Gerrymandering and computational redistricting.

Abstract: Partisan gerrymandering poses a threat to democracy. Moreover, the complexity of the districting task may exceed human capacities. One potential solution is using computational models to automate the districting process by optimizing objective and open criteria, such as how spatially compact districts are. We formulated one such model that minimised pairwise distance between voters within a district. Using US Census Bureau data, we confirmed our prediction that the difference in compactness between the computed and actual districts would be greatest for states that are large and, therefore, difficult for humans to properly district given their limited capacities. The computed solutions highlighted differences in how humans and machines solve this task with machine solutions more fully optimised and displaying emergent properties not evident in human solutions. These results suggest a division of labour in which humans debate and formulate districting criteria whereas machines optimise the criteria to draw the district boundaries. We discuss how criteria can be expanded beyond notions of compactness to include other factors, such as respecting municipal boundaries, historic communities, and relevant legislation.

Gerrymandering
Computational redistricting
Cognitive limitations
Weighted k-means


Water Intake and Markers of Hydration Are Related to Cardiometabolic Risk Biomarkers in Community-Dwelling Older Adults: A Cross-Sectional Analysis.

Abstract:
BACKGROUND
Emerging evidence links underhydration and habitual low water intake to higher cardiometabolic risk, but evidence is limited in community-dwelling older adults.

OBJECTIVES
The objective is to examine if higher water intake and better hydration are associated with better cardiometabolic health.

METHODS
This cross-sectional analysis using general linear models included 2238 participants from the Framingham Heart Study Second Generation and First Generation Omni cohorts with an estimated glomerular filtration rate >30 mL·min-1·1.73 m-2 and a valid FFQ for assessment of water intake. Of these participants, 2219 had fasting spot urinary creatinine data and 950 had 24-h urine creatinine data to assess hydration. Cardiometabolic risk factors included fasting glucose, triglycerides (TGs), total cholesterol (TC), HDL cholesterol, and calculated LDL cholesterol; glycated hemoglobin (HbA1c); C-reactive protein (CRP); and systolic (SBP) and diastolic (DBP) blood pressure.

RESULTS
The combined cohorts were on average aged 70 y; 55% were women. Mean (95% CI) daily total water intakes were 2098 (2048, 2150) mL for men and 2109 (2063, 2156) mL for women. Total daily water, beverage (including plain water), and plain water intakes demonstrated significant positive trends with HDL cholesterol (P < 0.01). TG concentrations were significantly lower among the highest plain water consumers (P < 0.05). The 24-h urine concentration, as measured by creatinine, was positively associated with LDL cholesterol and TG concentrations ( P < 0.01) and inversely associated with HDL cholesterol concentrations (P < 0.002). Neither water intake nor urine concentration was associated with glucose or HbA1c (P > 0.05).

CONCLUSIONS
Our findings of a consistent pattern between circulating lipid concentrations and different water sources and hydration markers support an association between hydration and lipid metabolism in older adults and add to the growing evidence that inadequate water intake and underhydration may lead to higher cardiometabolic risk.

Jacques|Paul F|PF|0000-0001-5567-3147
Rogers|Gail|G|
Stookey|Jodi Dunmeyer|JD|
Perrier|Erica T|ET|

water intake
hydration
cardiometabolic risk
triglycerides
HDL cholesterol


UPLC/Q‑TOF‑MS based plasma metabolomics and clinical characteristics of polycystic ovarian syndrome.

Abstract: The present study aimed to develop novel diagnostic methods for polycystic ovarian syndrome (PCOS) by screening and identifying specific PCOS‑associated metabolic markers using plasma metabolomics. Ultra‑performance liquid chromatography/quadrapole‑time of flight‑mass spectrometry was adopted to establish the plasma metabolic fingerprint of 49 patients and 50 normal controls, in order to screen the potential metabolic markers. In addition, these markers were integrated with the clinical indexes, followed by focused analysis to obtain diagnostic markers. The present results demonstrated that not only was the concentration of palmitoyl sphingomyelin in plasma of patients with PCOS significantly increased; however, a statistically significant difference between the two PCOS subgroups was additionally demonstrated. At the same time, the concentrations of cyclic guanosine monophosphate (cGMP) and dehydroepiandrosterone sulphate in the plasma of patients of the subgroup 1 were significantly elevated. These markers were additionally integrated with the clinical index number of follicles in the left ovary and high‑density lipoprotein (HDL‑C), followed by receiver operating characteristic curve analysis, which demonstrated a diagnostic accuracy of ~90% in the control and the two subgroups. The integrated marker system consisting of palmitoyl sphingomyelin, cGMP and androsterone sulfate, as well as the number of left follicles and HDL‑C may be used for the accurate diagnosis and classification of PCOS. These results confirmed that the abnormalities in hormone metabolism and lipid metabolism disorder were primarily involved in the onset of PCOS.

Fan|Xuemei|X| Jiang|Jianfa|J| Huang|Zhiqiang|Z| Gong|Jumei|J| Wang|Yiming|Y| Xue|Wei|W| Deng|Yan|Y| Wang|Yanfang|Y| Zheng|Tingping|T| Sun|Aijun|A| Luo|Guoan|G|

D021241:Spectrometry, Mass, Electrospray Ionization

metabolomics
integrated marker system
accurate diagnosis
polycystic  ovarian  syndrome
potential  metabolic marker


Tenosynovial giant cell tumor of the upper cervical spine arising from the posterior atlanto-occipital membrane: a case report.

Abstract: A tenosynovial giant cell tumor is a benign proliferative disease, mostly arising from the synovial membrane of tendon sheaths, bursae, and joints. Axial skeleton involvement is very rare, but it is often found in the cervical spine. Spinal tenosynovial giant cell tumors often arise at the facet joints; a completely extra-articular spinal tenosynovial giant cell tumor is rare. We report an extremely rare case of tenosynovial giant cell tumor in the upper cervical spine that extended from the posterior atlanto-occipital membrane rather than the facet joint. Herein, the clinical and radiological findings will be reviewed to better our understanding of the characteristics of spinal tenosynovial giant cell tumors, and to help improve their diagnosis despite their non-typical locations of origin.

D000070779:Giant Cell Tumor of Tendon Sheath


MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies.

Abstract: The susceptibility of cancer cells to different types of treatments can be restricted by intrinsic and acquired therapeutic resistance, leading to the failure of cancer regression and remission. To overcome this problem, a combination therapy has been proposed as a fundamental strategy to improve therapeutic responses; however, resistance is still unavoidable. MicroRNA (miRNAs) are associated with cancer therapeutic resistance. The modulation of dysregulated miRNA levels through miRNA-based therapy comprising a replacement or inhibition approach has been proposed to sensitize cancer cells to other anti-cancer therapies. The combination of miRNA-based therapy with other anti-cancer therapies (miRNA-based combinatorial cancer therapy) is attractive, due to the ability of miRNAs to target multiple genes associated with the signaling pathways controlling therapeutic resistance. In this article, we present an overview of recent findings on the role of therapeutic resistance-related miRNAs in different types of cancer. We review the feasibility of utilizing dysregulated miRNAs in cancer cells and extracellular vesicles as potential candidates for miRNA-based combinatorial cancer therapy. We also discuss innate properties of miRNAs that need to be considered for more effective combinatorial cancer therapy.

Seo|Hyun Ah|HA|
Moeng|Sokviseth|S|
Sim|Seokmin|S|
Kuh|Hyo Jeong|HJ|
Choi|Soo Young|SY|
Park|Jong Kook|JK|

D015972:Gene Expression Regulation, Neoplastic

cancer
microRNA
therapeutic resistance
combination therapy
chemosensitization


Impact of nanoparticles on transcriptional regulation of catabolic genes of petroleum hydrocarbon-degrading bacteria in contaminated soil microcosms.

Abstract: This study was conducted to determine what effects nanoparticles (NPs) like TiO2 , ZnO, and Ag may pose on natural attenuation processes of petroleum hydrocarbons in contaminated soils. The solid NPs used were identified using x-ray diffraction technique and their average size was certified as 18.2, 16.9, and 18.3 nm for Ag-NPs, ZnO-NPs, and TiO2 -NPs, respectively. NPs in soil microcosms behave differently where it was dissolved as in case of Ag-NPs, partially dissolved as in ZnO-NPs or changed into other crystalline phase as in TiO2 -NPs. In this investigation, catabolic gene encoding catechol 2,3 dioxygenase (C23DO) was selected specifically as biomarker for monitoring hydrocarbon biodegradation potential by measuring its transcripts by RT-qPCR. TiO2 -NPs amended microcosms showed almost no change in C23DO expression profile or bacterial community which were dominated by Bacillus sp., Mycobacterium sp., Microbacterium sp., Clostridium sp., beside uncultured bacteria, including uncultured proteobacteria, Thauera sp. and Clostridia. XRD pattern suggested that TiO2 -NPs in microcosms were changed into other non-inhibitory crystalline phase, consequently, showing the maximum degradation profile for most low molecular weight oil fractions and partially for the high molecular weight ones. Increasing ZnO-NPs concentration in microcosms resulted in a reduction in the expression of C23DO with a concomitant slight deteriorative effect on bacterial populations ending up with elimination of Clostridium sp., Thauera sp., and uncultured proteobacteria. The oil-degradation efficiency was reduced compared to TiO2 -NPs amended microcosms. In microcosms, Ag-NPs were not detected in the crystalline form but were available in the ionic form that inhibited most bacterial populations and resulted in a limited degradation profile of oil, specifically the low molecular weight fractions. Ag-NPs amended microcosms showed a significant reduction (80%) in C23DO gene expression and a detrimental effect on bacterial populations including key players like Mycobacterium sp., Microbacterium sp., and Thauera sp. involved in the biodegradation of petroleum hydrocarbons.

D015964:Gene Expression Regulation, Bacterial

nanoparticles
catechol 2,3 dioxygenase
biodegradation
RT-qPCR


A biorefinery approach for enzymatic complex production for the synthesis of xylooligosaccharides from sugarcane bagasse.

Abstract: The use of low-cost feedstock for enzyme production is an environmental and economic solution. Sugarcane bagasse and soybean meal are employed in this study for optimised xylanase production with the concomitant synthesis of proteases. The enzymatic complex is produced by submerged fermentation by Aspergillus niger. Optimisation steps lead to a 2.16-fold increase in enzymatic activity. The fermentation kinetics are studied in Erlenmeyer flasks, a stirred tank reactor and a bubble column reactor, with the xylanase activities reaching 52.9; 33.7 and 60.5 U.mL-1, respectively. The protease production profile is also better in the bubble column reactor, exceeding 7 U.mL-1. The enzyme complex is then evaluated for the synthesis of xylooligosaccharides from sugarcane extracted xylan with a production of 3.1 g.L-1 where xylotriose is the main product. Excellent perspectives are observed for the developed process with potential applications in the animal feed, prebiotics and paper industries.

Valladares-Diestra|Kim Kley|KK|
Porto de Souza Vandenberghe|Luciana|L|
Soccol|Carlos Ricardo|CR|

Xylooligosaccharides
Sugarcane bagasse
Xylanase
Protease
Submerged fermentation


Genome-Wide Identification of M35 Family Metalloproteases in Rhizoctonia cerealis and Functional Analysis of RcMEP2 as a Virulence Factor during the Fungal Infection to Wheat.

Abstract: Rhizoctonia cerealis is the causal pathogen of the devastating disease, sharp eyespot, of the important crop wheat (Triticum aestivum L.). In phytopathogenic fungi, several M36 metalloproteases have been implicated in virulence, but pathogenesis roles of M35 family metalloproteases are largely unknown. Here, we identified four M35 family metalloproteases from R. cerealis genome, designated RcMEP2-RcMEP5, measured their transcriptional profiles, and investigated RcMEP2 function. RcMEP2-RcMEP5 are predicted as secreted metalloproteases since each protein sequence contains a signal peptide and an M35 domain that includes two characteristic motifs HEXXE and GTXDXXYG. Transcription levels of RcMEP2-RcMEP5 markedly elevated during the fungus infection to wheat, among which RcMEP2 expressed with the highest level. Functional dissection indicated that RcMEP2 and its M35 domain could trigger H2O2 rapidly-excessive accumulation, induce cell death, and inhibit expression of host chitinases. This consequently enhanced the susceptibility of wheat to R. cerealis and the predicated signal peptide of RcMEP2 functions required for secretion and cell death-induction. These results demonstrate that RcMEP2 is a virulence factor and that its M35 domain and signal peptide are necessary for the virulence role of RcMEP2. This study facilitates a better understanding of the pathogenesis mechanism of metalloproteases in phytopathogens including R. cerealis.

Pan|Lijun|L| Wen|Shengxian|S| Yu|Jinfeng|J| Lu|Lin|L| Zhu|Xiuliang|X| Zhang|Zengyan|Z|

Rhizoctonia cerealis
virulence
wheat (Triticum aestivum L.)
cell death
M35 metalloprotease
reactive oxygen species


Spacial and Temporal Patterns of Gene Expression After Cardiac MEK1 Gene Transfer Improve Post-Infarction Remodeling Without Inducing Global Hypertrophy.

Abstract: Alteration of mitogen activated protein (MAP) kinase signaling in transgenic mice can ameliorate post-myocardial infarction (MI) remodeling. However, pre-existing changes in transgenic hearts and clinically unrealistic transgene expression likely affect the response to injury; it is unknown whether clinically relevant induction of transgene expression in an otherwise normal heart can yield similar benefits. Constitutively active MEK1 (aMEK1) or LacZ adeno-associated virus 9 (AAV9) vectors were injected into the left ventricular (LV) chambers of mice either just before or after coronary ligation. Hearts were evaluated via Western blot, quantitative polymerase chain reaction, histology, and echocardiography. AAV9-mediated aMEK1 delivery altered ERK1/2 expression/activation as in transgenic mice. Transgene expression was not immediately detectable but plateaued at 17 days, and therefore did not likely impact acute ischemia as it would in transgenics. With AAV9-aMEK1 injection just prior to MI, robust expression in the infarct border zone during post-MI remodeling increased border zone wall thickness and reduced infarct size versus controls at 4 weeks, but did not induce global hypertrophy. Significant improvements in local and global LV function were observed, as were trends toward a preservation of LV volume. Delivery after ligation significantly lowered transgene expression in the infarct border zone and did not yield structural or functional benefits. The primary benefits observed in transgenic mice, ameliorated remodeling, and reduced chronic infarct size, were achievable via clinically relevant gene transfer of aMEK1, supporting ongoing translational efforts. Important differences, however, were observed, and consideration must be given to the timing and distribution of transgene delivery and expression. J. Cell. Biochem. 118: 775-784, 2017. © 2016 Wiley Periodicals, Inc.

Fan|Yanying|Y|
Yang|Yi-Lin|YL|
Yeh|Che-Chung|CC|
Mann|Michael J|MJ|

REMODELING
HYPERTROPHY
ADENO-ASSOCIATED VIRUS 9
MITOGEN ACTIVATED PROTEIN KINASE
MYOCARDIAL INFARCTION


Post-operative pain after laparoscopic ventral hernia repair, the impact of mesh soakage with bupivacaine solution versus normal saline solution: A randomised controlled trial (HAPPIEST Trial).

Abstract:
Background and Aims
Early postoperative pain after laparoscopic ventral hernia repair remains a concern for patients. Local application of anaesthetic agent in the surgical dissection area can potentially overcome this problem. The objective of this study was to evaluate the impact of soaking mesh in 0.5% bupivacaine solution as compared to normal saline solution on the post-operative pain.

Methodology
We conducted a parallel-design double-blind randomised controlled trial. Adult patients with uncomplicated ventral abdominal wall hernias were included in the trial. Mesh was soaked in 0.5% solution of bupivacaine before application in patients in the intervention arm, whereas it was soaked in normal saline solution for patients in the control arm. Post-operative pain was assessed by trained staff at 6 h and 24 h from surgery. It was graded on visual analogue scale (VAS) from 0 to 10.

Results
Trial was conducted from 16 November, 2015, to 15 September, 2017. During the study period, a total of 114 patients were randomised. Nine patients were excluded after randomisation. A total of 55 patients were analysed in the intervention arm and 50 patients were analysed in the control arm. Mean pain score at VAS at 6 h after laparoscopic ventral hernia repair in the intervention arm was 5.05 ± 1.2, whereas in the control arm, it was 5.54 ± 1.1 and the difference was statistically significant (P = 0.03-independent sample t-test). Mean pain score at VAS at 24 h after laparoscopic ventral hernia repair in the intervention arm was 3.16 ± 1.2, whereas in the control arm, it was 3.58 ± 1.4 and the difference was not statistically significant (P = 0.11-independent sample t-test).

Conclusion
Soakage of mesh in 0.5% bupivacaine solution before application in laparoscopic ventral hernia repair significantly reduces early post-operative pain.

Trial Registration
Trial was registered with clinicaltrials. gov (NCT03035617)URL: https://clinicaltrials. gov.

Chawla|Tabish|T|
Shahzad|Noman|N|
Ahmad|Khabir|K|
Ali|Jehangir Farman|JF|

post-operative pain
ventral hernia
Bupivacaine
laparoscopic surgery
local anaesthetics
mesh repair


Intertwined Detection and Recognition Roles of Tetrazine in Synergistic Anion-π and H-bond Based Anion Receptor.

Abstract: The intrinsic properties of tetrazine as a π-anion receptor and as an on/off recognition probe merged with H-bond ability of an urea motif into a single architecture constitutes a new generation of well-defined anion receptors. Complexation properties directly benefit from the dual and synergistic contribution of tetrazine and urea. In this study, we report on the synthesis and assessment of binding properties to anions of diverse geometries. Association constants have been predicted by theoretical calculations and evaluated by multiple and complementary experimental techniques including electrospray-mass tandem spectroscopy, NMR, UV-visible, steady state fluorescence spectroscopies and time resolved fluorescence. These results provide the basis for a better understanding of both the complexation and the anion-dependent quenching mechanism.

Plais|Romain|R| Gouarin|Guy|G| Gaucher|Anne|A| Haldys|Violette|V| Brosseau|Arnaud|A| Clavier|Gilles|G| Salpin|Jean-Yves|JY| Prim|Damien|D|0000-0003-3363-8089

tetrazine
anion-π
fluorescence
anion recognition
mass spectroscopy


Occupational Disappointment: Why Did I Even Become a Nurse?

Abstract:
INTRODUCTION
The aim of this study was to identify patterns of feelings and behavior of ED RNs who have experienced verbal workplace violence.

METHODS
Twenty-eight registered nurses from across the state of California were recruited. Data were collected, using in-depth interviews, and were recorded. The tapes were transcribed and analyzed using Glaserian grounded-theory methodology.

RESULTS
The main experiences of participants included occupational disappointment, peer support, lack of preparation by mandatory violence prevention classes, and unrealistic patient expectations.

DISCUSSION
These findings can help staff, managers, and future educators of ED RNs examine feelings, mitigate the profound and pervasive effects of VWPV, and improve patient care. Contribution to Emergency Practice.

Howerton Child|Rebekah J|RJ|
Sussman|Elizabeth J|EJ|

Occupational disappointment
Workplace violence
Emergency nursing
Grounded theory


Tpz1TPP1 SUMOylation reveals evolutionary conservation of SUMO-dependent Stn1 telomere association.

Abstract: Elongation of the telomeric overhang by telomerase is counteracted by synthesis of the complementary strand by the CST complex, CTC1(Cdc13)/Stn1/Ten1. Interaction of budding yeast Stn1 with overhang-binding Cdc13 is increased by Cdc13 SUMOylation. Human and fission yeast CST instead interact with overhang-binding TPP1/POT1. We show that the fission yeast TPP1 ortholog, Tpz1, is SUMOylated. Tpz1 SUMOylation restricts telomere elongation and promotes Stn1/Ten1 telomere association, and a SUMO-Tpz1 fusion protein has increased affinity for Stn1. Our data suggest that SUMO inhibits telomerase through stimulation of Stn1/Ten1 action by Tpz1, highlighting the evolutionary conservation of the regulation of CST function by SUMOylation.

Garg|Mansi|M|
Gurung|Resham L|RL|
Mansoubi|Sahar|S|
Ahmed|Jubed O|JO|
Davé|Anoushka|A|
Watts|Felicity Z|FZ|
Bianchi|Alessandro|A|


Picomolar Biosensing and Conformational Analysis Using Artificial Bidomain Proteins and Terbium-to-Quantum Dot Förster Resonance Energy Transfer.

Abstract: Although antibodies remain a primary recognition element in all forms of biosensing, functional limitations arising from their size, stability, and structure have motivated the development and production of many different artificial scaffold proteins for biological recognition. However, implementing such artificial binders into functional high-performance biosensors remains a challenging task. Here, we present the design and application of Förster resonance energy transfer (FRET) nanoprobes comprising small artificial proteins (αRep bidomains) labeled with a Tb complex (Tb) donor on the C-terminus and a semiconductor quantum dot (QD) acceptor on the N-terminus. Specific binding of one or two protein targets to the αReps induced a conformational change that could be detected by time-resolved Tb-to-QD FRET. These single-probe FRET switches were used in a separation-free solution-phase assay to quantify different protein targets at sub-nanomolar concentrations and to measure the conformational changes with sub-nanometer resolution. Probing ligand-receptor binding under physiological conditions at very low concentrations in solution is a special feature of FRET that can be efficiently combined with other structural characterization methods to develop, understand, and optimize artificial biosensors. Our results suggest that the αRep FRET nanoprobes have a strong potential for their application in advanced diagnostics and intracellular live-cell imaging of ligand-receptor interactions.

Léger|Corentin|C|
Yahia-Ammar|Akram|A|
Susumu|Kimihiro|K|0000-0003-4389-2574
Medintz|Igor L|IL|0000-0002-8902-4687
Urvoas|Agathe|A|
Valerio-Lepiniec|Marie|M|
Minard|Philippe|P|
Hildebrandt|Niko|N|0000-0001-8767-9623

D031541:Fluorescence Resonance Energy Transfer

FRET
binding assay
lanthanides
molecular diagnostics
molecular ruler
protein structure


Trends in incidence rate, health care use, and costs due to rib fractures in the Netherlands.

Abstract:
PURPOSE
This study aimed to examine population-based trends in the incidence rate, health care consumption, and work absence with associated costs in patients with rib fractures.

METHODS
A retrospective nationwide epidemiologic study was performed with data from patients with one or more rib fractures presented or admitted to a hospital in the Netherlands between January 1, 2015 and December 31, 2018 and have been registered in the Dutch Injury Surveillance System (DISS) or the Hospital Discharge Registry (HDR). Incidence rates were calculated using data from Statistics Netherlands. The associated direct health care costs, costs for lost productivity, and years lived with disability (YLD) were calculated using data from a questionnaire.

RESULTS
In the 4-year study period, a total of 32,124 patients were registered of which 19,885 (61.9%) required hospitalization with a mean duration of 7.7 days. The incidence rate for the total cohort was 47.1 per 100,000 person years and increased with age. The mean associated direct health care costs were €6785 per patient and showed a sharp increase after the age of 75 years. The mean duration of work absence was 44.2 days with associated mean indirect costs for lost productivity of €22,886 per patient. The mean YLD was 0.35 years and decreased with age.

CONCLUSION
Rib fractures are common and associated with lengthy HLOS and work absenteeism as well as high direct and indirect costs which appear to be similar between patients with one or multiple rib fractures and mostly affected by admitted patients and age.

Van Lieshout|Esther M M|EMM|http://orcid.org/0000-0002-2597-7948

Incidence rate
Rib fractures
Health care consumption
Epidemiology
Health care costs
Hospital length of stay


Cost-efficient entrapment of β-glucosidase in nanoscale latex and silicone polymeric thin films for use as stable biocatalysts.

Abstract: β-Glucosidase is an ubiquitous enzyme which has enormous biotechnological applications. Its deficiency in natural enzyme preparations is often overcome by exogenous supplementation, which further increases the enzyme utilization cost. Enzyme immobilization offers a potential solution through enzyme recycling and easy recovery. In the present work Aspergillus niger β-glucosidase is immobilized within nanoscale polymeric materials (polyurethane, latex and silicone), through entrapment, and subsequently coated onto a fibrous support. Highest apparent activity (90 U g(-1) polymer) was observed with latex, while highest entrapment efficiency (93%) was observed for the silicone matrix. Immobilization resulted in the thermo-stabilization of the β-glucosidase with an increase in optimum temperature and activation energy for cellobiose hydrolysis. Supplementation to cellulases also resulted in an increased cellulose hydrolysis, while retaining more than 70% functional stability. Hence, the current study describes novel preparations of immobilized β-glucosidase as highly stable and active catalysts for industrial food- and bio-processing applications.

Javed|Muhammad Rizwan|MR|
Buthe|Andreas|A|
Rashid|Muhammad Hamid|MH|
Wang|Ping|P|

β-Glucosidase Latex Silicone Immobilization Polyurethane


Rivaroxaban program for acute venous thromboembolism upon ED discharge, with focus on utility of commercially available dose pack.

Abstract:
OBJECTIVE
To evaluate the impact of a rivaroxaban discharge initiative on the efficacy and safety of acute venous thromboembolism treatment in emergency department patients.

PRACTICE INNOVATION
Patients discharged on rivaroxaban from the emergency department were provided extensive counseling along with a commercially-available medication dose pack by the ED pharmacist. Patients were contacted by phone until they had obtained outpatient follow-up and remained adherent to anticoagulation beyond the initial first month of treatment.

METHODS
In this retrospective chart review over a thirteen month period, efficacy and safety outcomes were compared between patients with intervention versus those who received usual care. Efficacy was defined by reduced 90-day readmission rates due to nonadherence or treatment failure, and improved medication adherence beyond the first month from discharge. Safety was determined by comparing 90-day readmission rates due to bleeding or adverse event.

RESULTS
41 patients received intervention with rivaroxaban, and 34 patients received usual care, with 76% prescribed rivaroxaban and remaining patients started on enoxaparin alone (6%) or enoxaparin plus warfarin (18%). Improved treatment efficacy in the intervention group was not found to be statistically significant. Safety outcomes were similar between the two groups.

CONCLUSION
Home treatment of acute VTE, facilitated by medication dose pack, is a promising tactic to ensure both immediate and long-term treatment efficacy and safety. Further studies are warranted to demonstrate clinical superiority of this intervention.

D000284:Administration, Oral
D037001:Directive Counseling
D065427:Factor Xa Inhibitors
D005260:Female
D006801:Humans
D008297:Male
D055118:Medication Adherence
D008875:Middle Aged
D010351:Patient Discharge
D010360:Patient Transfer
D012189:Retrospective Studies
D000069552:Rivaroxaban
D014481:United States
D054556:Venous Thromboembolism

Venous thromboembolism
Anticoagulation
Medication adherence
Transitions of care


Pretreatment with inhaled procaterol improves symptoms of dyspnea and quality of life in patients with severe COPD.

Abstract:
BACKGROUND
The clinical efficacy of short-acting β(2)-agonists administered before performing daily activities in chronic obstructive pulmonary disease (COPD) is unclear. The aim of this study was to investigate the clinical effect of supplementary inhaled procaterol hydrochloride in patients with COPD.

METHODS
Thirty outpatients with moderate to severe COPD (Stage II-IV) regularly using inhaled tiotropium bromide alone and with dyspnea during daily activities were enrolled. Subjects self-administered 20 μg of inhaled procaterol before daily activities no more than four times daily. Dyspnea symptom scores, St George's Respiratory Questionnaire (SGRQ) activity domains, impulse oscillometry system parameters, and pulmonary function tests were recorded at the beginning and end of the 2-week study.

RESULTS
At baseline, more than 80% of subjects reported dyspnea when walking up a slope (100.0%), climbing stairs (100.0%), gardening (93.3%), walking on flat ground (90.0%), bathing (86.7%), getting on a bus or train (83.3%), and changing clothes (80.0%). After 2 weeks, subjects with Stage III symptoms had significantly improved dyspnea scores on walking up a slope (P = 0.047), climbing stairs (P = 0.014), gardening (P = 0.034), walking on flat ground (P = 0.006), getting on a bus or train (P = 0.039), and changing clothes (P = 0.045). Both symptom and activity SGRQ domains improved significantly in subjects with Stage III symptoms (P = 0.036 and P = 0.028, respectively). Resistance of small airways and low-frequency reactance area values improved significantly in subjects with Stage III symptoms (P = 0.003 and P = 0.004, respectively). No significant changes were found in pulmonary function tests.

CONCLUSION
Use of supplementary inhaled procaterol before performing daily activities improved dyspnea symptoms in subjects with Stage III COPD.

procaterol
quality of life
daily activities
chronic obstructive pulmonary disease
impulse oscillometry system


Pedometer determined physical activity and obesity prevalence of Greek children aged 4-6 years.

Abstract:
BACKGROUND
Pre-school age is important for developing healthy attitudes towards physical activity (PA). However, research on pre-schoolers' pedometer-determined PA is limited.

AIM
To describe pre-schoolers' ambulatory activity; investigate step count differences in respect to Body Mass Index (BMI) categories and examine the prevalence of obesity.

SUBJECTS AND METHODS
Pre-school aged children (n = 250; 5.5 ± 0.4 years) from Komotini (Greece) wore Omron HJ-720IT-E2 pedometers for 10 consecutive days. Height and weight were measured and BMI was calculated.

RESULTS
Three-way repeated measures ANOVAs revealed that children performed more steps on weekdays than during weekends (p < 0.001) and during leisure time than school (p < 0.001). Significant differences appeared between normal and obese children's counts on weekdays (p < 0.001), weekend days (p < 0.05), during school (p < 0.001), after school (p < 0.005) and in weekly steps (p < 0.005). No gender differences were detected. Moreover, according to a sample t-test analysis, children's daily steps were significantly different from the 10,000 steps/day guideline, while obesity prevalence was 15.6%.

CONCLUSION
School-based ambulatory activity is lower than after school ambulatory activity, independent of BMI-category and gender, although obese children demonstrated fewer steps. Taking into account the high rate of both the obesity prevalence and children not meeting the 10,000 steps/day guideline, the need for preventive policies becomes obvious.

Kambas|Antonis|A|
Venetsanou|Fotini|F|
Avloniti|Alexandra|A|
Giannakidou|Dimitra M|DM|
Gourgoulis|Vassilios|V|
Draganidis|Dimitrios|D|
Chatzinikolaou|Athanasios|A|
Fatouros|Ioannis|I|
Michalopoulou|Maria|M|

obesity
Omron HJ-720IT-E2
Leisure-time
preschoolers
school-time


Academic Performance in Children of Mothers With Schizophrenia and Other Severe Mental Illness, and Risk for Subsequent Development of Psychosis: A Population-Based Study.

Abstract:
OBJECTIVE
We examined the academic performance at age 12 years of children of mothers diagnosed with schizophrenia or other severe mental illness using a large whole-population birth cohort born in Western Australia. We investigated the association between academic performance and the subsequent development of psychotic illness.

METHOD
The sample comprised 3169 children of mothers with severe mental illness (schizophrenia, bipolar disorder, unipolar major depression, delusional disorder or other psychoses; ICD-9 codes 295-298), and 88 353 children of comparison mothers without known psychiatric morbidity. Academic performance of children was indexed on a mandatory state-wide test of reading, spelling, writing and numeracy.

RESULTS
A larger proportion of children (43.1%) of mothers with severe mental illness performed below the acceptable standard than the reference group (30.3%; children of mothers with no known severe mental illness). After adjusting for covariates, children of mothers with any severe mental illness were more likely than the reference group to perform below-benchmark on all domains except reading. For all children, poor spelling was associated with the later development of psychosis, but particularly for those at familial risk for severe mental illness (hazard ratio [HR] = 1.81; 95% CI for HR = 1.21, 2.72).

CONCLUSIONS
Children of mothers with a severe mental illness are at increased risk for sub-standard academic achievement at age 12 years, placing these children at disadvantage for the transition to secondary school. For children with familial risk for severe mental illness, very poor spelling skills at age 12 years may be an indicator of risk for later psychotic disorder.

Lin|Ashleigh|A|
Di Prinzio|Patsy|P|
Young|Deidra|D|
Jacoby|Peter|P|
Whitehouse|Andrew|A|
Waters|Flavie|F|
Jablensky|Assen|A|
Morgan|Vera A|VA|

academic performance
schizophrenia
psychosis
familial risk
at-risk
genetic risk
linked data
neurocognition
population
psychiatric disorder


Comparison of laparoscopic hernia repair and open herniotomy in children: a retrospective cohort study.

Abstract:
BACKGROUND
Laparoscopic hernia repair in infancy and childhood is still debatable. The objective of this study is to compare laparoscopic-assisted hernia repair (LH) versus open herniotomy (OH) as regards operative time, postoperative complications, recurrence rate, and contralateral metachronous hernia rate.

METHODS
We analyzed all the patients with inguinal hernia who underwent surgery in our hospital from January 1, 2015 to December 31, 2015. There were 1125 patients, of which 202 patients received laparoscopic inguinal hernia repair (group A) and 923 patients received open herniotomy (group B). We recalled all the patients' records to identify operative time, postoperative hydrocele formation, and contralateral patent processus vaginalis (CPP) detection; we recalled all the patients' parents to identify the ipsilateral and contralateral recurrence and the testis position.

RESULTS
During the study period, the lost to follow-up rate is 9.9% in group A and 14.1% in group B. The mean follow-up period was about 10.1 months. The mean operative time for females with bilateral hernia in group A was much shorter than that for those in group B (P = 0.001). The postoperative hydrocele formation rate in group A was 1.5%, compared with 8.2% in group B (P = 0.001). The recurrence rate was 0.64% in group A, whereas in group B the recurrence rate was 0.46%. Of patients with unilateral hernia, none in group A experienced a contralateral metachronous hernia (MH) compared with 10.1% in group B (P < 0.001) and 65% MH appeared in 3 months after the first hernia repair. Females and patients with initial left-sided hernia tended to have a contralateral MH after the first open hernia repair.

CONCLUSION
Laparoscopic hernia repair in children is safe and effective, especially for female patients and patients with initial left-sided hernia. We recommend repairing the CPP simultaneously when performing laparoscopic procedures.

Zhu|L L|LL|
Xu|W J|WJ|
Liu|J B|JB|
Huang|X|X|
Lv|Z B|ZB|

Laparoscopic hernia repair
Inguinal hernia
Pediatric


Phosphopeptide Detection with Biotin-Labeled Phos-tag.

Abstract: Protein kinases are widely considered to be invaluable target enzymes for drug discovery and for diagnosing diseases and assessing their prognosis. Effective analytical techniques for measuring the activities of cellular protein kinases are therefore required for studies in the field of phosphoproteomics. We have recently developed a highly sensitive microarray-based technique for tracing the activities of protein kinases. A series of peptides that are specific substrates of various protein kinases are immobilized on a glass slide and subjected to phosphorylation by cell lysates. The resulting phosphorylated forms of the various peptides are then selectively and simultaneously detected by using a phosphate-binding tag molecule, biotin-labeled Phos-tag, bound to horseradish peroxidase-conjugated streptavidin. Enhanced chemiluminescence signals can then be readily detected by using an automatic image analyzer. In this chapter, we describe a standard protocol for detecting phosphopeptides by biotin-labeled Phos-tag. We also describe a microarray system for high-throughput profiling of intracellular protein kinase activities. The Phos-tag-based method is expected to be useful in the rapid detection of the complex range of phosphorylation reactions involved in cellular signaling events, and it has potential applications in high-throughput screening of kinase activators or inhibitors.

Phos-tag
Protein kinase
Peptide
Phosphorylation
Enhanced chemiluminescence
Microarray
High-throughput profiling
Biotin


Institutional Barriers to On-Site Alternative Water Systems: A Conceptual Framework and Systematic Analysis of the Literature.

Abstract: Scientists are increasingly exploring on-site water systems to supplement conventional centralized water and wastewater infrastructure. While major technological advancements have been achieved, we still lack a systematic view on the non-technical, or institutional, elements that constitute important barriers to the uptake of on-site urban water management systems. This paper presents a conceptual framework distinguishing between institutional barriers in six key dimensions: Equity, Knowledge and Capabilities, Financial Investment, Legal and Regulatory Frameworks, Legitimacy, and Market Structures. The analysis of the existing literature covering these barriers is translated into a typology of the socio-technical complexity of different types of alternative water systems (e.g., non-potable reuse, rainwater systems, and nutrient recovery). Findings show that socio-technical complexity increases with the pollution load in the source water, correlating to potential health risk, and the number of sectors involved in the value chain of an alternative water system. For example, greywater reuse for toilet flushing might have systematically less complex institutional barriers than source separation for agricultural reuse. This study provides practitioners with easily accessible means of understanding non-technical barriers for various types of on-site reuse systems and provides researchers with a conceptual framework for capturing socio-technical complexity in the adoption of alternative water systems.

D062065:Waste Water
D014867:Water
D014881:Water Supply

institutional barriers
on-site
alternative water system
urban water management
socio-technical complexity
decentralized


The improvement effect of limited mental practice in individuals with poststroke hemiparesis: the influence of mental imagery and mental concentration.

Abstract: [Purpose] This study examined whether limited mental practice improves the motor performance of poststroke individuals with hemiparesis. [Subjects] Twenty-three participants with poststroke hemiparesis (40-82 years of age) participated in this study. [Methods] The subjects were divided into four groups with respect to a dart-throwing task: the no-practice, physical practice only, mental practice only, and mental and physical practice groups. The groups were compared in terms of gains in motor performance, mental imagery vividness, and level of concentration during mental practice. [Results] No statistically significant difference was found for gains in motor performance among groups, and there was no correlation between imagery vividness and motor performance gains. However, a correlation was found between gains in motor performance and mental concentration during mental practice. [Conclusion] The results suggested that limited mental practice for individuals with poststroke hemiparesis may not improve motor performance. However, a higher degree of concentration during mental practice may improve motor performance.

Mental practice
Mental concentration
Imagery vividness


Cyclo(Phe-Pro) produced by Vibrio species passes through biological membranes by simple diffusion.

Abstract: Cyclo(Phe-Pro) (cFP), produced by the Vibrio species, plays the dual roles of being a signaling molecule and a virulence factor. Acting modes of this compound have recently been characterized at the molecular level. Nevertheless, the method by which this compound passes across biological membranes remains obscure. Using radiolabeled cFP, we examined the kinetics of transport for this compound across membranes using V. vulnificus, Escherichia coli, and sheep red blood cells. We observed that cFP was taken up by these cells in a concentration-dependent manner and was not affected by the addition of the proton ionophore carbonyl cyanide m-chlorophenyl hydrazone (CCCP), suggesting that cFP is taken up by passive transport. The kinetics of uptake of cFP by the above three types of cells revealed no significant differences, indicating that no specific protein is involved in this process. When the intracellular accumulation of cFP in the tested cells was measured, the concentrations did not exhibit significant differences between the 1-min and 10-min time points after cFP was added to the culture. In contrast, the intracellular concentration of fumarate, which is well known to be taken up by cells via active transport, was significantly higher at the 10-min than at the 1-min time point after addition. Taken together, this study shows that cFP is a diffusible molecule that does not require energy for transportation across biological membranes, and that cFP does not need membrane machinery in order to cross membranes and consequently act as a virulence factor or signal. KEY POINTS: • Kinetics of cFP uptake into cells of V. vulnificus, E. coli, or RBS was studied. • The uptake was not saturated and required no energy, indicating passive transport. • The lack of cell specificity in cFP uptake means no specific protein is needed. • Therefore, the cFP moves across the biological membrane by simple diffusion.

Cyclo(Phe-Pro)
Simple diffusion
Cyclic dipeptide
Vibrio vulnificus


Urinary metabolites of organophosphate esters: Concentrations and age trends in Australian children.

Abstract: There is growing concern around the use of organophosphate esters (OPEs) due to their suspected reproductive toxicity, carcinogenicity, and neurotoxicity. OPEs are used as flame retardants and plasticizers, and due to their extensive application in consumer products, are found globally in the indoor environment. Early life exposure to OPEs is an important risk factor for children's health, but poorly understood. To study age and sex trends of OPE exposures in infants and young children, we collected, pooled, and analysed urine samples from children aged 0-5years from Queensland, Australia for 9 parent OPEs and 11 metabolites. Individual urine samples (n=400) were stratified by age and sex, and combined into 20 pools. Three individual breast milk samples were also analysed to provide a preliminary estimate on the contribution of breast milk to the intake of OPEs. Bis(1-chloroisopropyl) phosphate (BCIPP), 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP), bis(1,3-dichloroisopropyl) phosphate (BDCIPP), dibutyl phosphate (DBP), diphenyl phosphate (DPHP), bis(2-butoxyethyl) phosphate (BBOEP), bis(2-butoxyethyl) 3-hydroxyl-2-butoxyethyl phosphate (3OH-TBOEP), and bis(2-butoxyethyl) hydroxyethyl phosphate (BBOEHEP) were detected in all urine samples, followed by bis(methylphenyl) phosphate (80%), and bis(2-ethylhexyl) phosphate (BEHP, 20%), and bis(2-chloroethyl) phosphate (BCEP, 15%). Concentrations of tris(2-chloroethyl) phosphate (TCEP), BCEP, tris(2-ethylhexyl) phosphate (TEHP), and DBP decreased with age, while bis(methylphenyl) phosphate (BMPP) increased with age. Significantly higher concentrations of DPHP (p=0.039), and significantly lower concentrations of TEHP (p=0.006) were found in female samples compared to males. The estimated daily intakes (EDIs) via breastfeeding, were 4.6, 26 and 76ng/kg/day for TCEP, TBP and TEHP, respectively, and were higher than that via air and dust, suggesting higher exposure through consumption of breast milk.

He|Chang|C|
Toms|Leisa-Maree L|LL|
Thai|Phong|P|
Van den Eede|Nele|N|
Wang|Xianyu|X|
Li|Yan|Y|
Baduel|Christine|C|
Harden|Fiona A|FA|
Heffernan|Amy L|AL|
Hobson|Peter|P|
Covaci|Adrian|A|
Mueller|Jochen F|JF|

Metabolites
Children
Alternative flame retardants
Biomonitoring
Exposure assessment
Organophosphate flame retardants


New approach to the differentiation of marble samples using thermal analysis and chemometrics in order to identify provenance.

Abstract:
BACKGROUND
The possibility of applying a novel chemometric approach which could allow the differentiation of marble samples, all from different quarries located in the Mediterranean basin and frequently used in ancient times for artistic purposes, was investigated. By suggesting tentative or allowing to rule out unlikely attributions, this kind of differentiation could, indeed, be of valuable support to restorers and other professionals in the field of cultural heritage. EXPERIMENTAL DATA WERE OBTAINED ONLY USING THERMAL ANALYTICAL TECHNIQUES: Thermogravimetry (TG), Derivative Thermogravimetry (DTG) and Differential Thermal Analysis (DTA).

RESULTS
The extraction of kinetic parameters from the curves obtained using these thermal analytical techniques allowed Activation Energy values to be evaluated together with the logarithm of the Arrhenius pre-exponential factor of the main TG-DTG process. The main data thus obtained after subsequent chemometric evaluation (using Principal Components Analysis) have already proved useful in the identification the original quarry of a small number of archaeological marble finds.

CONCLUSION
One of the most evident advantages of the thermoanalytical - chemometric approach adopted seems to be that it allows the certain identification of an unknown find composed of a marble known to be present among the reference samples considered, that is, contained in the reference file. On the other hand with equal certainty it prevents the occurrence of erroneous or highly uncertain identification if the find being tested does not belong to the reference file considered.

Gatta|Tania|T| Gregori|Emanuela|E| Marini|Federico|F| Tomassetti|Mauro|M| Visco|Giovanni|G| Campanella|Luigi|L|

Marbles
Thermal analysis
Chemometrics
Principal component analysis
Wyden-widmann method


Implementing a continuum of care model for older people-results from a Swedish case study.

Abstract:
INTRODUCTION
There is a need for integrated care and smooth collaboration between care-providing organisations and professions to create a continuum of care for frail older people. However, collaboration between organisations and professions is often problematic. The aim of this study was to examine the process of implementing a new continuum of care model in a complex organisational context, and illuminate some of the challenges involved. The introduced model strived to connect three organisations responsible for delivering health and social care to older people: the regional hospital, primary health care and municipal eldercare.

METHODS
The actions of the actors involved in the process of implementing the model were understood to be shaped by the actors' understanding, commitment and ability. This article is based on 44 qualitative interviews performed on four occasions with 26 key actors at three organisational levels within these three organisations.

RESULTS AND CONCLUSIONS
The results point to the importance of paying regard to the different cultures of the organisations when implementing a new model. The role of upper management emerged as very important. Furthermore, to be accepted, the model has to be experienced as effectively dealing with real problems in the everyday practice of the actors in the organisations, from the bottom to the top.

implementation
continuum of care
integrated care
older people
Sweden
qualitative methods


Determination of natural radioactivity material concentrations consumed widely during Corona pandemic in Thi Qar province.

Abstract: The present study was carried out to assess the potential radiation hazards to the public, especially the persons who consumed onion and garlic plants widely during coronavirus disease in Thi Qar province South of Iraq. Nine samples collected from the market (5 samples onion and 4 sample Garlic), which classified according to their origin. Using 3″x3″ NaI (Tl) gamma ray spectroscopy system, the radioactivity concentrations of the natural radionuclides radium-226, thorium-232 and potassium-40 were determined. The results obtained showed that the average concentration of radioactivity of radium-226, thorium-232 and potassium-40 is 3.398 Bqkg-1, 4.667 Bqkg-1 and 216.738 Bqkg-1, respectively, for onion and 2.808 Bqkg-1, 3.524 Bqkg-1, and 172.064 Bqkg-1 for garlic. The results also showed that the average annual total effective dose of the three nuclides is 122.955  for onion and 97.231  for garlic. Other relevant risk parameters were also calculated, such as equivalent activity concentrations, absorbed dose, excess lifetime cancer risks, and other health risk parameters. One of the most important conclusions reached by this study is that the natural radioactive elements in onions and garlic do not pose a great danger to their consumers, especially those infected with the COVID-19. Because the concentrations of these radioactive elements do not exceed the permissible limits recommended by recognized scientific organizations and agencies such as International Commission on Radiological Protection (ICRP), United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR), and World Health Organization (WHO).

Onion
Garlic
Garlic radiation hazard
NORM
Onion radioactivity


The atypical small GTPase GEM/Kir is a negative regulator of the NADPH oxidase and NETs production through macroautophagy.

Abstract: Despite the important function of neutrophils in the eradication of infections and induction of inflammation, the molecular mechanisms regulating the activation and termination of the neutrophil immune response is not well understood. Here, the function of the small GTPase from the RGK family, Gem, is characterized as a negative regulator of the NADPH oxidase through autophagy regulation. Gem knockout (Gem KO) neutrophils show increased NADPH oxidase activation and increased production of extracellular and intracellular reactive oxygen species (ROS). Enhanced ROS production in Gem KO neutrophils was associated with increased NADPH oxidase complex-assembly as determined by quantitative super-resolution microscopy, but normal exocytosis of gelatinase and azurophilic granules. Gem-deficiency was associated with increased basal autophagosomes and autolysosome numbers but decreased autophagic flux under phorbol ester-induced conditions. Neutrophil stimulation triggered the localization of the NADPH oxidase subunits p22phox and p47phox at LC3-positive structures suggesting that the assembled NADPH oxidase complex is recruited to autophagosomes, which was significantly increased in Gem KO neutrophils. Prevention of new autophagosome formation by treatment with SAR405 increased ROS production while induction of autophagy by Torin-1 decreased ROS production in Gem KO neutrophils, and also in wild-type neutrophils, suggesting that macroautophagy contributes to the termination of NADPH oxidase activity. Autophagy inhibition decreased NETs formation independently of enhanced ROS production. NETs production, which was significantly increased in Gem-deficient neutrophils, was decreased by inhibition of both autophagy and calmodulin, a known GEM interactor. Intracellular ROS production was increased in Gem KO neutrophils challenged with live Gram-negative bacteria Pseudomonas aeruginosa or Salmonella Typhimurium, but phagocytosis was not affected in Gem-deficient cells. In vivo analysis in a model of Salmonella Typhimurium infection indicates that Gem-deficiency provides a genetic advantage manifested as a moderate increased in survival to infections. Altogether, the data suggest that Gem-deficiency leads to the enhancement of the neutrophil innate immune response by increasing NADPH oxidase assembly and NETs production and that macroautophagy differentially regulates ROS and NETs in neutrophils.

Johnson|Jennifer L|JL|
Ramadass|Mahalakshmi|M|
Rahman|Farhana|F|
Meneses-Salas|Elsa|E|
Zgajnar|Nadia R|NR|
Carvalho Gontijo|Raquel|R|
Zhang|Jinzhong|J|
Kiosses|William B|WB|
Zhu|Yanfang Peipei|YP|
Hedrick|Catherine C|CC|
Perego|Marta|M|
Gunton|Jenny E|JE|
Pestonjamasp|Kersi|K|
Napolitano|Gennaro|G|
Catz|Sergio D|SD|

D000818:Animals
D000071182:Autophagosomes
D002147:Calmodulin
D004195:Disease Models, Animal
D065206:Extracellular Traps
D042541:Intracellular Space
D000080550:Macroautophagy
D018345:Mice, Knockout
D008869:Microtubule-Associated Proteins
D020559:Monomeric GTP-Binding Proteins
D019255:NADPH Oxidases
D018375:Neutrophil Activation
D009504:Neutrophils
D011550:Pseudomonas aeruginosa
D017382:Reactive Oxygen Species
D012481:Salmonella Infections, Animal
D012486:Salmonella typhimurium

small GTPase
NADPH oxidase
NETs
inflammation
autophagy
innate immunity


Smartphone DNA or RNA Sensing Using Semisynthetic Luciferase-Based Logic Device.

Abstract: Detection of specific oligonucleotide sequences is central to numerous applications, and technologies amenable to point-of-care diagnostics or end users are needed. Here, we report a technology making use of a bioluminescent readout and smartphone quantification. The sensor is a semisynthetic luciferase (H-Luc-PNA conjugate) that is turned on by a strand-displacement reaction. We demonstrated sensing of three different microRNAs (miRs), as representative cancer biomarkers, and demonstrate the possibility to integrate an AND gate to sense two sequences simultaneously.

DNA
bioluminescence
PNA
biosensor
smartphone readout


Towards a poststructural understanding of abortion and social class in England.

Abstract: Despite previous research suggesting that social class influences experiences of and attitudes to abortion, there is a dearth of research which studies the intersection of abortion and social class in England. Across the UK, abortion rates and experiences differ by region and socio-economic status, reflecting broader health inequalities. Contemporary austerity in the UK creates an imperative for new research which contextualises the experience of abortion within this socio-historical moment, and the worsening inequalities which have accompanied it. Whilst work on abortion and social inequality exists, it has often approached class as an a priori category. I argue that contemporary post-structural work on class provides a framework to go beyond this approach by examining how these social classifications occur; who has the power to classify; and how these classifications might be resisted. This framework is demonstrated with emerging findings from a life history study of abortion experiences in England. The applications of this to the work on abortion are potentially rich, because the act of ending a pregnancy invites classification from many quarters, from the legal (legal/illegal) to the medical (early/late) to the moral (deserved/undeserved). This work, therefore, speaks to public health concerns about access to and stigma around abortion and social inequalities.

Abortion
social class
England
inequality
austerity


Adenosine A2A receptor signaling attenuates LPS-induced pro-inflammatory cytokine formation of mouse macrophages by inducing the expression of DUSP1.

Abstract: Adenosine is known to reduce inflammation by suppressing the activity of most immune cells. Previous studies have shown that lipopolysaccharide (LPS) stimulated mouse macrophages produce adenosine, and the adenosine A2A receptor (A2AR) signaling activated in an autocrine manner attenuates LPS-induced pro-inflammatory cytokine formation. It has been suggested that A2AR signaling inhibits LPS-induced pro-inflammatory cytokine production through a unique cAMP-dependent, but PKA- and Epac-independent signaling pathway. However, the mechanism of inhibition was not identified so far. Here we report that LPS stimulation enhances A2AR expression in mouse bone marrow derived macrophages, and loss of A2ARs results in enhanced LPS-induced pro-inflammatory response. Loss of A2ARs in A2AR null macrophages did not alter the LPS-induced NF-κB activation, but an enhanced basal and LPS-induced phosphorylation of MAP kinases (especially that of JNKs) was detected in A2AR null cells. A2AR signaling did not alter the LPS-induced phosphorylation of their upstream kinases, but by regulating adenylate cyclase activity it enhanced the expression of dual specific phosphatase (DUSP)1, a negative regulator of MAP kinases. As a result, lower basal and LPS-induced DUSP1 mRNA and protein levels can be detected in A2AR null macrophages. Silencing of DUSP1 mRNA expression resulted in higher basal and LPS-induced JNK phosphorylation and LPS-induced pro-inflammatory cytokine formation in wild type macrophages, but had no effect on that in A2AR null cells. Our data indicate that A2AR signaling regulates both basal and LPS-induced DUSP1 levels in macrophages via activating the adenylate cyclase pathway.

D048031:JNK Mitogen-Activated Protein Kinases

Adenosine A2A receptor
Macrophages
Lipopolysaccharide
Dual specific phosphatase-1
cAMP


Platelet-rich plasma versus corticosteroid injection for recalcitrant lateral epicondylitis: clinical and ultrasonographic evaluation.

Abstract:
PURPOSE
To evaluate the clinical and ultrasonographic changes in the morphology and vascularity of the common extensor tendon after injecting platelet-rich plasma (PRP) or corticosteroid (CS) for recalcitrant lateral epicondylitis (LE).

METHODS
30 patients aged 18 to 60 years with recalcitrant (>6 months) LE not responsive to oral medication or non-invasive treatment were randomised to receive PRP (n=15) or CS (n=15) injection. Patients were assessed using the visual analogue scale (VAS) for pain, Disabilities of the Arm, Shoulder and Hand Scale (DASH) score, Oxford Elbow Score, modified Mayo Clinic performance index for the elbow (modified Mayo score), and hand grip strength. Ultrasonography was performed by a musculoskeletal ultrasonologist to evaluate for tear at the common extensor origin, oedema at the common extensor origin, cortical erosion, probe-induced tenderness, and thickness of the tendon.

RESULTS
The VAS for pain, DASH score, Oxford Elbow Score, modified Mayo score, and hand grip strength all improved significantly from pre-injection to the 6-month follow-up in the PRP and CS groups. However, in the CS group, the scores generally peaked at 3 months and then deteriorated slightly at 6 months indicating recurrence of symptoms, which involved 46.7% of the CS patients. At 6 months, the number of patients positive for various ulrasonographic findings generally decreased. However, in the CS group, the number of patients with reduced thickness of the common extensor tendon increased from 2 to 12, and the number of patients with cortical erosion at the lateral epicondyle increased from 9 to 11.

CONCLUSION
PRP appeared to enable biological healing of the lesion, whereas CS appeared to provide short-term, symptomatic relief but resulted in tendon degeneration.

Gautam|V K|VK|
Verma|Saurabh|S|
Batra|Sahil|S|
Bhatnagar|Nidhi|N|
Arora|Sumit|S|

platelet-rich plasma
ultrasonography
tennis elbow


Effects of foreign direct investment on carbon emissions: Evidence from China and its Belt and Road countries.

Abstract: This paper examines the effects of China's foreign direct investment (FDI) on the carbon emissions of its domestic economy and the Belt and Road countries (BRCs). Total inward FDI into China as a host country shows a pollution reducing effect in the western and eastern regions while that in the central region remains unchanged. But China's outward FDI particularly from its eastern region reduces pollution in China. This suggests that China could be exporting carbon emissions via its FDI in the BRCs. The effects on BRCs' pollution from China's FDI is however different depending on the country's level of development. China's FDI was found to have no effect on high and upper middle income BRCs; a decreasing effect on low income BRCs; and an increasing effect on lower middle income BRCs. Evidence shows that China needs to consider a mix of policies to manage its inward and outward FDI to ensure its move to a low carbon economy benefits its own regional development and the BRCs by not contributing to increased carbon emissions.

Foreign direct investment
Carbon emissions
Belt and road countries


A global database of ant species abundances.

Abstract: What forces structure ecological assemblages? A key limitation to general insights about assemblage structure is the availability of data that are collected at a small spatial grain (local assemblages) and a large spatial extent (global coverage). Here, we present published and unpublished data from 51 ,388 ant abundance and occurrence records of more than 2,693 species and 7,953 morphospecies from local assemblages collected at 4,212 locations around the world. Ants were selected because they are diverse and abundant globally, comprise a large fraction of animal biomass in most terrestrial communities, and are key contributors to a range of ecosystem functions. Data were collected between 1949 and 2014, and include, for each geo-referenced sampling site, both the identity of the ants collected and details of sampling design, habitat type, and degree of disturbance. The aim of compiling this data set was to provide comprehensive species abundance data in order to test relationships between assemblage structure and environmental and biogeographic factors. Data were collected using a variety of standardized methods, such as pitfall and Winkler traps, and will be valuable for studies investigating large-scale forces structuring local assemblages. Understanding such relationships is particularly critical under current rates of global change. We encourage authors holding additional data on systematically collected ant assemblages, especially those in dry and cold, and remote areas, to contact us and contribute their data to this growing data set.

database
ants
abundance
local assemblage
occurrence
geo-referenced
habitat
disturbance
Winkler trap
Formicidae
pitfall trap


Peripheral arterial disease and revascularization of the diabetic foot.

Abstract: Diabetes is a complex disease with many serious potential sequelae, including large vessel arterial disease and microvascular dysfunction. Peripheral arterial disease is a common large vessel complication of diabetes, implicated in the development of tissue loss in up to half of patients with diabetic foot ulceration. In addition to peripheral arterial disease, functional changes in the microcirculation also contribute to the development of a diabetic foot ulcer, along with other factors such as infection, oedema and abnormal biomechanical loading. Peripheral arterial disease typically affects the distal vessels, resulting in multi-level occlusions and diffuse disease, which often necessitates challenging distal revascularisation surgery or angioplasty in order to improve blood flow. However, technically successful revascularisation does not always result in wound healing. The confounding effects of microvascular dysfunction must be recognised--treatment of a patient with a diabetic foot ulcer and peripheral arterial disease should address this complex interplay of pathophysiological changes. In the case of non-revascularisable peripheral arterial disease or poor response to conventional treatment, alternative approaches such as cell-based treatment, hyperbaric oxygen therapy and the use of vasodilators may appear attractive, however more robust evidence is required to justify these novel approaches.

Forsythe|R O|RO|
Brownrigg|J|J|
Hinchliffe|R J|RJ|


Effect of modifiable risk factors in Parkinson's disease: A case-control study looking at common dietary factors, toxicants, and anti-inflammatory medications.

Abstract:
OBJECTIVE
To investigate how common modifiable exposures, including dietary factors, select toxicants, and anti-inflammatory medications, may affect Parkinson's disease.

METHODS
Using surveys, a case-control study was conducted at a medical center, comparing Parkinson's disease patients (N  =  149) and healthy controls (N  =  105). Subjects reported exposure to red meats, vegetables, alcohol, tobacco, anti-inflammatory medications, and pesticides. The relationship between exposures and Parkinson's disease diagnosis was analyzed by logistic regression to generate odds ratio and 95% confidence interval.

RESULTS
Consuming red meat "sometimes" or "always" was positively associated with Parkinson's disease as compared to eating red meats "rarely" or "never"; (odds ratio  =   2.15, 95% confidence interval   =   1.06, 4.39; p  =  0.03) and (odds ratio   =   4.47, 95% confidence interval   =   1.67, 11.94; p  =  0.003), respectively. Exposure to pesticides showed a positive association with Parkinson's disease (odds ratio  =   2.84, 95% confidence interval   =   1.34, 6.00; p  =  0.007). "Always" use of aspirin was inversely associated with Parkinson's disease (odds ratio  =   0.32, 95% confidence interval   =   0.14, 0.70; p  =  0.004). "Ever" having used anti-histamines was inversely associated with Parkinson's disease (odds ratio  =   0.37, 95% confidence interval  =  0.17, 0.81; p  =  0.01).

DISCUSSION
Our study suggests that there are modifiable external factors that are associated with Parkinson's disease. The present study can thus assist clinicians, policy makers, and people living with Parkinson's disease in improving the experience and management of Parkinson's disease.

aspirin
Parkinson disease
diet
inflammation


Biosynthesis and Characterization of ZnO Nanoparticles Using Ochradenus arabicus and Their Effect on Growth and Antioxidant Systems of Maerua oblongifolia.

Abstract: Zincoxide nanoparticles (ZnO NPs) are among the most produced and used nanomaterials worldwide, and in recent times these nanoparticles have also been incorporate in plant science and agricultural research. The present study was planned to synthesize ZnO NPs biologically using Ochradenus arabicus leaves and examine their effect on the morphology and physiology properties of Maerua oblongifolia cultured in vitro. ZnO NPs were characterized by UV-visible spectroscopy (UV-vis), X-ray diffractometer (XRD), Fourier transform infrared spectroscopy (FT-IR), and transmission electron microscopy, which demonstrated hexagonal shape nanoparticles of size ranging from 10 to 50 nm. Thus, the study uncovered an efficient, eco-friendly and simple technique for biosynthesis of multifunctional ZnO NPs using Ochradenus arabicus following growth of Maerua oblongifolia shoots in different concentrations of ZnO NPs (0, 1.25, 2.5, 5, 10, or 20 mg L-1) in Murashige and Skoog medium. Remarkable increases in plant biomass, photosynthetic pigments, and total protein were recorded up to a concentration of 5 mg L-1; at the same time, the results demonstrated a significant reduction in lipid peroxidation levels with respect to control. Interestingly, the levels of proline and the antioxidant enzyme catalase (CAT), superoxide dismutase (SOD), and glutathione reductase (GR) activities were increased significantly in response to all ZnO NP treatments. These findings indicate that bioengineered ZnO NPs play a major role in accumulation of biomass and stimulating the activities of antioxidant enzymes in plant tissues. Thus, green-synthesized ZnO NPs might be of agricultural and medicinal benefit owing to their impacts on plants in vitro.

ZnO NPs
proline
antioxidant enzymes
green-synthesize
M. oblongifolia
chlorophyll


A case of diffuse alveolar hemorrhage associated with hyaluronic acid dermal fillers.

Abstract:
PATIENT
Male, 25 FINAL DIAGNOSIS: Diffuse alveolar hemorrhage Symptoms: Cough dry • short of breath

MEDICATION
- Clinical Procedure: - Specialty: -

OBJECTIVE
Unusual clinical course.

BACKGROUND
Hyaluronic acid is a substance that is naturally present in the human body, especially in joints and eyes. Hyaluronic acid injectable gels have been available for the general market since 2003 as cosmetic dermal fillers and skin boosters. Diffuse alveolar hemorrhage is an acute event that threatens the life of the patient and can lead to pulmonary fibrosis. Alveolar hemorrhage associated with hyaluronic acid dermal fillers is an entity that to the best of our knowledge has never been described in the medical literature.

CASE REPORT
We describe a patient who presented with dyspnea and cough after a subcutaneous injection of hyaluronic acid, with radiographic abnormalities including ground glass opacities and consolidation. The patient underwent flexible bronchoscopy and was diagnosed with diffuse alveolar hemorrhage.

CONCLUSIONS
This case emphasizes that this life threatening condition may occur with the use of this medication and physicians must be aware of this disorder, as early recognition and management can reduce morbidity.

Basora|Jose F|JF|
Fernandez|Ricardo|R|
Gonzalez|Modesto|M|
Adorno|Jose|J|

Diffuse Alveolar Hemorrhage
Hyaluronic Acid – adverse effects
Lung Diseases, Interstitial


Factors influencing effectiveness in postgraduate medical education - a qualitative study of experiences of the responsible clinical consultants.

Abstract:
BACKGROUND
Medical education leaders are important for educational quality in postgraduate medical education. Their work tasks are complex and contain different components. However, factors that are influencing leaders´ effectiveness in completing these tasks are unexplored. Understanding and developing these factors is most likely essential to strengthen postgraduate medical education and to consequently improve the quality in health care delivery. This study explores the experiences of factors that influence effectiveness of clinical consultants responsible for postgraduate medical education at clinical departments. Effectiveness was defined as fulfillment of work tasks.

METHODS
A qualitative study was performed with data gathered through semi-structured face-to-face interviews with 17 consultants responsible for postgraduate medical education. Data was analyzed by qualitative content analysis.

RESULTS
Findings clustered into four themes of factors influencing effectiveness: individual (being an expert, social competence), relational (support and cooperation, communication), attitudinal (shared vision, organizational values, colleagues' attitudes) and structural (organizational characteristics, regulations and guidelines, conditions for the role). The factors were experienced to influence effectiveness in a positive or a negative direction.

CONCLUSIONS
This study shed light on the complex and interrelated factors experienced to have impact on the role of consultant responsible for postgraduate medical education. Viewing the result through the concept of power, the role mainly relies on personal power sources like expert and referent power whereas power connected to the position often are lacking. To increase effectiveness of the role, a differentiated strategy which involves activities at both individual, group and organizational levels is needed.

Effectiveness
Postgraduate
Medical education
Clinical consultant
Educational effectiveness
Leadership
Professional development
Qualitative research


Ultrasound-guided internal jugular vein catheterization in critically ill pediatric patients.

Abstract:
PURPOSE
Continuous intravenous access is imperative in emergency situations. Ultrasound-guided internal jugular vein (IJV) catheterization was investigated in critically ill pediatric patients to assess the feasibility of the procedure.

METHODS
Patients admitted to the pediatric intensive care unit between February 2011 and September 2012 were enrolled in this study. All patients received a central venous catheter from attending house staff under ultrasound guidance. Outcome measures included successful insertion of the catheter, cannulation time, number of cannulation attempts, and number and type of resulting complications.

RESULTS
Forty-one central venous catheters (93.2%) were successfully inserted into 44 patients (21 males and 23 females; mean age, 6.54±1.06 years). Thirty-three patients (75.0%) had neurological disorders. The right IJV was used for catheter insertion in 34 cases (82.9%). The mean number of cannulation attempts and the mean cannulation time was 1.57±0.34 and 14.07±1.91 minutes, respectively, the mean catheter dwell time was 14.73±2.5 days. Accidental catheter removal was observed in 9 patients (22.0%). Six patients (13.6%) reported complications, the most serious being catheter-related sepsis, which affected 1 patient (2.3%). Other complications included 2 reported cases of catheter malposition (4.6%), and 1 case each of arterial puncture (2.3%), pneumothorax (2.3%), and skin infection (2.3%).

CONCLUSION
The results suggest that ultrasound-guided IJV catheterization can be performed easily and without any serious complications in pediatric patients, even when performed by visiting house staff. Therefore, ultrasound-guided IJV catheterization is strongly recommended for critically ill pediatric patients.

Yang|Eu Jeen|EJ|
Ha|Hyeong Seok|HS|
Kong|Young Hwa|YH|
Kim|Sun Jun|SJ|

Jugular veins
Catheterization
Child
Ultrasonography


Immune Responses to Pseudomonas aeruginosa Biofilm Infections.

Abstract: Pseudomonas aeruginosa is a key pathogen of chronic infections in the lungs of cystic fibrosis patients and in patients suffering from chronic wounds of diverse etiology. In these infections the bacteria congregate in biofilms and cannot be eradicated by standard antibiotic treatment or host immune responses. The persistent biofilms induce a hyper inflammatory state that results in collateral damage of the adjacent host tissue. The host fails to eradicate the biofilm infection, resulting in hindered remodeling and healing. In the present review we describe our current understanding of innate and adaptive immune responses elicited by P. aeruginosa biofilms in cystic fibrosis lung infections and chronic wounds. This includes the mechanisms that are involved in the activation of the immune responses, as well as the effector functions, the antimicrobial components and the associated tissue destruction. The mechanisms by which the biofilms evade immune responses, and potential treatment targets of the immune response are also discussed.

Moser|Claus|C|
Jensen|Peter Østrup|PØ|
Thomsen|Kim|K|
Kolpen|Mette|M|
Rybtke|Morten|M|
Lauland|Anne Sofie|AS|
Trøstrup|Hannah|H|
Tolker-Nielsen|Tim|T|

D056704:Adaptive Immunity
D000818:Animals
D000900:Anti-Bacterial Agents
D018441:Biofilms
D054884:Host-Pathogen Interactions
D006801:Humans
D007113:Immunity, Innate
D007116:Immunization, Passive
D007155:Immunologic Factors
D011552:Pseudomonas Infections
D011550:Pseudomonas aeruginosa

Pseudomonas aeruginosa
biofilm infections
adaptive immune response
innate immune response
novel treatment possibilities


A cell-based biosensor for nanomaterials cytotoxicity assessment in three dimensional cell culture.

Abstract: Nanoparticles (NPs) are widely used in consumer and medicinal products. The high prevalence of nanoparticles in the environment raises concerns regarding their effects on human health, but there is limited knowledge about how NPs interact with cells or tissues. Because the European Union has called for a substantial reduction of animal experiments for scientific purposes (Directive 2010/63), increased efforts are required to develop in vitro models to evaluate potentially hazardous agents. Here, we describe a new cell-based biosensor for the evaluation of NPs cytotoxicity. The new biosensor is based on transgenic human hepatoblastoma cells (HepG2) that express a secreted form of alkaline phosphatase (SEAP) as a reporter protein whose expression is induced upon activation of a stress response pathway controlled by the transcription regulator nuclear factor-κB (NF-κB). The NF-κB_HepG2 sensor cells were cultured in a Matrigel-based three dimensional environment to simulate the in vivo situation. The new biosensor cells offer the advantage of generating fast and reproducible readout at lower concentrations and shorter incubation time than conventional viability assays, avoid possible interaction between nanomaterials and assay compounds, therefore, minimize generation of false positive or negative results and indicate mechanism of toxicity through NF-κB signaling.

Dubiak-Szepietowska|Monika|M| Karczmarczyk|Aleksandra|A| Winckler|Thomas|T| Feller|Karl-Heinz|KH|

D020411:Oligonucleotide Array Sequence Analysis

Cell-based biosensor
Nanoparticles
NF-κB signaling
3D cell culture


Capillary electrophoresis method to determine siRNA complexation with cationic liposomes.

Abstract: Small interfering RNA (siRNA) inducing gene silencing has great potential to treat many human diseases. To ensure effective siRNA delivery, it must be complexed with an appropriate vector, generally nanoparticles. The nanoparticulate complex requires an optimal physiochemical characterization and the complexation efficiency has to be precisely determined. The methods usually used to measure complexation in gel electrophoresis and RiboGreen® fluorescence-based assay. However, those approaches are not automated and present some drawbacks such as the low throughput and the use of carcinogenic reagents. The aim of this study is to develop a new simple and fast method to accurately quantify the complexation efficiency. In this study, capillary electrophoresis (CE) was used to determine the siRNA complexation with cationic liposomes. The short-end injection mode applied enabled siRNA detection in less than 5 min. Moreover, the CE technique offers many advantages compared with the other classical methods. It is automated, does not require sample preparation and expensive reagents. Moreover, no mutagenic risk is associated with the CE approach since no carcinogenic product is used. Finally, this methodology can also be extended for the characterization of other types of nanoparticles encapsulating siRNA, such as cationic polymeric nanoparticles.

Furst|Tania|T| Bettonville|Virginie|V| Farcas|Elena|E| Frere|Antoine|A| Lechanteur|Anna|A| Evrard|Brigitte|B| Fillet|Marianne|M| Piel|Géraldine|G| Servais|Anne-Catherine|AC|

Capillary electrophoresis
siRNA
Liposomes
Complexation efficiency


Cross-linking of the DNA repair protein O6-alkylguanine DNA alkyltransferase to DNA in the presence of cisplatin.

Abstract: 1,1,2,2-cis-diamminedichloroplatinum (II) (cisplatin) is a chemotherapeutic agent widely used in the clinic to treat various cancers. The antitumor activity of cisplatin is generally attributed to its ability to form intrastrand and interstrand DNA-DNA cross-links via sequential platination of two nucleophilic sites within the DNA duplex. However, cisplatin also induces DNA- protein lesions (DPCs) that may contribute to its biological effects due to their ability to block DNA replication and transcription. We previously reported that over 250 nuclear proteins including high mobility group proteins, histone proteins, and elongation factors formed DPCs in human HT1080 cells treated with cisplatin (Ming et al. Chem. Res. Toxicol. 2017, 30, 980-995). Interestingly, cisplatin-induced DNA-protein conjugates were reversed upon heating, by an unknown mechanism. In the present work, DNA repair protein O6-alkylguanine DNA alkyltransferase (AGT) was used as a model to investigate the molecular details of cisplatin-mediated DNA-protein cross-linking and to establish the mechanism of their reversal. We found that AGT is readily cross-linked to DNA in the presence of cisplatin. HPLC-ESI+-MS/MS sequencing of tryptic peptides originating from dG-Pt-AGT complexes revealed that the cross-linking occurred at six sites within this protein including Glu110, Lys125, Cys145, His146, Arg147, and Cys150. Cisplatin-induced Lys-Gua cross-links (1,1-cis-diammine-2-(5-amino-5-carboxypentyl)amino-2-(2'-deoxyguanosine-7-yl)-platinum(II) (dG-Pt-Lys) were detected by HPLC-ESI+-MS/MS of total digests of modified protein in comparison with the corresponding authentic standard. Upon heating, dG-Pt-AGT complexes were subject to platination migration from protein to DNA, forming cis-[Pt(NH3)2{d(GpG)}] cross-links which were detected by HPLC-ESI+-MS/MS. Our results provide a new insight into the mechanism of cisplatin-mediated DNA-protein cross-linking and their dynamic equilibrium with the corresponding DNA-DNA lesions.

Ming|Xun|X|
Michaelson-Richie|Erin D|ED|
Groehler|Arnold S|AS|
Villalta|Peter W|PW|
Campbell|Colin|C|
Tretyakova|Natalia Y|NY|

D002851:Chromatography, High Pressure Liquid

Cisplatin
AGT
DNA-protein cross-links
Mass spectrometry


Identification of tissue-dependent proteins in knee OA synovial fluid.

Abstract:
OBJECTIVE
For many proteins from osteoarthritic synovial fluid, their intra-articular tissue of origin remains unknown. In this study we performed comparative proteomics to identify osteoarthritis-specific and joint tissue-dependent secreted proteins that may serve as candidates for osteoarthritis biomarker development on a tissue-specific basis.

DESIGN
Protein secretomes of cartilage, synovium, Hoffa's fat pad and meniscus from knee osteoarthritis patients were determined using liquid chromatography tandem mass spectrometry, followed by label-free quantification. Validation of tissue-dependent protein species was conducted by ELISA on independent samples. Differential proteomes of osteoarthritic and non-osteoarthritic knee synovial fluids were obtained via similar proteomics approach, followed by ELISA validation.

RESULTS
Proteomics revealed 64 proteins highly secreted from cartilage, 94 from synovium, 37 from Hoffa's fat pad and 21 from meniscus. Proteomic analyses of osteoarthritic vs non-osteoarthritic knee synovial fluid revealed 70 proteins with a relatively higher abundance and 264 proteins with a relatively lower abundance in osteoarthritic synovial fluid. Of the 70 higher abundance proteins, 23 were amongst the most highly expressed in the secretomes of a specific intra-articular tissue measured. Tissue-dependent release was validated for SLPI, C8, CLU, FN1, RARRES2, MATN3, MMP3 and TNC. Abundance in synovial fluid of tissue-dependent proteins was validated for IGF2, AHSG, FN1, CFB, KNG and C8.

CONCLUSIONS
We identified proteins with a tissue-dependent release from intra-articular human knee OA tissues. A number of these proteins also had an osteoarthritis-specific abundance in knee synovial fluid. These proteins may serve as novel candidates for osteoarthritis biomarker development on a tissue-specific basis.

Timur|U T|UT|
Jahr|H|H|
Anderson|J|J|
Green|D C|DC|
Emans|P J|PJ|
Smagul|A|A|
van Rhijn|L W|LW|
Peffers|M J|MJ|
Welting|T J M|TJM|

Tissue-dependent
Synovial fluid
Proteomics
Osteoarthritis
Biomarker
Knee joint


You Have Got a Fast CAR: Chimeric Antigen Receptor NK Cells in Cancer Therapy.

Abstract: The clinical success stories of chimeric antigen receptor (CAR)-T cell therapy against B-cell malignancies have contributed to immunotherapy being at the forefront of cancer therapy today. Their success has fueled interest in improving CAR constructs, identifying additional antigens to target, and clinically evaluating them across a wide range of malignancies. However, along with the exciting potential of CAR-T therapy comes the real possibility of serious side effects. While the FDA has approved commercialized CAR-T cell therapy, challenges associated with manufacturing, costs, and related toxicities have resulted in increased attention being paid to implementing CAR technology in innate cytotoxic natural killer (NK) cells. Here, we review the current landscape of the CAR-NK field, from successful clinical implementation to outstanding challenges which remain to be addressed to deliver the full potential of this therapy to more patients.

chimeric antigen receptors
immunotherapy
natural killer cells


Evidence for the existence of nociceptors in rat thoracolumbar fascia.

Abstract: Recently, the existence of nociceptive fibers in fascia tissue has attracted much interest. Fascia can be a source of pain in several disorders such as fasciitis and non-specific low back pain. However, little is known about the properties of fascia nociceptors and possible changes of the fascia innervation by nociceptors under pathological circumstances. In this histologic study, the density of presumably nociceptive fibers and free nerve endings was determined in the three layers of the rat TLF: inner layer (IL, covering the multifidus muscle), middle layer (ML) and outer layer (OL). As markers for nociceptive fibers, antibodies to the neuropeptides CGRP and SP as well as to the transient receptor potential vanilloid 1 (TRPV1) were used. As a pathological state, inflammation of the TLF was induced with injection of complete Freund's adjuvant. The density of CGRP- and SP-positive fibers was significantly increased in the inner and outer layer of the inflamed fascia. In the thick middle layer, no inflammation-induced change occurred. In additional experiments, a neurogenic inflammation was induced in the fascia by electrical stimulation of dorsal roots. In these experiments, plasma extravasation was visible in the TLF, which is clear functional evidence for the existence of fascia nociceptors. The presence of nociceptors in the TLF and the increased density of presumably nociceptive fibers under chronic painful circumstances may explain the pain from a pathologically altered fascia. The fascia nociceptors probably contribute also to the pain in non-specific low back pain.

Fasciitis
Non-specific low back pain
Fascia nociceptors
Inflammation
Neurogenic inflammation


Serotonergic Drugs Inhibit Chikungunya Virus Infection at Different Stages of the Cell Entry Pathway.

Abstract: Chikungunya virus (CHIKV) is an important reemerging human pathogen transmitted by mosquitoes. The virus causes an acute febrile illness, chikungunya fever, which is characterized by headache, rash, and debilitating (poly)arthralgia that can reside for months to years after infection. Currently, effective antiviral therapies and vaccines are lacking. Due to the high morbidity and economic burden in the countries affected by CHIKV, there is a strong need for new strategies to inhibit CHIKV replication. The serotonergic drug 5-nonyloxytryptamine (5-NT) was previously identified as a potential host-directed inhibitor for CHIKV infection. In this study, we determined the mechanism of action by which the serotonin receptor agonist 5-NT controls CHIKV infection. Using time-of-addition and entry bypass assays, we found that 5-NT predominantly inhibits CHIKV in the early phases of the replication cycle, at a step prior to RNA translation and genome replication. Intriguingly, however, no effect was seen during virus-cell binding, internalization, membrane fusion and genomic RNA (gRNA) release into the cell cytosol. In addition, we show that the serotonin receptor antagonist methiothepin mesylate (MM) also has antiviral properties toward CHIKV and specifically interferes with the cell entry process and/or membrane fusion. Taken together, pharmacological targeting of 5-HT receptors may represent a potent way to limit viral spread and disease severity.IMPORTANCE The rapid spread of mosquito-borne viral diseases in humans puts a huge economic burden on developing countries. For many of these infections, including those caused by chikungunya virus (CHIKV), there are no specific treatment possibilities to alleviate disease symptoms. Understanding the virus-host interactions that are involved in the viral replication cycle is imperative for the rational design of therapeutic strategies. In this study, we discovered an antiviral compound, elucidated its mechanism of action, and propose serotonergic drugs as potential host-directed antivirals for CHIKV.

Bouma|Ellen M|EM|
van de Pol|Denise P I|DPI|
Sanders|Ilson D|ID|
Rodenhuis-Zybert|Izabela A|IA|
Smit|Jolanda M|JM|

D000818:Animals
D000998:Antiviral Agents
D002460:Cell Line
D065632:Chikungunya Fever
D002646:Chikungunya virus
D002522:Chlorocebus aethiops
D006801:Humans
D008561:Membrane Fusion
D012367:RNA, Viral
D012701:Serotonin
D018490:Serotonin Agents
D017366:Serotonin Receptor Agonists
D014363:Tryptamines
D014709:Vero Cells
D053585:Virus Attachment
D053586:Virus Internalization
D014779:Virus Replication

chikungunya virus
5-NT
serotonin receptors
MM
virus-host interactions
host-directed antivirals


The 7SK snRNP associates with the little elongation complex to promote snRNA gene expression.

Abstract: The 7SK small nuclear RNP (snRNP), composed of the 7SK small nuclear RNA (snRNA), MePCE, and Larp7, regulates the mRNA elongation capacity of RNA polymerase II (RNAPII) through controlling the nuclear activity of positive transcription elongation factor b (P-TEFb). Here, we demonstrate that the human 7SK snRNP also functions as a canonical transcription factor that, in collaboration with the little elongation complex (LEC) comprising ELL, Ice1, Ice2, and ZC3H8, promotes transcription of RNAPII-specific spliceosomal snRNA and small nucleolar RNA (snoRNA) genes. The 7SK snRNA specifically associates with a fraction of RNAPII hyperphosphorylated at Ser5 and Ser7, which is a hallmark of RNAPII engaged in snRNA synthesis. Chromatin immunoprecipitation (ChIP) and chromatin isolation by RNA purification (ChIRP) experiments revealed enrichments for all components of the 7SK snRNP on RNAPII-specific sn/snoRNA genes. Depletion of 7SK snRNA or Larp7 disrupts LEC integrity, inhibits RNAPII recruitment to RNAPII-specific sn/snoRNA genes, and reduces nascent snRNA and snoRNA synthesis. Thus, through controlling both mRNA elongation and sn/snoRNA synthesis, the 7SK snRNP is a key regulator of nuclear RNA production by RNAPII.

Egloff|Sylvain|S|0000-0002-9798-125X Vitali|Patrice|P| Tellier|Michael|M| Raffel|Raoul|R| Murphy|Shona|S| Kiss|Tamás|T|0000-0003-0293-3093

D047369:Chromatin Immunoprecipitation
D005786:Gene Expression Regulation
D006367:HeLa Cells
D006801:Humans
D012319:RNA Polymerase II
D012342:RNA, Small Nuclear
D012261:Ribonucleoproteins
D014157:Transcription Factors

7SK snRNP
little elongation complex
RNA polymerase II
regulatory RNA
snRNA gene transcription


In silico identification of a therapeutic target for photo-activated disinfection with indocyanine green: Modeling and virtual screening analysis of Arg-gingipain from Porphyromonas gingivalis.

Abstract:
BACKGROUND
Porphyromonas gingivalis is a momentous bacterial etiological agent associated with periodontitis, peri-implantitis as well as endodontic infections. The potential advantage of Photo-activated disinfection (PAD) as a promising novel approach is the choice of a suitable target site, specific photosensitizer, and wavelength of light for delivery of the light from source to target. Since Arg-gingipain is a cysteine proteinase that is involved in the virulence of P. gingivalis, it was evaluated as a target site for PAD with indocyanine green (ICG) as a photosensitizer.

METHODS
In this study, we used a range of in silico strategies, bioinformatics tools, biological databases, and computer simulation molecular modeling to evaluate the capacity of Arg-gingipain.

RESULTS
The predicted structure of Arg-gingipain indicated that it is located outside the cell and has nine domains and 17 ligands, including two calcium ions and three sodium ions with positive charges which can be a site of interaction for anionic ICG.

CONCLUSION
Based on the results of this study, anionic ICG desires to bind and interact with residues of Arg-gingipain during PAD as a main site to enhance the yield of treatment of endo-periodontal lesions.

in silico
Photo-activated disinfection
Indocyanine green
Arg-gingipain
Porphyromonas gingivalis
Periodontitis
Endodontic infections
Bioinformatics


Innovative Ultrasound-Assisted Approaches towards Reduction of Heavy Metals and Iodine in Macroalgal Biomass.

Abstract: The aim of this work was to evaluate the potential of ultrasound (US), alone or in combination with mild heating and/or EDTA towards reduction of As, Cd, I, and Hg content of Laminaria hyperborea. Concentrations of As, Cd, I, and Hg of 56.29, 0.596, 7340, and <0.01 mg kg-1 of dry weight, respectively, were found in L. hyperborea blades. Treatment with US at 50 °C increased approx. 2-fold the amount of As released, although did not affect significantly the content of Cd or I, as compared to control (no US) samples. Reducing the temperature to 8 °C significantly decreased the effect of US, but heating at 80 °C did not cause a significant effect as compared to treatments at 50 °C. On the other hand, treatment with 0.1 N EDTA at 50 °C enhanced the percentage of Cd released by approximately 7-fold, regardless of sonication. In the present work, the combination of US and EDTA at 50 °C for 5 min led to a significant reduction of the As (32%), Cd (52%) and I (31%) content in L. hyperborea, thus improving the product's safety for consumers.

iodine
mild heat
EDTA
Laminaria hyperborea
arsenic
brown macroalgae
cadmium
hurdle technology
nonthermal technologies


Can social support and physical activity buffer cognitive impairment in individuals with depressive symptoms? Results from a representative sample of young to older adults.

Abstract:
BACKGROUND
Previous study results on associations between depressive symptoms and cognitive functioning, mainly based on clinical samples and explanatory mechanisms including potential protective factors, are yet to be clarified. To this end, we investigated relations between depressive symptoms and executive functioning as well as episodic memory in a representative population sample. Furthermore, we determined the role of social support and physical activity in the explanation of cognitive performance differences in individuals with depressive symptoms.

METHODS
A total of N = 3661 participants (52% female) from the German Health and Examination Interview for Adults (18-79 years; M = 52.71, SD = 16.06) were included in the present study. Within a larger assessment protocol, participants answered a depressive symptom questionnaire and completed a neuropsychological test battery including executive functioning and episodic memory.

RESULTS
Depressive symptoms significantly predicted executive functioning and episodic memory scores with small effects of β = -0.04. Social support and physical activity mediated the relationships between depressive symptoms and cognitive functioning.

LIMITATIONS
As the present study is cross-sectional, future research is warranted to provide more insight into causality by following individuals with depressive symptoms over time.

CONCLUSIONS
The present findings indicate that effects from depressive symptoms on cognitive functioning (a) have been overestimated and do not generalize to non-clinical populations and (b) vary owing to behavioral lifestyle factors such as social support and physical activity. Thereby, the present results highlight opportunities for buffering cognitive decline in individuals with depressive symptoms in the general population.

Cognitive impairment
Depressive symptoms
Adulthood
Behavioral coping strategies
Non-hospitalized population


Relationship between the depression levels and nutritional statuses of advanced stage cancer patients.

Abstract:
OBJECTIVE
This study aimed to determine the depression and nutritional statuses of advanced stage cancer patients and investigate the relationship between depression and malnutrition.

METHOD
The descriptive, cross-sectional, and correlational study was conducted with 245 patients with advanced cancer. The data were collected by using an Information Form, the Visual Analog Scale, the NRS-2002-Nutritional Risk Score, and the Beck Depression Inventory.

RESULTS
The mean NRS-2002 score of the patients was 2.22, and when the cutoff value was accepted as 3, it was determined that 39.2% of the patients had malnutrition. The mean Beck Depression Inventory score of the patients was 35.06, and they were found to experience severe depression. There was a positive and significant relationship between the NRS-2002 scores and the Beck Depression Inventory scores (r = 0.409; p < 0.001).

SIGNIFICANCE OF RESULTS
These results showed that there was a strong relationship between the depression and malnutrition levels of advanced stage cancer patients. Deterioration in the nutritional status of the advanced stage cancer patients was associated with a significant worsening effect in terms of depression and pain.

Depression
Nutrition
Malnutrition
Advanced cancer