Opportunities and Limitations of Modelling Alzheimer's Disease with Induced Pluripotent Stem Cells.

Abstract: Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) has opened the way for patient-specific disease modelling. Following their differentiation into neuronal cell types, iPSC have enabled the investigation of human neurodegenerative diseases, such as Alzheimer's disease (AD). While human iPSCs certainly provide great opportunities to repeatedly interrogate specific human brain cell types of individuals with familial and sporadic forms of the disease, the complex aetiology and timescale over which AD develops in humans poses particular challenges to iPSC-based AD models. Here, we discuss the current state-of-play in the context of these and other iPSC model-related challenges and elaborate on likely future developments in this field of research.

Ovchinnikov|Dmitry A|DA|
Wolvetang|Ernst J|EJ|

induced pluripotent stem cells
reprogramming
Alzheimer’s disease
disease  modelling


Validation of the Intermittent and Constant Osteoarthritis Pain Questionnaire in Patients with Hand Osteoarthritis: Results from the Nor-Hand Study.

Abstract:
OBJECTIVE
To examine the validity of a modified Intermittent and Constant Osteoarthritis Pain (ICOAP) questionnaire for assessment of pain in hand osteoarthritis (OA).

METHODS
The modified ICOAP-hand questionnaire was administered to 300 patients [89% female, median (interquartile range) age: 61 (57-66) yrs] in the Nor-Hand observational cohort study. The questionnaire was completed twice by 31 patients and test-retest reliability was assessed by intraclass correlation coefficients (ICC) for sum scores and weighted κ scores for individual items. Internal consistency was assessed by Cronbach's alpha coefficient and item-total correlations. Correlations between the ICOAP-hand questionnaire, the Australian/Canadian Hand OA Index (AUSCAN) hand pain subscale, and pain on a numerical rating scale (NRS) were analyzed using Spearman correlation analyses.

RESULTS
We found a substantial overlap between constant and intermittent pain (46% reporting constant + intermittent pain and 33% reporting no pain). Test-retest reliability analysis of ICOAP-hand showed an ICC of 0.89 for the total scale and weighted κ values between 0.39-0.70 for the individual items. Principal component analysis revealed one component with an eigenvalue of 7.9, explaining 72% of the total variance. Cronbach's alpha coefficient values > 0.93 and strong item-total correlations proved high internal consistency. ICOAP-hand was strongly correlated with NRS hand pain and the AUSCAN pain subscale.

CONCLUSION
ICOAP-hand is a reliable pain index that correlates with other available pain questionnaires. However, our results indicate that constant and intermittent pain do not represent separate constructs in hand OA, questioning the usefulness of the 2 subscales. [ClinicalTrials.gov: NCT03083548].

OSTEOARTHRITIS
PAIN
HAND
OUTCOME ASSESSMENT


Flavonoids from Nelumbo nucifera Gaertn., a Medicinal Plant: Uses in Traditional Medicine, Phytochemistry and Pharmacological Activities.

Abstract: Nelumbo nucifera Gaertn. has been used as an important ingredient for traditional medicines since ancient times, especially in Asian countries. Nowadays, many new or unknown phytochemical compounds from N. nucifera are still being discovered. Most of the current research about pharmacological activity focus on nuciferine, many other alkaloids, phenolic compounds, etc. However, there is no current review emphasizing on flavonoids, which is one of the potent secondary metabolites of this species and its pharmacological activities. Therefore, following a taxonomic description, we aim to illustrate and update the diversity of flavonoid phytochemical compounds from N. nucifera, the comparative analysis of flavonoid compositions and contents in various organs. The uses of this species in traditional medicine and the main pharmacological activities such as antioxidant, anti-inflammatory, anti-diabetic, anti-obesity, anti-angiogenic and anti-cancer activities are also illustrated in this works.

flavonoids
Nelumbo nucifera
traditional medicine
pharmacological activities


Water quality induced corrosion of stainless steel valves during long-term service in a reverse osmosis system.

Abstract: The current study analyzes the contribution of 10 water quality parameters (including pH, turbidity, conductivity, total dissolved solids (TDS), hardness, total organic carbon (TOC), alkalinity, calcium ions, chlorides and sulfates) to corrosion extent of stainless steel valves taken from different locations in a reverse osmosis system of a reclaimed water plant. The valves were in service for 5 years. Raman spectroscopy and X-ray photoelectron spectroscopy analyses are conducted to quantify corrosion products on different valves under various water quality conditions. On that basis, bivariate and multivariate regression analyses between the 10 water quality parameters and the corrosion extent of valve specimens (represented by metal loss percentage (MLP) values) are carried out to check the contribution of those water quality parameters to MLP. The results indicate that the proportions of metal oxides as corrosion products vary according to the corrosion extent of the valves. Although no linear correlation is found, all 10 water quality parameters except for pH show a significant positive correlation with the MLP values of the valve specimens. Moreover, results of multivariate regression suggest that the variation of MLP can be explained by turbidity, TDS, TOC and sulfates. A positive contribution of turbidity, TDS and TOC to MLP is observed, whereas the contribution of sulfates is negative. The results from the current work help to identify the reasons for water quality-induced failure of stainless steel equipment in RO systems.

Xu|Xiyan|X| Liu|Shuming|S| Liu|Ying|Y| Smith|Kate|K| Wang|Xiaoting|X| Li|Junyu|J| Ma|Ziqing|Z| Wang|Zhangqing|Z| Cui|Yong|Y|

D003343:Corrosion
D009995:Osmosis
D013193:Stainless Steel
D018508:Water Purification
D060753:Water Quality
D014881:Water Supply

Water quality
Corrosion
Stainless steel
Reverse osmosis system
Correlation


How to Simplify the Evaluation of Newly Introduced Chemotherapeutic Interventions in Myeloma.

Abstract: When the bortezomib [PS341], adriamycin and dexamethasone (PAD) regimen was first evaluated, the response rate in untreated patients was much superior to that elicited by conventional chemotherapeutic agents. We demonstrated the efficacy of PAD in relapsed or refractory patients by comparing the response rate obtained in 53 patients who received vincristine, adriamycin and dexamethasone (VAD) or equivalent regimen as induction therapy, using a comparative design in which each patient acted as their own control. Whereas 25 patients had a positive response to VAD, 37 patients had a response to PAD ≤ partial remission (PR) (p = 0.023). Using the more stringent response level of very good PR (VGPR) the results favored the PAD regimen very significantly (p = 0.006) (McNemars test). Similar results were seen using paired M-protein levels from individual patient comparisons. As the PAD regimen was subsequently adopted as the re-induction therapy in the British Society for Blood and Marrow Transplantation/United Kingdom Myeloma Forum Myeloma X (Intensive) trial, now concluded, we have retrospectively analyzed the findings from both studies. Comparison of response rates and adverse effects of patients having had previous autologous transplantation (Cohort 1) with the corresponding data from Myeloma X showed close correlation. These findings provide evidence that rapid results may be obtained in the evaluation of newly introduced, and potentially highly effective, anti-tumour agents by direct comparison to the response to the immediately preceding standard regimen, particularly in relatively resistant tumours.

Morris|Treen Carson Michael|TCM|
Drake|Mary B|MB|
Kettle|Paul J|PJ|
McGuigan|Tracey|T|
Leahy|Maeve|M|
O'Dwyer|Michael|M|
Enright|Helen|H|
O'Shea|Tanya|T|
Popat|Rakesh|R|
Oakervee|Heather E|HE|
Yong|Kwee|K|
Cavenagh|Jamie D|JD|
Cairns|David A|DA|
Alvarez-Iglesias|Alberto|A|
Cook|Gordon|G|

Myeloma
bortezomib
adriamycin
dexamethasone
PAD
response
relapse
Myeloma X


Enrichment of naturally occurring radionuclides and trace elements in Yatagan and Yenikoy coal-fired thermal power plants, Turkey.

Abstract: Coal, residues and waste produced by the combustion of the coal contain naturally occurring radionuclides such as 238U, 226Ra, 210Pb, 232Th and 40K and trace elements such as Cd, Cr, Pb, Ni and Zn. In this work, coal and its combustion residues collected from Yatagan and Yenikoy coal fired thermal power plants (CPPs) in Turkey were studied to determine the concentrations of natural radionuclides and trace elements, and their enrichments factors to better understand the radionuclide concentration processes within the combustion system. In addition, the utilization of coal fly ash as a secondary raw material in building industry was also studied in terms of radiological aspects. Fly ash samples were taken at different stages along the emission control system of the thermal power plants. Activity concentrations of naturally occurring radionuclides were determined with Canberra Broad Energy Germanium (BEGe) detector BE3830-P and ORTEC Soloist PIPS type semiconductor detector. The particle size distribution and trace elements contents were determined in various ash fractions by the laser scattering particle size distribution analyzer and inductively coupled plasma (ICP-OES). From the obtained data, natural radionuclides tend to condense on fly ash with and the activity concentrations increase as the temperature drop in CPPs. Measured 210Pb and 210Po concentration varied between 186 ± 20-1153 ± 44 Bq kg-1, and 56 ± 5-1174 ± 45 Bq kg-1, respectively. The highest 210Pb and 210Po activity concentrations were determined in fly ash taken from the temporary storage point as 1153 ± 44 Bq kg-1 and 1174 ± 45 Bq kg-1, respectively. There were significant differences in the activity concentrations of some natural radionuclide and trace elements (Pb and Zn) contents in ash fractions among the sampling point inside both of the plants (ANOVA, p < 0.001). Coal and ash sample analysis showed an increase activity concentration and enrichment factors towards the electrostatic precipitators for both of the power plants. The enrichment factors for Zn follow a similar trend as Pb, increasing in value towards the end of the emission control system. The calculated activity indexes were above 1.0 value for both of the power plants, assuming the utilization of fly ash at 100%. It can be concluded that the reuse of fly ash as a secondary raw material may not be hazardous depending on the percentage of utilization of ash.

Ozden|Banu|B| Guler|Erkan|E| Vaasma|Taavi|T| Horvath|Maria|M| Kiisk|Madis|M| Kovacs|Tibor|T|

D000396:Air Pollutants, Radioactive
D060729:Coal Ash
D011210:Power Plants
D011834:Radiation Monitoring
D011868:Radioisotopes
D014131:Trace Elements

Naturally occurring radioactive material


Spinal Cord Injury as a Model of Bone-Muscle Interactions: Therapeutic Implications From in vitro and in vivo Studies.

Abstract: Spinal cord injuries (SCIs) represent a variety of conditions related to the damage of the spinal cord with consequent musculoskeletal repercussions. The bone and muscle tissues share several catabolic pathways that lead to variable degrees of disability in SCI patients. In this review article, we provide a comprehensive characterization of the available treatment options targeting the skeleton and the bone in the setting of SCI. Among the pharmacological intervention, bisphosphonates, anti-sclerostin monoclonal antibodies, hydrogen sulfide, parathyroid hormone, and RANKL pathway inhibitors represent valuable options for treating bone alterations. Loss phenomena at the level of the muscle can be counteracted with testosterone, anabolic-androgenic steroids, and selective androgen receptor modulators. Exercise and physical therapy are valuable strategies to increase bone and muscle mass. Nutritional interventions could enhance SCI treatment, particularly in the setting of synergistic and multidisciplinary interventions, but there are no specific guidelines available to date. The development of multidisciplinary recommendations is required for a proper clinical management of SCI patients.

Invernizzi|Marco|M|
de Sire|Alessandro|A|
Renò|Filippo|F|
Cisari|Carlo|C|
Runza|Letterio|L|
Baricich|Alessio|A|
Carda|Stefano|S|
Fusco|Nicola|N|

spinal cord injury
bone
muscle
bone loss
osteoporosis
rehabilitation
sarcopenia


Synthesis and structures of three isoxazole-containing Schiff bases.

Abstract: The synthesis and structures of three isoxazole-containing Schiff bases are reported, namely, (E)-2-{[(isoxazol-3-yl)imino]methyl}phenol, C10H8N2O2, (E)-2-{[(5-methylisoxazol-3-yl)imino]methyl}phenol, C11H10N2O2, and (E)-2,4-di-tert-butyl-6-{[(isoxazol-3-yl)imino]methyl}phenol, C18H24N2O2. All three structures contain an intramolecular O-H...N hydrogen bond, alongside weaker intermolecular C-H...N and C-H...O contacts. The C-O(H) and imine C=N bond lengths were consistent with structures existing in the enol rather than the keto form. Despite having dihedral angles <25°, none of the compounds were observed to be strongly thermochromic, unlike their anil counterparts; however, all three compounds showed a visible colour change upon irradiation with UV light.

Mason|Helen E|HE|
Howard|Judith A K|JAK|
Sparkes|Hazel A|HA|

Schiff base
hydrogen bonding
chromism
crystal structure
isoxazole
phenol


Risk Y-haplotypes and pathogenic variants of Arab-ancestry boys with autism by an exome-wide association study.

Abstract: Autism is heterogeneous multifactorial neurodevelopmental and neuropsychiatric disorder with repetitive and limited behaviors as well as communication deficits. Prevalence of autism in males is predominant than females, but their genetic association is unclear. The study was performed to investigate Y-chromosome haplotypes, significant risk variants and susceptibility genes associated with autistic Saudi young males with autism. Exome genotyping microarray analysis was performed in Saudi young boys with autism (cases, n = 47) and without autism and other genetic or neurodevelopmental disorders (control, n = 43) to identify the functional exonic risk variations among 243,345 exonic variations. The most significant single nucleotide polymorphisms (SNPs) of protein coding associated with autism in Saudi young boys were studied for functional enrichment. Y-chromosome haplotyping analysis of 6 SNPs such as rs1865680, rs2032624, rs2032658, rs2032631, rs9786153 and rs13447352 uncovered the most significant protective (ACGACA p = 2.94 × 10-9) among the controls and the high risk Y-haplotype (GAAGTC p = 6.85 × 10-6) among autistic boys. Exome association study revealed 6 susceptible genes, MCC, AUTS2, VSX1, SETBP1, CNTN3, and PCDH11Y that were known for autistic disorder. The significant predisposed genes with functional variants of Y-chromomere are strongly connected with spermatogenic failure (p = 8.02 × 10-8), azoospermia (p = 6.32 × 10-7), partial chromosome Y deletion (p = 7.66 × 10-6), HDMs demethylate histones pathway (p = 3.55 × 10-4) and immune system diseases (p = 4.11 × 10-3). Y-haplotypes and highly significant pathogenic exonic variants in MCC, AUTS2, VSX1, SETBP1, CNTN3 and PCDH11Y genes are more influential genetic factors for developing autism in boys of Arab origin.

D020022:Genetic Predisposition to Disease

Boy
Y-chromosome
Haplotype
Polymorphism
SNPs
Autism spectrum disorder


Application of a highly sensitive magnetic solid phase extraction for phytochemical compounds in medicinal plant and biological fluids by ultra-high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry.

Abstract: A highly sensitive method using reduced graphene oxide with iron oxide (rGO/Fe3 O4 ) as the sorbent in magnetic SPE has been developed for the purification of five anthraquinones (emodin, rhein, aloeemodin, physcion, and chrysophanol) in rhubarb and rat urine by ultra-HPLC coupled with quadrupole TOF/MS. The extraction was accomplished by adding trace amount rGO/Fe3 O4 suspension to 200 mL of aqueous mixture, and the excellent adsorption capacity of the nanoparticles was fully demonstrated in this procedure. Under the optimized conditions, the calibration curves were linear in the concentration range of 0.05-27.77 ng/mL with correlation coefficients varying from 0.9902 to 0.9978. The LODs ranged from 0.28 to 58.99 pg/mL. The experimental results indicated that the proposed method was feasible for the analysis of anthraquinones in rhubarb and urine samples.

Cao|Wan|W| Yi|Ling|L| Ye|Li-Hong|LH| Cao|Jun|J| Hu|Shuai-Shuai|SS| Xu|Jing-Jing|JJ| Peng|Li-Qing|LQ| Zhu|Qiong-Yao|QY| Zhang|Qian-Yun|QY|

D002851:Chromatography, High Pressure Liquid

Ultra-HPLC coupled with quadrupole TOF/MS


A polymorphism of the TIM-1 IgV domain: implications for the susceptibility to filovirus infection.

Abstract: Filoviruses, including Ebola and Marburg viruses, cause severe hemorrhagic fever in humans and nonhuman primates with mortality rates of up to 90%. Human T-cell immunoglobulin and mucin domain 1 (TIM-1) is one of the host proteins that have been shown to promote filovirus entry into cells. In this study, we cloned TIM-1 genes from three different African green monkey kidney cell lines (Vero E6, COS-1, and BSC-1) and found that TIM-1 of Vero E6 had a 23-amino acid deletion and 6 amino acid substitutions compared with those of COS-1 and BSC-1. Interestingly, Vero E6 TIM-1 had a greater ability to promote the infectivity of vesicular stomatitis viruses pseudotyped with filovirus glycoproteins than COS-1-derived TIM-1. We further found that the increased ability of Vero E6 TIM-1 to promote virus infectivity was most likely due to a single amino acid difference between these TIM-1s. These results suggest that a polymorphism of the TIM-1 molecules is one of the factors that influence cell susceptibility to filovirus infection, providing a new insight into the molecular basis for the filovirus host range.

Kuroda|Makoto|M| Fujikura|Daisuke|D| Noyori|Osamu|O| Kajihara|Masahiro|M| Maruyama|Junki|J| Miyamoto|Hiroko|H| Yoshida|Reiko|R| Takada|Ayato|A|

Polymorphism TIM-1 Susceptibility Filovirus Entry Receptor


Remote electrochemical modulation of pKa in a rotaxane by co-conformational allostery.

Abstract: Allosteric control, one of Nature's most effective ways to regulate functions in biomolecular machinery, involves the transfer of information between distant sites. The mechanistic details of such a transfer are still an object of intensive investigation and debate, and the idea that intramolecular communication could be enabled by dynamic processes is gaining attention as a complement to traditional explanations. Mechanically interlocked molecules, owing to the particular kind of connection between their components and the resulting dynamic behavior, are attractive systems to investigate allosteric mechanisms and exploit them to develop functionalities with artificial species. We show that the pKa of an ammonium site located on the axle component of a [2]rotaxane can be reversibly modulated by changing the affinity of a remote recognition site for the interlocked crown ether ring through electrochemical stimulation. The use of a reversible ternary redox switch enables us to set the pKa to three different values, encompassing more than seven units. Our results demonstrate that in the axle the two sites do not communicate, and that in the rotaxane the transfer of information between them is made possible by the shuttling of the ring, that is, by a dynamic intramolecular process. The investigated coupling of electron- and proton-transfer reactions is reminiscent of the operation of the protein complex I of the respiratory chain.

Ragazzon|Giulio|G| Schäfer|Christian|C| Franchi|Paola|P| Silvi|Serena|S| Colasson|Benoit|B| Lucarini|Marco|M| Credi|Alberto|A|0000-0003-2546-9801

D001665:Binding Sites
D004558:Electric Stimulation
D055664:Electrochemical Techniques
D004579:Electron Transport
D004735:Energy Transfer
D008956:Models, Chemical
D008968:Molecular Conformation
D015394:Molecular Structure
D011522:Protons
D043862:Rotaxanes

acid–base processes
electrochemistry
free energy change
molecular machine
molecular switch


Another invisible enemy indoors: COVID-19, human health, the home, and United States indoor air policy.

Abstract: After the emergence of the respiratory virus SARS-CoV-2 (COVID-19), many exposure and environmental health scientists promptly recognized the potentially catastrophic public health ramifications of concurrent infectious and air pollution-mediated disease. Nevertheless, much of this attention has been focused on outdoor interactions. Each year, 3.8 million people worldwide prematurely die from illnesses attributable to indoor air. Hence, poor household indoor air quality is a long-standing public health issue with even greater relevance now that many individuals are spending more time at home. At present, the Environmental Protection Agency does not regulate indoor air, and state-level legislation has resulted in a patchwork of national coverage. Here, we describe common sources of indoor air pollution, the health impacts of indoor pollutants, and populations disparately impacted by COVID-19 and poor indoor air quality. Furthermore, we detail the need for better legislation that promotes the integrity of the indoor air environment, and what individuals can do to personally protect themselves as we await more comprehensive indoor air legislation.


Attenuation of quorum sensing regulated virulence and biofilm development in Pseudomonas aeruginosa PAO1 by Diaporthe phaseolorum SSP12.

Abstract: In recent years, Pseudomonas aeruginosa PAO1 emerged as the significant pathogenic microorganism in majority of the hospital-acquired infections due to its resistance to the conventional antibiotics by virtue of its highly organized quorum sensing and associated biofilm formation. In the present study, quorum sensing attenuation potential of Diaporthe phaseolorum SSP12 extract was investigated against P. aeruginosa PAO1 amply supported by molecular docking studies. D. phaseolorum SSP12 extract significantly inhibited the production of LasI/R mediated LasA protease, LasB elastase and chitinase with 66.52 ± 5.41, 71.26 ± 4.58 and 61.16 ± 4.28% of inhibition respectively at a concentration of 750 μg mL-1. In addition, RhlI/R mediated production of pyocyanin, exopolysaccharides and rhamnolipids were also down-regulated by 74.71 ± 3.97, 66.41 ± 3.62 and 63.75 ± 3.76% respectively on treatment with sub-MIC concentration of D. phaseolorum SSP12. The light, fluorescence and confocal laser scanning microscopic (CLSM) analysis confirmed the significant disruption in biofilm formation. The presence of bioactive constituents such as phenyl ethylalcohol, 2, 4-di-tert-butylphenol, fenaclon, 1, 4-phenylenediacetic acid, and benzyl hydrazine in D. phaseolorum SSP12 extract was evident from Gas chromatography-mass spectrophotometric (GC-MS) analysis. From the in silico molecular docking studies, fenaclon and 2, 4-di-tert-butylphenol competitively binds to QS receptors LasR and RhlR and alters the binding of its cognate ligands and modulates the expression of virulence phenotypes. The promising anti quorum sensing efficacy of D. phaseolorum SSP12 extract suggested new avenues for development of anti-infective drugs from fungal derived metabolites to counteract the problems associated with conventional antibiotic therapies.

Pattnaik|Subha Swaraj|SS|
Ranganathan|SampathKumar|S|
Ampasala|Dinakara Rao|DR|
Syed|Asad|A|
Ameen|Fuad|F|
Busi|Siddhardha|S|

D057927:Hydrophobic and Hydrophilic Interactions

Quorum sensing
Biofilm
Pseudomonas aeruginosa
Molecular docking
CLSM


Human cytomegalovirus induces and exploits Roquin to counteract the IRF1-mediated antiviral state.

Abstract: RNA represents a pivotal component of host-pathogen interactions. Human cytomegalovirus (HCMV) infection causes extensive alteration in host RNA metabolism, but the functional relationship between the virus and cellular RNA processing remains largely unknown. Through loss-of-function screening, we show that HCMV requires multiple RNA-processing machineries for efficient viral lytic production. In particular, the cellular RNA-binding protein Roquin, whose expression is actively stimulated by HCMV, plays an essential role in inhibiting the innate immune response. Transcriptome profiling revealed Roquin-dependent global down-regulation of proinflammatory cytokines and antiviral genes in HCMV-infected cells. Furthermore, using cross-linking immunoprecipitation (CLIP)-sequencing (seq), we identified IFN regulatory factor 1 (IRF1), a master transcriptional activator of immune responses, as a Roquin target gene. Roquin reduces IRF1 expression by directly binding to its mRNA, thereby enabling suppression of a variety of antiviral genes. This study demonstrates how HCMV exploits host RNA-binding protein to prevent a cellular antiviral response and offers mechanistic insight into the potential development of CMV therapeutics.

Song|Jaewon|J| Lee|Sanghyun|S| Cho|Dong-Yeon|DY| Lee|Sungwon|S| Kim|Hyewon|H| Yu|Namhee|N| Lee|Sanghyuk|S| Ahn|Kwangseog|K|

D045744:Cell Line, Tumor
D002478:Cells, Cultured
D016207:Cytokines
D003587:Cytomegalovirus
D003586:Cytomegalovirus Infections
D015536:Down-Regulation
D005347:Fibroblasts
D020869:Gene Expression Profiling
D054884:Host-Pathogen Interactions
D006801:Humans
D057131:Immune Evasion
D007113:Immunity, Innate
D050856:Interferon Regulatory Factor-1
D061251:Primary Cell Culture
D012333:RNA, Messenger
D016601:RNA-Binding Proteins
D044767:Ubiquitin-Protein Ligases
D014779:Virus Replication

human cytomegalovirus
RNA-binding protein
proinflammatory cytokine
immune evasion


Overexpression of melanoma-associated antigen D4 is an independent prognostic factor in squamous cell carcinoma of the esophagus.

Abstract: To pursue an urgently needed treatment target for esophageal cancer (EC), we investigated the function of the recently discovered melanoma-associated antigen (MAGE)-D4 in squamous cell EC. MAGE-D4 messenger RNA (mRNA) expression was analyzed in nine EC cell lines using quantitative reverse transcription polymerase chain reaction. In 65 surgical specimens of squamous cell EC with no prior neoadjuvant therapy, MAGE-D4 mRNA expression in EC tissues and corresponding normal tissues was analyzed and compared, and evaluated in terms of clinicopathological factors. In representative cases, MAGE-D4 protein distribution was analyzed immunohistochemically. The heterogeneity of MAGE-D4 mRNA expression was confirmed in EC cell lines by quantitative reverse transcription polymerase chain reaction. In surgical specimens, MAGE-D4 mRNA expression was significantly higher in EC tissues than in corresponding normal tissues (P < 0.001). Patients with the highest MAGE-D4 mRNA expression in EC tissues (top quartile, n = 17) had significantly shorter overall survival than patients with low expression (2-year survival: 44% and 73%, respectively, P = 0.006). Univariate analysis identified age (≥65 years), lymphatic involvement, and high MAGE-D4 mRNA expression as significant prognostic factors; high MAGE-D4 mRNA expression was also an independent prognostic factor in multivariable analysis (hazard ratio: 2.194; P = 0.039) and was significantly associated with Brinkman index (P = 0.008) and preoperative carcinoembryonic antigen level (P = 0.002). Immunohistochemical MAGE-D4b expression was consistent with MAGE-D4 mRNA profiling. Our results suggest that MAGE-D4 overexpression influences tumor progression, and MADE-D4 can be a prognostic marker and a potential molecular target in squamous cell EC.

Oya|H|H| Kanda|M|M| Takami|H|H| Hibino|S|S| Shimizu|D|D| Niwa|Y|Y| Koike|M|M| Nomoto|S|S| Yamada|S|S| Nishikawa|Y|Y| Asai|M|M| Fujii|T|T| Nakayama|G|G| Sugimoto|H|H| Fujiwara|M|M| Kodera|Y|Y|

D000077277:Esophageal Squamous Cell Carcinoma

esophageal cancer
MAGE-D4
expression
progression


A phase I study of intermediate dose cytarabine in combination with lenalidomide in relapsed/refractory acute myeloid leukemia.

Abstract: Relapsed/refractory (r/r) Acute Myeloid Leukemia (AML) remains a therapeutic challenge. Cytarabine arabinoside (AraC) forms the backbone of most regimens, with complete responses (CR) ranging from 17 to 20%. Lenalidomide (Len) is approved by the FDA for multiple myeloma and myelodysplasia and has demonstrated activity in AML. We developed a phase I study to evaluate the safety and tolerability of Len in combination with intermediate dose AraC (1.5 g/m(2)/day given on days 1-5) in adults with r/r AML. The maximally tolerated dose for this combination was 10mg daily on days 6-26 of a 28 day cycle. Dose de-escalation from 25mg was required due to rash, liver function abnormalities, and hypokalemia. Of 32 evaluable patients, five achieved CR (16%), 5CRi (16%) and 3 had hematological improvements for an overall response rate of 41% (13/32). Median overall survival (95% confidence interval) for patients treated on study was 5.8 (2.5-10.6) months and disease free survival was 3.4 (2.3-6.2) months. This single institute phase I trial of Len and intermediate dose AraC was associated with marked skin and other toxicities. At the dose and schedule tested, this combination did not appear to result in improved CR over single agent AraC for r/r AML.

Griffiths|Elizabeth A|EA|
Brady|William E|WE|
Tan|Wei|W|
Vigil|Carlos E|CE|
Thompson|James E|JE|
Ford|Laurie A|LA|
Dickey|Noelle M|NM|
L Bashaw|Heather|H|
Sperrazza|Jill|J|
Wetzler|Meir|M|
Wang|Eunice S|ES|

D000971:Antineoplastic Combined Chemotherapy Protocols

Phase I
Cytarabine
Lenalidomide
Acute myeloid leukemia
Clinical trial
Relapse/refractory AML


Increased chemotherapy-induced ovarian reserve loss in women with germline BRCA mutations due to oocyte deoxyribonucleic acid double strand break repair deficiency.

Abstract:
OBJECTIVE
To assess whether woman who have BRCA mutations (WBM) experience more declines in ovarian reserve after chemotherapy treatment, as it induces oocyte death by deoxyribonucleic acid (DNA) damage, and BRCA mutations result in DNA damage repair deficiency.

DESIGN
Longitudinal cohort study.

SETTING
Academic centers.

PATIENT(S)
The 108 evaluable women with breast cancer were stratified into those never tested (negative family history; n = 35) and those negative (n = 59) or positive (n = 14) for a pathogenic BRCA mutation.

INTERVENTION(S)
Sera were longitudinally obtained before and 12-24 months after chemotherapy treatment, assayed for antimüllerian hormone (AMH), and adjusted for age at sample collection.

MAIN OUTCOME MEASURE(S)
Ovarian recovery, defined as the geometric mean of the after chemotherapy age-adjusted AMH levels compared with baseline levels.

RESULT(S)
Compared with the controls, the before chemotherapy treatment AMH levels were 24% and 34% lower in those negative or positive for BRCA mutations, consistent with accelerated ovarian aging in WBM. The WBM had a threefold difference in AMH recovery after chemotherapy treatment (1.6%), when compared with BRCA negative (3.7%) and untested/low risk controls (5.2%). Limiting the analysis to the most common regimen, doxorubicin and cyclophosphamide followed by paclitaxel, showed similar results. These findings were mechanistically confirmed in an in vitro mouse oocyte BRCA knockdown bioassay, which showed that BRCA deficiency results in increased oocyte susceptibility to doxorubicin.

CONCLUSION(S)
Women who have pathogenic BRCA mutations are more likely to lose ovarian reserve after chemotherapy treatment, suggesting an emphasis on fertility preservation. Furthermore, our findings generate the hypothesis that DNA repair deficiency is a shared mechanism between aging, infertility, and cancer.

CLINICAL TRIAL REGISTRATION NUMBER
NCT00823654.

Oktay|Kutluk H|KH|
Bedoschi|Giuliano|G|
Goldfarb|Shari B|SB|
Taylan|Enes|E|
Titus|Shiny|S|
Palomaki|Glenn E|GE|
Cigler|Tessa|T|
Robson|Mark|M|
Dickler|Maura N|MN|

D000328:Adult
D000818:Animals
D054304:Anti-Mullerian Hormone
D000970:Antineoplastic Agents
D019313:BRCA1 Protein
D024682:BRCA2 Protein
D015415:Biomarkers
D001943:Breast Neoplasms
D053903:DNA Breaks, Double-Stranded
D004260:DNA Repair
D005260:Female
D018095:Germ-Line Mutation
D006801:Humans
D008137:Longitudinal Studies
D051379:Mice
D009865:Oocytes
D065851:Ovarian Reserve
D016649:Primary Ovarian Insufficiency
D011446:Prospective Studies
D013997:Time Factors
D016896:Treatment Outcome

ovarian reserve
BRCA
chemotherapy
fertility preservation
ovarian insufficiency


The effects of neurochemical balance in the anterior cingulate cortex and dorsolateral prefrontal cortex on volitional control under irrelevant distraction.

Abstract: Volitional control has been related to the excitatory/inhibitory (E/I) ratio of glutamate-glutamine to γ-aminobutyric acid concentration in the different parts of the frontal cortex. Yet, how the neurochemical balance in each of the brain areas modulates volitional control remains unclear. Here, participants performed an auditory Go/No-Go task with and without task-irrelevant face distractors. Neurochemical balance was measured with magnetic resonance spectroscopy at rest. Participants with higher E/I ratios in the dorsolateral prefrontal cortex (DLPFC) showed less control over No-Go cues under no distraction, whereas participants with higher E/I ratios in the anterior cingulate cortex (ACC) were more prompted to make speeded Go responses under distraction. Therefore, the neurochemical balance in the DLPFC and ACC may be involved in the control over task-relevant and -irrelevant cues respectively.

Koizumi|Ai|A|
Lau|Hakwan|H|
Shimada|Yasuhiro|Y|
Kondo|Hirohito M|HM|

Volitional control
Go/No-Go task
Dorsolateral prefrontal cortex (DLPFC)
Anterior cingulate cortex (ACC)
Magnetic resonance spectroscopy (MRS)


Osteopontin regulates the proliferation of rat aortic smooth muscle cells in response to gingipains treatment.

Abstract:
OBJECTIVE
The present study aimed to explore the possible effects of osteopontin (OPN) in the proliferation of rat aortic smooth muscle cells (RASMCs) stimulated by gingipains.

METHODS
The proliferation of RASMCs in response to active gingipains treatment was evaluated by CCK-8 assay. OPN siRNA was designed, constructed and transfected into RASMCs at different concentrations. The cell cycle of RASMCs was analyzed by flow cytometry. OPN, α-SMA and calponin expression were examined by real-time PCR and western blot analysis.

RESULTS
Gingipains promoted the proliferation of RASMCs and OPN expression. With siRNA-mediated OPN expression knockdown, the cell cycle of RASMCs was blocked in the G0/G1 phase. Furthermore, the expression of specific differentiation markers, α-SMA and calponin, also decreased.

CONCLUSIONS
These results demonstrate that OPN has an impact on the proliferation and differentiation of RASMCs stimulated by gingipains.

Cao|Chong|C| Luo|Xin|X| Ji|Xiaowei|X| Wang|Yao|Y| Zhang|Yuan|Y| Zhang|Pengtao|P| Zhong|Liangjun|L|

Proliferation
OPN
Rat smooth muscle cell


ACR Appropriateness Criteria® Ovarian Cancer Screening.

Abstract: There has been much interest in the identification of a successful ovarian cancer screening test, in particular, one that can detect ovarian cancer at an early stage and improve survival. We reviewed the currently available data from randomized and observational trials that examine the role of imaging for ovarian cancer screening in average-risk and high-risk women. We found insufficient evidence to recommend ovarian cancer screening, when considering the imaging modality (pelvic ultrasound) and population (average-risk postmenopausal women) for which there is the greatest available published evidence; randomized controlled trials have not demonstrated a mortality benefit in this setting. Screening high-risk women using pelvic ultrasound may be appropriate in some clinical situations; however, related data are limited because large, randomized trials have not been performed in this setting. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

|||
Pandharipande|Pari V|PV|
Lowry|Kathryn P|KP|
Reinhold|Caroline|C|
Atri|Mostafa|M|
Benson|Carol B|CB|
Bhosale|Priyadarshani R|PR|
Green|Edward D|ED|
Kang|Stella K|SK|
Lakhman|Yulia|Y|
Maturen|Katherine E|KE|
Nicola|Refky|R|
Salazar|Gloria M|GM|
Shipp|Thomas D|TD|
Simpson|Lynn|L|
Sussman|Betsy L|BL|
Uyeda|Jennifer|J|
Wall|Darci J|DJ|
Whitcomb|Bradford|B|
Zelop|Carolyn M|CM|
Glanc|Phyllis|P|

Appropriateness Criteria
Ovarian cancer
Cancer screening
AUC
Appropriate Use Criteria
CA-125
Pelvic US


Occupational ultraviolet exposure and risk of non-Hodgkin's lymphomas: a meta-analysis.

Abstract: Non-Hodgkin lymphoma is a heterogeneous group of lympho-proliferative disorders. We performed a meta-analysis to summarize the available evidence from case-control studies and cohort study on the inconsistent association between occupational sun exposure and the risk of non-Hodgkin lymphoma. We searched PubMed, ISI web of science, the Cochrane Library, EMBASE and reference lists for relevant articles. Study specific odds ratios or relative risk and 95% confidence intervals were pooled by using fixed-effects or random-effects models. Ten case-control studies and one cohort study were included in the meta-analysis. Overall, the pooled odds ratios for occupational ultraviolet exposure and non-Hodgkin lymphoma risk was 1.15(95% confidence intervals: 0.99, 1.32; I2 = 44.4%). Occupational sun exposure was positively associated with the risk of NHL 1.14 (95% confidence intervals: 1.05, 1.23; I2=25.4% p for heterogeneity =0.202) in Caucasian population. Common subtypes of non-Hodgkin lymphoma and ultraviolet exposure had the negative results. The pooled odds ratios was 1.16, (95%confidence intervals: 0.90, 1.50) for T-cell non-Hodgkin lymphoma; 0.79, (95%confidence intervals: 0.61, 1.02) for B-cell non-Hodgkin lymphoma; 1.13, (95%confidence intervals: 0.96, 1.34) for chronic lymphocytic leukemia; 1.25, (95%confidence intervals: 0.95, 1.64) for males; 1.49, (95%confidence intervals: 0.99, 2.25) for females. Data suggested that occupational ultraviolet exposure was a risk factor for non-Hodgkin lymphoma in Caucasian population. While, there had no relationship between occupational ultraviolet exposure and risk of non-Hodgkin lymphoma in general population as well as non-Hodgkin lymphoma common subtypes. Besides, gender specific occupational sun exposure also indicated no association on risk of non-Hodgkin lymphoma.

Lu|Demin|D| Xu|Fei|F| Hu|Kaiming|K| Yin|Li|L| Duan|Huijie|H| Zhang|Jiaojiao|J| Zhang|SuZhan|S|

occupational ultraviolet exposure
meta-analysis
non-Hodgkin lymphoma


Anatomical basis and design of the distally based lateral dorsal cutaneous neuro-lateral plantar venofasciocutaneous flap pedicled with the lateral plantar artery perforator of the fifth metatarsal bone: a cadaveric dissection.

Abstract:
BACKGROUND
Detailed investigation of the vasculature of the lateral aspect of the foot has rarely been presented. However, harvesting the flap in this area to cover defects of the foot and hand is highly important. Repair of soft-tissue defects at the forefoot remains a challenge in reconstructive surgery. This study explores the characteristics of the distal-based lateral dorsal cutaneous neuro-lateral plantar venofasciocutaneous flap pedicled with the lateral plantar artery perforator of the fifth metatarsal bone to establish a repair procedure for ulcers or defects in the forefoot region.

METHODS
This study is divided into two parts: anatomical study and simulated operation. Thirty cadavers were utilized in the anatomical study after arterial injection. The tuberosity of the fifth metatarsal bone was used as the anatomical landmark. The lateral plantar artery perforator of the fifth metatarsal bone was identified through dissection. The perforators were dissected under a microscope. The details of the lateral plantar artery perforators, the distribution of the lateral dorsal cutaneous nerve and lateral plantar vein, the anastomosis in the lateral plantar artery perforator of the fifth metatarsal bone, the nutrient vessels of the lateral dorsal cutaneous nerve and lateral plantar vein, and other arteries of the lateral foot were recorded. The flap-raising procedure was performed on three fresh cadavers.

RESULTS
The lateral dorsal cutaneous nerve originated from sural nerve, traveled obliquely downward along the anterior lateral margin of the foot, and accompanied by the lateral plantar vein after bifurcation, and was eventually distributed on the lateral aspect of the foot. The nutrifying arteries to the lateral dorsal cutaneous nerve and lateral plantar vein were present segmentally and mainly originated from the lateral plantar artery perforator of the fifth metatarsal bone. These nitrifying arteries constantly originated from the lateral plantar artery in the area of tuberosity of the fifth metatarsal, ran along the medial side of the fifth metatarsal, traveled between the fifth metatarsal bone and the lateral muscle group (the flexor digitorum brevis and the abductor digiti minimi muscles), pierced the aponeurosis, vascularized the skin of the anterior lateral plantar region, and resulted in many minute branches, which anastomosed with the lateral tarsal artery and fourth dorsal metatarsal artery. The anatomical study showed that (1) the vasculature pattern can roughly be classified into three types and (2) constant anastomoses occurred between the above-mentioned arteries in the lateral-dorsum region of the foot.

CONCLUSION
A reliable large- or medium-sized neuro-venocutaneous flap with lateral dorsal cutaneous nerve, lateral plantar vein, and nutrient vessels can be raised using only the perforator of the lateral plantar artery of the fifth metatarsal bone, which is thin, is in the immediate vicinity of the forefoot, and has a reliable retrograde blood supply. This flap can be considered an alternative means to reconstruct soft-tissue defects of the forefoot.

Wang|Tianquan|T| Lin|Jian|J| Song|Dajiang|D| Zheng|Heping|H| Hou|Chunlin|C| Li|Lei|L| Wu|Zedong|Z|

Lateral plantar artery
Fifth metatarsal bone
Lateral dorsal cutaneous nerve
Lateral plantar vein
Forefoot defect


Monocyte-Chemoattractant Protein-1 Levels in Human Atherosclerotic Lesions Associate With Plaque Vulnerability.

Abstract: [Figure: see text].

Georgakis|Marios K|MK|
van der Laan|Sander W|SW|
Asare|Yaw|Y|
Mekke|Joost M|JM|
Haitjema|Saskia|S|
Schoneveld|Arjan H|AH|
de Jager|Saskia C A|SCA|
Nurmohamed|Nick S|NS|
Kroon|Jeffrey|J|
Stroes|Erik S G|ESG|
de Kleijn|Dominique P V|DPV|
de Borst|Gert J|GJ|
Maegdefessel|Lars|L|
Soehnlein|Oliver|O|
Pasterkamp|Gerard|G|
Dichgans|Martin|M|

D000368:Aged
D015415:Biomarkers
D016893:Carotid Stenosis
D018932:Chemokine CCL2
D003430:Cross-Sectional Studies
D016894:Endarterectomy, Carotid
D005260:Female
D006801:Humans
D008137:Longitudinal Studies
D008297:Male
D008875:Middle Aged
D058226:Plaque, Atherosclerotic
D011237:Predictive Value of Tests
D018570:Risk Assessment
D012307:Risk Factors
D012422:Rupture, Spontaneous
D020521:Stroke
D013997:Time Factors

atherosclerosis
carotid stenosis
chemokines
collagen
macrophages


Potential Drug Targets in the Pentose Phosphate Pathway of Trypanosomatids.

Abstract: The trypanosomatids, Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp, are causative agents of important human diseases such as African sleeping sickness, Chagas' disease and Leishmaniasis, respectively. The high impact of these diseases on human health and economy worldwide, the unsatisfactory available chemotherapeutic options and the absence of human effective vaccines, strongly justifies the search for new drugs. The pentose phosphate pathway has been proposed to be a viable strategy to defeat several infectious diseases, including those from trypanosomatids, as it includes an oxidative branch, important in the maintenance of cell redox homeostasis, and a non-oxidative branch in which ribose 5-phosphate and erythrose 4-phosphate, precursors of nucleic acids and aromatic amino acids, are produced. This review provides an overview of the available chemotherapeutic options against these diseases and discusses the potential of genetically validated enzymes from the pentose phosphate pathway of trypanosomatids to be explored as potential drug targets.

Loureiro|Inês|I|
Faria|Joana|J|
Santarem|Nuno|N|
Smith|Terry K|TK|
Tavares|Joana|J|
Cordeiro-da-Silva|Anabela|A|

D000981:Antiprotozoal Agents
D014355:Chagas Disease
D005954:Glucosephosphate Dehydrogenase
D006801:Humans
D007896:Leishmaniasis
D010427:Pentose Phosphate Pathway
D015800:Protozoan Proteins
D014346:Trypanosoma brucei brucei
D014349:Trypanosoma cruzi
D014353:Trypanosomiasis, African

drug targets
pentose phosphate pathway
Trypanosomatids
treatment.


0.2 V Electrolysis Voltage-Driven Alkaline Hydrogen Production with Nitrogen-Doped Carbon Nanobowl-Supported Ultrafine Rh Nanoparticles of 1.4 nm.

Abstract: The development of highly effective and low-cost electrocatalysts for energy-saving hydrogen production via water splitting is still a great challenge. Herein, porous nitrogen-doped carbon nanobowls (N-CBs) have been designed and used for the controlled growth of ultrafine rhodium (Rh) nanoparticles. With the aid of interfacial bonding of Rh and N, ultrafine Rh nanoparticles with an average size of 1.4 nm have been successfully immobilized on the N-CBs. This Rh/N-CB electrocatalyst shows superior activity and high stability for the hydrogen evolution reaction (HER) and the hydrazine oxidation reaction (HzOR). More importantly, the Rh/N-CBs exhibit high activity for hydrogen production from water electrolysis, marking with a cell voltage of 0.2 V to achieve a current density of 20 mA cm-2 when they serve as cathodic electrocatalysts for the HER and anodic electrocatalysts for the HzOR in 1 M KOH with 0.5 M hydrazine. The density functional theory calculations demonstrate that a near-zero hydrogen adsorption free energy produced by the chemical bonding of Rh with the pyrrole-N doped in N-CBs is responsible for the excellent HER activity of Rh/N-CBs electrocatalysts.

hydrogen production
ultrafine Rh nanoparticles
nitrogen-doped carbon nanobowls
bifunctional electrocatalyst
low voltage


The application of uterine wall local resection and reconstruction to preserve the uterus for the management of morbidly adherent placenta: Case series.

Abstract:
OBJECTIVE
We aimed to evaluate our experience with the application of uterine wall local resection and reconstruction to preserve the uterus in patients with morbidly adherent placenta.

MATERIALS AND METHODS
In a retrospective study, data from patients with morbidly adherent placenta who delivered by cesarean section between January 1, 2013 and May 31, 2016 were analyzed. Prophylactic abdominal aorta balloon occlusion and tourniquet were used to prevent massive hemorrhage in all 62 cases, followed by uterine wall local resection and reconstruction to preserve the uterus. The quantity of estimated blood loss (EBL), operation time, and complications were analyzed.

RESULTS
The placenta penetrated to the myometrium in 10 cases, involved the posterior bladder wall in 46 cases, and penetrated the posterior bladder wall in six cases. For all cases, the mean EBL in the surgery was 1377.3 ± 605.2 mL, the mean EBL in the initial postoperative 24 h was 140.6 ± 66.3 mL, the mean operation time was 72.3 ± 24.5 min, and the mean postoperative hospital stay was 5.8 ± 1.6 days. The six cases of placenta penetrating the bladder underwent bladder repair. Sixty-one cases had preserved uterus, and only one case had a hysterectomy due to amniotic fluid embolism (AFE).

CONCLUSION
Combined with prophylactic abdominal aorta balloon occlusion and tourniquet, uterine wall local resection and reconstruction is highly effective to reduce the intraoperative blood loss and hysterectomy in morbidly adherent placenta.

Zhao|Xianlan|X| Tao|Ya|Y| Du|Yingying|Y| Zhao|Lei|L| Liu|Cai|C| Zhou|Yan|Y| Wei|Peng|P|

Morbidly adherent placenta
Abdominal aorta
Balloon occlusion
Cesarean delivery
Hysterectomy prevention


Overlap at the molecular and immunohistochemical levels between angioimmunoblastic T-cell lymphoma and a subgroup of peripheral T-cell lymphomas without specific morphological features.

Abstract: The overlap of morphology and immunophenotype between angioimmunoblastic T-cell lymphoma (AITL) and other nodal peripheral T-cell lymphomas (n-PTCLs) is a matter of current interest whose clinical relevance and pathogenic background have not been fully established. We studied a series of 98 n-PTCL samples (comprising 57 AITL and 41 PTCL-NOS) with five TFH antibodies (CD10, BCL-6, PD-1, CXCL13, ICOS), looked for mutations in five of the genes most frequently mutated in AITL (TET2, DNMT3A, IDH2, RHOA and PLCG1) using the Next-Generation-Sequencing Ion Torrent platform, and measured the correlations of these characteristics with morphology and clinical features. The percentage of mutations in the RHOA and TET2 genes was similar (23.5% of cases). PLCG1 was mutated in 14.3%, IDH2 in 11.2% and DNMT3A in 7.1% of cases, respectively. In the complete series, mutations in RHOA gene were associated with the presence of mutations in IDH2, TET2 and DNMT3A (p < 0.001, p = 0.043, and p = 0.029, respectively). Fourteen cases featured RHOA mutations without TET2 mutations. A close relationship was found between the presence of these mutations and a TFH-phenotype in AITL and PTCL-NOS patients. Interestingly, BCL-6 expression was the only TFH marker differentially expressed between AITL and PTCL-NOS cases. There were many fewer mutated cases than there were cases with a TFH phenotype. Overall, these data suggest alternative ways by which neoplastic T-cells overexpress these proteins. On the other hand, no clinical or survival differences were found between any of the recognized subgroups of patients with respect to their immunohistochemistry or mutational profile.

Manso|Rebeca|R|
González-Rincón|Julia|J|
Rodríguez-Justo|Manuel|M|
Roncador|Giovanna|G|
Gómez|Sagrario|S|
Sánchez-Beato|Margarita|M|
Piris|Miguel A|MA|
Rodríguez-Pinilla|Socorro M|SM|


Alteration of human macrophage phenotypes by the anti-fibrotic drug nintedanib.

Abstract: The tyrosine kinase inhibitor, Nintedanib (NTD), has been approved for the treatment of idiopathic pulmonary fibrosis (IPF). In cell-free systems, NTD was recently shown to inhibit kinase activity of the human recombinant colony-stimulating factor 1 (CSF1) receptor (CSF1R) which mediates major functions of pulmonary macrophages. In the present study, we have investigated the effects of NTD on the phenotype of human monocyte-derived macrophages controlled by CSF1 in order to identify its anti-inflammatory properties via CSF1R inhibition. NTD (0.01 to 1 μM) prevented the CSF1-induced phosphorylation of CSF1R and activation of the downstream signaling pathways. NTD, like the CSF1R inhibitor GW2580, significantly decreased the adhesion of macrophages and production of the chemokine ligand (CCL) 2. NTD also altered the polarization of macrophages to classical M1 and alternative M2a macrophages. It reduced the secretion of several pro-inflammatory and/or pro-fibrotic cytokines (IL-1β, IL-8, IL-10 and CXCL13) by M1 macrophages but did not prevent the expression of M1 markers. While NTD (50-200 nM) partially blocked the synthesis of M2a markers (CD11b, CD200R, CD206, and CD209), it did not reduce synthesis of the M2a pro-fibrotic cytokines CCL22 and PDGF-BB, and increased CCL18 release when used at its highest concentration (1 μM). The effects of NTD on macrophage polarization only was partially mimicked by GW2580, suggesting that the drug inhibits other molecules in addition to CSF1R. In conclusion, NTD alters the CSF1-controlled phenotype of human macrophages mainly by blocking the activation of CSF1R that thus constitutes a new molecular target of NTD, at least in vitro.

Bellamri|Nessrine|N| Morzadec|Claudie|C| Joannes|Audrey|A| Lecureur|Valérie|V| Wollin|Lutz|L| Jouneau|Stéphane|S| Vernhet|Laurent|L|

D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor

Macrophages
Nintedanib
Idiopathic pulmonary fibrosis
CSF1R
Polarization
Inflammation


Linear extrapolation of missing radiographic change scores in clinical trials does not spuriously overestimate group radiographic changes in rheumatoid arthritis.

Abstract:
OBJECTIVE
To assess linear extrapolation (LE) and last observation carried forward (LOCF) as imputation methods for radiographic change in patients with RA.

METHODS
The OSKIRA-1 trial enrolled 918 patients with active RA for studying the efficacy of fostamatinib. Radiographs were scheduled for all patients at baseline and week 12, regardless of early escape, and at weeks 24 and 52 for patients who remained in the study. Complete radiographic data for the 24-week follow-up were available for 623 patients and were assessed according to the Sharp/van der Heijde score. From this complete set of data, a random selection of 10% missingness was generated. This was done 1000 times, and for each replicate the missing radiographic change at week 24 was imputed, first by LE, then by LOCF. The mean of the mean and mean of the s.d. across the 1000 replications was calculated. A similar approach was iterated for different proportions of missingness.

RESULTS
The mean (s.d.) observed Sharp/van der Heijde score change from baseline to week 24 was 0.36 (2.39). With LE, the mean (s.d.) change was estimated as 0.36 (2.65), 0.35 (2.88), 0.35 (3.17), 0.34 (3.57) and 0.32 (4.45) with 10/20/30/50/90% missingness, respectively. With LOCF, the mean (s.d.) change was estimated as 0.34 (2.39), 0.32 (2.38), 0.30 (2.37), 0.26 (2.36) and 0.18 (2.34) with 10/20/30/50/90% missingness, respectively.

CONCLUSION
LE led to stable estimates of progression at the group level, but increasing variability with increasing proportions of missingness. In contrast, LOCF imputation systemically underestimated mean progression with increasing proportions of missingness, with artificially reduced variability estimates.

Markusse|Iris M|IM|
Landewé|Robert|R|
Wolterbeek|Ron|R|
Ho|Meilien|M|
Jenkins|Martin|M|
van der Heijde|Désirée|D|

rheumatoid arthritis
imputation
missing data
radiographic progression


Kupffer Cell and Monocyte-Derived Macrophage Identification by Immunofluorescence on Formalin-Fixed, Paraffin-Embedded (FFPE) Mouse Liver Sections.

Abstract: Kupffer cells are the liver-resident macrophages and represent the first line of defense between the pathogens circulating from the intestines through the portal vein and systemic circulation. Recent works have highlighted the complex heterogeneity of macrophage functions and origins, thus raising awareness on the need for a better characterization of macrophage populations. The immunohistochemistry method here described, allows for a rapid distinction between Kupffer cells and monocyte-derived macrophages present on formalin-fixed, paraffin-embedded mouse liver samples. This protocol has been optimized for its reproducibility, reliability, and simplicity.

Kupffer cell
Macrophage
Immunofluorescence
Liver
CLEC4F/CLECSF13
Confocal microscopy
FFPE liver sections
IBA1
Monocyte


Safety of tocilizumab in the treatment of juvenile idiopathic arthritis.

Abstract: Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody and IL-6 receptor antagonist, currently approved for the treatment of systemic juvenile idiopathic arthritis (sJIA) and polyarticular juvenile idiopathic arthritis (pJIA) in children aged 2 years or older refractory to conventional treatment. The most common adverse events in patients treated with TCZ were infections, especially in the respiratory tract. The most frequent laboratory abnormalities were altered liver function, neutropenia and elevated cholesterol levels. Areas covered: The safety of TCZ in the treatment of children with JIA was determined based on a review of published clinical trials, including two multicenter studies of patients with sJIA and pJIA (the TENDER and CHERISH trials, respectively). The frequency of adverse events (AEs), serious adverse events (SAEs) and deaths reported in these studies was analyzed and discussed. Expert opinion: TCZ was effective and well tolerated in the treatment of severe forms of sJIA and pJIA, and can be considered a treatment of choice for these conditions. The risk of infections and laboratory abnormalities, such as neutropenia, should be constantly monitored. There is still a need for comparative studies of the risks and benefits of biological agents in patients with refractory JIA.

Machado|Sandra Helena|SH|
Xavier|Ricardo Machado|RM|

safety
treatment
juvenile idiopathic arthritis
IL-6 inhibitors


Modification of the Forms of Self-Determined Regulation and Quality of Life after a Cardiac Rehabilitation Programme: Tennis-Based vs. Bicycle Ergometer-Based.

Abstract:
BACKGROUND
The objective is to analyse and compare the effects of an adapted tennis cardiac rehabilitation programme and a classical bicycle ergometer-based programme on the type of motivation towards sports practice and quality of life in patients classified as low risk after suffering acute coronary syndrome.

METHODS
The Behavioural Regulation in Exercise Questionnaire (BREQ-2) and Velasco's Qualityof Life Test were applied. The sample comprised 110 individuals (age = 55.05 ± 9.27) divided into two experimental groups (tennis and bicycle ergometer) and a control group.

RESULTS
The intra-group analysis showed a significant increase between pre- and post-test results in intrinsic regulation in the tennis group and in the control group. In identified regulation, the bicycle ergometer group presented significant differences from the control group. On the other hand, in the external regulation variable, only the tennis group showed significant differences, which decreased. Significant improvements in all quality-of-life factors when comparing the pre-test period with the post-test period were only found in the experimental groups. As per the inter-group analysis, significant differences were observed in favour of the tennis group with respect to the control group in the variables of health, social relations and leisure, and work time as well as in favour of the bicycle ergometer group compared with the control group in the variables of health, sleep and rest, future projects and mobility. No significant differences were found in any of the variables between the tennis group and the bicycle ergometer group.

CONCLUSION
It is relevant to enhance the practice of physical exercise in infarcted patients classified as low risk as it improves the forms of more self-determined regulation towards sporting practice and their quality of life.

tennis
motivation
acute coronary syndrome
CRP
HRQoL


Abiotic Synthesis of Nucleoside 5'-Triphosphates with Nickel Borate and Cyclic Trimetaphosphate (CTMP).

Abstract: While nucleoside 5'-triphosphates are precursors for RNA in modern biology, the presumed difficulty of making these triphosphates on Hadean Earth has caused many prebiotic researchers to consider other activated species for the prebiotic synthesis of RNA. We report here that nickel(II), in the presence of borate, gives substantial amounts (2-3%) of nucleoside 5'-triphosphates upon evaporative heating in the presence of urea, salts, and cyclic trimetaphosphate (CTMP). Also recovered are nucleoside 5'-diphosphates and nucleoside 5'-monophosphates, both likely arising from 5'-triphosphate intermediates. The total level of 5'-phosphorylation is typically 30%. Borate enhances the regiospecificity of phosphorylation, with increased amounts of other phosphorylated species seen in its absence. Experimentally supported paths are already available to make nucleosides in environments likely to have been present on Hadean Earth soon after a midsized 1021 to 1023 kg impactor, which would also have delivered nickel to the Hadean surface. Further, sources of prebiotic CTMP continue to be proposed. Thus, these results fill in one of the few remaining steps needed to demystify the prebiotic synthesis of RNA and support a continuous model from atmospheric components to oligomeric RNA that is lacking only a mechanism to obtain homochirality in the product RNA.

Cyclic trimetaphosphate
Activated nucleotides
Nickel borate.
Prebiotic RNA synthesis


Resource recovery from waste by Roma in the Balkans: A case study from Zavidovici (BiH).

Abstract: Roma communities represent the main involved actors in the informal activities in the Balkan regions, especially because the state does not formally recognize them as formal inhabitants. The Roma community in Zavidovici, despite being resident since the beginning of the 20th century, is still considered a marginalized and vulnerable group. They are actively involved in and dependent on the informal solid waste sector. Waste collection is a 'family business', a kind of self-employment and the main source of income for households. Informal recyclers have a central role in the solid waste management system and they recover a significant amount of materials, especially iron, copper, brass, lead and exhausted batteries. Despite the negative fluctuations of the raw material prices, because of the international economic crisis, informal recyclers remain dependent on the waste recycling sector. They are crucial actors in the value chain of recyclables: though they cannot access the final buyers of recyclables, they provide more than 50% of the market to the middle dealers in the Zenica-Doboj Canton. This research activity consists of a deep socio-economic analysis of the informal recyclers' community living in Zavidovici city. In particular, this paper describes the composition and welfare status of informal recyclers' households, the role of informal recyclers in waste collection, the geographical coverage and the related pattern of waste picking, types, volumes and price fluctuations of recyclable materials, and the middle dealers involved in the informal recycling system.

D017522:Bosnia and Herzegovina
D000070100:Informal Sector
D059027:Recycling
D006178:Roma
D062611:Solid Waste
D018505:Waste Management

Roma community
informal recycling
socio-economic analysis
Bosnia-Herzegovina
waste recovery


Whale jaw joint is a shock absorber.

Abstract: The non-synovial temporomandibular jaw joint of rorqual whales is presumed to withstand intense stresses when huge volumes of water are engulfed during lunge feeding. Examination and manipulation of temporomandibular joints (TMJs) in fresh carcasses, plus CT scans and field/lab mechanical testing of excised tissue blocks, reveals that the TMJ's fibrocartilage pad fully and quickly rebounds after shrinking by 68-88% in compression (by axis) and stretching 176-230%. It is more extensible along the mediolateral axis and less extensible dorsoventrally, but mostly isotropic, with collagen and elastin fibers running in all directions. The rorqual TMJ pad compresses as gape increases. Its stiffness is hypothesized to damp acceleration, whereas its elasticity is hypothesized to absorb shock during engulfment, allow for rotation or other jaw motion during gape opening/closure, and aid in returning jaws to their closed position during filtration via elastic recoil with conversion of stored potential energy into kinetic energy.

Temporomandibular TMJ Elasticity Biomechanics Cetacea Morphology Mysticete


Exosomes in virus-associated cancer.

Abstract: Exosomes are phospholipid bilayer membrane-enclosed vesicles in a size from 30 to 150 nm, carrying a variety of active components, such as proteins, mRNA and miRNAs, and are involved in intercellular communication. Exosomes are released by almost all living cells and detected in various biological fluids. Viruses especially oncogenic viruses have been reported to influence the formation of virus-associated cancer through reshaping the tumor microenvironment via exosomes. In this review, a role of exosomes released by oncogenic virus-infected cells in promoting or inhibiting cancer formation is outlined. Moreover, the prospects and challenges of exosome applications in cancer therapies are critically discussed.

Wu|Jin'en|J| Yang|Jing|J| Ding|Juntao|J| Guo|Xiaola|X| Zhu|Xing-Quan|XQ| Zheng|Yadong|Y|

D015972:Gene Expression Regulation, Neoplastic

Exosome
Virus-associated cancer
miRNAs
Onco-virus


DRD1, a SWI/SNF-like chromatin remodeling protein, regulates a heat-activated transposon in Arabidopsis thaliana.

Abstract: ONSEN is a heat-activated LTR retrotransposon in Arabidopsis thaliana. Screens to identify transcriptional regulatory factors of ONSEN revealed a SWI/SNF-like chromatin remodeling protein, DRD1, which cooperates with plant-specific RNA polymerase and is involved in RNA-directed DNA methylation. ONSEN transcript level was increased in the drd1 mutant relative to wild-type under heat stress, indicating that DRD1 plays a significant role in the silencing of activated ONSEN under the stress condition. The transcript level of HsfA2, which is directly involved in transcriptional activation of ONSEN, was not higher in the drd1 mutant than in the wild-type. Interestingly, no transgenerational transposition of ONSEN was observed in the drd1 mutant, even though DNA methylation levels were significantly reduced and expression levels were increased compared to the wild-type. These results suggest that other factors are involved in the regulation of ONSEN transposition in addition to the transcript level of ONSEN.

Takehira|Kanako|K| Hayashi|Yui|Y| Nozawa|Kosuke|K| Chen|Lu|L| Suzuki|Takamasa|T| Masuta|Yukari|Y| Kato|Atsushi|A| Ito|Hidetaka|H|

DRD1
transposon
ONSEN
RNA-directed DNA methylation
heat stress


Gender Disparities in Osteoporosis.

Abstract: Osteoporosis is a growing health concern worldwide and its complications are as prevalent as other common chronic disease complications such as hypertension and diabetes. In this review, we will discuss the role of gender in osteoporosis, especially related to peak bone mass and maturation, rate of annual bone loss, screening, prevalence of osteoporosis and its related fractures, mortality after osteoporosis-related fracture, fracture risk predication using different technologies and the impact of gender on osteoporosis management.

Fracture and dual energy X-ray absorptiometry


Organoid and Spheroid Tumor Models: Techniques and Applications.

Abstract: Techniques to develop three-dimensional cell culture models are rapidly expanding to bridge the gap between conventional cell culture and animal models. Organoid and spheroid cultures have distinct and overlapping purposes and differ in cellular sources and protocol for establishment. Spheroids are of lower complexity structurally but are simple and popular models for drug screening. Organoids histologically and genetically resemble the original tumor from which they were derived. Ease of generation, ability for long-term culture and cryopreservation make organoids suitable for a wide range of applications. Organoids-on-chip models combine organoid methods with powerful designing and fabrication of micro-chip technology. Organoid-chip models can emulate the dynamic microenvironment of tumor pathophysiology as well as tissue-tissue interactions. In this review, we outline different tumor spheroid and organoid models and techniques to establish them. We also discuss the recent advances and applications of tumor organoids with an emphasis on tumor modeling, drug screening, personalized medicine and immunotherapy.

Gunti|Sreenivasulu|S|
Hoke|Austin T K|ATK|
Vu|Kenny P|KP|0000-0002-9396-1120
London|Nyall R|NR|0000-0002-2902-4407

organoids
spheroids
tumor modeling
drug screening
organoids-on-chip
personalized medicine
immunotherapy
air–liquid interface
microfluidics
organoid biobanks


Case for diagnosis. Ulcerated lesions: a diagnostic challenge in Behçet's syndrome.

Abstract: This study reports the clinical case of a 42-year-old patient with ulcerated lesions who was followed up by general practitioners with the diagnosis of recurrent cellulitis. However, when referred to the Dermatology division a diagnosis of Behçet's syndrome was established based on clinical criteria. Although there are defined clinical criteria for this syndrome, sometimes its diagnosis can be challenging, due to lack of knowledge of the disease and extremely heterogeneous clinical phenotype. The authors highlight the potential difficulties in establishing the diagnosis considering the multiple clinical findings during the investigation process, contributing to the risk of increased morbidity and mortality.

Sbroglio|Lissiê Lunardi|LL|
Araújo|Karin Milleni de|KM|
Santos|Bianca Passos Leite Dos|BPLD|
Gripp|Alexandre Carlos|AC|

Behçet syndrome
Delayed diagnosis
Diagnosis, differential
Signs and symptoms


Impact of brain arousal and time-on-task on autonomic nervous system activity in the wake-sleep transition.

Abstract:
BACKGROUND
Autonomic nervous system (ANS) activity has been shown to vary with the state of brain arousal. In a previous study, this association of ANS activity with distinct states of brain arousal was demonstrated using 15-min EEG data, but without directly controlling for possible time-on-task effects. In the current study we examine ANS-activity in fine-graded EEG-vigilance stages (indicating states of brain arousal) during two conditions of a 2-h oddball task while controlling for time-on-task. In addition, we analyze the effect of time-on-task on ANS-activity while holding the level of brain arousal constant.

METHODS
Heart rate and skin conductance level of healthy participants were recorded during a 2-h EEG with eyes closed under simultaneous presentation of stimuli in an ignored (N = 39) and attended (N = 39) oddball condition. EEG-vigilance stages were classified using the Vigilance Algorithm Leipzig (VIGALL 2.1). The time-on-task effect was tested by dividing the EEG into four 30-min consecutive time blocks. ANS-activity was compared between EEG-vigilance stages across the entire 2 h and within each time block.

RESULTS
We found a coherent decline of ANS-activity with declining brain arousal states, over the 2-h recording and in most cases within each 30-min block in both conditions. Furthermore, we found a significant time-on-task effect on heart rate, even when arousal was kept constant. It was most pronounced between the first and all subsequent blocks and could have been a consequence of postural change at the beginning of the experiment.

CONCLUSION
Our findings contribute to the validation of VIGALL 2.1 using ANS parameters in 2-h EEG recording under oddball conditions.

Huang|Jue|J|0000-0003-1830-9340 Ulke|Christine|C| Sander|Christian|C| Jawinski|Philippe|P| Spada|Janek|J| Hegerl|Ulrich|U| Hensch|Tilman|T|

Brain arousal
Time-on-task effect
EEG-vigilance stages
Heart rate
Skin conductance level
VIGALL 2.1


Overuse injuries in the knee, back and hip of top elite female alpine skiers during the off-season preparation period: prevalence, severity and their association with traumatic preinjuries and training load.

Abstract:
Objectives
To investigate knee, back and hip overuse injuries in top female elite alpine skiers during the off-season preparation, which has so far received little attention, and to assess their relationship with traumatic preinjuries and overall training load.

Methods
A cohort of 26 females of the Swiss Alpine Ski-Team were prospectively surveyed by the use of the Oslo Sports Trauma Research Centre questionnaire. Along with the surveys also total training loads were monitored. Data on preinjuries were assessed retrospectively by baseline questionnaires and were verified by team medical records.

Results
57.7% of the female skiers suffered from at least one severe traumatic knee injury during their preceding career. The average 2-weekly prevalence of overuse injuries was highest for the knee, followed by the back and hip. Technique specialists (major giant slalom and slalom) were more prone to back overuse injuries than speed specialists (major super-G and downhill). The occurrence of knee overuse complaints was directly associated to previous severe traumatic knee injuries and athletes' total training hours.

Conclusion
In top female elite alpine skiers, knee, back and hip overuse injuries are relatively frequent. Moreover, discipline preferences, previous traumatic injuries and the overall training load may play an important role for their manifestation.

Fröhlich|Stefan|S|
Pazeller|Seraina|S|
Cherati|Afsaneh Safar|AS|
Müller|Erich|E|
Frey|Walter O|WO|
Spörri|Jörg|J|0000-0002-0353-1021

overuse injury athlete epidemiology skiing


Impact evaluation of a payments for ecosystem services program on vegetation quantity and quality restoration in Inner Mongolia.

Abstract: Globally, the payments for ecosystem services (PES) program has become a helpful tool that serves the purpose of mitigating ecosystem degradation and protecting ecosystem services. However, the ecological effects of existing PES programs based on counterfactual baselines, quantification and sophisticated statistical analyses are still poorly understood. Taking Inner Mongolia as an example, this study evaluated the ecological effectiveness of the Natural Forest Conservation Program (NFCP) using the matching approach. The findings are as follows. First, 49.8% and 41.5% of the townships had significant gains in vegetation quantity and quality between 2000 and 2015, respectively; while 9.5% and 13.7% of the townships had significant losses in vegetation quantity and quality, respectively. Second, for forest quantity recovered townships, comparing to the NFCP unenrolled townships, the enrolled townships had increased forest quantity by additional 0.377 million ha (5.2%) from 2000 to 2015. Third, for forest quality recovered townships, the enrolled townships on average additionally increased forest quality by 465.513 Gg carbon (3.6%) from 2000 to 2015. Our study helps to promote sophisticated impact evaluation of conservation policies, which would improve the understanding and management of conservation practices in China and abroad.

Zhou|Ting|T| Shen|Weiwei|W| Qiu|Xiao|X| Chang|Hong|H| Yang|Hongbo|H| Yang|Wu|W|

Impact evaluation
Counterfactual baseline
Natural Forest Conservation Program
Environmental protection
Matching method


TNF-α regulates miRNA targeting mitochondrial complex-I and induces cell death in dopaminergic cells.

Abstract: Parkinson's disease (PD) is a complex neurological disorder of the elderly population and majorly shows the selective loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc) region of the brain. The mechanisms leading to increased cell death of DAergic neurons are not well understood. Tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine is elevated in blood, CSF and striatum region of the brain in PD patients. The increased level of TNF-α and its role in pathogenesis of PD are not well understood. In the current study, we investigated the role of TNF-α in the regulation of cell death and miRNA mediated mitochondrial functions using, DAergic cell line, SH-SY5Y (model of dopaminergic neuron degeneration akin to PD). The cells treated with low dose of TNF-α for prolonged period induce cell death which was rescued in the presence of zVAD.fmk, a caspase inhibitor and N-acetyl-cysteine (NAC), an antioxidant. TNF-α alters mitochondrial complex-I activity, decreases adenosine triphosphate (ATP) levels, increases reactive oxygen species levels and mitochondrial turnover through autophagy. TNF-α differentially regulates miRNA expression involved in pathogenesis of PD. Bioinformatics analysis revealed that the putative targets of altered miRNA included both pro/anti apoptotic genes and subunits of mitochondrial complex. The cells treated with TNF-α showed decreased level of nuclear encoded transcript of mitochondrial complexes, the target of miRNA. To our knowledge, the evidences in the current study demonstrated that TNF-α is a potential regulator of miRNAs which may regulate mitochondrial functions and neuronal cell death, having important implication in pathogenesis of PD.

Prajapati|Paresh|P| Sripada|Lakshmi|L| Singh|Kritarth|K| Bhatelia|Khyati|K| Singh|Rochika|R| Singh|Rajesh|R|

D000111:Acetylcysteine
D000255:Adenosine Triphosphate
D000590:Amino Acid Chloromethyl Ketones
D016923:Cell Death
D002460:Cell Line
D059290:Dopaminergic Neurons
D042967:Electron Transport Complex I
D016166:Free Radical Scavengers
D006801:Humans
D035683:MicroRNAs
D008928:Mitochondria
D010300:Parkinson Disease
D011480:Protease Inhibitors
D014409:Tumor Necrosis Factor-alpha

TNF-α
miRNA
Parkinson's disease
Inflammation
Mitochondria


The effect of high-energy environments on the structure of laccase-polymerized poly(catechol).

Abstract: The laccase polymerization of catechol was performed using different reactors namely a water bath (WB), an ultrasonic bath (US) and a high-pressure homogenizer (HPH). The total content of free OH and the MALDI-TOF spectra of polymers obtained demonstrated that reactions are favored in the presence of high-energy environments. Higher conversion yields and polymerization degrees (DP) were obtained after polymerization using US or HPH. Molecular dynamic simulation studies supported these findings by revealing a more open enzyme active site upon environments with high molecular agitation. The higher mass transport generated by US and HPH is the main feature responsible for a higher substrate accessibility to the enzyme which contributed to produce longer polymers.

Su|Jing|J|
Castro|Tarsila G|TG|
Noro|Jennifer|J|
Fu|Jiajia|J|
Wang|Qiang|Q|
Silva|Carla|C|
Cavaco-Paulo|Artur|A|

D066244:Proton Magnetic Resonance Spectroscopy

D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Laccase
Polymerization
Catechol
Ultrasonic bath
High-pressure homogenizer


Leaky Optoelectrical Fiber for Optogenetic Stimulation and Electrochemical Detection of Dopamine Exocytosis from Human Dopaminergic Neurons.

Abstract: In Parkinson's disease, the degeneration of dopaminergic neurons in substantia nigra leads to a decrease in the physiological levels of dopamine in striatum. The existing dopaminergic therapies effectively alleviate the symptoms, albeit they do not revert the disease progression and result in significant adverse effects. Transplanting dopaminergic neurons derived from stem cells could restore dopamine levels without additional motor complications. However, the transplanted cells disperse in vivo and it is not possible to stimulate them on demand to modulate dopamine release to prevent dyskinesia. In order to address these issues, this paper presents a multifunctional leaky optoelectrical fiber for potential neuromodulation and as a cell substrate for application in combined optogenetic stem cell therapy. Pyrolytic carbon coated optical fibers are laser ablated to pattern micro-optical windows to permit light leakage over a large area. The pyrolytic carbon acts as an excellent electrode for the electrochemical detection of dopamine. Human neural stem cells are genetically modified to express the light sensitive opsin channelrhodopsin-2 and are differentiated into dopaminergic neurons on the leaky optoelectrical fiber. Finally, light leaking from the micro-optical windows is used to stimulate the dopaminergic neurons resulting in the release of dopamine that is detected in real-time using chronoamperometry.

optogenetics
dopamine exocytosis
human neural stem cells
leaky optical fibers
pyrolysis


Empathy and cultural competence in clinical nurses: A structural equation modelling approach.

Abstract:
BACKGROUND
Forgiveness has the potential to resolve painful feelings arising from nurse-patient conflicts. It would be useful to evaluate direct and indirect important factors which are related to forgiveness in order to design interventions that try to facilitate forgiveness.

AIM/OBJECTIVE
The purpose of this study was to evaluate the intermediating role of empathy in the cultural competence-forgiveness association among nurses using structural equation modeling.

RESEARCH DESIGN
The research applied a cross-sectional correlational design.

PARTICIPANTS AND RESEARCH CONTEXT
The study included 380 nurses eight hospitals in southern Iran.

ETHICAL CONSIDERATIONS
The Ethics and Research Committee of Birjand University of Medical Sciences approved the study protocol. The voluntary nature of participation was explained consent was obtained from participants, and anonymity was guaranteed.

FINDINGS
Most of the participants were married and female and fell in the 20- to 30-year-old category. Most of them (89.5%) had a working experience of 1-10 years. The proposed model showed that nurses' empathy intermediated the association between nurses' cultural competence and forgiveness which has fitted the data acceptably (root mean square error approximation = 0.070; comparative fit index = 0.993; goodness-of-fit index = 0.983; and χ2/df = 2.85).

CONCLUSION
Empathy skills and cultural competence training were essential for interventions aimed at increasing the tendency to forgive patients. In such interventions, planners should aim at increasing nurses' cultural competence in order to enhance their empathy toward patients, which can, in turn, lead to a greater wish to forgive patients.

Zarei|Bahare|B|
Salmabadi|Mohaddeseh|M|
Amirabadizadeh|Alireza|A|
Vagharseyyedin|Seyyed Abolfazl|SA|

empathy
Cultural competence
nursing
structural equation modeling
forgiveness


A registry-based 2-year follow-up comparative study of two meshes used in transinguinal preperitoneal (TIPP) groin hernia repair.

Abstract:
PURPOSE
Onflex™ mesh has replaced Polysoft™ patch on the market, without being clinically evaluated thus far in the transinguinal preperitoneal (TIPP) technique.

METHODS
All consecutive TIPP registered in our registry during the overlap period of availability of both meshes were included and studied with the chronic postoperative inguinal pain (CPIP) as primary endpoint, assessed with a verbal rating scale (VRS), and included in a patient-related outcome measurement (PROM) phone questionnaire.

RESULTS
A total of 181 Onflex cases vs 182 Polysoft cases were studied with a 2-year follow-up rate of 92% vs 88%. The overall rate of pain or discomfort was not statistically different in the 2 studied subgroups (16.5% vs 17.6%; p = 0.71), while moderate or severe pain were significantly more frequent in the Polysoft subgroup (5.5% vs 11.6%; p = 0.01). These symptoms did not interfere with the patient daily life in 16% vs 16.5% of cases, and they were self-assessed as more bothersome than the hernia in only 0.5% vs 0.5% of cases, suggesting an overestimation of the pain by the VRS. Patients assessed the result of their hernia repair as excellent or good in 97.8% vs 96.7% and medium or bad in 2.2% vs 3.3% (p = 0.53). The cumulative recurrence rate was 0% vs 2.2%. Two reoperations (one for early and one for late recurrence) were reported in the Polysoft subgroup (1%), none related to the non-absorbable memory ring.

CONCLUSIONS
These results suggest that TIPP with Onflex provides results at least similar than those with Polysoft.

TIPP
Groin hernia repair
PROM
Chronic pain
Memory ring patch
PROs


Data on water quality index development for groundwater quality assessment from Obulavaripalli Mandal, YSR district, A.P India.

Abstract: Groundwater is a vital resource for most developmental activities. Demand for groundwater is increasing due to paucity of surface water and recurrent failures of monsoons. Increasing demand for groundwater causes water level to decline and water quality to deteriorate. This data article is aimed to investigate the quality of drinking water of Obulavaripalli Mandal YSR district based on water quality Index (WQI). To evaluate WQI in the study area, twenty groundwater samples were collected and different physico-chemical parameters viz., pH, EC, TDS, TH, total alkalinity (TA), calcium (Ca2+), magnesium (Mg2+), chloride (Cl-), sulphate (SO4 2-) and fluoride (F-) were analyzed. WQI data for groundwater samples indicated that 30% of the samples fall under excellent rating, 40% of the samples fall under good category and another 30% of the groundwater is under poor category. Overall groundwater quality is not suitable for drinking purpose.

Prasad|M|M|
Sunitha|V|V|
Reddy|Y Sudharshan|YS|
Suvarna|B|B|
Reddy|B Muralidhara|BM|
Reddy|M Ramakrishna|MR|

Water quality index
Obulavaripalli
Water quality assessment
Y.S.R district


Determinants of adherence to seasonal influenza vaccination among healthcare workers from an Italian region: results from a cross-sectional study.

Abstract:
OBJECTIVES
Notwithstanding decades of efforts to increase the uptake of seasonal influenza (flu) vaccination among European healthcare workers (HCWs), the immunisation rates are still unsatisfactory. In order to understand the reasons for the low adherence to flu vaccination, a study was carried out among HCWs of two healthcare organisations in Liguria, a region in northwest Italy.

METHODS
A cross-sectional study based on anonymous self-administered web questionnaires was carried out between October 2013 and February 2014. Through univariate and multivariate regression analysis, the study investigated the association between demographic and professional characteristics, knowledge, beliefs and attitudes of the study participants and (i) the seasonal flu vaccination uptake in the 2013/2014 season and (ii) the self-reported number of flu vaccination uptakes in the six consecutive seasons from 2008/2009 to 2013/2014.

RESULTS
A total of 830 HCWs completed the survey. Factors statistically associated with flu vaccination uptake in the 2013/2014 season were: being a medical doctor and agreeing with the statements 'flu vaccine is safe', 'HCWs have a higher risk of getting flu' and 'HCWs should receive flu vaccination every year'. A barrier to vaccination was the belief that pharmaceutical companies influence decisions about vaccination strategies.

DISCUSSION
All the above-mentioned factors, except the last one, were (significantly) associated with the number of flu vaccination uptakes self-reported by the respondents between season 2008/2009 and season 2013/2014. Other significantly associated factors appeared to be level of education, being affected by at least one chronic disease, and agreeing with mandatory flu vaccination in healthcare settings.

CONCLUSIONS
This survey allows us to better understand the determinants of adherence to vaccination as a fundamental preventive strategy against flu among Italian HCWs. These findings should be used to improve and customise any future promotion campaigns to overcome identified barriers to immunisation.

Durando|P|P|
Alicino|C|C|0000-0002-6473-9870
Dini|G|G|
Barberis|I|I|
Bagnasco|A M|AM|
Iudici|R|R|
Zanini|M|M|
Martini|M|M|
Toletone|A|A|
Paganino|C|C|
Massa|E|E|
Orsi|A|A|0000-0002-2433-9610
Sasso|L|L|

D007722:Health Knowledge, Attitudes, Practice

D010342:Patient Acceptance of Health Care

adherence
Influenza vaccine
healthcare workers
Italy


Attention Deficit/Hyperactivity Disorder and risk for non-affective psychotic disorder: The role of ADHD medication and comorbidity, and sibling comparison.

Abstract: Attention Deficit/Hyperactivity Disorder (ADHD) is the most common psychiatric disorder in childhood. It is unclear whether ADHD increases the risk of non-affective psychotic disorder (NAPD). The study included a matched cohort, drawn from all born in Sweden 1987-1991 (n = 548,852). ADHD was defined as ICD diagnosis and/or prescription of ADHD medication. We distinguished between stimulants and non-stimulants, and usage duration (<1 year, 1-2 years and ≥2 years). We calculated odds ratios (OR) with 95% confidence intervals (CI) for NAPD, adjusted for confounders, comorbid autism spectrum disorder (ASD) and substance abuse. ADHD cases were also compared to their unaffected full siblings. We analyzed 18,139 ADHD cases and 72,437 sex and birth year matched controls. NAPD was more common in cases than controls (2.7 and 0.4%, respectively). After adjustment for confounders, ADHD cases had markedly high risk for NAPD (OR: 6.99; 95% CI 6.03-8.10), which attenuated further after adjustment for ASD and substance abuse (OR: 2.57; 95% CI 2.09-3.16). Utilization of ADHD medication increased the risk for NAPD (ORs for change in odds of NAPD for every 5 extra prescriptions of stimulants 1.06 (95% CI 1.02-1.10) and, non-stimulants 1.15 (95% CI 1.01-1.30)). There was no association between usage length of medication and risk for NAPD. The risk was higher in individuals with ADHD than their unaffected siblings (OR: 2.95 (95% CI 2.07-4.20)). Overall, ADHD was associated with elevated risk for NAPD, which is not entirely explained by shared familial factors. The clinical severity leading to medical treatment may also increase NAPD risk. Ethics approval: Approved by the ethical committee in Stockholm, Sweden (dnrs: 2010-1185-31/5 and 2013/1118-32).

Björkenstam|Emma|E| Pierce|Matthias|M| Björkenstam|Charlotte|C| Dalman|Christina|C| Kosidou|Kyriaki|K|

D001289:Attention Deficit Disorder with Hyperactivity


Conquering the pneumococcal nemesis with oral antibiotics.

Abstract: Introduction: Streptococcus pneumoniae endocarditis (SPE) occurs in <3% of all EI cases due to the evolution of penicillin and vaccination. However, immunocompromised and unvaccinated patients are still at grave risk. Case: A 58-year-old African American male who used alcohol and intravenous (IV) drugs presented with confusion, fever, and hemoptysis. He had coarse rhonchi with a grade 2/5 holosystolic apical murmur. CT chest showed diffuse bilateral infiltrates. Blood cultures were positive for pansensitive Streptococcus pneumoniae. Echocardiogram demonstrated large vegetations on the anterior and posterior leaflets of the mitral valve with flail leaflet and severe eccentric mitral regurgitation. Patient was started on IV ceftriaxone, but after 3 weeks of therapy, he wished to leave against medical advice. He was discharged on combination oral therapy with successful resolution of SPE on follow-up. Discussion: Invasive pneumococcus is highly virulent causing irreversible valvular destruction or death. IV beta-lactams are first-line treatment, but there are currently no guideline-recommended alternatives for oral therapy. Recent data suggest partial oral therapy may be noninferior to IV only therapy. Conclusion: Switching to oral combination antibiotics after at least 2 weeks of IV therapy is an acceptable alternative to treat SPE.

Garris|Rana|R|0000-0002-1710-4944
Abanoub|Rushdy|R|
Qaqa|Firas|F|
Rana|Chirag|C|
Guragai|Nirmal|N|0000-0002-6477-7789
Habib|Habib A|HA|
Shamoon|Fayez|F|
Bikkina|Mahesh|M|

pneumococcus
Infectious endocarditis
treatment strategies


New therapeutic directions for advanced pancreatic cancer: cell cycle inhibitors, stromal modifiers and conjugated therapies.

Abstract: Pancreatic adenocarcinoma is a devastating malignancy with an extremely poor prognosis. These tumors progress rapidly and somewhat silently with few specific symptoms and are relatively resistant to chemotherapeutic agents. Many agents, including cell cycle inhibitors, are under development for the treatment of this cancer for which there are disappointingly few treatment options. Areas covered: Here we outline the existing approved treatments for advanced pancreatic disease and discuss a range of novel therapies currently under development including cell cycle inhibitors, stromal modifiers and conjugated therapies. We also describe the current state of the pancreatic cancer therapeutics market both past and future. Expert opinion: Despite the recent explosion of novel therapies with an array of unique targets, the core treatment of pancreatic cancer still with traditional cytotoxic agents with a few exceptions. However, as these novel treatments move through the pipeline, we are hopeful that there will soon be a number of effective options for patients with advanced pancreatic cancer.

therapeutics
Carcinoma
drug therapy
gemcitabine
neoplasm metastasis
pancreas
pancreatic neoplasms


The Influence of Health Messaging Source and Frequency on Maternal Smoking and Child Exposure among Low-Income Mothers.

Abstract: Addressing maternal smoking and child tobacco smoke exposure (TSE) remains a public health priority, particularly in low-income, underserved populations which are known to experience the highest TSE rates and tobacco-related morbidity/mortality. Little is known about the types of TSE messaging received in high-risk populations, and which communication channels are influential in promoting smokers' efforts to protect children from TSE. The purpose of this study was to examine associations between reported sources and frequency of TSE-reduction health messages maternal smokers received and the effects of the messaging on smoking-and TSE-reduction related behaviors. Maternal smokers from low-income communities in Philadelphia, Pennsylvania who were enrolled at baseline in the Family Rules for Establishing Smokefree Homes (FRESH) trial (N=359) were included in this study. Each participant completed a 60-minute in-home baseline interview, which included questions about their smoking history, current smoking patterns, children's TSE, and the TSE-related health messaging they had received prior to enrollment. Multivariable analyses were conducted to determine the effect of source messaging on mothers' knowledge, behavior, and intention regarding their baby's TSE. Results suggest that different sources of messaging may differentially impact smoking behavior and intention to change. For example, messaging from healthcare and dental providers may influence efforts to protect children from TSE whereas friends and family may influence intention to quit. Future studies could examine the value of multilevel health communication strategies, utilizing advice from healthcare providers that is augmented by family and peers to help promote smoking behavior change in this high-risk group of underserved postpartum smokers.

Lavery|Amy M|AM|
Nair|Uma|U|
Bass|Sarah Bauerle|SB|
Collins|Bradley N|BN|

health communication
Secondhand smoke
passive smoking


Coherent anti-Stokes Raman scattering and two photon excited fluorescence for neurosurgery.

Abstract:
OBJECTIVE
There is no established method for in vivo imaging during biopsy and surgery of the brain, which is capable to generate competitive images in terms of resolution and contrast comparable with histopathological staining.

METHODS
Coherent anti-Stokes Raman scattering (CARS) and two photon excited fluorescence (TPEF) microscopy are non-invasive all optical imaging techniques that are capable of high resolution, label-free, real-time, nondestructive examination of living cells and tissues. They provide image contrast based on the molecular composition of the specimen which allows the study of large tissue areas of frozen tissue sections ex vivo.

RESULTS
Here, preliminary data on 55 lesions of the central nervous system are presented. The generated images very nicely demonstrate cytological and architectural features required for pathological tumor typing and grading. Furthermore, information on the molecular content of a probe is provided. The tool will be implemented into a biopsy needle or endoscope in the near future for in vivo studies.

CONCLUSION
With this promising multimodal imaging approach the neurosurgeon might directly see blood vessels to minimize the risk for biopsy associated hemorrhages. The attending neuropathologist might directly identify the tumor and guide the selection of representative specimens for further studies. Thus, collection of non-representative material could be avoided and the risk to injure eloquent brain tissue minimized.

Romeike|Bernd F M|BF|
Meyer|Tobias|T|
Reichart|Rupert|R|
Kalff|Rolf|R|
Petersen|Iver|I|
Dietzek|Benjamin|B|
Popp|Jürgen|J|