Regulation of Fibroblast Growth Factor 23 by Iron, EPO, and HIF.

Abstract:
Purpose of review
Fibroblast growth factor-23 (FGF23) is the key hormone produced in bone critical for phosphate homeostasis. Elevated serum phosphorus and 1,25dihydroxyvitaminD stimulates FGF23 production to promote renal phosphate excretion and decrease 1,25dihydroxyvitaminD synthesis. Thus completing the feedback loop and suppressing FGF23. Unexpectedly, studies of common and rare heritable disorders of phosphate handling identified links between iron and FGF23 demonstrating novel regulation outside the phosphate pathway.

Recent Findings
Iron deficiency combined with an FGF23 cleavage mutation was found to induce the autosomal dominant hypophosphatemic rickets phenotype. Physiological responses to iron deficiency, such as erythropoietin production as well as hypoxia inducible factor activation, have been indicated in regulating FGF23. Additionally, specific iron formulations, used to treat iron deficiency, alter post-translational processing thereby shifting FGF23 protein secretion.

Summary
Molecular and clinical studies revealed that iron deficiency, through several mechanisms, alters FGF23 at the transcriptional and post-translational level. This review will focus upon the novel discoveries elucidated between iron, its regulators, and their influence on FGF23 bioactivity.

Wheeler|Jonathan A|JA|
Clinkenbeard|Erica L|EL|

iron
phosphate
erythropoietin
FGF-23
hypoxia-inducible factor


Beamline P02.1 at PETRA III for high-resolution and high-energy powder diffraction.

Abstract: Powder X-ray diffraction techniques largely benefit from the superior beam quality provided by high-brilliance synchrotron light sources in terms of photon flux and angular resolution. The High Resolution Powder Diffraction Beamline P02.1 at the storage ring PETRA III (DESY, Hamburg, Germany) combines these strengths with the power of high-energy X-rays for materials research. The beamline is operated at a fixed photon energy of 60 keV (0.207 Å wavelength). A high-resolution monochromator generates the highly collimated X-ray beam of narrow energy bandwidth. Classic crystal structure determination in reciprocal space at standard and non-ambient conditions are an essential part of the scientific scope as well as total scattering analysis using the real space information of the pair distribution function. Both methods are complemented by in situ capabilities with time-resolution in the sub-second regime owing to the high beam intensity and the advanced detector technology for high-energy X-rays. P02.1's efficiency in solving chemical and crystallographic problems is illustrated by presenting key experiments that were carried out within these fields during the early stage of beamline operation.

Dippel|Ann-Christin|AC|
Liermann|Hanns-Peter|HP|
Delitz|Jan Torben|JT|
Walter|Peter|P|
Schulte-Schrepping|Horst|H|
Seeck|Oliver H|OH|
Franz|Hermann|H|

high-energy X-rays
X-ray total scattering
high angular resolution
synchrotron powder diffraction
time-resolved experiments


Advances of vibrational spectroscopic methods in phytomics and bioanalysis.

Abstract: During the last couple of years great advances in vibrational spectroscopy including near-infrared (NIR), mid-infrared (MIR), attenuated total reflection (ATR) and imaging and also mapping techniques could be achieved. On the other hand spectral treatment features have improved dramatically allowing filtering out relevant information from spectral data much more efficiently and providing new insights into the biochemical composition. These advances offer new possible quality control strategies in phytomics and enable to get deeper insights into biochemical background in terms of medicinal relevant questions. It is the aim of the present article pointing out the technical and methodological advancements in the NIR and MIR field and to demonstrate the individual methods efficiency by discussing distinct selected applications.

Phytomics
Bioanalysis
NIR
Attenuated total reflection
Attenuated total reflection
ATR
Imaging
CA
CE
CEC
DR
EPO
FPA
FT
Focal Plane Array
Fourier transform
HDL
LC
LDL
MCT
MEIRS
MIA
MLR
MVA
Mercury Cadmium Telluride
Near infrared spectroscopy
OSC
PCA
PLSR
TCM
Traditional Chinese Medicine
Vis
attenuated total reflection
capillary electrochromatography
capillary electrophoresis
cluster analysis
diffuse reflection
external parameter orthogonalization
high-density lipoprotein
liquid chromatography
low-density lipoprotein
material enhanced infrared spectroscopy
multiple linear regression
multivariate analysis
multivariate image analysis
near infrared spectroscopy
orthogonal scatter correction
partial least square regression
principal component analysis
visible

P P P P P P P U U U U U U U U U U U U U U U U U U M U U U U M U P U U U M U U U U M U U M M U U U U


Consensus Recommendations on Initiating Prescription Therapies for Opioid-Induced Constipation.

Abstract:
OBJECTIVE
Aims of this consensus panel were to determine (1) an optimal symptom-based method for assessing opioid-induced constipation in clinical practice and (2) a threshold of symptom severity to prompt consideration of prescription therapy.

METHODS
A multidisciplinary panel of 10 experts with extensive knowledge/experience with opioid-associated adverse events convened to discuss the literature on assessment methods used for opioid-induced constipation and reach consensus on each objective using the nominal group technique.

RESULTS
Five validated assessment tools were evaluated: the Patient Assessment of Constipation-Symptoms (PAC-SYM), Patient Assessment of Constipation-Quality of Life (PAC-QOL), Stool Symptom Screener (SSS), Bowel Function Index (BFI), and Bowel Function Diary (BF-Diary). The 3-item BFI and 4-item SSS, both clinician administered, are the shortest tools. In published trials, the BFI and 12-item PAC-SYM are most commonly used. The 11-item BF-Diary is highly relevant in opioid-induced constipation and was developed and validated in accordance with US Food and Drug Administration guidelines. However, the panel believes that the complex scoring for this tool and the SSS, PAC-SYM, and 28-item PAC-QOL may be unfeasible for clinical practice. The BFI is psychometrically validated and responsive to changes in symptom severity; scores range from 0 to 100, with higher scores indicating greater severity and scores >28.8 points indicating constipation.

CONCLUSIONS
The BFI is a simple assessment tool with a validated threshold of clinically significant constipation. Prescription treatments for opioid-induced constipation should be considered for patients who have a BFI score of ≥30 points and an inadequate response to first-line interventions.

Argoff|Charles E|CE|
Brennan|Michael J|MJ|
Camilleri|Michael|M|
Davies|Andrew|A|
Fudin|Jeffrey|J|
Galluzzi|Katherine E|KE|
Gudin|Jeffrey|J|
Lembo|Anthony|A|
Stanos|Steven P|SP|
Webster|Lynn R|LR|

D000701:Analgesics, Opioid
D003248:Constipation
D004334:Drug Administration Schedule
D011307:Drug Prescriptions
D006801:Humans
D017410:Practice Guidelines as Topic
D011795:Surveys and Questionnaires
D014481:United States

Bowel Function Index
Chronic Pain
Lubiprostone
Methylnaltrexone
Naloxegol
PAMORAs


The Effect of Aggressive Wire Recanalization in Calcified Atheroma and Dilatation (ARCADIA) Technique in Eccentric Calcified Lesion of No-stenting Zone.

Abstract:
PURPOSE
The endovascular approach for eccentric calcified lesions of the no-stenting zone is challenging. This study aimed to investigate the effect of a novel technique for these lesions.

METHODS
We performed EVT for severe and eccentric calcified lesions using the technique, which is presented previously and named aggressive wire recanalization in calcified atheroma and dilatation (ARCADIA). In brief, a guidewire is passed to the residual lumen firstly. Next, another guidewire is advanced into and cross through the calcified plaque and returned to the distal original lumen with intravascular ultrasound (IVUS) guided. The calcified plaque is dilated by using a scoring-balloon or non-compliant balloon.

RESULTS
Consecutive 14 peripheral artery disease patients with isolated and eccentric calcification in a no-stenting zone were treated using ARCADIA technique between January 2018 and March 2020. In IVUS data, lumen cross-section area was significantly increased from 5.2 ± 2.0 mm2 to 18.1 ± 6.9 mm2 (p < 0.01), lumen area was expanded roundly evaluating as symmetry index from 0.45 ± 0.09 to 0.81 ± 0.12 (p < 0.01). There were no distal embolization and perforation after ARCADIA technique. One-year target lesion revascularization occurred in only 2 cases. The primary patency of 1 year was 85.7%.

CONCLUSION
ARCADIA technique is safe and appropriate, and can be 1 option to treat for eccentric calcified lesions of the no-stenting zone as an optimal wire crossing method.

eccentric calcified lesion
no-stenting zone
novel technique


Enrichment of the amnion with threonine in chicken embryos affects the small intestine development, ileal gene expression and performance of broilers between 1 and 21 days of age.

Abstract: The effects of in ovo feeding with threonine (Thr) on intestinal morphology, ileal gene expression and performance of broiler chicken between 1 and 21 d of age (d) were assessed. On day 17.5 of incubation, fertile eggs were randomly allotted to 5 treatments of Thr injection in the amniotic fluid (0; 1.75; 3.5; 5.25; 7%, corresponding to 17.5; 35; 52.5 and 70 mg Thr/mL). After hatch, chicks were given a commercial corn-soybean diet up to 21 d. Daily feed intake (FI), body weight (BW), and food conversion ratio (FCR) were measured from 1 to 7, 14, and 21 d of age. The ileal gene expression of mucin (MUC2), peptide transporter (PepT1), and aminopeptidase enzyme (APN) were evaluated on day of hatch and at 21 d, as well as intestinal morphometric traits. In ovo feeding with threonine significantly increased final weight (FI) and weight gain (WG) and decreased FCR in the period from 1 to 21 d. Threonine levels affected beneficially the villus height, vilo: crypt ratio and villus area on day of hatch and at 21 d. At hatch, all Thr levels increased the expression of MUC2 and PepT1 compared to the control group. APN expression also increased, but for the lowest and the highest threonine levels (1.75 and 7%). At 21 d, there was no effect of threonine on the expression of MUC2, PepT1, and APN. In conclusion, in ovo threonine feeding beneficially affected the morphological and functional development of the intestinal mucosa, which ensured improved performance of chicks at hatch and at 21 d.

Moreira Filho|A L B|ALB|
Ferket|P R|PR|
Malheiros|R D|RD|
Oliveira|C J B|CJB|
Aristimunha|P C|PC|
Wilsmann|D E|DE|
Givisiez|P E N|PEN|

intestinal mucosa
embryonic development
mucin production
nutrient absorption


Blood donation barriers and facilitators of Sub-Saharan African migrants and minorities in Western high-income countries: a systematic review of the literature.

Abstract:
OBJECTIVES
The present study aimed to gain more insight into, and summarise, blood donation determinants among migrants or minorities of Sub-Saharan heritage by systematically reviewing the current literature.

BACKGROUND
Sub-Saharan Africans are under-represented in the blood donor population in Western high-income countries. This causes a lack of specific blood types for transfusions and prevention of alloimmunisation among Sub-Saharan African patients.

METHODS/MATERIALS
Medline, EMBASE, PsycINFO and BIOSIS were searched for relevant empirical studies that focused on barriers and facilitators of blood donation among Sub-Saharan Africans in Western countries until 22 June 2017. Of the 679 articles screened by title and abstract, 152 were subsequently screened by full text. Paired reviewers independently assessed the studies based on predefined eligibility and quality criteria.

RESULTS
Of the 31 included studies, 24 used quantitative and 7 used qualitative research methods. Target cohorts varied from Black African Americans and refugees from Sub-Sahara Africa to specific Sub-Saharan migrant groups such as Comorians or Ethiopians. Main recurring barriers for Sub-Saharan Africans were haemoglobin deferral, fear of needles and pain, social exclusion, lack of awareness, negative attitudes and accessibility problems. Important recurring facilitators for Sub-Saharan Africans were altruism, free health checks and specific recruitment and awareness-raising campaigns.

CONCLUSION
The findings of this review can be used as a starting point to develop recruitment and retention strategies for Sub-Saharan African persons. Further research is needed to gain more insight in the role of these determinants in specific contexts as socioeconomic features, personal histories and host country regulations may differ per country.

African migrant
blood type
Africa south of the Sahara
ethnic minorities
inheritable blood disorder
motivators
needle fear
personal discrimination


Distribution of anticoagulant rodenticide resistance in Rattus norvegicus in the Netherlands according to Vkorc1 mutations.

Abstract:
BACKGROUND
Rodenticide resistance to anticoagulants in Rattus norvegicus will lead to increased difficulties in combating these pest animals. Here, the authors present the results of a survey in the Netherlands where tissue samples and droppings were tested using a newly developed TaqMan PCR test for genotypic variation at codon 139 in the Vkorc1 gene associated with anticoagulant rodenticide resistance. Test results are linked to results of a questionnaire that was conducted among pest controllers.

RESULTS
Genetic mutations at codon 139 of the Vkorc1 gene in R. norvegicus can be encountered in many parts of the Netherlands. In 34/61 rat tails, a genotype was found that is linked to anticoagulant rodenticide resistance (56%). In droppings, 42/169 samples (25%) showed a resistance-mediating genotype. In addition, indications of a clear genetic substructure in the Netherlands were found. In some regions, only resistance-mediating genotypes were found, corroborating results from the questionnaire in which pest controllers indicated they suspected resistance to anticoagulant rodenticides.

CONCLUSION
This is the first study to demonstrate the presence of multiple genetic mutations at codon 139 of the Vkorc1 gene in R. norvegicus in the Netherlands. As rodenticides should keep their efficacy because they are a last resort in rodent management, more studies are urgently needed that link specific genetic mutations to the efficacy of active substances.

Meerburg|Bastiaan G|BG|
van Gent-Pelzer|Marga P E|MP|
Schoelitsz|Bruce|B|
Esther|Alexandra|A|
van der Lee|Theo A J|TA|

D060888:Real-Time Polymerase Chain Reaction

anticoagulants, integrated pest management


Immunomodulation by systemic administration of human-induced pluripotent stem cell-derived mesenchymal stromal cells to enhance the therapeutic efficacy of cell-based therapy for treatment of myocardial infarction.

Abstract: Rationale: Poor survival and engraftment are major hurdles of stem cell therapy in the treatment of myocardial infarction (MI). We sought to determine whether pre-transplantation systemic intravenous administration of human induced pluripotent stem cell (hiPSC)-derived mesenchymal stromal cells (hiPSC-MSCs) could improve the survival of hiPSC-MSCs or hiPSC-derived cardiomyocytes (hiPSC-CMs) following direct intramyocardial transplantation in a mouse model of MI. Methods: Mice were randomized to undergo intravenous administration of saline or 5×105 hiPSC-MSCs one week prior to MI, induced by ligation of the left anterior descending coronary artery. Mice were further assigned to undergo direct intramyocardial transplantation of hiPSC-MSCs (1×106) or hiPSC-CMs (1×106) 10 minutes following MI. Echocardiographic and invasive hemodynamic assessment were performed to determine cardiac function. In-vivo fluorescent imaging analysis, immunofluorescence staining and polymerase chain reaction were performed to detect cell engraftment. Flow cytometry of splenic regulatory T cells (Tregs) and natural killer (NK) cells was performed to assess the immunomodulatory effects. Results: Pre-transplantation systemic administration of hiPSC-MSCs increased systemic Tregs activation, decreased the number of splenic NK cells and inflammation, and enhanced survival of transplanted hiPSC-MSCs and hiPSC-CMs. These improvements were associated with increased neovascularization and decreased myocardial inflammation and apoptosis at the peri-infract zone with consequent improved left ventricular function four weeks later. Co-culture of splenic CD4 cells with hiPSC-MSCs also modulated their cytokine expression profile with a decreased level of interferon-γ, tumor necrosis factor-α, and interleukin (IL)-17A, but not IL-2, IL-6 and IL-10. Conclusion: Pre-transplantation systemic intravenous administration of hiPSC-MSCs induced immunomodulation and facilitated the survival of intramyocardially transplanted cells to improve cardiac function in MI.

Sun|Si-Jia|SJ| Lai|Wing-Hon|WH| Jiang|Yu|Y| Zhen|Zhe|Z| Wei|Rui|R| Lian|Qizhou|Q| Liao|Song-Yan|SY| Tse|Hung-Fat|HF|

D045164:Mesenchymal Stem Cell Transplantation

immunomodulation
mesenchymal stromal cell
myocardial infarction
human induced pluripotent stem cell
cardiomyocyte


Advertising exposure and use of e-cigarettes among female current and former tobacco users of childbearing age.

Abstract:
OBJECTIVE
The study examined the relationship between exposure to e-cigarette advertising and e-cigarette use by pregnancy status, including use of flavored e-cigarette products, among women of childbearing age.

DESIGN
A cross-sectional, correlational design was used.

SUBJECTS
Female current or former tobacco users in Central and Eastern Kentucky, 18-45 years old (N = 194, 52% pregnant).

MEASURES
Demographics, pregnancy status, cigarette and e-cigarette use, and exposure to e-cigarette advertising.

RESULTS
Younger age, white non-Hispanic race, and greater exposure to e-cigarette advertising were associated with a higher likelihood of ever using e-cigarettes (p < .05 for each variable). Pregnancy was not associated with ever use (p = .11). Younger age was associated with use of flavored e-cigarettes (p = .0027). Among e-cigarette users, those who used flavored products were more likely to have seen advertisements or information about e-cigarettes on social media, compared to those who used unflavored e-cigarettes only (p = .016).

CONCLUSION
There is a link between advertising exposure and ever use of e-cigarettes. Pregnancy status is not significantly associated with ever use. Use of flavored e-cigarettes is associated with younger age. E-cigarette users with greater exposure to advertising on social media were more likely to use flavored products.

D066300:Electronic Nicotine Delivery Systems

advertising exposure
e-cigarettes
flavored e-cigarettes
women
tobacco use


Effect of chitosan based active packaging film on the keeping quality of chilled stored barracuda fish.

Abstract: In the present study, active antimicrobial (AM) packaging films were prepared from chitosan (CH) incorporated with ginger (Zingiber officinale) essential oil at different concentrations (0.1, 0.2 and 0.3 % v/v) and characterized. GC-MS analysis revealed zingiberene (22.54 ± 0.13), geranial (12.34 ± 0.33), β-sesquiphellandrene (8.14 ± 0.14), camphene (7.44 ± 0.54) and neral (5.45 ± 0.23) as the major components of essential oil extracted from ginger. Addition of ginger essential oil (GEO) improved the AM activity of the CH film against food borne pathogens, without significantly (p < 0.05) affecting the mechanical properties of the film. CH film with GEO was more effective against Gram-positive bacteria than Gram-negative bacteria and maximum antibacterial property against Staphylococcus aureus and Escherichia coli was shown by 0.3 % GEO added CH film. In a further experiment, steaks of barracuda (Sphyraena jello) fish were wrapped with the CH-GEO (0.3 %) film and stored at 2 °C for 20 days. Throughout the storage period, the total volatile basic nitrogen (TVB-N) value and total mesophilic count of fish steak wrapped with the CH-GEO film were significantly (p < 0.05) lesser than both the unwrapped control fish steak and aerobically packed fish steak in synthetic multilayer film of ethylene vinyl alcohol (EVOH) (nylon, EVOH and polyethylene). Sensorily, CH-GEO film wrapped sample was acceptable till the end of storage for 20 days compared to 12 days for unwrapped control and fish steak packed in EVOH film. The results indicate that the developed CH-GEO film is efficient in extending the storage life of fish.

Remya|S|S|
Mohan|C O|CO|
Bindu|J|J|
Sivaraman|G K|GK|
Venkateshwarlu|G|G|
Ravishankar|C N|CN|

Chitosan
Barracuda fish
Essential oil
Antimicrobial film
Shelf-life


The association between personal sun exposure, serum vitamin D and global methylation in human lymphocytes in a population of healthy adults in South Australia.

Abstract:
BACKGROUND
There is a positive association between solar UV exposure and micronucleus frequency in peripheral blood lymphocytes (PBL) and this association may be stronger when serum vitamin D (25(OH)D) levels are insufficient (<50 nmol/L). Micronucleus formation can result from global hypomethylation of DNA repeat sequences. The aim of this analysis was to evaluate the relationship between solar UV exposure and methylation pattern in LINE-1 repetitive elements in PBL DNA and to see if serum 25(OH)D levels modify it.

METHOD
Personal solar UV exposure was estimated from hours of outdoor exposure over 6 weeks recalled at the time of blood collection in 208 male and female participants living in South Australia. Methylation in LINE-1 repetitive elements was assessed in PBL using pyrosequencing.

RESULTS
Methylation in LINE-1 decreased with increasing solar UV exposure (% decrease = 0.5% per doubling of sUV; 95%CI: -0.7 to -0.2 p(value) = 0.00003). Although there was no correlation between LINE-1 methylation and micronucleus frequency, there was a 4.3% increase (95%CI: 0.6-8.1 p-value = 0.02) in nucleoplasmic bridges and a 4.3% increase in necrosis (CI: 1.9-6.8 p-value = 0.0005) for every 1% increase in LINE-1 methylation. Serum 25(OH)D was not associated with DNA methylation; or did it modify the association of solar UV with DNA methylation.

CONCLUSION
Exposure to solar UV radiation may reduce DNA methylation in circulating lymphocytes. This association does not appear to be influenced or mediated by vitamin D status.

Nair-Shalliker|Visalini|V|
Dhillon|Varinderpal|V|
Clements|Mark|M|
Armstrong|Bruce K|BK|
Fenech|Michael|M|

D020084:Long Interspersed Nucleotide Elements

Vitamin D
Global methylation
Solar UV exposure
LINE-1 repetitive elements
DNA damage


Complete mitochondrial genome of the wild Diptychus maculatus (Cypriniformes, Cyprinidae, Schizothoracinae) from Yeken River using next generation sequencing and the phylogenetic relationship of Cyprinidae species.

Abstract: The complete mitochondrial genome of the wild Diptychus maculatus collected from Yeken River was determined using next generation sequencing. The mitogenome is a circular molecule 16,765 bp in length, including 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and a control region. The TAS, central CSB, and CSB were detected in the control region. The gene contents of the mitogenome are identical to those observed in most bony fishes. The NJ phylogenetic tree showed that D. maculatus clustered into one separate branch which is close to genus Gymnodiptychus from the same subfamily.

mitochondrial genome
Diptychus maculatus
next generation sequencing
wild fish


Known unknowns: Examining the burden of neurocognitive impairment in the end-stage renal failure population.

Abstract: The burden of neurocognitive impairment (NCI) in patients receiving maintenance dialysis represents a spectrum of deficits across multiple cognitive domains that are associated with hospitalization, reduced quality-of-life, mortality and forced decision-making around dialysis withdrawal. Point prevalence data suggest that dialysis patients manifest NCI at rates 3- to 5-fold higher than the general population, with executive function the most commonly affected cognitive domain. The unique physiology of the renal failure state and maintenance dialysis appears to drive an excess of vascular dementia subtype compared to the general population where classical Alzheimer's disease predominates. Despite the absence of evidence-based cost-effective therapies for NCI, detecting it in this population creates opportunity to proactively personalize care through education, supported decision making and targeted communication strategies to cover specific areas of deficit and help define goals of care. This review discusses NCI in the dialysis setting, including developments in the definition of neurocognitive impairment, dialysis-specific epidemiology across modalities, screening strategies and opportunities for dialysis providers in this space.

Wilson|Scott|S| Dhar|Arup|A| Tregaskis|Peter|P| Lambert|Gavin|G| Barton|David|D| Walker|Rowan|R|

D000073216:Mental Status and Dementia Tests

dementia
cognitive dysfunction
renal dialysis


The impact of racial/ethnic disparities on survival for children and adolescents with extremity sarcomas: A population-based study.

Abstract:
PURPOSE
The purpose of this study was to determine whether racial/ethnic disparities exist in disease presentation, treatment, and survival among children and adolescents with extremity sarcoma.

METHODS
The Surveillance, Epidemiology, and End Results (SEER) data were analyzed for patients <20years old with soft-tissue extremity sarcomas from 1973 to 2013. Multivariate logistic regression was performed to determine the association between race/ethnicity and disease stage at presentation and likelihood of surgical resection. Overall survival (OS) was evaluated using hazard ratios with 95% confidence intervals.

RESULTS
1261 cases were identified: 650 (52%) non-Hispanic whites (NHW), 313 (25%) Hispanics, 182 (14%) non-Hispanic blacks (NHB), and 116 (9%) other race/ethnicity. Logistic regression results showed that Hispanics and NHB were 51% and 44%, respectively, less likely to undergo surgical resection compared to NHW (OR=0.49, 95% CI: 0.30-0.80; OR=0.56, 95% CI: 0.32-0.98, respectively). Factors associated with failure to undergo surgical resection included histology, lower extremity site, tumor size, and distant metastases. OS based on race/ethnicity significantly differed using the log-rank test, with NHB having the worst survival (p<0.05).

CONCLUSIONS
We conclude that NHB, Hispanics, and other race/ethnicity were less likely to undergo surgical resection for extremity sarcoma. Further work is needed to better characterize and eliminate disparities in the management and outcomes of children with extremity sarcomas.

TYPE OF STUDY
Prognosis study.

LEVEL OF EVIDENCE
IV.

Joseph|Michael|M|
Hamilton|Emma C|EC|
Hayes-Jordan|Andrea|A|
Huh|Winston W|WW|
Austin|Mary T|MT|

Extremity sarcoma
Cancer epidemiology
Racial disparity


Congenital dengue in neonate.

Abstract: Congenital dengue should be considered as a cause of fever and rash in a neonate born to a mother especially in endemic areas.

Congenital Dengue
Neonatal rash
Neonatal sepsis
Thrombocytopenia


Ten-year change in neighborhood socioeconomic status and colorectal cancer.

Abstract:
BACKGROUND
A growing body of research has demonstrated that individuals who live in neighborhoods with more severe socioeconomic deprivation may have higher risks for colorectal cancer (CRC). However, previous studies have examined neighborhood socioeconomic status (SES) at only 1 point in time, and it is unclear whether changes in neighborhood SES also can influence the risks of CRC.

METHODS
Cox regression analysis was used to examine different trajectories of change in neighborhood SES over 10 years in relation to the incidence of CRC among 266,804 participants (ages 51-70 years) in the National Institutes of Health-AARP Diet and Health Study. Eligible participants reported living in the same neighborhood at baseline (1995-1996) and from 2004 to 2006 according to a follow-up questionnaire. Changes in neighborhood SES were measured between 1990 and 2000 by SES indices derived from Census data. Neighborhoods were grouped into 4 categories based on median SES indices in 1990 and 2000 (low-low, low-high, high-low, and high-high).

RESULTS
Compared with residents whose neighborhoods were in the higher SES group at both time points (reference category), those whose neighborhoods were consistently in the low SES group had a 7% higher risk of developing CRC (hazard ratio, 1.07; 95% confidence interval, 1.00-1.14). Moreover, the risk of CRC was 15% higher (hazard ratio, 1.15; 95% confidence interval, 1.02-1.28) for those living in neighborhoods with decreasing SES (high-low) over time.

CONCLUSIONS
The current findings suggest that exposure to consistently low SES neighborhoods and/or a decrease in neighborhood SES over a period of time may be associated with higher risks of CRC.

Zhang|Dong|D|0000-0002-7522-9630
Matthews|Charles E|CE|
Powell-Wiley|Tiffany M|TM|
Xiao|Qian|Q|

neighborhood socioeconomic status
cancer risk
colon cancer
long-term trajectory
rectal cancer


Simultaneous electrical-field-effect modulation of both top and bottom Dirac surface states of epitaxial thin films of three-dimensional topological insulators.

Abstract: It is crucial for the studies of the transport properties and quantum effects related to Dirac surface states of three-dimensional topological insulators (3D TIs) to be able to simultaneously tune the chemical potentials of both top and bottom surfaces of a 3D TI thin film. We have realized this in molecular beam epitaxy-grown thin films of 3D TIs, as well as magnetic 3D TIs, by fabricating dual-gate structures on them. The films could be tuned between n-type and p-type by each gate alone. Combined application of two gates can reduce the carrier density of a TI film to a much lower level than with only one of them and enhance the film resistance by 10,000%, implying that Fermi level is tuned very close to the Dirac points of both top and bottom surface states without crossing any bulk band. The result promises applications of 3D TIs in field effect devices.

Chang|Cui-Zu|CZ| Zhang|Zuocheng|Z| Li|Kang|K| Feng|Xiao|X| Zhang|Jinsong|J| Guo|Minghua|M| Feng|Yang|Y| Wang|Jing|J| Wang|Li-Li|LL| Ma|Xu-Cun|XC| Chen|Xi|X| Wang|Yayu|Y| He|Ke|K| Xue|Qi-Kun|QK|

Topological insulator
ambipolar effect
anomalous Hall effect
electrical field effect
molecular beam epitaxy
ultrathin films


Potential Occupational Risks Associated with Pulmonary Toxicity of Carbon Nanotubes.

Abstract: Given their remarkable properties, carbon nanotubes (CNTs) have made their way through various industrial and medicinal applications and the overall production of CNTs is expected to grow rapidly in the next few years, thus requiring an additional recruitment of workers. However, their unique applications and desirable properties are fraught with concerns regarding occupational exposure. The concern about worker exposure to CNTs arises from the results of recent animal studies. Short-term and sub-chronic exposure studies in rodents have shown consistent adverse health effects such as pulmonary inflammation, granulomas, fibrosis, genotoxicity and mesothelioma after inhalation or instillation of several types of CNTs. Furthermore, physicochemical properties of CNTs such as dispersion, functionalization and particle size can significantly affect their pulmonary toxicity. Risk estimates from animal studies necessitate implementation of protective measures to limit worker exposure to CNTs. Information on workplace exposure is very limited, however, studies have reported that CNTs can be aerosolized and attain respirable airborne levels during synthesis and processing activities in the workplace. Quantitative risk assessments from sub-chronic animal studies recommend the health-based need to reduce exposures below the recommended exposure limit of 1 µg/m3. Practice of prevention measures including the use of engineering controls, personal protective equipment, health surveillance program, safe handling and use, as well as worker training can significantly minimize worker exposure and improve worker health and safety.

Pulmonary toxicity
Carbon nanotube
Worker exposure
Fibrosis
Occupational hazard


Effect of the Content of Micro-Active Copper Tailing on the Strength and Pore Structure of Cementitious Materials.

Abstract: This study investigates the effect of micr-oaggregate filling with copper tailing on the pore structure of cement paste containing copper tailing (CPCT). The particle size of the CPCT and the pore structure of CPCT were analyzed by laser particle size analysis and mercury instruction porosimetry (MIP). Results showed that at the early stage of curing time, with increasing copper tailing content, the compressive strength of cement mortar with copper tailing (CMCT) was lower, and the porosity and pore diameter of CPCT were higher and greater; with the extension of curing age, when the content of copper tailing was less than 30%, the compressive strength of CMCT and the porosity of CPCT changed slightly with the increase of the content of copper tailing. However, the maximum hole diameter of CPCT decreased gradually (a curing age between 7 d and 365 d under standard conditions). Scanning electron microscopy analysis showed that at the early stage of cement hydration in the CPCT, the copper tailing did not fill the pores in CPCT well, while in the later stage of cement hydration, the microaggregates of copper tailing filled the pores well and closely combined with the surrounding hydration products. In the later stage of cement hydration, the microaggregate filling of copper tailing was primarily responsible for the strength increase of the CMCT.

copper tailing
pore structure
compressive strength
microaggregate filling
particle size distribution


Inositol polyphosphate multikinase is a transcriptional coactivator required for immediate early gene induction.

Abstract: Profound induction of immediate early genes (IEGs) by neural activation is a critical determinant for plasticity in the brain, but intervening molecular signals are not well characterized. We demonstrate that inositol polyphosphate multikinase (IPMK) acts noncatalytically as a transcriptional coactivator to mediate induction of numerous IEGs. IEG induction by electroconvulsive stimulation is virtually abolished in the brains of IPMK-deleted mice, which also display deficits in spatial memory. Neural activity stimulates binding of IPMK to the histone acetyltransferase CBP and enhances its recruitment to IEG promoters. Interestingly, IPMK regulation of CBP recruitment and IEG induction does not require its catalytic activities. Dominant-negative constructs, which prevent IPMK-CBP binding, substantially decrease IEG induction. As IPMK is ubiquitously expressed, its epigenetic regulation of IEGs may influence diverse nonneural and neural biologic processes.

Xu|Risheng|R|
Paul|Bindu D|BD|
Smith|Dani R|DR|
Tyagi|Richa|R|
Rao|Feng|F|
Khan|A Basit|AB|
Blech|Daniel J|DJ|
Vandiver|M Scott|MS|
Harraz|Maged M|MM|
Guha|Prasun|P|
Ahmed|Ishrat|I|
Sen|Nilkantha|N|
Gallagher|Michela|M|
Snyder|Solomon H|SH|

D017853:Phosphotransferases (Alcohol Group Acceptor)


Point-of-Care Testing for Anemia, Diabetes, and Hypertension: A Pharmacy-Based Model in Lima, Peru.

Abstract:
BACKGROUND
Prevention and control of chronic diseases is a high priority for many low- and middle-income countries. This study evaluated the feasibility and acceptability of training pharmacy workers to provide point-of-care testing for 3 chronic diseases-hypertension, diabetes, and anemia-to improve disease detection and awareness through private pharmacies.

METHODS
We developed a multiphase training curriculum for pharmacists and pharmacy technicians to build capacity for identification of risk factors, patient education, point-of-care testing, and referral for abnormal results. We conducted a pre-post evaluation with participants and evaluated results using Student t test for proportions. We conducted point-of-care testing with pharmacy clients and evaluated acceptability by patient characteristics (age, gender, and type of patient) using multiple logistic regression.

RESULTS
In total, 72 pharmacy workers (66%) completed the full training curriculum. Pretest scores indicated that pharmacists had more knowledge and skills in chronic disease risk factors, patient education, and testing than pharmacy technicians. All participants improved their knowledge and skills after the training, and post-test scores indicated that pharmacy technicians achieved the same level of competency as pharmacists (P < .01). Additionally, 698 clients received at least 1 test during the study; 53% completed the acceptability survey. Nearly 100% thought the pharmacy could provide faster results, faster and better attention, and better access to basic screening for hypertension, diabetes, and anemia than a traditional health center. Fast service was very important: 41% ranked faster results and 30% ranked faster attention as the most important factor for receiving diagnostic testing in the pharmacy.

DISCUSSION
We found that it is both feasible for pharmacies and acceptable to clients to train pharmacy workers to provide point-of-care testing for anemia, diabetes, and hypertension. This innovative approach holds potential to increase early detection of risk factors and bolster disease prevention and management efforts in Peru and other low- and middle-income settings.

Saldarriaga|Enrique M|EM|
Vodicka|Elisabeth|E|
La Rosa|Sayda|S|
Valderrama|Maria|M|
Garcia|Patricia J|PJ|

D010342:Patient Acceptance of Health Care

point-of-care testing
anemia
diabetes
hypertension
Peru
pharmacies
POC test
rapid test


Potential drug-drug interaction between sodium-glucose co-transporter 2 inhibitors and statins: pharmacological and clinical evidence.

Abstract:
INTRODUCTION
Recent case reports suggested that concomitant use of sodium-glucose co-transporter 2 (SGLT2) inhibitors with statins could lead to increased statin toxicity. We provide a comprehensive overview of the available pharmacological and clinical evidence on this potential drug-drug interaction (DDI).

AREAS COVERED
We searched MEDLINE PubMed until November 2020 for (i) pharmacokinetic studies on SGLT2 inhibitors, statins, and their potential interaction, and (ii) case reports and clinical studies assessing the safety of concomitant use of SGLT2 inhibitors and statins. We also searched regulatory documents submitted to the United States Food and Drug Administration for unpublished data on this potential DDI.

EXPERT OPINION
SGLT2 inhibitors are increasingly used for type 2 diabetes, chronic heart failure, and chronic kidney disease, and concomitant use with statins is common given the comorbidity of indications. While pharmacokinetic studies in healthy subjects showed no clinically relevant changes in statin levels during SGLT2 inhibitor co-administration, the published case reports and pharmacologic reasoning support the possibility of an interaction. Underlying mechanisms could be pharmacokinetic or pharmacodynamic, and canagliflozin appears to be the SGLT2 inhibitor with the highest interaction potential. Further research including 'real-world' pharmacoepidemiologic studies is needed to better understand the clinical significance of this DDI.

D000077203:Sodium-Glucose Transporter 2 Inhibitors


Association of basal forebrain volumes and cognition in normal aging.

Abstract: The basal forebrain cholinergic system (BFCS) is known to undergo moderate neurodegenerative alterations during normal aging and severe atrophy in Alzheimer's disease (AD). It has been suggested that functional and structural alterations of the BFCS mediate cognitive performance in normal aging and AD. But, it is still unclear to what extend age-associated cognitive decline can be related to BFCS in normal aging. We analyzed the relationship between BFCS volume and cognition using MRI and a comprehensive neuropsychological test battery in a cohort of 43 healthy elderly subjects spanning the age range from 60 to 85 years. Most notably, we found significant associations between general intelligence and BFCS volumes, specifically within areas corresponding to posterior nuclei of the nucleus basalis of Meynert (Ch4p) and the nucleus subputaminalis (NSP). Associations between specific cognitive domains and BFCS volumes were less pronounced. Supplementary analyses demonstrated that especially the volume of NSP but also the volume of Ch4p was related to the volume of widespread temporal, frontal, and parietal gray and white matter regions. Volumes of these gray and white matter regions were also related to general intelligence. Higher volumes of Ch4p and NSP may enhance the effectiveness of acetylcholine supply in related gray and white matter regions underlying general intelligence and hence explain the observed association between the volume of Ch4p as well as NSP and general intelligence. Since general intelligence is known to attenuate the degree of age-associated cognitive decline and the risk of developing late-onset AD, the BFCS might, besides the specific contribution to the pathophysiology in AD, constitute a mechanism of brain resilience in normal aging.

Wolf|D|D|
Grothe|M|M|
Fischer|F U|FU|
Heinsen|H|H|
Kilimann|I|I|
Teipel|S|S|
Fellgiebel|A|A|

Cognition
Normal aging
Basal forebrain cholinergic system
General intelligence
Nucleus basalis of Meynert
Brain resilience


Upper cervical instability associated with rheumatoid arthritis: a case report.

Abstract: Rheumatoid arthritis (RA) affects between 1 and 2 million individuals in the United States. Atlantoaxial instability (AAI) has been shown to have 40-85% prevalence among individuals with RA. Despite the high incidence of craniovertebral involvement, overt symptoms of instability are rare. The high risk of AAI and limited symptomology should increase therapist suspicion of potential contraindications and precautions to initiation of therapy for the cervical spine without prior diagnostic imaging. The purpose of this case study is to describe the historical, clinical, and diagnostic imaging complexity of AAI associated with RA, and to illustrate the use of these factors in the clinical reasoning within a patient case.

Cervical instability
Rheumatoid arthritis
Atlantoaxial instability
Physical therapy


Genotype of FLOWERING LOCUS T homologue contributes to flowering time differences in wild and cultivated roses.

Abstract: Rose flowers have long delighted humans as ornamental plants. To improve the ornamental value of roses it is necessary to understand the regulatory mechanisms of flowering. We previously found that flowering time is controlled by three minor quantitative trait loci (QTLs) and a major QTL co-localised with RoFT. In this study, we isolated three RoFT alleles encoding completely identical amino acid sequences from the parents of a mapping population. Correlation analysis of the RoFT genotypes and flowering time phenotypes in the mapping population showed that the RoFT_f and RoFT_g alleles contribute to the early-flowering phenotype, while the RoFT_e allele contributes to the late-flowering phenotype. We developed two novel cleaved amplified polymorphic sequence (CAPS) markers based on the genomic sequences of the RoFT alleles and clearly showed that the relationship between RoFT genotype and flowering time was applicable to 12 of 13 cultivated roses grown at the Higashiyama Botanical Gardens, Japan. Allele-specific expression analysis using a reverse transcription CAPS assay suggested that these RoFT alleles are regulated differentially at the transcription level. Furthermore, transgenic Arabidopsis thaliana plants ectopically expressing the RoFT gene showed an early-flowering phenotype. Conversely, in roses, RoFT was continuously expressed after floral bud formation, and RoFT transcript accumulation reached its peak after that of the floral meristem identity gene RoAP1b. These data suggest that RoFT may be essential not only for floral transition but also for normal floral development and flowering in roses.

Otagaki|S|S|
Ogawa|Y|Y|
Hibrand-Saint Oyant|L|L|
Foucher|F|F|
Kawamura|K|K|
Horibe|T|T|
Matsumoto|S|S|


Sex-Mediated Differences in LPS Induced Alterations of TNFα, IL-10 Expression, and Prostaglandin Synthesis in Primary Astrocytes.

Abstract: Although many neurological and psychiatric disorders reveal clear sex-dependent variations, the molecular mechanism of this process is not clear enough. Astrocytes are involved in the response of neural tissue to injury and inflammation, produce steroid hormones, and sense steroid presence. To explore the hypothesis that astrocytes may participate in sex-mediated differences of inflammatory responses, we have examined whether male and female primary rat astrocytes show different responses to lipopolysaccharide (LPS) as a toll-like receptor 4 (TLR4) agonist. Levels of mRNA and proteins of tumor necrosis factor alpha (TNFα), interleukin-10 (IL-10), and cyclooxygenase (COX)-2 were assessed using qPCR, immunoblotting, and ELISA. UPLC-MS/MS was used to detect prostaglandins (PGs). LPS stimulation resulted in different levels of cytokine production; more TNFα and less IL-10 were produced in female cells compared with male astrocytes. Although the levels of the COX-2 expression were not altered, LPS significantly induced the synthesis of PGs with notable sex-related differences. PGE₂ and PGD₂ were less and 6-keto-PGF1α was more upregulated in female astrocytes, and TXB₂ had similar levels in cells obtained from males and females. Trilostane, an inhibitor of 3β-Hydroxysteroid dehydrogenase (3β-HSD), inhibited the LPS-induced TNFα production and the release of PGE₂, PGD₂, and 6-keto-PGF1α in female astrocytes. Thus, male and female astrocytes differentially respond to inflammatory challenges on the level of production of cytokines and steroid hormones. Sex-mediated differences in pro- and anti-inflammatory responses should be taken into consideration for the effective treatment of disorders with neuroinflammation.


Regulation of ROS in myeloid-derived suppressor cells through targeting fatty acid transport protein 2 enhanced anti-PD-L1 tumor immunotherapy.

Abstract: Despite the remarkable success and efficacy of immune checkpoint blockade (ICB) therapy against the PD-1/PD-L1 axis, it induces sustained responses in a sizeable minority of cancer patients due to the activation of immunosuppressive factors such as myeloid-derived suppressor cells (MDSCs). Inhibiting the immunosuppressive function of MDSCs is critical for successful cancer ICB therapy. Interestingly, lipid metabolism is a crucial factor in modulating MDSCs function. Fatty acid transport protein 2 (FATP2) conferred the function of PMN-MDSCs in cancer via the upregulation of arachidonic acid metabolism. However, whether regulating lipid accumulation in MDSCs by targeting FATP2 could block MDSCs reactive oxygen species (ROS) production and enhance PD-L1 blockade-mediated tumor immunotherapy remains unexplored. Here we report that FATP2 regulated lipid accumulation, ROS, and immunosuppressive function of MDSCs in tumor-bearing mice. Tumor cells-derived granulocyte macrophage-colony stimulating factor (GM-CSF) induced FATP2 expression in MDSCs by activation of STAT3 signaling pathway. Pharmaceutical blockade of FATP2 expression in MDSCs by lipofermata decreased lipid accumulation, reduced ROS, blocked immunosuppressive activity, and consequently inhibited tumor growth. More importantly, lipofermata inhibition of FATP2 in MDSCs enhanced anti-PD-L1 tumor immunotherapy via the upregulation of CD107a and reduced PD-L1 expression on tumor-infiltrating CD8+T-cells. Furthermore, the combination therapy blocked MDSC's suppressive role on T- cells thereby enhanced T-cell's ability for the production of IFN-γ. These findings indicate that FATP2 plays a key role in modulating lipid accumulation-induced ROS in MDSCs and targeting FATP2 in MDSCs provides a novel therapeutic approach to enhance anti-PD-L1 cancer immunotherapy.

Adeshakin|Adeleye Oluwatosin|AO|
Liu|Wan|W|
Adeshakin|Funmilayo O|FO|
Afolabi|Lukman O|LO|
Zhang|Mengqi|M|
Zhang|Guizhong|G|
Wang|Lulu|L|
Li|Zhihuan|Z|
Lin|Lilong|L|
Cao|Qin|Q|
Yan|Dehong|D|
Wan|Xiaochun|X|

ROS
Anti-PD-L1 tumor immunotherapy
MDSCs
Lipid metabolism
FATP2


Analyzing and Reanalyzing the Genome: Findings from the MedSeq Project.

Abstract: Although genome sequencing is increasingly available in clinical and research settings, many questions remain about the interpretation of sequencing data. In the MedSeq Project, we explored how much effort is required to evaluate and report on more than 4,500 genes reportedly associated with monogenic conditions, as well as pharmacogenomic (PGx) markers, blood antigen serotyping, and polygenic risk scores in 100 individuals (50 with cardiomyopathy and 50 healthy) randomized to the sequencing arm. We defined the quality thresholds for determining the need for Sanger confirmation. Finally, we examined the effort needed and new findings revealed by reanalyzing each genome (6-23 months after initial analysis; mean 13 months). Monogenic disease risk and carrier status were reported in 21% and 94% of participants, respectively. Only two participants had no monogenic disease risk or carrier status identified. For the PGx results (18 genotypes in six genes for five drugs), the identified diplotypes prompted recommendation for non-standard dosing of at least one of the analyzed drugs in 95% of participants. For blood antigen studies, we found that 31% of participants had a rare blood antigen genotype. In the cardiomyopathy cohort, an explanation for disease was identified in 48% of individuals. Over the course of the study, 14 variants were reclassified and, upon reanalysis, 18 new variants met criteria for reporting. These findings highlight the quantity of medically relevant findings from a broad analysis of genomic sequencing data as well as the need for periodic reinterpretation and reanalysis of data for both diagnostic indications and secondary findings.

Machini|Kalotina|K|
Ceyhan-Birsoy|Ozge|O|
Azzariti|Danielle R|DR|
Sharma|Himanshu|H|
Rossetti|Peter|P|
Mahanta|Lisa|L|
Hutchinson|Laura|L|
McLaughlin|Heather|H|
|||
Green|Robert C|RC|
Lebo|Matthew|M|
Rehm|Heidi L|HL|

D020022:Genetic Predisposition to Disease

D016032:Randomized Controlled Trials as Topic

genome
MedSeq
sequencing
reanalysis
secondary findings
clinical genomes
genomic interpretation


Attachment and alcohol use amongst athletes: the mediating role of conscientiousness and alexithymia.

Abstract:
OBJECTIVE
The present study aims to explore the mediating effects of conscientiousness and alexithymia in the relationship between parental attachment style and alcohol use in a large sample of athletic young people.

METHOD
Participants included 434 French sport sciences students. Alcohol use, parental attachment style, conscientiousness and alexithymia were assessed. The hypotheses were tested by using regression and bootstrapping mediation analyses.

RESULTS
Maternal insecure attachment style is positively associated with alcohol use. The current study highlights a multiple pathway in this relationship. The results reveal the mediating effect of low conscientiousness and alexithymia between maternal insecure attachment and alcohol use.

CONCLUSION
Athletes' alcohol use seems to be the result of a complex association of underlying psychological factors.

Andres|Fanny|F|
Castanier|Carole|C|
Le Scanff|Christine|C|

Alcohol
Athletes
Mediation
Conscientiousness
Alexithymia
Attachment styles


Regulatory function of microRNAs in microglia.

Abstract: Microglia are CNS-resident cells involved in immune surveillance and maintenance of intercellular homeostasis, while also contributing to neurologic pathologies. MicroRNAs (miRNAs) are a class of small (~22 nucleotides) single-stranded noncoding RNAs that participate in gene regulation at the post-transcriptional level. miRNAs typically bind to the untranslated region (3' UTR) of RNAs. It has been shown that miRNAs are important players in controlling inflammation and that their abnormal expression is linked to cancer and ageing, and to the onset and progression of neurodegenerative disease. Furthermore, miRNAs participate in intercellular trafficking. Thus, miRNAs are released from cells in a free form, bound to proteins or packaged within extracellular vesicles (EVs), exerting paracrine and long distance signaling. In this review, recent findings on the role of miRNAs as drivers of microglia phenotypic changes and their cotribution in neurological disease are addressed. MAIN POINTS: miRNAs have a key role in microglia function/dysfunction, polarization, and restoration. Microglia are both a source and recipient of extracellular vesicles (EVs) containing miRNAs. Extracellular miRNAs may be found as soluble (free and EV cargo) and protein complexes.

microglia
miRNAs
neurodegenerative diseases
extracellular vesicles


Nasolacrimal anatomy and haplorhine origins.

Abstract: Computed tomography X-ray imaging of the internal face in well-preserved primate fossil crania permits reconstruction of the nature of their nasal anatomy, including some soft-tissue features. These features are diagnostic of the primate suborder Haplorhini, and allow reevaluation of the phylogenetic status of several purported early members of the group. Here we examine the nasolacrimal morphology of a broad sample of extant primates, as well as a number of Paleogene fossils. The extant sample confirms the distinctiveness of the two suborders. Of the fossils studied, only Shoshonius cooperi from the late-early Eocene exhibits evidence of a haplorhine nose. This suggests that the haplorhine oronasal complex may have evolved before the postorbital septum, and strengthens the claim that Shoshonius is a close relative of tarsiers and anthropoids. These results indicate that Omomyiformes is not a monophyletic group, and that few of its members possessed the derived oronasal morphology that characterizes crown haplorhines.

Rossie|James B|JB|
Smith|Timothy D|TD|
Beard|K Christopher|KC|
Godinot|Marc|M|
Rowe|Timothy B|TB|

Anthropoid
Omomyiformes
Fossil primates
Rhinarium
Schizocheilism
Syncheilism


Gluten Intake and Risk of Digestive System Cancers in 3 Large Prospective Cohort Studies.

Abstract:
BACKGROUND & AIMS
In patients with celiac disease, gluten triggers an immune reaction that damages small intestinal villi and may increase long-term risk of gastrointestinal cancer. However, the health impacts of gluten in the general population are understudied. We aimed to examine the association between gluten intake and risk of digestive system cancers among individuals without celiac disease.

METHODS
We leveraged longitudinal data from 3 prospective cohorts, the Nurses' Health Study (1984-2018, 73,166 women aged 65.1 ± 10.8 years), Nurses' Health Study II (1991-2017, 90,423 women aged 49.1 ± 8.2 years), and Health Professionals Follow-Up Study (1986-2016, 42,617 men aged 64.8 ± 10.8 years). Using Cox proportional hazards regression, we estimated hazard ratios and 95% confidence intervals of digestive system cancers according to quintiles of gluten intake assessed from food frequency questionnaires.

RESULTS
During 4,801,513 person-years of follow-up, we documented 6231 incident digestive system cancer cases among 3 cohorts. After adjusting for a wide-range of risk factors, including body mass index, physical activity, diet quality, gluten intake was not associated with an increased risk of digestive system cancer, with a hazard ratio of 0.94 (95% confidence interval, 0.87-1.02) comparing the highest with the lowest quintile of gluten intake (P trend = .05). Similar null associations were found for individual digestive system cancers: oral cavity and oropharyngeal cancer, esophageal cancer, stomach cancer, small intestine cancer, colorectal cancer, pancreatic cancer, gallbladder cancer, and liver cancer.

CONCLUSIONS
Gluten intake was not associated with risk of digestive system cancers in adults without celiac disease. Restricting dietary gluten is unlikely to be beneficial to the prevention of digestive system cancers in the general population.

Wang|Yiqing|Y|
Cao|Yin|Y|
Lebwohl|Benjamin|B|
Song|Mingyang|M|
Sun|Qi|Q|
Green|Peter H R|PHR|
Giovannucci|Edward L|EL|
Willett|Walter C|WC|
Chan|Andrew T|AT|

Celiac Disease
Diet
Epidemiology
Gastrointestinal Carcinogenesis


Blister formation during graphite surface oxidation by Hummers' method.

Abstract: Graphite oxide has a complex structure that can be modified in many ways to obtain materials for a wide range of applications. It is known that the graphite precursor has an important role in the synthesis of graphite oxide. In the present study, the basal-plane surface of highly annealed pyrolythic graphite (HAPG) was oxidized by Hummers' method and investigated by Raman spectroscopy and atomic force microscopy. HAPG was used as a graphite precursor because its surface after cleavage contains well-ordered millimeter-sized regions. The treatment resulted in graphite intercalation by sulfuric acid and blister formation all over the surface. Surprisingly, the destruction of the sp2-lattice was not detected in the ordered regions. We suggest that the reagent diffusion under the basal plane surface occurred through the cleavage steps and dislocations with the Burgers vector parallel to the c-axis in graphite.


Hepatoprotective phenylethanoid glycosides from Cirsium setosum.

Abstract: Two new phenylethanoid glycosides, namely β-D-glucopyranoside, 1″-O-(7S)-7-(3-methoxyl-4-hydroxyphenyl)-7-methoxyethyl-3″-α-L-rhamnopyranosyl-4″-[(8E)-7-(3-methoxyl-4-hydroxyphenyl)-8-propenoate] (1) and β-D-glucopyranoside, 1″-O-(7S)-7-(3-methoxyl-4-hydroxyphenyl)-7-methoxyethyl-3″-α-L-rhamnopyranosyl-4″-[(8E)-7-(4-hydroxyphenyl)-8-propenoate] (2), together with six phenylethanoid glycosides were isolated from Cirsium setosum. Their structures were elucidated by their spectroscopic data and references. Compounds 2, 4, 5, 7 and 8 (10 μM) exhibited moderate hepatoprotective activities. Compounds (3-8) were obtained from this plant for the first time.

Ma|Qinge|Q| Guo|Yongming|Y| Luo|Baomin|B| Liu|Wenmin|W| Wei|Rongrui|R| Yang|Chunxia|C| Ding|Chenghua|C| Xu|Xuefeng|X| He|Minghui|M|

phenylethanoid glycoside
Cirsium setosum
hepatoprotective activity


Real world experience of approved chimeric antigen receptor T-cell therapies outside of clinical trials.

Abstract: Advances in the field of immuno-oncology brought chimeric antigen receptor T (CAR T) cell therapy from the bench to the bedside for treatment of relapsed and/or refractory B-cell lymphoid malignancies. Two CAR T products, namely axicabtagene ciloleucel and tisagenlecleucel, are commercially available and represent genetically engineered T cells expressing chimeric receptors for CD19. These CAR T-cell products have undoubtedly revolutionized the treatment of these diseases yielding impressive complete remission rates and improving survival. This review aims at assessing the published evidence pertaining to the efficacy of these two products in the real world practice as enrollment in clinical trials often follows stringent eligibility criteria and involves possible selection bias. Results of various observational analyses from patients treated in the real world setting show comparable results to those reported in clinical trials in terms of efficacy and toxicities. This is certainly noteworthy considering that many of these patients would have been considered ineligible to participate in clinical trials owing to their less than optimal performance scores, among other reasons. We believe that the prohibitive cost of these treatments poses a serious challenge to wider applicability in the less privileged populations throughout the world, especially in developing countries.

Yassine|Farah|F|
Iqbal|Madiha|M|
Murthy|Hemant|H|
Kharfan-Dabaja|Mohamed A|MA|
Chavez|Julio C|JC|

D001688:Biological Products
D005818:Genetic Engineering
D006801:Humans
D016393:Lymphoma, B-Cell
D011948:Receptors, Antigen, T-Cell
D000076962:Receptors, Chimeric Antigen
D016896:Treatment Outcome

Chimeric antigen receptor T-cell therapy


Enhancing the quality of bio-oil and selectivity of phenols compounds from pyrolysis of anaerobic digested rice straw.

Abstract: This study investigated the thermal decomposition characteristics and pyrolytic products of anaerobic digested rice straw (ADRS) by thermogravimetric (TG) and pyrolysis-gas chromatograph/mass spectrometry (Py-GC/MS) analysis. Compared with the raw rice straw (RS), the thermal decomposition temperature of ADRS was shifted to higher temperature zone and the second decomposition zone of cellulose (Toffset(c)-Tpeak) became narrower (14 °C less), which indicated that the composition of rice straw were changed significantly by the anaerobic digestion pretreatment. Py-GC/MS analysis showed that the quality of the bio-oil and the selectivity of pyrolytic products could be obviously improved by anaerobic digestion. The total yields of alcohols, acids, aldehydes, furans, anhydrosugars, and ketones pyrolysis substances decreased, while the yield of phenols increased. The yield of 4-Vinylphenol (4-VP) increased from 29.33%, 8.21% and 5.76% to 34.93%, 12.46% and 7.68% at 330, 450 and 650 °C, respectively, after anaerobic digestion.

Liang|Jiajin|J| Lin|Yunqin|Y| Wu|Shubin|S| Liu|Chao|C| Lei|Ming|M| Zeng|Chao|C|

Anaerobic digested rice straw
Thermal decomposition characteristic
Pyrolytic product
Raw rice straw


Incidence and clinical outcomes of intestinal Behçet's disease in Korea, 2011-2014: a nationwide population-based study.

Abstract:
BACKGROUND
Intestinal Behçet's disease (BD) is very rare, and epidemiologic data regarding BD are scarce. Moreover, there have been no population-based studies focusing on intestinal BD. We conducted a nationwide population-based study to examine the incidence and clinical course of Korean patients with intestinal BD.

METHODS
We collected data on 365 patients diagnosed with intestinal BD from 2011 to 2014 using the Health Insurance Review and Assessment Services claims database. We analyzed the incidence and clinical outcomes, including cumulative rates of bowel resection, hospitalization, and medication use.

RESULTS
During the study period, the average annual incidence for intestinal BD was 0.18 per 105 population, and the proportion of cases with intestinal involvement was 3.9%. At 1 and 4 years after diagnosis, the cumulative rates of surgery were 5.0 and 10.9%, respectively, whereas those of hospitalization were 27.8 and 32.4%, respectively. The 1- and 4-year cumulative rates of requirements for medications were 39.8 and 49.1% for moderate- to high-dose corticosteroids, 33.6 and 42.1% for immunomodulators, and 3.5 and 6.8% for biologics, respectively. The cumulative probability of corticosteroid and immunomodulator use was higher in male than in female patients and in younger (<40 years) than in older (≥40 years) patients. However, there were no significant differences in the cumulative probabilities of surgery, hospitalization, and biologics use according to sex and age group.

CONCLUSIONS
The incidence of intestinal BD in Korea is quite low and has been stable in recent years.

Han|Minkyung|M|
Jung|Yoon Suk|YS|
Kim|Won Ho|WH|
Cheon|Jae Hee|JH|
Park|Sohee|S|

D013505:Digestive System Surgical Procedures

Incidence
Korea
Clinical course
Intestinal Behçet’s disease


Male-Male Competition Causes Parasite-Mediated Sexual Selection for Local Adaptation.

Abstract: AbstractSexual selection has been suggested to accelerate local adaptation and promote evolutionary rescue through several ecological and genetic mechanisms. Condition-dependent sexual selection has mainly been studied in laboratory settings, while data from natural populations are lacking. One ecological factor that can cause condition-dependent sexual selection is parasitism. Here, we quantified ectoparasite load (Arrenurus water mites) in a natural population of the common bluetail damselfly (Ischnura elegans) over 15 years. We quantified the strength of sexual selection against parasite load in both sexes and experimentally investigated the mechanisms behind such selection. Then we investigated how parasite resistance and tolerance changed over time to understand how they might influence population density. Parasites reduced mating success in both sexes, and sexual selection was stronger in males than in females. Experiments show that male-male competition is a strong force causing precopulatory sexual selection against parasite load. Although parasite resistance and male parasite tolerance increased over time, suggestive of increasing local adaptation against parasites, no signal of evolutionary rescue could be found. We suggest that condition-dependent sexual selection facilitates local adaptation against parasites and discuss its effects in evolutionary rescue.

Gómez-Llano|Miguel|M|
Narasimhan|Aaditya|A|
Svensson|Erik I|EI|

sexual selection
local adaptation
evolutionary rescue
parasitism
condition dependence


Examining the relationship between psychosis and immigration in Spain: The effect of cannabis use and language barrier in a large psychosis sample.

Abstract: The main aim of this study is to examine the association between psychosis and immigration, independent of the language barrier, drug consumption, and the social support index. The second aim is to explore the clinical and demographic characteristics of the immigrants in the catchment area, compared with the native Spanish population suffering from psychosis. All consecutive patients admitted to a hospital in Spain during 2018 and 2019 (n = 1484) were identified through the hospital's clinical records. The general representative sample (n=1484) was divided into two groups: immigrants (n=131) and non-immigrants (n=1353). Demographic, clinical, and social variables were then obtained and included in a logistic regression model. A subsample with all consecutive cases with psychosis (93 immigrants and 543 no immigrants) was also analysed to describe the diagnosis and evolution after admission. Our results show that there is higher significant prevalence of admissions due to psychosis in the immigrant population than in the non-immigrant population. This association is prominent in the population of Sub-Saharans, and is independent of cannabis use, a low social support index, or a language barrier. Understanding the specificities not only in the social context of this population but also the clinical needs is determinant for being able to shape the therapeutic intervention.

Garrido-Torres|Nathalia|N|
Alameda|Luis|L|
Cristóbal|Julio Piedra|JP|
Padilla|Michael Vincent|MV|
Robles|Cristina Sánchez|CS|
Canal-Rivero|Manuel|M|
Crespo-Facorro|Benedicto|B|
Ruiz-Veguilla|Miguel|M|


Core muscles thickness is not associated with knee frontal plane projection angle during single-leg squat in healthy people.

Abstract:
BACKGROUND
Core muscles play an important role in lower limb stability and alignment, with their weakness being associated with poor alignment and, consequently, with injuries. Despite muscle structure being critical to muscle strength production, we did not find studies associating the morphology of the core muscles and lower limb alignment during functional tasks.

RESEARCH QUESTION
Is there association between thickness of core muscles (external oblique - EO, internal oblique - IO, transversus abdominis - TrA and gluteus medius - GMed) and lower limb alignment during the single-leg squat in healthy subjects?

METHODS
Forty-six healthy participants (27 male and 19 female) performed the following evaluations: (i) measurements of muscle thickness of the EO, IO, TrA and GMed using ultrasound and (ii) measurements of lower limb alignment using the knee frontal plane projection angle (FPPA) during the single-leg squat. A Spearman rank correlation coefficient (rs) was performed between the thickness of selected core muscles (OE, OI, TrA and GMed) and the knee FPPA. In addition, a partial correlation (r) was performed, using sex, physical activity level and body mass index as control variables.

RESULTS
We did not observe significant correlations between the knee FPPA and the thickness of the EO (rs = 0.194; p = 0.197), IO (rs = 0.182; p = 0.225), TrA (rs = 0.073; p = 0.627) and GMed (rs = -0.092; p = 0.542). When controlling for sex, physical activity level and body mass index, similar results were observed [EO (r = 0.157; p = 0.316), IO (r = 0.261; p = 0.092), TrA (r = 0.030; p = 0.850) and GMed (r = -0.144; p = 0.356)] SIGNIFICANCE: Our results demonstrated that core muscles' thickness is not associated with lower limb alignment during the single-leg squat in healthy people.

Fitarelli|Luan|L| Ramos|Giovana|G| Scudiero|Felipe|F| Rabello|Rodrigo|R| Rodrigues|Rodrigo|R|

Core
Muscle thickness
Lower limb alignment
Kinematics


Computerised cognitive testing of individuals with Down's syndrome and Alzheimer's disease.

Abstract:
BACKGROUND
Although Alzheimer's disease neuropathology is present by age 40 years, in Down's syndrome, ante-mortem diagnosis is difficult. No standard for cognitive assessment is well established or easy to administer.

METHOD
We used a simple, widely available computerised test (NeuroTrax Moderate to Severe Impairment Assessment Battery, Mindstreams, Newark, NJ) to evaluate 14 patients in this population. Orientation, memory, executive function, verbal function and visual spatial function were evaluated every 6 months for 18 months.

RESULTS
Mean scaled scores in this longitudinal study were evaluated with repeated measures analysis of variance. Memory, executive function, verbal function and visual spatial function scores did not significantly change. There was no significant depression or anxiety on self-reported measures.

CONCLUSIONS
Reproducibility of test results supports the reliability of this battery to quantify function and prospectively follow performance in this population over an 18-month period.

Gutman|Michael|M|
Moskovic|Ethan|E|
Jeret|Joseph S|JS|

Down's syndrome
Alzheimer's disease
computerised testing
intellectual disability


STI/HIV test result disclosure between female sex workers and their primary, non-commercial male partners in two Mexico-US border cities: a prospective study.

Abstract:
OBJECTIVES
Disclosure of sexually transmitted infections (STI)/HIV diagnoses to sexual partners is not mandated by public health guidelines in Mexico. To assess the feasibility of couples-based STI/HIV testing with facilitated disclosure as a risk-reduction strategy within female sex workers' (FSW) primary partnerships, we examined STI/HIV test result disclosure patterns between FSWs and their primary, non-commercial male partners in two Mexico-US border cities.

METHODS
From 2010 to 2013, 335 participants (181 FSWs and 154 primary male partners) were followed for 24 months. At semiannual visits, participants were tested for STIs/HIV and reported on their disclosure of test results from the previous visit. Multilevel logistic regression was used to identify individual-level and partnership-level predictors of cumulative (1) non-disclosure of ≥1 STI test result and (2) non-disclosure of ≥1 HIV test result within couples during follow-up.

RESULTS
Eighty-seven percent of participants reported disclosing all STI/HIV test results to their primary partners. Non-disclosure of ≥1 STI test result was more common among participants who reported an STI diagnosis as part of the study (adjusted OR=3.05, 95% CI 1.13 to 8.25), while non-disclosure of ≥1 HIV test result was more common among participants in longer-duration partnerships (AOR=1.15 per year, 95% CI 1.03 to 1.28). Drug use before/during sex within partnerships was associated with non-disclosure of both STI (AOR=5.06, 95% CI 1.64 to 15.62) and HIV (AOR=4.51, 95% CI: 1.32 to 15.39) test results.

CONCLUSIONS
STI/HIV test result disclosure was highly prevalent within FSWs' primary partnerships, suggesting couples-based STI/HIV testing with facilitated disclosure may be feasible for these and potentially other high-risk, socially marginalised couples.

HIV
CHLAMYDIA INFECTION
GONORRHOEA
PREVENTION
SYPHILIS


Infections in pediatric solid-organ transplant recipients.

Abstract: Solid-organ transplantation in pediatrics can be a life-saving procedure, but it cannot be accomplished without risk of infection-related morbidity and mortality. Evaluation of the recipient during candidacy and donor during evaluation can assist with identification of risk. Further, risk of infection from the surgical procedure can be mitigated through careful planning and attention to infection prevention processes. Finally, early recognition of infection posttransplant can limit the impact of these events.

Infections in solid-organ transplantation


Technology-mediated just-in-time adaptive interventions (JITAIs) to reduce harmful substance use: a systematic review.

Abstract:
BACKGROUND AND AIMS
Lapse risk when trying to stop or reduce harmful substance use is idiosyncratic, dynamic and multi-factorial. Just-in-time adaptive interventions (JITAIs) aim to deliver tailored support at moments of need or opportunity. We aimed to synthesize evidence on decision points, tailoring variables, intervention options, decision rules, study designs, user engagement and effectiveness of technology-mediated JITAIs for reducing harmful substance use.

METHODS
Systematic review of empirical studies of any design with a narrative synthesis. We searched Ovid MEDLINE, Embase, PsycINFO, Web of Science, the ACM Digital Library, the IEEE Digital Library, ClinicalTrials.gov, the ISRCTN register and dblp using terms related to substance use/mHealth/JITAIs. Outcomes were user engagement and intervention effectiveness. Study quality was assessed with the mHealth Evidence Reporting and Assessment checklist.

FINDINGS
We included 17 reports of 14 unique studies, including two randomized controlled trials. JITAIs targeted alcohol (S = 7, n = 120 520), tobacco (S = 4, n = 187), cannabis (S = 2, n = 97) and a combination of alcohol and illicit substance use (S = 1, n = 63), and primarily relied on active measurement and static (i.e. time-invariant) decision rules to deliver support tailored to micro-scale changes in mood or urges. Two studies used data from prior participants and four drew upon theory to devise decision rules. Engagement with available JITAIs was moderate-to-high and evidence of effectiveness was mixed. Due to substantial heterogeneity in study designs and outcome variables assessed, no meta-analysis was performed. Many studies reported insufficient detail on JITAI infrastructure, content, development costs and data security.

CONCLUSIONS
Current implementations of just-in-time adaptive interventions (JITAIs) for reducing harmful substance use rely on active measurement and static decision rules to deliver support tailored to micro-scale changes in mood or urges. Studies on JITAI effectiveness are lacking.

just-in-time adaptive intervention
substance use
systematic review
tailoring
mHealth
alcohol


Clinic based biopsy vs. theatre biopsy of bone and soft tissue extremity tumours: comparable diagnostic modalities.

Abstract:
OBJECTIVE
To compare the diagnostic accuracy of clinic-based biopsy versus theatre biopsy against final histopathology in patients presenting with extremity tumours.

METHODS
The retrospective study was conducted at Aga Khan University Hospital, Karachi, and comprised record of patients who underwent biopsy procedure of extremity tumours from January 2008 to December 2011. Data regarding socio-demographic status, disease-related and procedure-related variables were collected from the files. Histopathology report of biopsy was compared with the final histopathology after definite procedure of the tumour for concordance.

RESULTS
Of the 87 patients whose records were reviewed, 42(48%) had undergone biopsy in theatre and 45(52%) in clinic. The overall median age was 29 years (Inter-quartile range: 18-58 years). As compared to final histopathology after the definite procedure, diagnostic accuracy of theatre and clinic-based biopsy was 97.7% vs. 95.5% respectively. Surgical site infection was observed in 2(5%) in theatre and in 1(2.2%) in clinic.

CONCLUSIONS
Clinic-based biopsy was accurate and safe with diagnostic accuracy comparable to theatre-based biopsy. Clinic-based biopsy, being cost-efficient along with low morbidity, should be preferred in patients with extremity tumours.

Ahmed|Waseem|W|
Umer|Masood|M|
Mohib|Yasir|Y|
Rashid|Rizwan Haroon|RH|

Biopsy, Histopathology, Clinic based biopsy, Theatre based biopsy, Tumour.


Protective Mechanism of Edible Food Plants against Alcoholic Liver Disease with Special Mention to Polyphenolic Compounds.

Abstract: Alcoholic liver disease (ALD) is one type of liver disease, causing a global healthcare problem and mortality. The liver undergoes tissue damage by chronic alcohol consumption because it is the main site for metabolism of ethanol. Chronic alcohol exposure progresses from alcoholic fatty liver (AFL) to alcoholic steatohepatitis (ASH), which further lead to fibrosis, cirrhosis, and even hepatocellular cancer. Therapeutic interventions to combat ALD are very limited such as use of corticosteroids. However, these therapeutic drugs are not effective for long-term usage. Therefore, additional effective and safe therapies to cope with ALD are urgently needed. Previous studies confirmed that edible food plants and their bioactive compounds exert a protective effect against ALD. In this review article, we summarized the hepatoprotective potential of edible food plants and their bioactive compounds. The underlying mechanism for the prevention of ALD by edible food plants was as follows: anti-oxidation, anti-inflammation, lipid regulation, inhibition of apoptosis, gut microbiota composition modulation, and anti-fibrosis.

alcoholic liver disease
polyphenols
bioactive compounds
gut microbiota
antioxidants


Cytomegalovirus reactivation in patients with multiple myeloma.

Abstract: The introduction of novel antimyeloma agents has improved the outcome of multiple myeloma (MM) dramatically. However, it has also led to an increasing incidence of Herpesviridae family virus infections, including a high incidence of post-transplant cytomegalovirus (CMV) reactivation after treatment with novel agents. We herein retrospectively assessed the CMV reactivation in all 120 newly diagnosed patients with MM consecutively seen and treated at our hospital. CMV antigenemia tests were ordered in 58 patients depending on the clinical context, and the incidence of CMV reactivation and proven/suspected CMV disease requiring antiviral therapy was 20% (24 of 120) and 11% (13 of 120) respectively, including those without stem cell transplantation (SCT). The clinical and laboratory characteristics of these patients were compared with those in 34 CMV antigenemia-negative (CMV-negative) patients. Patients with extramedullary disease or a low absolute lymphocyte count (ALC) had a higher risk of developing CMV reactivation. In addition, the median duration from the time of MM diagnosis to CMV reactivation was 5.0 months. These results suggest that, regardless of whether or not undergoing SCT, elderly patients with MM receiving novel agents should be monitored for CMV reactivation to allow for the timely diagnosis and treatment, especially for those with extramedullary disease.

Hasegawa|Tetsuo|T| Aisa|Yoshinobu|Y| Shimazaki|Kengo|K| Ito|Chisako|C| Nakazato|Tomonori|T|

cytomegalovirus
reactivation
multiple myeloma


The Michelangelo Effect: Art Improves the Performance in a Virtual Reality Task Developed for Upper Limb Neurorehabilitation.

Abstract: The vision of an art masterpiece is associated with brain arousal by neural processes occurring quite spontaneously in the viewer. This aesthetic experience may even elicit a response in the motor areas of the observers. In the neurorehabilitation of patients with stroke, art observation has been used for reducing psychological disorders, and creative art therapy for enhancing physical functions and cognitive abilities. Here, we developed a virtual reality task which allows patients, by moving their hand on a virtual canvas, to have the illusion of painting some art masterpieces, such as The Creation of Adam of Michelangelo or The birth of Venus of Botticelli. Twenty healthy subjects (experiment 1) and four patients with stroke (experiment 2) performed this task and a control one in which they simply colored the virtual canvas. Results from User Satisfaction Evaluation Questionnaire and the NASA Task Load Index highlighted an appropriate level of usability. Moreover, despite the motor task was the same for art and control stimuli, the art condition was performed by healthy subjects with shorter trajectories (p = 0.001) and with a lower perception of physical demand (p = 0.049). In experiment 2, only the patients treated with artistic stimuli showed a reduction in the erroneous movements performed orthogonally to the canvas (p < 0.05). This finding reminds the so-called Mozart effect that improves the performance of subjects when they listen to classic music. Thus, we called this improvement in the performance when interacting with an artistic stimulus as Michelangelo effect.

Iosa|Marco|M| Aydin|Merve|M| Candelise|Carolina|C| Coda|Natascia|N| Morone|Giovanni|G| Antonucci|Gabriella|G| Marinozzi|Franco|F| Bini|Fabiano|F| Paolucci|Stefano|S| Tieri|Gaetano|G|

art
virtual reality
aesthetics
stroke
cognition
neuroscience
psychophysics
rehabilitation


Nutritional Care of Gastric Cancer Patients with Clinical Outcomes and Complications: A Review.

Abstract: The incidence and mortality of gastric cancer have been steadily decreased over the past few decades. However, gastric cancer is still one of the leading causes of cancer deaths across many regions of the world, particularly in Asian countries. In previous studies, nutrition has been considered one of significant risk factors in gastric cancer patients. Especially, malnourished patients are at greater risk of adverse clinical outcomes (e.g., longer hospital stay) and higher incidence of complications (e.g., wound/infectious complications) compared to well-nourished patients. Malnutrition is commonly found in advanced gastric cancer patients due to poor absorption of essential nutrients after surgery. Therefore, nutritional support protocols, such as early oral and enternal feeding, have been proposed in many studies, to improve unfavorable clinical outcomes and to reduce complications due to delayed application of oral nutritional support or parental feeding. Also, the supplied with enternal immune-enriched diet had more benefits in improving clinical outcomes and fewer complications compared to a group supplied with control formula. Using nutritional screening tools, such as nutritional risk index (NRI) and nutritional risk screening (NRS 2002), malnourished patients showed higher incidence of complications and lower survival rates than non-malnourished patients. However, a long-term nutritional intervention, such as nutritional counseling, was not effective in the patients. Therefore, early assessment of nutritional status in patients using a proper nutritional screening tool is suggested to prevent malnutrition and adverse health outcomes. Further studies with numerous ethnic groups may provide stronger scientific evidences in association between nutritional care and recovery from surgery in patients with gastric cancer.

Nutrition
Gastric cancer
Clinical outcome
Complication
Review


The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of prostate carcinoma.

Abstract: Prostate cancer is the most commonly diagnosed malignancy and second leading cause of cancer death among men in the United States. In recent years, several new agents, including cancer immunotherapies, have been approved or are currently being investigated in late-stage clinical trials for the management of advanced prostate cancer. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel, including physicians, nurses, and patient advocates, to develop consensus recommendations for the clinical application of immunotherapy for prostate cancer patients. To do so, a systematic literature search was performed to identify high-impact papers from 2006 until 2014 and was further supplemented with literature provided by the panel. Results from the consensus panel voting and discussion as well as the literature review were used to rate supporting evidence and generate recommendations for the use of immunotherapy in prostate cancer patients. Sipuleucel-T, an autologous dendritic cell vaccine, is the first and currently only immunotherapeutic agent approved for the clinical management of metastatic castrate resistant prostate cancer (mCRPC). The consensus panel utilized this model to discuss immunotherapy in the treatment of prostate cancer, issues related to patient selection, monitoring of patients during and post treatment, and sequence/combination with other anti-cancer treatments. Potential immunotherapies emerging from late-stage clinical trials are also discussed. As immunotherapy evolves as a therapeutic option for the treatment of prostate cancer, these recommendations will be updated accordingly.

McNeel|Douglas G|DG|
Bander|Neil H|NH|
Beer|Tomasz M|TM|
Drake|Charles G|CG|
Fong|Lawrence|L|
Harrelson|Stacey|S|
Kantoff|Philip W|PW|
Madan|Ravi A|RA|
Oh|William K|WK|
Peace|David J|DJ|
Petrylak|Daniel P|DP|
Porterfield|Hank|H|
Sartor|Oliver|O|
Shore|Neal D|ND|
Slovin|Susan F|SF|
Stein|Mark N|MN|
Vieweg|Johannes|J|
Gulley|James L|JL|

Immunotherapy
Treatment
Prostate Cancer
Guidelines


Anti-Toxoplasma IgG assays: What performances for what purpose? A systematic review.

Abstract: Chronic infection with Toxoplasma gondii is attested by the detection of specific anti-Toxoplasma IgG. A wide panel of serologic methods is currently marketed, and the most suitable method should be chosen according to the laboratory resources and the screened population. This systematic review of evaluation studies aimed at establishing an overview of the performances, i.e. sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of marketed anti-Toxoplasma IgG assays, and discussing their technical characteristics to guide further choice for routine diagnostic use. According to PRISMA guidelines, the search performed in PubMed and Web of Science databases recovered 826 studies, of which 17 were ultimately included. Twenty commercial anti-Toxoplasma IgG assays were evaluated, in comparison with an accepted reference method. Most of them were enzyme-immunoassays (EIAs, n = 12), followed by agglutination tests (n = 4), immunochromatographic tests (n = 3), and a Western-Blot assay (WB, n = 1). The mean sensitivity of IgG assays ranged from 89.7% to 100% for standard titers and from 13.4% to 99.2% for low IgG titers. A few studies pointed out the ability of some methods, especially WB to detect IgG early after primary infection. The specificity of IgG assays was generally high, ranging from 91.3% to 100%; and higher than 99% for most EIA assays. The PPV was not a discriminant indicator among methods, whereas significant disparities (87.5%-100%) were reported among NPVs, a key-parameter assessing the ability to definitively rule out a Toxoplasma infection in patients at-risk for opportunistic infections.

Anti-Toxoplasma IgG
Specificity
Serology
Sensitivity
Diagnosis
Toxoplasmosis


Sulphate, more than a nutrient, protects the microalga Chlamydomonas moewusii from cadmium toxicity.

Abstract: Sulphur is an essential macroelement that plays important roles in living organisms. The thiol rich sulphur compounds, such as cysteine, γ-Glu-Cys, glutathione and phytochelatins participate in the tolerance mechanisms against cadmium toxicity. Plants, algae, yeasts and most prokaryotes cover their demand for reduced sulphur by reduction of inorganic sulphate. The aim of this study was to investigate, using a bifactorial experimental design, the effect of different sulphate concentrations in the nutrient solution on cadmium toxicity in the freshwater microalga Chlamydomonas moewusii. Cell growth, kinetic parameters of sulphate utilization and intracellular concentrations of low-molecular mass thiol compounds were determined. A mathematical model to describe the growth of this microalga based on the effects of sulphate and cadmium was obtained. An ANOVA revealed an interaction between them, 16% of the effect sizes was explained by this interaction. A higher amount of sulphate in the culture medium allowed a higher cadmium tolerance due to an increase in the thiol compound biosynthesis. The amount of low-molecular mass thiol compounds, mainly phytochelatins, synthesized by this microalga was significantly dependent on the sulphate and cadmium concentrations; the higher phytochelatin content was obtained in cultures with 4 mg Cd/L and 1mM sulphate. The maximum EC50 value (based on nominal cadmium concentration) reached for this microalga was 4.46 ± 0.42 mg Cd/L when the sulphate concentration added to the culture medium was also 1mM. An increase in the sulphate concentration, in deficient environments, could alleviate the toxic effect of this metal; however, a relative excess is also negative. The results obtained showed a substrate inhibition for this nutrient. An uncompetitive model for sulphate was chosen to establish the mathematical model that links both factors.

Sulphate
Chlamydomonas moewusii
Cadmium
Toxicity
Tolerance
Low-molecular mass thiol compounds


Hypoxia inducible NOD2 interacts with 3-O-sulfogalactoceramide and regulates vesicular homeostasis.

Abstract:
BACKGROUND
Oxygen sensing in mammalian cells is a conserved signaling pathway regulated by hypoxia inducible factor type 1 (HIF-1). Inadequate oxygen supply (hypoxia) is common to many pathological disorders where autophagy plays an import role. The aim of this study was the identification and characterization of novel HIF-1 target genes that promote autophagy during hypoxia.

METHODS
Whole genome Chromatin Immune Precipitation from hypoxic HeLa cells was used to identify novel HIF-1 target genes. Hypoxia induced expression and transcription regulation was studied in wild type and HIF-deficient cells. siRNA silencing of candidate genes was used to establish their role during autophagy. Recombinant protein was used for screening immobilized glycosylated lipids to identify potential ligands.

RESULTS
We identified the Nucleotide Oligomerization Domain 2 (NOD2/CARD15) as a novel HIF-1 target and 3-O-sulfo-galactoceramide (sulfatide) and Mycobacterium sp. specific sulfolipid-1 as the first NOD2 ligands that both compete for binding to NOD2. Loss of NOD2 function impaired autophagy upstream of the autophagy inhibitor chloroquine by reducing the number of acidic vesicles. Inhibition of sulfatide synthesis elicited defects in autophagy similar to the NOD2 loss of function but did not influence NOD2-mediated NF-kB signaling.

CONCLUSIONS
Our findings suggest that the interaction of NOD2 with sulfatide may mediate the balance between autophagy and inflammation in hypoxic cells.

GENERAL SIGNIFICANCE
These findings may lead to a better understanding of complex inflammatory pathologies like Crohn's disease and tuberculosis where both NOD2 and hypoxia are implicated.

Nabatov|Alexey A|AA|
Hatzis|Pantelis|P|
Rouschop|Kasper M A|KM|
van Diest|Paul|P|
Vooijs|Marc|M|

D051795:Hypoxia-Inducible Factor 1, alpha Subunit

Nucleotide-binding oligomerization domain-containing protein 2


Establishing a warning index for evaluating the physiological stress of sanitation workers in high temperature weather.

Abstract: High temperature weather occurs frequently in recent years. As a heat-vulnerable group, sanitation workers suffer great physiological safety risks in high temperature weather. In this paper, a physiological warning index (PWI) is established to quantify the physiological stress of the sanitation workers. Firstly, the dynamic weights of the physiological parameters are calculated by the norm grey correlation method. Secondly, the PWI is established by the efficacy coefficient method and the warning level of the PWI is divided based on the relationships between the PWI and thermal sensation vote (TSV). Finally, the reasonability of the PWI is verified. The results show that the weights of the physiological parameters are dynamic, changing with the environments and the physiological states. The weight ranges of the mean skin temperature (MST), tympanic temperature (TT), systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) are 0.036-0.538, 0.000-0.369, 0.000-0.362, 0.018-0.367 and 0.009-0.348. And the MST and DBP are more affected by the high temperature than the TT, SBP and HR. The warning interval of PWI is: (0, 0.25] (no warning), (0.25, 0.45] (mild warning), (0.45, 0.7] (moderate warning), and (0.7, 1.0] (severe warning). The PWI can provide simple real-time physiological warning and guarantee physiological health for sanitation workers in high temperature weather.

Zheng|Guozhong|G| Fan|Zhuangzhuang|Z| Ge|Meng|M| Li|Cong|C|

Warning
Physiological stress
High temperature
Dynamic weight
Norm grey correlation
Efficacy coefficient method


Thulium fiber laser utilization in urological surgery: A narrative review.

Abstract: The thulium fiber laser (TFL) is a novel technology under active investigation as an conceivable alternative to the Holmium:yttrium-aluminum-garnet (Ho:YAG) laser, which is currently the gold standard for an array of urologic procedures. The purpose of this review is to discuss the existing literature on the functionality and effectiveness of TFL in urological practice. We conducted a search of the PubMed, Medline, Web of Science Core Collection, SCOPUS, Embase (OVID), and Cochrane Databases for all full articles and systematic reviews on the TFL. We found a total of 35 relevant pieces of literature. The early research findings pertaining to the TFL exhibit numerous potential advantages over the Ho:YAG laser. In vitro and ex vivo studies have highlighted the TFL's ability to utilize smaller laser fibers, obtain faster stone ablation rates, and achieve less retropulsion when tested against the Ho:YAG laser in lithotripsy. Currently, there is limited in vivo research that investigates the utilization of the TFL. The in vivo results that are available, however, look promising both for laser lithotripsy and soft tissue ablation. Indeed, the existing literature suggests that the TFL has great potential and may possess numerous technological advantages over the Ho:YAG laser, especially in laser lithotripsy. Although these early studies are promising, randomized control trials are needed to assess the full applicability of the TFL in urology.

Thulium
Urology
Lithotripsy
Laser therapy
Surgical endoscopy


Chemical composition and antimicrobial activity of essential oils from Acantholippia deserticola, Artemisia proceriformis, Achillea micrantha and Libanotis buchtormensis against phytopathogenic bacteria and fungi.

Abstract: Essential oils from aerial parts of Acantholippia deserticola, Artemisia proceriformis, Achillea micrantha and Libanotis buchtormensis were analysed by GC-MS. The major compounds identified were β-thujone (66.5 ± 0.2%), and trans-sabinyl acetate (12.1 ± 0.2%) in A. deserticola; α-thujone (66.9 ± 0.4%) in A. proceriformis; 1,8-cineole (26.9 ± 0.5%), and camphor (17.7 ± 0.3%) in A. micrantha and cis-β-ocimene (23.3 ± 0.3%), and trans-β-ocimene (18.4 ± 0.2%) in L. buchtormensis. The oils showed a weak antimicrobial effect (MIC100 > 1.5 mg/ml) on most phytopathogens tested. A moderate antimicrobial activity (MIC100 between 0.5 and 1.5 mg/ml) was displayed by the oils of A. deserticola, A. micrantha and L. buchtormensis on Septoria tritici and by the oil of A. deserticola on Septoria glycine. The antimicrobial activity was associated to the contents of β-thujone, trans-sabinyl acetate and trans-sabinol. Our results indicate that the tested essential oils have little inhibitory potency not suitable for use as plant protection products against the phytopathogens assayed.

Sampietro|Diego A|DA|
Lizarraga|Emilio F|EF|
Ibatayev|Zharkyn A|ZA|
Omarova|Akerke B|AB|
Suleimen|Yerlan M|YM|
Catalán|Cesar A N|CA|

essential oils
Septoria
Aspergillus
Erwinia
Fusarium
Pseudomonas
Xanthomonas


Complete mitogenome for the ber fruit fly, Carpomya vesuviana (Diptera: Tephritidae) from Toksun, Northwest China and its phylogenetic relationship within family Tephritidae.

Abstract: Carpomya vesuviana (Diptera: Tephritidae), commonly known as the ber fruit fly, is the most destructive insect pest of 'ber' (jujube) throughout Asia and Western Europe. Complete sequence of the mitogenome of C. vesuviana has been determined in this study. The circular genome is 15,267 bp long and contains a standard gene complement, that is, the large and small ribosomal RNA subunits, 22 transfer RNA genes, 13 genes encoding mitochondrial proteins, and a non-coding A + T-rich control region. The phylogeny showed that C. vesuviana of subfamily Trypetinae was monophyletic and clearly separated from both Dacinae and Tephritinae with maximum support (p = 1).

Jia|Ping-Fan|PF| Liu|Jian-Hong|JH| Xu|Jin|J| Li|Xiao-Jun|XJ| Dan|Wen-Li|WL|

Carpomya vesuviana
mitochondrial genome
molecular phylogeny


The Impact of Health, Wealth, and Attractiveness on Romantic Evaluation from Photographs of Faces.

Abstract: A large literature suggests that men and women differ in their self-reported mate preferences such that men place greater weight on physical attractiveness than women do, whereas women value financial prospects more than men. Yet, little research has addressed how these differences generalize to other contexts, such as modern online dating in which mate selection may largely depend on visual cues. Distinct from the sex differences observed in previous studies relying on self-reports, we found that men and women both used perceptions of health and attractiveness to select hypothetical partners based on photographs of their faces. Importantly, although people reliably identified others' wealth from their photographs, these perceptions did not influence men's or women's partner selections. Thus, men and women may select romantic partners similarly based on limited visual information.

Tskhay|Konstantin O|KO|
Clout|Jerri M|JM|
Rule|Nicholas O|NO|

D007722:Health Knowledge, Attitudes, Practice

Mate preferences
Online dating
Sex differences
Social perception