesha|A|
Woodward|Brian D|BD|
Husain|Hatim|H|

D000970:Antineoplastic Agents
D002289:Carcinoma, Non-Small-Cell Lung
D016503:Drug Delivery Systems
D006801:Humans
D008175:Lung Neoplasms
D009154:Mutation
D009363:Neoplasm Proteins

ROS1
RET
MET
BRAF
KRAS
Driver mutations
NSCLC
NTRK


Characteristics of isolated lactic acid bacteria and their effects on the silage quality.

Abstract:
OBJECTIVE
Four lactic acid bacteria (LAB) strains isolated from common vetch, tall fescue and perennial ryegrass on the Tibetan Plateau were characterized, and their effects on the fermentation quality of Italian ryegrass (Lolium multiflorum Lam.) silage were studied.

METHODS
The four isolated strains and one commercial inoculant (G, Lactobacillus plantarum MTD-1) were evaluated using the acid production ability test, morphological observation, Gram staining, physiological, biochemical and acid tolerance tests. The five LAB strains were added to Italian ryegrass for ensiling at three different temperatures (10°C, 15°C, and 25°C).

RESULTS
All isolated strains (LCG3, LTG7, I5, and LI3) could grow at 5°C to 20°C, pH 3.0 to 8.0 and NaCl (3.0%, 6.5%). Strains LCG3, LTG7, I5, and LI3 were identified as Lactobacillus plantarum, Pediococcus acidilactici, Lactobacillus paraplantarum, and Lactobacillus casei by sequencing 16S rDNA, respectively. All LAB inoculants significantly (p<0.05) increased lactic acid (LA) contents and ratios of lactic acid to acetic acid, and reduced pH and ammonia nitrogen/total nitrogen (AN/TN) compared with uninoculated silages at various temperatures (10°C, 15°C, and 25°C). Compared to the commercial inoculant G, I5, and LI3 showed similar effects on improving the silage quality of Italian ryegrass at 10°C and 15°C, indicated by similar pH, LA content and AN/TN.

CONCLUSION
All inoculants could improve the silage fermentation quality at various temperatures (10°C, 15°C, and 25°C). At the temperature of 10°C and 15°C, strain I5 and LI3 had similar effects with the commercial inoculant G on improving the silage quality of Italian ryegrass.

Wang|Siran|S| Yuan|Xianjun|X| Dong|Zhihao|Z| Li|Junfeng|J| Guo|Gang|G| Bai|Yunfeng|Y| Zhang|Junyu|J| Shao|Tao|T|

Isolation
Lactic Acid Bacteria
Silage
Low Temperature


Anonymous sperm donors' attitude towards donation and the release of identifying information.

Abstract:
INTRODUCTION
Belgian legislation allows only strictly anonymous gamete donation and known donation (donation to a recipient known by the donor). Recently, an amendment of the legislation was proposed to grant donor offspring, as of 18 years old, the right to claim identifying information about their donor.

PURPOSE
The aim is to explore the attitude of actual sperm donors towards donation and the release of identifying information and to investigate which donors would be willing to donate when anonymity would be prohibited by law.

METHODS
All men who were accepted as sperm donors (n = 242) by AZ Jan Palfijn Hospital (Ghent, Belgium) were invited to complete an anonymous online survey. The response rate was 65.5%.

RESULTS
One in five (20.1%; n = 30) would continue sperm donation upon a legislation change towards identifiable donation. Three in four donors (75.2%) would agree to provide basic non-identifiable information about themselves and one in three (32.9%) would provide extra non-identifiable information such as a baby photo or a personal letter. Almost half of the donors (45.6%) would agree to donate in a system where the hospital can trace the donor at the child's request and contact the donor, leaving it to the donor to decide whether or not to have contact with the requesting donor child.

CONCLUSION
These findings show that only one in five current donors would continue to donate when identifiable. The study also demonstrates that current donors think more positive about alternative options and that nearly half of them are willing to be contacted by the hospital at the donor child's request, providing the donor can decide at that time whether or not to release his identity.

Anonymity
Attitude
Disclosure
Donor conception
Motivation
Semen donor


Cryo-EM structure of the native butyrylcholinesterase tetramer reveals a dimer of dimers stabilized by a superhelical assembly.

Abstract: The quaternary structures of the cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), are essential for their localization and function. Of practical importance, BChE is a promising therapeutic candidate for intoxication by organophosphate nerve agents and insecticides, and for detoxification of addictive substances. Efficacy of the recombinant enzyme hinges on its having a long circulatory half-life; this, in turn, depends strongly on its ability to tetramerize. Here, we used cryoelectron microscopy (cryo-EM) to determine the structure of the highly glycosylated native BChE tetramer purified from human plasma at 5.7 Å. Our structure reveals that the BChE tetramer is organized as a staggered dimer of dimers. Tetramerization is mediated by assembly of the C-terminal tryptophan amphiphilic tetramerization (WAT) helices from each subunit as a superhelical assembly around a central lamellipodin-derived oligopeptide with a proline-rich attachment domain (PRAD) sequence that adopts a polyproline II helical conformation and runs antiparallel. The catalytic domains within a dimer are asymmetrically linked to the WAT/PRAD. In the resulting arrangement, the tetramerization domain is largely shielded by the catalytic domains, which may contribute to the stability of the human BChE (HuBChE) tetramer. Our cryo-EM structure reveals the basis for assembly of the native tetramers and has implications for the therapeutic applications of HuBChE. This mode of tetramerization is seen only in the cholinesterases but may provide a promising template for designing other proteins with improved circulatory residence times.

butyrylcholinesterase
superhelical assembly
acetylcholinesterase
cryoelectron microscopy
bioscavenger


A heptamethine cyanine dye serves as a potential marker for myeloid-derived suppressor cells.

Abstract: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells with inhibitory effects on T cell-mediated immune response. MDSCs accumulate under many pathological conditions, including cancers, to avoid anticancer immunity. Unlike mouse MDSCs, common specific surface markers for human MDSCs are not clearly defined, mainly due to the complexity of MDSC subsets. In this study, we investigate specific responses of the infrared dye MHI-148 to MDSCs. Mice bearing 4T1 breast cancer cells were established, and splenocytes were isolated. Flow cytometric analyses demonstrated that MHI-148 was reactive to over 80% of MDSC-specific cells manifesting CD11b+/Gr-1+ acquired from both tumor-bearing mice and naive mice. Cells sorted positive for either CD11b/Gr-1 or MHI-148 were also identical to their counterparts (99.7% and 97.7%, respectively). MHI-148, however, was not reactive to lymphocyte or monocyte populations. To determine whether MHI-148-reactive cells exert inhibitory effects on T cell proliferation, an EdU-based T cell assay was performed. MHI-148 reactive cells significantly reduced T cell proliferation with increased arginase activity and nitrite production. In an attempt to test MHI-148 as a marker for human MDSCs, MHI-148 was specifically reactive to CD11b+/CD33+/CD14- granulocytic MDSCs acquired from selected cancer patients. This study demonstrates that the near-infrared dye MHI-148 specifically reacts to mouse splenocytes with known MDSC-specific markers that have T cell suppressive functions. The dye also selectively binds to a subpopulation of immature myeloid cells acquired from cancer patients. While it is not clear how MHI-148 specifically stains MDSCs, this dye can be a novel tool to detect MDSCs and to predict the prognosis of human cancer patients.

Cho|Young-Suk|YS|
Do|Manh-Hung|MH|
Duong Thanh|Hien|H|
Moon|Changjong|C|
Kim|Kwonseop|K|
Cho|Sang-Hee|SH|
Kim|Hangun|H|
Ha|Hyung-Ho|HH|
Jung|Chaeyong|C|

heptamethine cyanine dye
Myeloid-derived suppressor cells
MDSC
MHI-148
IR-783
near infrared dye


Earth, Air, Water, and Fire: Histopathology of Environmental Death.

Abstract: Interpretation of deaths in hostile environments may be informed by postmortem microscopic examination of injured tissues. In context with their macroscopic correlates, the commonly observed histologic changes seen in environmental deaths are reviewed-these include exposure (i.e., hypothermia and hyperthermia), fire, electrocution, and water. Rarely observed pathognomonic findings are highlighted. While it may not yield specific findings, microscopic examination is one of the necessary steps of a thorough postmortem examination.

Ball|Christopher G|CG|
Herath|Jayantha C|JC|

Death
Hostile environment
Histology
Autopsy
Forensic pathology


Comparative assessment of anatomical details of thoracic limb bones of a horse to that of models produced via scanning and 3D printing.

Abstract:
BACKGROUND
Three-dimensional (3D) scanning and printing for the production of models is an innovative tool that can be used in veterinary anatomy practical classes. Ease of access to this teaching material can be an important aspect of learning the anatomy of domestic animals. In this study, a scanner was used to capture 3D images and a 3D printer that performs die-cast printing was used to produce skeletal models of the thoracic limb of a horse.

METHODS
Bones from a horse were selected for scanning and creation of 3D-printed models. The printer used a filamentous thermoplastic material (acrylonitrile-butadiene-styrene [ABS]) which was deposited together with a support resin. Comparisons of the anatomical characteristics (measurements from the original and printed bone) were analyzed to determine the p-value.

RESULTS
Bones from the thoracic limb: scapula, humerus, radius and ulna, carpus and phalanges were used to produce digital and physical models for 3D impressions. Then the anatomical characteristics of the 3D printed models were compared with those of the original bones. The p-value was measured to be 0.9126, indicative of a strong evidence of similarity between the 3D-printed models and specimens. Thus, there was no significant statistical difference between the models and the original anatomical parts.

CONCLUSIONS
The anatomical characteristics were successfully identified in the 3D-printed copies, demonstrating that models of animal bones can be reproduced using 3D printing technology for use in veterinary education.

de Alcântara Leite Dos Reis|Daniela|D|
Gouveia|Beatriz Laura Rojas|BLR|
Júnior|José Carlos Rosa|JCR|
de Assis Neto|Antônio Chaves|AC|

3D printing
Additive manufacturing
Anatomical models
Comparative anatomy


Discrepancy between bone density and bone material strength index in three siblings with Camurati-Engelmann disease.

Abstract:
Camurati-Engelmann (CE) is a very rare disease affecting one in every million persons worldwide. It is characterized by an enlargement of long bones. We aimed to assess bone characteristics in three siblings with different tools. Even if there was an excess of bone density, quality seemed to be deteriorated.

INTRODUCTION
CE disease is a rare monogenic disorder affecting approximately one in every million persons worldwide. It is mainly characterized by a progressive hyperostosis of the periosteum and endosteum of the diaphysis of long bones. Limited data are available about bone characteristics in these patients. In three siblings with CE disease, we aimed to assess bone mineral density (BMD) and trabecular bone score (TBS) by dual-energy X-ray absorptiometry (DXA) and material characteristics at tissue level using bone impact reference point indentation.

METHODS
Clinical data were collected and a general laboratory workup was performed. At the lumbar spine and hip, BMD and TBS were measured using DXA imaging. Bone material strength index (BMSi) was measured by bone impact microindentation using an Osteoprobe instrument.

RESULTS
All three cases had densitometric values consistent with high bone mass (sum of Z-score at the lumbar spine and hip > 4). Hip BMD was extremely high in all three siblings at both total hip and femoral neck, while at the lumbar spine, two of them had normal values but the third again had very high BMD. TBS values were in the normal range. In contrast, BMSi measurements were at low or very low levels, compared with normal controls.

CONCLUSION
Despite strikingly increased BMD and normal microarchitecture, BMSi is affected in patients with CE. Microindentation could be an appropriate tool for assessing bone fragility in these patients. Bone disease in this group of patients requires further study to better understand the underlying regulatory mechanisms and their alterations.

Herrera|S|S|0000-0002-5057-354X Soriano|R|R| Nogués|X|X| Güerri-Fernandez|R|R| Grinberg|D|D| García-Giralt|N|N| Martínez-Gil|N|N| Castejón|S|S| González-Lizarán|A|A| Balcells|S|S| Diez-Perez|A|A|

Camurati-Engelmann
Microindentation
Progressive diaphyseal dysplasia
Rare bone disease


Attitudes towards polygenic risk testing in individuals with glaucoma.

Abstract:
PURPOSE
Glaucoma is the leading cause of irreversible blindness worldwide however, vision loss from glaucoma can generally be prevented through early identification and timely implementation of treatment. Recently, polygenic risk scores (PRS) have shown promise in stratifying individual risk and prognostication for primary open-angle glaucoma to reduce disease burden. Integrating PRS testing into clinical practice is becoming an increasingly realistic prospect, however, little is known about the attitudes of patients towards such testing.

DESIGN
Cross-sectional, questionnaire-based study.

PARTICIPANTS
2369 participants were invited to participate from the Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG), who fit the inclusion criteria of adults with a diagnosis of POAG, had not received genetic results that explain their condition, were not known to be deceased, resided in Australia and had agreed to receive correspondence.

METHODS
1169 individuals (response rate 49%) with primary open-angle glaucoma completed the survey evaluating their attitudes towards polygenic risk testing for glaucoma.

MAIN OUTCOME MEASURES
Sociodemographic, health, perception, and emotional factors were examined to assess associations with interest in PRS testing. Interest in PRS testing was evaluated through assessing likelihood to take the test to predict personal risk of disease and disease severity, and whether the individual would recommend the test to family or non-family members.

RESULTS
Our results show strong interest in the test, with 69.4% of individuals (798 of 1150) indicating a keenness in testing prior to diagnosis, had it been available. In particular, interest was seen in those from an urban area (OR 1.70, 95%CI (1.15-2.49), p=0.007), those who perceived their risk of developing glaucoma as higher (OR 2.05, 95%CI (1.28-3.29), p=0.003), and those who were worried about developing glaucoma (OR 2.07, 95%CI (1.27-3.37), p=0.004). People who were interested in testing were more likely to change their eye health-seeking intentions and recommend testing to family and non-family members, as well as undergo testing for prognostication.

CONCLUSIONS
These findings will help to facilitate the clinical implementation of PRS testing for glaucoma to reduce irreversible vision loss.

Hollitt|Georgina L|GL|
Siggs|Owen M|OM|
Ridge|Bronwyn|B|
Keane|Miriam C|MC|
Mackey|David A|DA|
MacGregor|Stuart|S|
Hewitt|Alex W|AW|
Craig|Jamie E|JE|
Souzeau|Emmanuelle|E|

attitude
glaucoma
polygenic risk score
POAG
genetic testing


Level of education and asthma control in adult-onset asthma.

Abstract:
OBJECTIVE
Education in itself and as a proxy for socioeconomic status, may influence asthma control, but remains poorly studied in adult-onset asthma. Our aim was to study the association between the level of education and asthma control in adult-onset asthma.

METHODS
Subjects with current asthma with onset >15 years were examined within the Obstructive Lung Disease in Northern Sweden study (OLIN, n = 593), Seinäjoki Adult Asthma Study (SAAS, n = 200), and West Sweden Asthma Study (WSAS, n = 301) in 2009-2014 in a cross-sectional setting. Educational level was classified as primary, secondary and tertiary. Uncontrolled asthma was defined as Asthma Control Test (ACT) score ≤19. Altogether, 896 subjects with complete data on ACT and education were included (OLIN n = 511, SAAS n = 200 and WSAS n = 185).

RESULTS
In each cohort and in pooled data of all cohorts, median ACT score was lower among those with primary education than in those with secondary and tertiary education. Uncontrolled asthma was most common among those with primary education, especially among daily ICS users (42.6% primary, 28.6% secondary and 24.2% tertiary; p = 0.001). In adjusted analysis, primary education was associated with uncontrolled asthma in daily ICS users (OR 1.92, 95% CI 1.15-3.20). When stratified by atopy, the association between primary education and uncontrolled asthma was seen in non-atopic (OR 3.42, 95% CI 1.30-8.96) but not in atopic subjects.

CONCLUSIONS
In high-income Nordic countries, lower educational level was a risk factor for uncontrolled asthma in subjects with adult-onset asthma. Educational level should be considered in the management of adult-onset asthma.

education
Asthma
asthma control
adult-onset asthma
socioeconomic status
ACT
inhaled corticosteroids
non-atopic asthma
treatment


In vitro Effect of Harmine Alkaloid and Its N-Methyl Derivatives Against Toxoplasma gondii.

Abstract: Toxoplasmosis is one of the most prevalent and neglected zoonotic global diseases caused by Toxoplasma gondii. The current pharmacological treatments show clinical limitations, and therefore, the search for new drugs is an urgent need in order to eradicate this infection. Due to their intrinsic biological activities, β-carboline (βC) alkaloids might represent a good alternative that deserves further investigations. In this context, the in vitro anti-T. gondii activity of three βCs, harmine (1), 2-methyl-harminium (2), and 9-methyl-harmine (3), was evaluated herein. Briefly, the three alkaloids exerted direct effects on the parasite invasion and/or replication capability. Replication rates of intracellular treated tachyzoites were also affected in a dose-dependent manner, at noncytotoxic concentrations for host cells. Additionally, cell cycle analysis revealed that both methyl-derivatives 2 and 3 induce parasite arrest in S/M phases. Compound 3 showed the highest irreversible parasite growth inhibition, with a half maximal inhibitory concentration (IC50) value of 1.8 ± 0.2 μM and a selectivity index (SI) of 17.2 at 4 days post infection. Due to high replication rates, tachyzoites are frequently subjected to DNA double-strand breaks (DSBs). This highly toxic lesion triggers a series of DNA damage response reactions, starting with a kinase cascade that phosphorylates a large number of substrates, including the histone H2A.X to lead the early DSB marker γH2A.X. Western blot studies showed that basal expression of γH2A.X was reduced in the presence of 3. Interestingly, the typical increase in γH2A.X levels produced by camptothecin (CPT), a drug that generates DSB, was not observed when CPT was co-administered with 3. These findings suggest that 3 might disrupt Toxoplasma DNA damage response.

Alomar|Maria L|ML|
Yañuk|Juan G|JG|
Angel|Sergio O|SO|
Gonzalez|M Micaela|MM|
Cabrerizo|Franco M|FM|


Diffuse Nickel Hypersensitivity Reaction Post-cholecystectomy in a Young Female.

Abstract: Nickel, a silvery-hard metallic element used in corrosion-resistant alloys, is widely used in the medical field. Nickel has aided in medical advancements; however, it has been known to cause hypersensitivity reactions. Retained foreign bodies due to surgical procedures may cause postoperative complications such as allergic reactions. This case involves a 30-year-old female presenting with non-specific symptoms involving multiple organ systems, notably with abdominal pain. Due to chronic symptoms, the patient was tested for metal allergies and diagnosed with hypersensitivity reactions to nickel surgical clips that were previously inserted during cholecystectomy. Subsequently, the patient had surgical removal of the foreign bodies, which led to significant improvement of her symptoms immediately. This case demonstrates a delayed hypersensitivity reaction to a foreign body involving multiple body systems and vague symptoms making the diagnosis challenging. It is important to carefully evaluate the patient's past medical history including history of any allergies. It also brings attention to the necessity of performing metal skin patch tests preoperatively for individuals with a history of any type of allergies.

Luvsannyam|Enkhmaa|E|
Jayaraman|Arathi|A|
Jain|Molly S|MS|
Jagani|Ravi P|RP|
Velez|Veronica|V|
Mirji|Anushka S|AS|
Tiesenga|Frederick|F|
Jorge|Juaquito|J|

nickel
foreign body
abdominal pain
case report
post cholecystectomy
type iv hypersensitivity


Recorded atypical hallucinations in psychotic and affective disorders and associations with non-benzodiazepine hypnotic use: the South London and Maudsley Case Register.

Abstract:
OBJECTIVES
Hallucinations are present in many conditions, notably psychosis. Although under-researched, atypical hallucinations, such as tactile, olfactory and gustatory (TOGHs), may arise secondary to hypnotic drug use, particularly non-benzodiazepine hypnotics ('Z drugs'). This retrospective case-control study investigated the frequency of TOGHs and their associations with prior Z drug use in a large mental healthcare database.

METHODS
TOGHs were ascertained in 2014 using a bespoke natural language processing algorithm and were analysed against covariates (including use of Z drugs, demographic factors, diagnosis, disorder severity and other psychotropic medications) ascertained prior to 2014.

RESULTS
In 43 339 patients with International Classification of Diseases, Tenth Edition schizophreniform or affective disorder diagnoses, 324 (0.75%) had any TOGH recorded (0.54% tactile, 0.24% olfactory, 0.06% gustatory hallucinations). TOGHs were associated with male gender, black ethnicity, schizophreniform diagnosis and higher disorder severity on Health of the National Outcome Scales. In fully adjusted models, tactile and olfactory hallucinations remained independently associated with prior mention of Z drugs (ORs 1.86 and 1.60, respectively).

CONCLUSIONS
We successfully developed a natural language processing algorithm to identify instances of TOGHs in the clinical record. TOGHs overall, tactile and olfactory hallucinations were shown to be associated with prior mention of Z drugs. This may have implications for the diagnosis and treatment of patients with comorbid sleep and psychiatric conditions.

Birnie|Karen Isabel|KI|
Stewart|Robert|R|
Kolliakou|Anna|A|


Increased serum levels of tumor necrosis factor receptor-associated factor 1 (TRAF1) correlate with disease activity and autoantibodies in rheumatoid arthritis.

Abstract:
BACKGROUND
In 2007 a genome wide association analyses revealed an additional risk-associated genetic region in rheumatoid arthritis (RA), the tumor necrosis factor receptor-associated factor 1-complement 5 (TRAF1-C5) containing locus on chromosome 9, comprehensive evaluation of the TRAF1 in RA patients remains necessary.

METHODS
Serum was obtained from 79 RA patients and from 38 healthy individuals. Concentrations of TRAF1 were measured by enzyme-linked immune sorbent assay (ELISA).

RESULTS
We found that the serum concentration of TRAF1 in RA patients was 35.9±51.2pg/ml, the serum concentration of TRAF1 in healthy controls was 12.5±8.6pg/ml. The difference between these 2 groups was significant (p=0.003). Patients with high disease activity had significantly higher TRAF1 concentration in comparison to patients with low and moderate disease activity (p<0.05). We also found that the numerical DAS28 had a significant positive correlation with TRAF1 concentration (r=0.419, p<0.001). We found that serum GPI and RF concentrations showed a significant positive correlation with TRAF1 concentrations respectively (r=0.767, p<0.001; r=0.365, p=0.001), while CCP concentration showed no significant correlation.

CONCLUSIONS
TRAF1 plays a crucial role in the pathogenesis of autoantibodies and may serve as a serologic inflammatory marker of disease activity in RA patients.

Cheng|Tao|T|
Sun|Xue|X|
Wu|Jian|J|
Wang|Mingjun|M|
Eisenberg|Robert A|RA|
Chen|Zhiwei|Z|

D047990:TNF Receptor-Associated Factor 1

TRAF1
Disease activity
Autoantibody
Arthritis


Exercise rescued chronic kidney disease by attenuating cardiac hypertrophy through the cardiotrophin-1 -> LIFR/gp 130 -> JAK/STAT3 pathway.

Abstract:
BACKGROUND
Chronic kidney disease (CKD) is usually associated with cardiac apoptosis and/or cardiac hypertrophy. We hypothesized that exercise can reduce the CKD-induced cardiac damage.

METHODS AND RESULTS
The doxorubicin-induced CKD (DRCKD) model was used in rats to compare two exercise models: 60-min running and 60-min swimming. Results indicated that in healthy normal groups, the signals cardiotrophin-1 (CT-1), interleukin 6 (IL-6), leukaemia inhibitory factor receptor (LIFR), and gp130 were upregulated and janus kinase (JAK) and signal transducer and activation of transcription (STAT) were downregulated by both exercises. In contrast, all signals were highly upregulated in CKD. After exercise training, all signals (CT-1, IL-6, LIFR, gp130, and STAT) were downregulated, with JAK being only slightly upregulated in the running group but not in the swimming group. The myocyte death pathway (CT-1/IL-6 → LIFR/gp130 → PI3K → Akt → Bad) was excluded due to no change found for Bad. Nitric oxide (NO; normal, 15.63 ± 0.86 µmol/l) was significantly suppressed in CKD rats (2.95 ± 0.32 µmol/l), and both running and swimming training highly upregulated the NO level to 30.33 ± 1.03 µmol/l and 27.82 ± 2.47 µmol/l in normal subjects and 24.0 ± 3.2 µmol/l and 22.69 ± 3.79 µmol/l in the DRCKD rats, respectively. The endothelial progenic cells CD34 were significantly suppressed in DRCKD rats, which were not rescued significantly by exercise. In contrast, the CD 34 cells were only slightly suppressed in the healthy subjects by exercise.

CONCLUSION
Both exercise regimens were beneficial by rescuing cardiac function in CKD victims. Its action mechanism was by way of inhibiting myocyte death and rescuing cardiac hypertrophy.

Chen|Kuan-Chou|KC|
Hsieh|Chiu-Lan|CL|
Peng|Chiung-Chi|CC|
Peng|Robert Y|RY|

D053680:Leukemia Inhibitory Factor Receptor alpha Subunit

Cardiac hypertrophy
chronic kidney disease (CKD)
doxorubicin


Correlation between Degree of Radiologic Signs of Osteoarthritis and Functional Status in Patients with Chronic Mechanical Low Back Pain.

Abstract:
BACKGROUND
Osteoarthritis is the most intervening factors in producing mechanical low back pain (LBP). We aimed to evaluate the correlation between radiologic signs of osteoarthritis and functional status in patients with chronic mechanical LBP.

METHODS
Severity of osteoarthritis and disability were evaluated with Kellgren and Lawrence Grading Scale (K&L) by simple lumbar X-ray and Oswestry Disability Questionnaire (ODQ) respectively.

RESULTS
Although there was no significant correlation between ODQ and K&L score in general, the correlation was seen in female group (P = 0.024, r = 0.207).

CONCLUSION
Mechanical LBP provides more disability in females suffering from more advanced osteoarthritis.

Ashraf|Alireza|A|
Farahangiz|Siamak|S|
Pakniat Jahromi|Bita|B|
Setayeshpour|Nazanin|N|
Naseri|Mahshid|M|

osteoarthritis
low back pain
disability
radiography
spondylosis


Optimal risk cut-offs for Down syndrome contingent maternal serum screening.

Abstract:
OBJECTIVES
The objective of this study is to identify the optimal cut-off points of contingent serum screening excluding nuchal translucency (NT) measurement, to categorize the risk level in the first trimester.

METHODS
A prospective database of women undergoing contingent serum screening, without NT measurement, was reviewed. In conventional categorization, the results of first-trimester screening were categorized into high risk (>1:30) (invasive diagnosis was offered); intermediate risk (1:30-1:1500) (second-trimester screening was needed); and low risk (<1:1500) (no further test). We recategorized the risk levels using various upper and lower cut-offs and compared detection rates, false-positive rates, and rates of intermediate risk.

RESULTS
Among 24,874 women, the prevalence of Down syndrome was 1:691. The previously agreed cut-offs had a detection rate of 88.9% and a false-positive rate of 8.5% with high rate of intermediate risk (38.2%). Re-categorization provided the optimal lower and upper cut-offs 1/900 and 1/50, respectively, giving a detection rate of 86.1%, a false-positive rate of 8.1%, and a rate of intermediate risk of 24.8%.

CONCLUSIONS
This is the first study on contingent serum screening without NT measurement which shows a high detection rate with an acceptable false-positive rate. The optimal cut-offs to categorize the risk levels of the upper and the lower cut-off was 1:30-1:50 and 1:900, respectively.

Charoenratana|Cholaros|C| Wanapirak|Chanane|C| Sirichotiyakul|Supatra|S| Tongprasert|Fuanglada|F| Srisupundit|Kasemsri|K| Luewan|Suchaya|S| Tongsong|Theera|T|

Down syndrome
maternal serum screening
Contingent serum screening
prenatal screening


Osteoporosis in liver disease: pathogenesis and management.

Abstract: Osteoporosis affects a substantial proportion of patients with chronic liver disease. Pathologic fracture in osteoporosis significantly affects quality of life and life expectancy. By some estimates, 40% of patients with chronic liver disease may experience osteoporotic fracture. In this study we review the pathogenesis, diagnosis and treatment of specific liver disease entities and their relation to osteoporosis.

Handzlik-Orlik|Gabriela|G| Holecki|Michał|M| Wilczyński|Krzysztof|K| Duława|Jan|J|

osteoporosis
bone metabolism
cirrhosis
hemochromatosis
nonalcoholic fatty liver disease


αII-spectrin controls calcium-regulated exocytosis in neuroendocrine chromaffin cells through neuronal Wiskott-Aldrich Syndrome protein interaction.

Abstract: Besides a fundamental structural role at the plasma membrane, spectrin- and actin-based skeletons have been proposed to participate in various processes including vesicular trafficking. Neuroendocrine cells release hormones and neuropeptides through calcium-regulated exocytosis, a process that is coordinated by a fine remodeling of the actin cytoskeleton. We describe here that calcium-regulated exocytosis is impaired in chromaffin and PC12 cells with reduced αII-spectrin expression levels. Using yeast two-hybrid screening, we show that neuronal Wiskott-Aldrich Syndrome protein (N-WASP) is a partner of the αII-spectrin SH3 domain and demonstrate that secretagogue-evoked N-WASP recruitment at cell periphery is blocked in the absence of αII-spectrin. Additionally, experiments performed with ectopically expressed αII-spectrin mutant unable to bind N-WASP indicated that the interaction between SH3 domain and N-WASP is pivotal for neuroendocrine secretion. Our results extend the list of spectrin interactors and strengthen the idea that αII-spectrin is an important scaffold protein that gathers crucial actin-related players of the exocytic machinery.

Houy|Sébastien|S| Nicolas|Gaël|G| Momboisse|Fanny|F| Malacombe|Magali|M| Bader|Marie-France|MF| Vitale|Nicolas|N|0000-0002-4752-4907 Lecomte|Marie-Christine|MC| Ory|Stéphane|S|0000-0003-4359-1157 Gasman|Stéphane|S|0000-0001-8415-1276

D051317:Wiskott-Aldrich Syndrome Protein, Neuronal

exocytosis
N-WASP
spectrin
PC12 and chromaffin cells


Experimental Design for Vector Output Systems.

Abstract: We formulate an optimal design problem for the selection of best states to observe and optimal sampling times for parameter estimation or inverse problems involving complex nonlinear dynamical systems. An iterative algorithm for implementation of the resulting methodology is proposed. Its use and efficacy is illustrated on two applied problems of practical interest: (i) dynamic models of HIV progression and (ii) modeling of the Calvin cycle in plant metabolism and growth.

optimal selection of observables and sampling times


The interaction with fungal cell wall polysaccharides determines the salt tolerance of antifungal plant defensins.

Abstract: The fungal cell wall is the first point of contact between fungal pathogens and host organisms. It serves as a protective barrier against biotic and abiotic stresses and as a signal to the host that a fungal pathogen is present. The fungal cell wall is made predominantly of carbohydrates and glycoproteins, many of which serve as binding receptors for host defence molecules or activate host immune responses through interactions with membrane-bound receptors. Plant defensins are a large family of cationic antifungal peptides that protect plants against fungal disease. Binding of the plant defensin NaD1 to the fungal cell wall has been described but the specific component of the cell wall with which this interaction occurred was unknown. The effect of binding was also unclear, that is whether the plant defensin used fungal cell wall components as a recognition motif for the plant to identify potential pathogens or if the cell wall acted to protect the fungus against the defensin. Here we describe the interaction between the fungal cell wall polysaccharides chitin and β-glucan with NaD1 and other plant defensins. We discovered that the β-glucan layer protects the fungus against plant defensins and the loss of activity experienced by many cationic antifungal peptides at elevated salt concentrations is due to sequestration by fungal cell wall polysaccharides. This has limited the development of cationic antifungal peptides for the treatment of systemic fungal diseases in humans as the level of salt in serum is enough to inactivate most cationic peptides.

Bleackley|Mark R|MR|
Dawson|Charlotte S|CS|
Payne|Jennifer A E|JAE|
Harvey|Peta J|PJ|
Rosengren|K Johan|KJ|
Quimbar|Pedro|P|
Garcia-Ceron|Donovan|D|
Lowe|Rohan|R|
Bulone|Vincent|V|
van der Weerden|Nicole L|NL|
Craik|David J|DJ|
Anderson|Marilyn A|MA|


Effects of a Ruthenium Schiff Base Complex on Glucose Homeostasis in Diet-Induced Pre-Diabetic Rats.

Abstract: Pre-diabetes is a condition that precedes type 2 diabetes mellitus (T2DM) that is characterised by elevated glycated haemoglobin (HbA1c). The management of pre-diabetes includes the combination of dietary and pharmacological interventions to increase insulin sensitivity. However, poor patient compliance has been reported with regard to dietary interventions, therefore, new alternative drugs are required that can be effective even without the dietary intervention. In our laboratory, we have synthesised a novel ruthenium complex that has been shown to have elevated biological activity. This study investigated the effects of this complex in both the presence and absence of dietary intervention on glucose handling in a diet-induced pre-diabetes rat model. Pre-diabetic animals were randomly assigned to respective treatment groups. The ruthenium complex was administered to pre-diabetic rats once a day every third day for 12 weeks. The administration of the ruthenium complex resulted in reduced fasting blood glucose, food intake, and body weight gain which was associated with decreased plasma ghrelin, insulin, and HbA1c levels in both the presence and absence of dietary intervention. The administration of the ruthenium complex ameliorated glycaemic control and insulin sensitivity in pre-diabetic rats. The results of this study warrant further investigations as this compound could potentially be able to re-sensitize insulin resistant cells and reduce the incidence of T2DM.

Mabuza|Lindokuhle Patience|LP|
Gamede|Mlindeli Wilkinson|MW|
Maikoo|Sanam|S|
Booysen|Irvin Noel|IN|
Ngubane|Phikelelani Siphosethu|PS|
Khathi|Andile|A|

pre-diabetes
glycated haemoglobin
dietary intervention
ruthenium complex


The Emergence and Collapse of Knowledge Boundaries.

Abstract: The dynamics of knowledge transfer is an important topic for engineering managers. In this paper, we study knowledge boundaries - barriers to knowledge transfer - in groups of experts, using topic modeling, a natural language processing technique, applied to transcript data from the U.S. Food and Drug Administration's Circulatory Systems Advisory Panel. As predicted by prior theory, we find that knowledge boundaries emerge as the group faces increasingly challenging problems. Beyond this theory, we find that knowledge boundaries cease to structure communications between communities of practice when the group's expert ability is insufficient to solve its task, such as in the presence of high novelty. We conjecture that the amount of expert knowledge that the group can collectively bring to bear is a determining factor in boundary formation. This implies that some of the factors underlying knowledge boundary formation may aid - rather than hinder - knowledge aggregation. We briefly explore this conjecture using qualitative exploration of several relevant meetings. Finally, we discuss implications of these results for organizations attempting to leverage their expertise given the state of their collective knowledge.

Broniatowski|David A|DA|
Magee|Christopher L|CL|

Knowledge boundaries
Group decision-making
Natural-language processing
Network analysis


Attributing seizures to TBI: Validation of a brief patient questionnaire.

Abstract:
PURPOSE
Traumatic brain injury (TBI) is an important cause of epilepsy and has also been associated with psychogenic nonepileptic seizures (PNES). We designed a brief questionnaire assessing patient beliefs regarding TBI as the cause of their seizures (Patient Seizure Etiology Questionnaire; PSEQ). This study reports content validity for the PSEQ.

METHODS
Ninety Veterans undergoing comprehensive evaluation at 3 VA epilepsy centers completed the PSEQ, a series of questions regarding possible causes for their seizures, including TBI. The PSEQ was scored as YES vs. NO for TBI as the proposed cause of seizures. For each patient, two expert reviewers independently completed a structured chart review to determine whether TBI was the proposed cause of seizures (n=180 reviews). Kappa statistic was used to assess agreement between the PSEQ and each chart review and between the PSEQ and combined chart reviews where both reviewers agreed on a TBI seizure etiology.

RESULTS
The PSEQ scored higher overall rates for a TBI seizure etiology than did expert chart reviews (40% vs. 28%; p<0.001). The PSEQ agreed with 82% of 180 independent chart reviews (sensitivity 88%; specificity 79%). Kappa statistic for agreement was 0.60. The two reviewers agreed on a probable TBI seizure etiology for 83% of chart reviews. The PSEQ sensitivity increased to 100% when both reviewers were in agreement.

CONCLUSION
The PSEQ provides a direct, standardized measure of patient beliefs regarding TBI as the cause of their seizures and has moderate-substantial agreement with expert chart reviews.

Salinsky|Martin|M| Parko|Karen|K| Rutecki|Paul|P| Boudreau|Eilis|E| Storzbach|Daniel|D|

TBI
Epilepsy
Veterans
Psychogenic seizures


FUNCTIONAL LIMITATIONS AND ADIPOKINES IN HIV-INFECTED OLDER ADULTS.

Abstract:
BACKGROUND
There is a significant increase in the number of HIV-infected older adults (HOA). This population may experience functional decline at a much younger age. Little is known about the relationship between functional limitations and systemic adipokines in HOA.

OBJECTIVE
Our study aimed to evaluate the relationship between functional limitations and systemic adipokine levels in HOA population.

DESIGN
Cross-sectional.

SETTING
Academic hospital-based infectious disease clinic.

PARTICIPANTS
The study investigated community-dwelling HIV-infected adults >50 years old and compared this group with age, gender and BMI comparable healthy controls.

MEASUREMENTS
We measured functional status, body composition and plasma concentrations of adipokines.

RESULTS
Fifty-four HOA were studied (mean: age 57 years, BMI 29 kg/m2, CD4 604, duration of HIV 17 years) and compared with thirty-two age, gender and BMI comparable healthy controls. The HOA group showed significantly higher functional limitations compared to the age, gender and BMI comparable controls (p<0.05). Levels of adipokines were significantly different between the two groups (p<0.05). Multiple regression analyses indicated that adiponectin and visfatin were significantly correlated with several physical function measures after controlling for age, sex, and metabolic comorbidities. Adiponectin was negatively correlated with functional limitations, and this relationship was stronger in the control group compared to the HOA group. Conversely, visfatin was positively correlated with functional limitations only in the HOA group.

CONCLUSION
HOA have significant functional limitations and alteration in adipokine levels compared to controls. Adiponectin and visfatin were associated with functional limitations. Visfatin was a correlate of physical function only in the HOA group. Prospective longitudinal studies could provide further insight on the role of adipokines in HIV-related functional decline.

Shah|K N|KN|
Majeed|Z|Z|
Yang|H|H|
Guido|J J|JJ|
Hilton|T N|TN|
Polesskaya|O|O|
Hall|W J|WJ|
Luque|A E|AE|

adipokines
older adults
HIV
physical function
fat redistribution


Broken Knife Blade Completely Penetrating the Humerus: A Case Report and Literature Review.

Abstract: We present a case of a 23-year-old male patient who presented with a blade knife completely wedged and penetrated on his humerus after a stab wound to his left upper extremity. On palpation, a foreign body was palpated under the skin on the deltoid area. The blade was stuck in the bone, so the surrounding bone tissue was osteotomised until the blade was released. The patient evolved favorably, and at three months follow up, he has a full functional recovery of his arm. Stab wounds are prevalent in emergency departments; however, stab wounds with bone involvement have rarely been reported in the literature. When encountering a blade stuck in bone tissue, removing the blade while avoiding orthopedic, neurological and vascular injuries should be the main goal of the treatment. To the best of our knowledge, this is the third reported case of an intraosseous foreign body in the humerus secondary to a stab wound.


Establishment and Characterisation of Metastatic Extraskeletal Ewing Sarcoma Mouse Models.

Abstract:
BACKGROUND/AIM
Ewing sarcomas most commonly arise in the bones, but can also manifest as extraskeletal tumours in soft tissues. Metastases from extraskeletal Ewing sarcomas occur in more diverse anatomical sites than skeletal tumours, and have poorer survival rates. Few animal models replicate the extraskeletal form of Ewing sarcoma, and those that have been developed do not reflect the widespread metastatic spread of these cancers.

MATERIALS AND METHODS
Luciferase-expressing Ewing sarcoma cells derived from a muscle tumour were intramuscularly or intravenously injected into nude mice.

RESULTS
Both models achieved metastatic spread to numerous sites including the lungs, liver, kidneys, and brain. We characterized the cellular composition of primary and metastatic tumours, observing a greater level of immune cell infiltration in metastases compared to primary intramuscular tumours.

CONCLUSION
These pre-clinical models will hopefully facilitate the evaluation of novel therapies and contribute to better understanding the disease progression of metastatic extraskeletal Ewing sarcoma.

Cerra|Carmelo|C|
Harris|Michael A|MA|
Hawkins|Christine J|CJ|

D000818:Animals
D001859:Bone Neoplasms
D004195:Disease Models, Animal
D051379:Mice
D008819:Mice, Nude
D016609:Neoplasms, Second Primary
D012512:Sarcoma, Ewing

extraskeletal
Ewing sarcoma
mouse model
A673
extraosseous
metastasis


Dual-energy X-ray absorptiometry and fracture prediction in patients with spinal cord injuries and disorders.

Abstract:
Low T-scores at the hip predict incident fractures in persons with a SCI.

INTRODUCTION
Persons with a spinal cord injury (SCI) have substantial morbidity and mortality following osteoporotic fractures. The objective of this study was to determine whether dual-energy X-ray absorptiometry (DXA) measurements predict osteoporotic fractures in this population.

METHODS
A retrospective historical analysis that includes patients (n = 552) with a SCI of at least 2 years duration who had a DXA performed and were in the VA Spinal Cord Disorders Registry from fiscal year (FY) 2002-2012 was performed.

RESULTS
The majority of persons (n = 455, 82%) had a diagnosis of osteoporosis or osteopenia, with almost half having osteoporosis. BMD and T-scores at the lumbar spine were not significantly associated with osteoporotic fractures (p > 0.48) for both. In multivariable analyses, osteopenia (OR = 4.75 95% CI 1.23-17.64) or osteoporosis (OR = 4.31, 95% CI 1.15-16.23) compared with normal BMD was significantly associated with fractures and higher T-scores at the hip were inversely associated with fractures (OR 0.73 (95% CI 0.57-0.92)). There was no significant association of T-scores or World Health Organization (WHO) classification with incident fractures in those with complete SCI (p > 0.15 for both).

CONCLUSION
The majority (over 80%) of individuals with a SCI have osteopenia or osteoporosis. DXA-derived measurements at the hip, but not the lumbar spine, predict fracture risk in persons with a SCI. WHO-derived bone density categories may be useful in classifying fracture risk in persons with a SCI.

Abderhalden|L|L|
Weaver|F M|FM|
Bethel|M|M|
Demirtas|H|H|
Burns|S|S|
Svircev|J|J|
Hoenig|H|H|
Lyles|K|K|
Miskevics|S|S|
Carbone|L D|LD|

D014493:United States Department of Veterans Affairs

Dual-energy X-ray absorptiometry
Fractures
Spinal cord injury
Osteoporosis


Radiology workload in clinical implementation of thrombectomy for acute ischemic stroke: experience from The Netherlands.

Abstract:
PURPOSE
To investigate the number of acute stroke patients undergoing CT angiography (CTA) for suspected large vessel occlusion (LVO) and those eligible for thrombectomy in relation to the population.

METHODS
Consecutive patients in a Western population who underwent CTA for suspected LVO of the proximal anterior circulation between January and August 2019 were included. The date and time of CTA and the number of patients eligible for thrombectomy were assessed. Our hospital's service area population was estimated using the Central Bureau for Statistics data. One-way analysis of variance with post-hoc tests and chi-squared tests were used for statistical analyses.

RESULTS
Of 520 patients (49% males, mean age of 72 years) undergoing CTA, 84 (16.2%) were eligible for thrombectomy. Our hospital's service area population was estimated at 420,000. Therefore, 3.6 CTA scans were performed and 0.6 patients were eligible for thrombectomy per 100,000 people per week. The number of patients undergoing CTA and the number of patients eligible for thrombectomy both did not significantly differ between any days of the week (P > 0.05). A total of 236 (45%) and 284 patients (55%) underwent CTA during office and on-call hours, respectively. The percentage of patients eligible for thrombectomy did not significantly differ between office and on-call hours (P = 0.834).

CONCLUSION
Our study estimated the number of stroke patients undergoing CTA for suspected LVO and those eligible for thrombectomy in relation to the population. Numbers were essentially the same throughout the week, and during office and on-call hours. Our data can be used to make adequate staffing plans.

Fasen|Bram A C M|BACM|
Heijboer|Roeland J J|RJJ|
Hulsmans|Frans-Jan H|FH|
Kwee|Robert M|RM|

Workload
Thrombectomy
Stroke
Computed tomography angiography


Sexuality as part of rehabilitation? A qualitative study on the perceptions of rehabilitation nurses on discussing patient sexuality during clinical rehabilitation.

Abstract:
INTRODUCTION
Spinal cord injury may seriously affect sexual health and sexuality, which can lead to lower self-esteem, social isolation, lower quality of life, and an increased risk of depression. Nurses play an extensive role in providing patient education. However, a gap between the patients' need for information and the lack of information provided by nurses still exists. Therefore, knowledge about barriers and facilitators regarding discussing patient sexuality is necessary.

METHODS
Semi-structured interviews were conducted with 25 nurses working in Spinal Cord Injury rehabilitation in one clinic in the Netherlands. The following themes were discussed during the interviews: (1) attitude, (2) social factors, (3) affect, (4) habits and (5) facilitating conditions.

RESULTS
Addressing patient sexuality was difficult due to the nurses' attitude and their environment. Sexuality was considered important but respondents were reserved to discuss the topic due to taboo, lack of knowledge, and common preconceptions. Participants expressed the need for education, a clear job description, time and privacy.

CONCLUSION
Nurses consider discussing patient sexuality as important but are hindered due to multiple factors. Organizational efforts targeted at knowledge expansion are needed to break the taboo and remove preconceptions. Nurses should provide opportunities to discuss the subject to intercept sexuality-related problems.IMPLICATIONS FOR REHABILITATIONThe specific tasks of each profession within the multidisciplinary team regarding patient sexuality should be discussed, agreed upon and protocolized.Adding a sexologist in the multidisciplinary team may be of benefit as well as structurally incorporating an appointment with the sexologist within the patients' schedule.If a sexologist is not available, opt for a nurse practitioner who is specialized - or wants to further specialize - in sexual health and sexuality.In order to create more awareness on patient sexuality within the nursing team, a working group can be arranged to give special attention to discussing the subject by organizing trainings and coaching fellow nurses to address sexuality.Create a safe and private environment for the patient when addressing sexuality.Educational interventions to enhance the nurses' knowledge in order to make nurses feel capable to provide basic sexuality-related patient education.

Pascual|April|A|
Wighman|Amber|A|
Littooij|Elsbeth C|EC|
Janssen|Thomas W J|TWJ|

rehabilitation
rehabilitation nursing
patient sexuality
Spinal cord injury
sexual health
SCI rehabilitation


A New Metric Quantifying Chemical and Biological Property of Small Molecule Metabolites and Drugs.

Abstract: One prominent class of drugs is chemical small molecules (CSMs), but the majority of CSMs are of very low druggable potential. Therefore, it is quite important to predict drug-related properties (druggable properties) for candidate CSMs. Currently, a number of druggable properties (e.g., logP and pKa) can be calculated by in silico methods; still the identification of druggable CSMs is a high-risk task, and new quantitative metrics for the druggable potential of CSMs are increasingly needed. Here, we present normalized bond energy (NBE), a new metric for the above purpose. By applying NBE to the DrugBank CSMs whose properties are largely known, we revealed that NBE is able to describe a number of critical druggable properties including logP, pKa, membrane permeability, blood-brain barrier penetration, and human intestinal absorption. Moreover, given that the human endogenous metabolites can serve as important resources for drug discovery, we applied NBE to the metabolites in the Human Metabolome Database. As a result, NBE showed a significant difference in metabolites from various body fluids and was correlated with some important properties, including melting point and water solubility.

Huang|Chuanbo|C| Zhou|Yuan|Y| Yang|Jichun|J| Cui|Qinghua|Q| Li|Yanhui|Y|

metabolites
drug
chemical small molecule
druggable property
normalized bond energy


Bevacizumab in high-grade glioma patients following intraparenchymal hemorrhage.

Abstract:
Background
Intraparenchymal hemorrhage (IPH) is a relative contraindication to bevacizumab therapy, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody approved for the treatment of recurrent glioblastoma. However, in patients with symptomatic enhancing tumors and poor functional status, bevacizumab may be the only beneficial therapeutic option.

Methods
We retrospectively reviewed all patients with high-grade glioma who were treated between January 1, 2005 and December 31, 2014 with bevacizumab despite prior IPH.

Results
Eighteen patients met our study criteria. There were 12 women and 6 men with a median age of 56 years. Tumor types were glioblastoma (n = 15), anaplastic astrocytoma (n = 2), and anaplastic oligodendroglioma (n = 1). Seventeen patients had prior spontaneous intratumoral bleed (13 grade 1-2; 4 grade 3-4); the 1 remaining patient had a grade 3 bleed due to cerebral venous thrombosis. Among them, identifiable risk factors for hemorrhage were anti-VEGF therapy, anticoagulation use, thrombocytopenia, and hypertension; seven had no identifiable risk factors. The median duration from IPH to (re-)initiation of bevacizumab was 113 days (range 13-1367). Brain imaging performed prior to bevacizumab treatment showed persistent or evolving hemorrhage in 8 patients and complete resolution in 10 patients. With a median follow-up duration of 137 days after bevacizumab re-initiation, only 1 (6%) of the 18 patients re-bled; this patient had an anaplastic oligodendroglioma and developed a grade 2 intratumoral bleed after 3 doses of bevacizumab.

Conclusions
The incidence of re-bleed is rare. Bevacizumab use was safe in patients with recurrent high-grade glioma following IPH for whom no other meaningful treatment options existed.

Lin|Xuling|X|
Daras|Mariza|M|
Pentsova|Elena|E|
Nolan|Craig P|CP|
Gavrilovic|Igor T|IT|
DeAngelis|Lisa M|LM|
Kaley|Thomas J|TJ|

bevacizumab
glioma
intracranial hemorrhage
vascular endothelial growth factor


Quantitative contrast-enhanced ultrasound for monitoring vedolizumab therapy in inflammatory bowel disease patients: a pilot study.

Abstract: Background Microvascularization of the bowel wall can be visualized and quantified non-invasively by software-assisted analysis of derived time-intensity curves. Purpose To perform software-based quantification of bowel wall perfusion using quantitative contrast-enhanced ultrasound (CEUS) according to clinical response in patients with inflammatory bowel disease treated with vedolizumab. Material and Methods In a prospective study, in 18 out of 34 patients, high-frequency ultrasound of bowel wall thickness using color Doppler flow combined with CEUS was performed at baseline and after 14 weeks of treatment with vedolizumab. Clinical activity scores at week 14 were used to differentiate between responders and non-responders. CEUS parameters were calculated by software analysis of the video loops. Results Nine of 18 patients (11 with Crohn's disease and seven with ulcerative colitis) showed response to treatment with vedolizumab. Overall, the responder group showed a significant decrease in the semi-quantitative color Doppler vascularization score. Amplitude-derived CEUS parameters of mural microvascularization such as peak enhancement or wash-in rate decreased in responders, in contrast with non-responders. Time-derived parameters remained stable or increased during treatment in all patients. Conclusion Analysis of bowel microvascularization by CEUS shows statistically significant changes in the wash-in-rate related to response of vedolizumab therapy.

contrast-enhanced ultrasound
vedolizumab
quantification
CEUS
ulcerative colitis
Crohn’s disease


Dihydromyricetin induces autophagy in HepG2 cells involved in inhibition of mTOR and regulating its upstream pathways.

Abstract: Dihydromyricetin (DHM), a bioactive flavonoid compound extracted from the stems and leaves of Ampelopsis grossedentata, has oxidation resistance, anti-tumor and free radical scavenging capabilities. In this study, we found that DHM-induced autophagy inhibited the cell proliferation in HepG2 cells. The transmission electron microscopy results showed that DHM induced significantly autophagosome characteristics like autophagolysosome containing degraded cellular content. GFP labled LC3 plasma transfection showed that LC3 largely diffused to punctate structures with DHM treatment, while lysosomal-rich/acidic compartments detected using LysoTracker Red staining. In addition, DHM promoted the expressions of LC3-II and Beclin-1 in a dose- and time-dependent manner. Further study showed that DHM suppressed the activation of mTOR (mammalian targets of rapamycin) involved in regulating its upstream signaling pathways including extracellular signal-regulated kinase 1/2 (ERK1/2), AMPK (AMP-activated kinase) and class III phosphatidylinositol 3-kinase/phosphoinositide-dependent protein kinase 1/protein kinase B (PI3K/PDK 1/Akt) pathways. Taken together, all the results demonstrated that DHM-induced autophagy inhibited the cell proliferation in HepG2 cells, the possible mechanism involved in inhibition of mTOR activation and regulating the related upstream signaling pathways.

Xia|Juan|J| Guo|Shiwei|S| Fang|Tao|T| Feng|Du|D| Zhang|Xingli|X| Zhang|Qingyu|Q| Liu|Jie|J| Liu|Bin|B| Li|Mingyi|M| Zhu|Runzhi|R|


Cardiovascular Responses to an Isometric Handgrip Exercise in Females with Prehypertension.

Abstract:
BACKGROUND
Hypertensive individuals are known to exhibit greater increases in blood pressure during an isometric handgrip exercise (IHE) than their normotensive counterparts.

AIM
This study tests the hypothesis that, compared to normotensive individuals, prehypertensive individuals exhibit an exaggerated response to IHE.

MATERIALS AND METHODS
In this study, the effects of IHE were compared in matched prehypertensive vs. normotensive healthy African-American females. Six healthy young adult African-American female university students were screened in a physician's office for blood pressure in the range of prehypertension, systolic blood pressure (SBP) 120-139 mmHg and diastolic blood pressure (DBP) 80-89 mmHg. Six young adult African-American women were also recruited to serve as a healthy normotensive control group with SBP ≤119 mmHg and DBP ≤79 mmHg. Cardiovascular fitness was determined by peak oxygen uptake (VO2 peak) measured during a progressive exercise test.

RESULTS
During the handgrip exercise, the prehypertensive group exhibited greater increases in SBP (from 139 ± 6 to 205 ± 11 mmHg, +48%) than the controls (from 132 ± 3 to 145 ± 3 mmHg, +10%); intergroup difference P < 0.001. The prehypertensive group also exhibited greater increases in DBP (from 77 ± 2 to 112 ± 5 mmHg, +46%) compared to the controls (from 72 ± 3 to 78 ± 4 mmHg, +8%); intergroup difference P < 0.001. The increase in systemic vascular resistance was also greater in the prehypertensive group (from 1713 ± 91 to 2807 ± 370 dyne.s.cm(-5), +64%) than in the controls (from 1668 ± 80 to 1812 ± 169 dyne.s.cm(-5), +9%); intergroup difference P < 0.05.

CONCLUSION
These results suggest that blood pressure measurements performed during IHE may be a useful screening tool in evaluating prehypertensive individuals for antihypertensive treatments.

Bond|Vernon|V|
Curry|Bryan H|BH|
Adams|Richard G|RG|
Obisesan|Thomas|T|
Pemminati|Sudhakar|S|
Gorantla|Vasavi R|VR|
Kadur|Kishan|K|
Millis|Richard M|RM|

blood pressure
systemic vascular resistance
Arterial compliance
heart rate
myocardial oxygen demand


Surgery in elderly people: preoperative, operative and postoperative care to assist healing.

Abstract: Surgery for elderly women is likely to increase steadily as the population of elderly people increases globally. Although increasing age increases perioperative morbidity and mortality, the functional age and physiologic reserve rather than chronological age is more important in preventing complications. Preparation for surgery, with special attention to functional capacity and activity, mental status, and existing comorbid conditions, can improve outcomes. Perioperative management must be tailored to physiologic changes of ageing, which affect respiratory, cardiac and renal function, as well as guidelines for preventing infection and thrombotic events. Of particular note is the enhanced effect of narcotic medications in elderly people, which affects intraoperative and postoperative management of pain. Prevention of postoperative delirium is accomplished through preoperative and postoperative planning. Discharge planning, particularly for frail elderly people, must start before surgery.

Hughes|Sarah|S| Leary|Antonella|A| Zweizig|Susan|S| Cain|Joanna|J|

D000368:Aged
D000375:Aging
D003693:Delirium
D005260:Female
D006801:Humans
D059408:Pain Management
D010149:Pain, Postoperative
D010351:Patient Discharge
D056888:Patient Positioning
D011182:Postoperative Care
D011300:Preoperative Care
D020127:Recovery of Function
D012307:Risk Factors
D013514:Surgical Procedures, Operative
D054556:Venous Thromboembolism
D014945:Wound Healing


Effects of anti-VEGF treatment on the recovery of the developing retina following oxygen-induced retinopathy.

Abstract:
PURPOSE
Inhibition of VEGF is widely used in patients to control neovascularization and decrease vascular permeability. To date, the effect of VEGF inhibition has not been evaluated in the developing retina such as that seen in premature infants. The goal of this study was to address the effect of anti-VEGF treatment on retinal development of a mouse model of retinopathy.

METHODS
C57BL/6J mice were evaluated using a model of oxygen-induced retinopathy. Test animals were treated at postnatal day (P) 14 with intravitreal injections of the VEGF inhibitor aflibercept (2.5 or 10 μg) in one eye. Control animals were treated with injection of PBS in one eye. The noninjected fellow eyes were used as internal controls. Areas of avascular retina and neovascular tufts in injected (treated) eyes and noninjected fellow eyes were determined at P17, and the difference related to these characteristics was obtained among them. To evaluate the effect of VEGF inhibition on neurogenesis, focal ERG was performed at P21 and P42. Histologic evaluation of the retinal structure was also evaluated at P42.

RESULTS
Aflibercept treatment reduced the amount of neovascular tufts but significantly increased the area of avascular retina (low dose and high dose) at P17. The delayed vascular growth corresponded to decreased ERG amplitudes (at P21 and P42) and structural changes in the retinal layers that persisted (at P42), despite vascular recovery.

CONCLUSIONS
Inhibition of VEGF in developing eyes has the short-term effect of delayed vascular growth and the long-term effects of decreased function with persistent changes in the neuroretinal structures.

Tokunaga|Clayton C|CC|
Mitton|Kenneth P|KP|
Dailey|Wendelin|W|
Massoll|Charlotte|C|
Roumayah|Kevin|K|
Guzman|Ed|E|
Tarabishy|Noor|N|
Cheng|Mei|M|
Drenser|Kimberly A|KA|

D040262:Receptors, Vascular Endothelial Growth Factor

D042461:Vascular Endothelial Growth Factor A

anti-VEGF
VEGF
aflibercept
neurovascular niche
retinopathy of prematurity


Focusing on butterfly eyespot focus: uncoupling of white spots from eyespot bodies in nymphalid butterflies.

Abstract:
BACKGROUND
Developmental studies on butterfly wing color patterns often focus on eyespots. A typical eyespot (such as that of Bicyclus anynana) has a few concentric rings of dark and light colors and a white spot (called a focus) at the center. The prospective eyespot center during the early pupal stage is known to act as an organizing center. It has often been assumed, according to gradient models for positional information, that a white spot in adult wings corresponds to an organizing center and that the size of the white spot indicates how active that organizing center was. However, there is no supporting evidence for these assumptions. To evaluate the feasibility of these assumptions in nymphalid butterflies, we studied the unique color patterns of Calisto tasajera (Nymphalidae, Satyrinae), which have not been analyzed before in the literature.

RESULTS
In the anterior forewing, one white spot was located at the center of an eyespot, but another white spot associated with either no or only a small eyespot was present in the adjacent compartment. The anterior hindwing contained two adjacent white spots not associated with eyespots, one of which showed a sparse pattern. The posterior hindwing contained two adjacent pear-shaped eyespots, and the white spots were located at the proximal side or even outside the eyespot bodies. The successive white spots within a single compartment along the midline in the posterior hindwing showed a possible trajectory of a positional determination process for the white spots. Several cases of focus-less eyespots in other nymphalid butterflies were also presented.

CONCLUSIONS
These results argue for the uncoupling of white spots from eyespot bodies, suggesting that an eyespot organizing center does not necessarily differentiate into a white spot and that a prospective white spot does not necessarily signify organizing activity for an eyespot. Incorporation of these results in future models for butterfly wing color pattern formation is encouraged.

Butterfly
Eyespot
Focus
White spot
Color pattern
Organizing center
Calisto tasajera
Nymphalidae
Morphometry


Extracellular vesicles on demand (EVOD) chip for screening and quantification of cancer-associated extracellular vesicles.

Abstract: While significant advancements have been made in cancer therapeutics and treatments, early disease detection and diagnosis remains critical to ensuring favorable outcomes for patients. To that end, we propose a microfluidic based approach to the sensitive detection of an intriguing cancer biomarker, extracellular vesicles (EVs). Our extracellular vesicles on demand (EVOD) chip utilizes a catalyst-free click chemistry to rapidly and specifically isolate EVs of interest. This specific isolation is followed by subsequent dithiothreitol release of the isolated EVs for downstream functional analysis. This joint isolation and release provide a powerful tool for the screening and quantification of EVs of interest. By incorporating antibodies against cancer associated surface proteins into the click-chemistry, we were able to selectively recover cancer-associated exosomes, allowing for important insights into patient disease. This platform was also tested using non-small cell lung cancer (NSCLC) patient samples, where anti-epidermal growth factor receptor (EGFR) assisted platform were able to selectively isolate and release 76% more exosomes from NSCLC patients than from healthy donors. This matches the previously reported higher EGFR expression commonly found in NSCLC EVs. Through its rapid isolation kinetics and adaptability in marker targeting, the EVOD device provides a highly versatile liquid biopsy platform for clinicians to use in the fight against cancer.

Kang|Yoon-Tae|YT| Hadlock|Thomas|T| Jolly|Shruti|S| Nagrath|Sunitha|S|

D015374:Biosensing Techniques
D002289:Carcinoma, Non-Small-Cell Lung
D055088:Early Detection of Cancer
D000067128:Extracellular Vesicles
D006801:Humans
D008175:Lung Neoplasms

Extracellular vesicles
Microfluidics
Click chemistry
Immunoaffinity isolation
Vesicle release


Impact of legislative reform on benefit access and disability duration in workers' compensation: an interrupted time series study.

Abstract:
OBJECTIVES
To determine the impact of legislative changes to the New South Wales (NSW) workers' compensation scheme on injured workers access to benefits, insurer claim processing and work disability duration.

METHODS
Population-based interrupted time series study of workers' compensation claims made in NSW 2 years before and after legislative amendment in June 2012. Outcomes included incidence of accepted claims per 100 000 workers, the median and 75th percentile insurer decision time in days, and the median and 75th percentile of work disability duration in weeks. Effects were assessed relative to a comparator of seven other Australian workers' compensation jurisdictions.

RESULTS
n=1 069 231 accepted workers' compensation claims were analysed. Claiming in NSW fell 15.3% following legislative reform, equivalent to 46.6 fewer claims per 100 000 covered workers per month. This effect was greater in time loss claims (17.3%) than medical-only claims (10.3%). Across models, there were consistent trend increases in insurer decision time. Median work disability duration increased following the legislative reform.

CONCLUSIONS
The observed reduction in access to benefits was consistent with the policy objective of improving the financial sustainability of the compensation scheme. However, this was accompanied by changes in other markers of performance that were unintended, and are suggestive of adverse health consequences of the reform. This study demonstrates the need for care in reform of workers' compensation scheme policy.

D065186:Interrupted Time Series Analysis

time series study
epidemiology
public health


Is 8860 variation a rare polymorphism or associated as a secondary effect in HCM disease?

Abstract:
INTRODUCTION
mtDNA defects, both deletions and point mutations, have been associated with hypertrophic cardiomyopathies. The aim of this study was to establish a spectrum for mtDNA mutations in Iranian hypertrophic cardiomyopathy (HCM) patients.

MATERIAL AND METHODS
The control group was chosen among the special medical centre visitors who did not have hypertrophic cardiomyopathy or any related heart disease. Hypertrophic cardiomyopathy (HCM) is widely accepted as a pluricausal or multifactorial disease. Because of the linkage between energy metabolism in the mitochondria and cardiac muscle contraction, it is reasonable to assume that mitochondrial abnormalities may be responsible for some forms of HCM. Point mutations and deletions in the two hot spot regions of mtDNA were investigated by PCR and sequencing methods.

RESULTS
Some unreported point mutations have been found in this study but no deletion was detected. Meanwhile some of these point mutations have been investigated among HCM patients for the first time.

CONCLUSIONS
A8860G transition was detected in a high proportion, raising the question whether this rare polymorphism is associated as a secondary effect in HCM disease.

Houshmand|Massoud|M| Montazeri|Maryam|M| Kuchekian|Nafiseh|N| Noohi|Freidoon|F| Nozar|Givtaj|G| Zamani|Akram|A|

hypertrophic cardiomyopathy
mtDNA mutation disease


Is Umbilical Cord Blood Therapy an Effective Treatment for Early Lung Injury in Growth Restriction?

Abstract: Fetal growth restriction (FGR) and prematurity are often co-morbidities, and both are risk factors for lung disease. Despite advances in early delivery combined with supportive ventilation, rates of ventilation-induced lung injury (VILI) remain high. There are currently no protective treatments or interventions available that target lung morbidities associated with FGR preterm infants. Stem cell therapy, such as umbilical cord blood (UCB) cell administration, demonstrates an ability to attenuate inflammation and injury associated with VILI in preterm appropriately grown animals. However, no studies have looked at the effects of stem cell therapy in growth restricted newborns. We aimed to determine if UCB treatment could attenuate acute inflammation in the first 24 h of ventilation, comparing effects in lambs born preterm following FGR with those born preterm but appropriately grown (AG). Placental insufficiency (FGR) was induced by single umbilical artery ligation in twin-bearing ewes at 88 days gestation, with twins used as control (appropriately grown, AG). Lambs were delivered preterm at ~126 days gestation (term is 150 days) and randomized to either immediate euthanasia (unventilated controls, AGUVC and FGRUVC) or commenced on 24 h of gentle supportive ventilation (AGV and FGRV) with additional cohorts receiving UCB treatment at 1 h (AGCELLS, FGRCELLS). Lungs were collected at post-mortem for histological and biochemical examination. Ventilation caused lung injury in AG lambs, as indicated by decreased septal crests and elastin density, as well as increased inflammation. Lung injury in AG lambs was attenuated with UCB therapy. Ventilated FGR lambs also sustained lung injury, albeit with different indices compared to AG lambs; in FGR, ventilation reduced septal crest density, reduced alpha smooth muscle actin density and reduced cell proliferation. UCB treatment in ventilated FGR lambs further decreased septal crest density and increased collagen deposition, however, it increased angiogenesis as evidenced by increased vascular endothelial growth factor (VEGF) expression and vessel density. This is the first time that a cell therapy has been investigated in the lungs of growth restricted animals. We show that the uterine environment can alter the response to both secondary stress (ventilation) and therapy (UCB). This study highlights the need for further research on the potential impact of novel therapies on a growth restricted offspring.

Allison|Beth J|BJ|
Youn|Hannah|H|
Malhotra|Atul|A|
McDonald|Courtney A|CA|
Castillo-Melendez|Margie|M|
Pham|Yen|Y|
Sutherland|Amy E|AE|
Jenkin|Graham|G|
Polglase|Graeme R|GR|
Miller|Suzanne L|SL|

treatment
growth restriction
umbilical cord blood (UCB)
animal model
ventilation induced lung injury


Implication of increased serum stromal cell-derived factor-1 for primary biliary cholangitis.

Abstract:
BACKGROUND
Stromal cell-derived factor-1 (SDF-1), also called chemokine (C-X-C motif) ligand 12 (CXCL12), as a chemokine for premature B cells, T cells and monocytes, is detected in liver, pancreas, spleen and heart. However, its diagnostic value for primary biliary cholangitis (PBC) as well as the association of SDF-1 with inflammatory and fibrotic progression is unclear. The aim of this study was to determine serum stromal cell-derived factor-1 (SDF-1) level and to explore its diagnostic value for primary biliary cholangitis (PBC) as well as the association of SDF-1 with inflammatory and fibrotic progression of PBC.

METHODS
A total of 60 PBC patients who received liver biopsy, 32 age- and sex-matched patients with chronic hepatitis B (CHB) and 30 age- and sex-matched healthy controls (HC) were recruited. The sera were measured for SDF-1, interleukin-4 (IL-4), interferon gamma (IFN-γ) and IL-17 using multiplex immunoassay. PBC was divided into four histologic stages according to Scheuer's classification.

RESULTS
The results showed significantly higher median level of serum SDF-1 (median, interquartile (IQR), 1186.96, 1002.05-1471.33 pg/mL) in PBC patients than those with CHB (median, IQR, 740.69,600.30-1239.27 pg/mL) and HC (median, IQR, 738.44, 687.65-879.33 pg/mL) (P < 0.001). There was no significant difference between CHB patients and HC (P = 0.526). The receiver operating characteristic curves (ROC) showed good diagnostic performance of serum SDF-1 for PBC, AMA-positive and -negative PBC. In particular for AMA-negative PBC, the area under ROC was 0.817, with optimal cutoff value of 802.64 pg/mL and the sensitivity of 100%. Serum SDF-1 level was not associated with other immune, inflammatory and fibrotic indicators, including AMA, ANA, anti-gp210, sp100 and centromere antibodies, bilirubin, ALT, AST, ALP, GGT, WBC, neutrophil, lymphocyte, platelet, Neutrophil- (NLR) and platelet-lymphocyte (PLR), AST to ALT ratio, AST to platelet ratio index (APRI) and FIB-4 index (P > 0.05). Also, there was no significant difference for serum SDF-1 among histological stages (P = 0.091). However, Serum SDF-1 level was significantly correlated with serum IL-17 (r = 0.373, P = 0.004), but not with IL-4 (r = 0.110, P = 0.407) and IFN-γ (r = 0.215, P = 0.098) in those with PBC.

CONCLUSION
Serum SDF-1 is increased in and may be a potential useful marker for PBC. Moreover, it may be associated with Th17 recruitment and differentiation in PBC. However, serum SDF-1 may not be associated with the progression of PBC.

Yang|Zaixing|Z| Liang|Yan|Y| Lin|Feng|F| Zhang|Zhencheng|Z| Luo|Wanwan|W| Zhang|Yuting|Y| Zhong|Renqian|R|

Stromal cell-derived factor-1
Primary biliary cholangitis
Diagnostic performance
Interleukin-17


Experimental model proposed to deduce pharmacological evidence of the beta-cell neogenesis activity of Argyrolobium roseum vis-a-vis an evaluation of its hypoglycemic activity.

Abstract:
BACKGROUND
Argyrolobium roseum is described in texts for its botanical aspects with no mention of its therapeutic uses. Recently, a solvent fraction of this plant has been reported to possess insulin secretagogue activity.

OBJECTIVE
Primary objective of the study was to evaluate the hypoglycemic activity of different fractions of Argyrolobium roseum plant. Secondary objective was to devise a model for detecting its beta-cell neogenesis activity.

MATERIALS AND METHODS
Alcoholic fraction (AR) was studied in fasting, glucose-loaded and streptozotocin (STZ)-treated hyperglycemic rats. For deducing beta-cell neogenesis activity, a sub-lethal dose of STZ, causing delayed death in the animals, was administered.

RESULTS
AR in a dose of 200 mg/kg showed hypoglycemic activity in fasting and STZ-treated rats. With sub-lethal dose of STZ, recovery from hyperglycemia was seen.

CONCLUSION
AR of Argyrolobium roseum possesses hypoglycemic and a possible beta-cell neogenesis activity. Further studies are required to confirm its beta-cell neogenesis potential by cytological methods and to establish its role in the treatment of type 2 diabetes.

Gupta|Op|O| Malhotra|Pavan|P| Kudyar|Surbhi|S| Singh|Aneeta|A| Gupta|Geetika|G|

Argyrolobium roseum
hypoglycemic
streptozotocin
D-pinitol
regeneration