Photodynamic therapy combined with laser drilling successfully prevents the recurrence of refractory oral proliferative verrucous leukoplakia.

Abstract: Oral proliferative verrucous leukoplakia is a potentially malignant disorder with high rates of recurrence and malignant transformation. Proliferative verrucous leukoplakia is often refractory to various treatments, including topical drugs, surgical resection, cryotherapy, and laser therapy. Topical 5-aminolevulinic acid-mediated photodynamic therapy is an innovative and effective treatment for potentially malignant oral disorders and has the potential to control the recurrence of precancerous lesions and cancer. Various pre-treatments or combined therapies have been proposed to increase the efficacy of topical 5-aminolevulinic acid-mediated photodynamic therapy, especially for large, thick, or highly keratinised lesions. We report a case of refractory proliferative verrucous leukoplakia in a 58-year-old female patient who showed rapid recurrence within 1 week of topical 5-aminolevulinic acid-mediated photodynamic therapy despite pre-treatment with microneedle puncture, combined intralesional injection of 5-aminolevulinic acid, and shortened treatment interval. We applied three sessions of topical 5-aminolevulinic acid-mediated photodynamic therapy combined with diode laser drilling pre-treatment at 1-week intervals, which successfully eradicated the lesions without any adverse effects and without any signs of recurrence at the 10-month follow-up. Topical 5-aminolevulinic acid-mediated photodynamic therapy combined with diode laser drilling pre-treatment is safe and well-tolerated and could have synergistic efficacy against refractory oral proliferative verrucous leukoplakia.

Wang|Fei|F| Shi|Yujie|Y| Dong|Yunmei|Y| Liu|Tiannan|T| Dan|Hongxia|H| Wang|Jiongke|J| Zeng|Xin|X|

Photodynamic therapy
Laser drilling
Proliferative verrucous leukoplakia
Diode laser
Oral leukoplakia


Fruit extract of red pitaya (Hylocereus undatus) prevents and reverses stress-induced impairments in the cholinergic and antioxidant systems of Caenorhabditis elegans.

Abstract: The addition of fruit to the diet is very important, and we can use nutraceutical and functional foods for this supplement. A little-known fruit is a red pitaya (Hylocereus undatus) that has been widely reported to have a high antioxidant potential. In this study, we analyzed the in vitro and in vivo antioxidant capacity of microencapsulated pitaya extract on the behavior, antioxidant, and nervous system of the nematode Caenorhabditis elegans. The worms were treated with fruit extract before and after juglone-induced stress, to determine the protective or curative effects of pitaya. We have been evaluated cholinergic, antioxidant, and behavioral biomarkers. We have evidenced that the pulp of pitaya contains antioxidant compounds and can serve as a potential nutraceutical product. In addition, the fruit extract was effective in preventing and/or reverse the stress-induced damages, even at high levels of chemical stress at all evaluated parameters. PRACTICAL APPLICATIONS: The potential applications and uses aimed by this research are related to the supplementation of foods given the antioxidant effect. Our data suggested that the effect of the pitaya fruit microencapsulated pulp extract was effective to prevent and repair the damage caused by oxidative stress. Besides the use of this microencapsulated extract can be an auxiliary in the treatment of diseases related to oxidative damage as well as promoting senescent aging. Another important use is the application of this extract as a dietary supplement to fortify the antioxidant system.

pitaya
antioxidant system
antioxidant potential
C. elegans
microencapsulation process
reactive oxygen species


Identity of Ṭaṅkārī (Physalis Minima Linn.) in Ayurvedic Classics: A Literature Review.

Abstract: Proper identification of drugs and their use in proper doses are important for successful treatment. Physalis minima Linn commonly known as country gooseberry has anti-cancerous, anti-diabetic, analgesic, antipyretic and anti-inflammatory potentials. The present paper is aimed to ascertain the proper identity of Ṭaṅkārī (Physalis minima Linn.) in Ayurvedic classics by a meticulous search and hence a review of the drug Ṭaṅkārī (Physalis minima Linn) was carried out in the texts of Ayurveda, modern literature, journals and online publications. The result of the search showed that the name "Ṭaṅkārī" is not found in Vedic lore. In Saṃhitās, it is mentioned in Bhāvaprakāśa. Reference of the drug "Śārṅgeṣṭhā" is found in Bṛhattrayī, Bhela, Kāśyapa, Cakradatta and Vaṅgasena. It is variously named as Cirapoṭikā, Kākatikta, and Vāyasī by ḍalhaṇa and he describes it as gaura (pale), vartula (round), and as having avaguṇṭhita/veṣṭhita (covered) fruit which matches the description of Ṭaṅkārī (P. minima Linn). A search for terms Kākatikta and Vāyasī showed Kākatikta to be synonymous to Śārṅgeṣṭhā and Vāyasī to be synonymous to both Kākatikta and Kākamācī (Solanum nigrum). Madanapāla and Śāligrāma Nighaṇṭus have mentioned the name Cirapoṭikā to be synonymous with Ṭaṅkārī. Śodhala has used the term Parpoṭī as a synonym of Ṭaṅkārī, which is the Gujarati name of P. minima Linn. Recent authors have considered Śārṅgeṣṭhā as either P. minima or Cardiospermum helicabum. The regional names of P. minima are Cirpoṭi (Hindi), Cirboli (Marathi), also the folklore uses and pharmacological activities of P. minima are in accordance with the indications of Śārṅgeṣṭhā in classics. Thus with a complete review of both Ayurveda and modern literatures, it can be concluded that the drug mentioned as Ṭaṅkārī in Bhāvaprakāśa is the same as Śārṅgeṣṭhā mentioned in the classics. Cirapoṭikā and Kākatikta are its synonyms. Cardiospermum helicabum is Karṇaspoṭha, and hence Śārṅgeṣṭhā of classics is P. minima which is supported by the regional names, pharmacological activity and folklore claims.

Kallianpur|Supriya S|SS|
Gokarn|Rohit A|RA|
Rajashekhar|N|N|

Ṭaṅkārī
Physalis minima Linn.
Ayurveda
Śārṅgeṣṭhā
Cirapoṭikā
Kākamācī


What Causes Racial Health Care Disparities? A Mixed-Methods Study Reveals Variability in How Health Care Providers Perceive Causal Attributions.

Abstract: Progress to address health care equity requires health care providers' commitment, but their engagement may depend on their perceptions of the factors contributing to inequity. To understand providers' perceptions of causes of racial health care disparities, a short survey was delivered to health care providers who work at 3 Veterans Health Administration sites, followed by qualitative interviews (N = 53). Survey data indicated that providers attributed the causes of disparities to social and economic conditions more than to patients' or providers' behaviors. Qualitative analysis revealed differences in the meaning that participants ascribed to these causal factors. Participants who believed providers contribute to disparities discussed race and racism more readily, identified the mechanisms through which disparities emerge, and contextualized patient-level factors more than those who believed providers contributed less to disparities. Differences in provider understanding of the underlying causal factors suggest a multidimensional approach to engage providers in health equity efforts.

Gollust|Sarah E|SE|0000-0001-6109-5953
Cunningham|Brooke A|BA|
Bokhour|Barbara G|BG|
Gordon|Howard S|HS|
Pope|Charlene|C|
Saha|Somnath S|SS|
Jones|Dina M|DM|0000-0002-7002-0547
Do|Tam|T|
Burgess|Diana J|DJ|0000-0003-1139-7739

D014493:United States Department of Veterans Affairs

health care disparities
Veterans health
qualitative interviews
health equity
health personnel
surveys and questionnaires


Comparison of effectiveness and cost for different HIV screening strategies implemented at large urban medical centre in the United States.

Abstract:
INTRODUCTION
Incident HIV infections persist in the United States (U.S.) among marginalized populations. Targeted and cost-efficient testing strategies can help in reaching HIV elimination. This analysis compares the effectiveness and cost of three HIV testing strategies in a high HIV burden area in the U.S. in identifying new HIV infections.

METHODS
We performed a cost analysis comparing three HIV testing strategies in Chicago: (1) routine screening (RS) in an inpatient and outpatient setting, (2) modified partner services (MPS) among networks of the recently HIV infected and diagnosed, and (3) a respondent drive sampling (RDS)-based social network (SN) approach targeting young African-American men who have sex with men. All occurred at the same academic medical centre during the following times: routine testing, 2011 to 2016; MPS, 2013 to 2016; SN: 2013 to 2014. Costs were in 2016 dollars and included personnel, HIV testing, training, materials, overhead. Outcomes included cost per test, HIV-positive test and new diagnosis. Sensitivity analyses were performed to assess the impact of population demographics.

RESULTS
The RS programme completed 57,308 HIV tests resulting in 360 (0.6%) HIV-positive tests and 165 new HIV diagnoses (0.28%). The MPS completed 146 HIV tests, resulting in 79 (54%) HIV-positive tests and eight new HIV diagnoses (5%). The SN strategy completed 508 HIV tests, resulting in 210 (41%) HIV-positive tests and 37 new HIV diagnoses (7.2%). Labour accounted for the majority of costs in all strategies. The estimated cost per new HIV diagnosis was $16,773 for the RS programme, $61,418 for the MPS programme and $15,683 for the SN testing programme. These costs were reduced for the RS and MPS strategies in sensitivity analyses limiting testing efficacy to the highest prevalence patient populations ($2,841 and $33,233 respectively).

CONCLUSIONS
The SN strategy yielded the highest proportion of new diagnoses, followed closely by the MPS programme. Both the SN strategy and RS programme were comparable in the cost per new diagnosis. A simultaneous approach that consists of RS in combination with SN testing may be most effective for identifying new HIV infections in settings with heterogeneous epidemics with both high rates of HIV prevalence and HIV testing.

Skaathun|Britt|B|0000-0001-8780-3612
Pho|Mai T|MT|
Pollack|Harold A|HA|
Friedman|Samuel R|SR|
McNulty|Moira C|MC|0000-0002-9651-254X
Friedman|Eleanor E|EE|
Schmitt|Jessica|J|
Pitrak|David|D|0000-0002-6663-2436
Schneider|John A|JA|

D000046:Academic Medical Centers
D000328:Adult
D001741:African Americans
D002641:Chicago
D003362:Cost-Benefit Analysis
D005260:Female
D015658:HIV Infections
D006679:HIV Seropositivity
D000082922:HIV Testing
D018451:Homosexuality, Male
D006801:Humans
D008297:Male
D008403:Mass Screening
D000072339:Sexual and Gender Minorities
D060756:Social Networking
D055815:Young Adult

cost
HIV
screening
social networks
undiagnosed HIV infection


Risk of Cognitive Decline Associated With Paroxetine Use in Elderly Nursing Home Patients With Depression.

Abstract:
OBJECTIVE
This study evaluated the risk of cognitive decline associated with paroxetine use in elderly nursing home patients with depression.

METHODS
A retrospective cohort study was conducted using the 2007 to 2010 Medicare Part D claims and minimum data set (MDS) data involving new users of paroxetine and other selective serotonin reuptake inhibitors (SSRIs). The primary outcome was MDS Cognition Scale. The repeated-measures mixed model was used to examine the effect of paroxetine on cognition after controlling for other factors.

RESULTS
The baseline MDS Cognition Scale measures for paroxetine (n = 63) and other SSRI users (n =1018) were 2.02 (±1.85) and 2.50 (±2.39), respectively. The repeated-measures mixed model did not find statistically significant difference in cognition with the use of paroxetine (β = 0.02, 95% CI: -0.16 to 0.21]) when compared to other SSRIs.

CONCLUSIONS
There was no differential effect of paroxetine on cognition when compared to other SSRIs.

Bali|Vishal|V|
Chatterjee|Satabdi|S|
Johnson|Michael L|ML|
Chen|Hua|H|
Carnahan|Ryan M|RM|
Aparasu|Rajender R|RR|


Cytotoxic activity of N, N'-Bis (2-hydroxybenzyl) ethylenediamine derivatives in human cancer cell lines.

Abstract:
BACKGROUND
Compounds containing ethylenediamine (-NCH2CH2N-) moiety are known to exhibit antimicrobial, -fungal, -bacterial, -tuberculosis and -cancer activities.

MATERIALS AND METHODS
In the present study, we evaluated the in vitro cytotoxic activity of N,N'-bis(2-hydroxybenzyl)- (6), N,N'-bis(5-bromo-2-hydroxybenzyl)- (7) and N,N'-bis(5-chloro-2-hydroxybenzyl) (8)- ethylenediamine dihydrochlorides; and N,N'-bis(2-hydroxybenzyl)- (9), N,N'-bis(5-bromo-2-hydroxybenzyl)- (10) and N,N'-bis(5-chloro-2-hydroxybenzyl) (11)- ethylenediamine toward human lung (A549), breast (MDA-MB-231) and prostate (PC3) cancer cell lines after 24-h treatment using crystal violet dye binding assay. Effects on the cell cycle the using flow cytometry, and mitochondrial membrane potential using rhodamine-123 florescent dye were also evaluated.

RESULTS
Compounds 7 and 8 exhibit cytotoxic activity, causing cell arrest at different phases of the cell cycle and loss of mitochondrial membrane potential in the above cancer cell lines.

CONCLUSION
These findings clearly demonstrate, to our knowledge for the first time, that ethylenediamine dihydrochloride salts-compounds 7 and 8-exhibit concentration-dependent cytotoxic activity towards A549, MDA-MB-231 and PC3 cancer cell lines, which may serve as a basis for future work on novel therapeutic agents.

Musa|Musiliyu A|MA|
Badisa|Veera L D|VL|
Latinwo|Lekan M|LM|


Assessment of EVAR Competence: Validity of a Novel Rating Scale (EVARATE) in a Simulated Setting.

Abstract:
OBJECTIVES
The aims of this study were to investigate the validity evidence for a novel procedure specific assessment tool of competence in endovascular aortic repair (EVAR) and to establish a pass/fail level for the assessment.

METHODS
Computed tomography angiography data of a 55 mm in diameter infrarenal aortic aneurysm was implemented into an endovascular simulator. Twenty-three physicians with varying EVAR experiences were video-recorded when performing a standard EVAR procedure on the simulator. Two experienced EVAR operators assessed the participants using the novel rating scale, "EndoVascular Aortic Repair Assessment of Technical Expertise" (EVARATE). Validity was studied according to the framework endorsed by the American Educational Research Association.

RESULTS
The EVARATE scale had a high internal consistency (Cronbach's alpha = .90). The inter-rater reliability was acceptable (Intraclass Correlation Coefficient = .68, p = .005). Specific EVAR experience correlated significantly with the EVARATE score (Spearman's rho = .62, p = .002), but general endovascular experience did not. Consequence analysis showed that the EVARATE assessment could distinguish novices from intermediates (p < .01) and from experts (p < .001). A pass/fail score was determined using the contrasting groups' method.

CONCLUSION
This paper presents the initial validity evidence for a novel procedure specific assessment tool, EVARATE, for operator competence in endovascular aortic repair investigated in a simulated setting. The assessment tool can be used to provide structured formative feedback to trainees.

Strøm|Michael|M|
Lönn|Lars|L|
Konge|Lars|L|
Schroeder|Torben V|TV|
Lindgren|Hans|H|
Nyheim|Thomas|T|
Venermo|Maarit|M|
Bech|Bo|B|

D019917:Blood Vessel Prosthesis Implantation

EVAR
Simulation
Endovascular
Abdominal aortic aneurysm
Educational assessment
Training


Visual perspective and the characteristics of mind wandering.

Abstract: When the mind wanders away from the here-and-now toward imaginary events, it typically does so from one of two visual vantage points-a first-person perspective (i.e., the world is seen as it is in everyday life) or a third-person perspective (i.e., the world is seen from the viewpoint of an outside observer). While extant evidence has detailed consequences that ensue from the utilization of these distinct points of view, less is known about their more basic properties. Here, we investigated the prevalence, demographics and qualities associated with the visual perspective that people spontaneously adopt when the mind wanders. The results from a cross-cultural survey (N = 400) revealed that almost half of the participants (46%) typically utilize a third-person perspective when mind wandering. Further, culture and gender were shown to impact the distribution of first- and third-person imagers. Specifically, a first-person perspective was more common among participants from Western nations and females, while participants from Eastern cultures resonated more strongly with a third-person perspective. Moreover, these factors were also shown to impact qualities (e.g., temporal locus, vividness) of mental imagery. Taken together, the current findings elucidate the prevalence of first- and third-person visual perspectives and detail individual differences that influence the qualia of mind wandering.

Christian|Brittany M|BM|
Miles|Lynden K|LK|
Parkinson|Carolyn|C|
Macrae|C Neil|CN|

visual perspective
mind wandering
mental imagery
cross cultural
third person
vantage point


The Multi-Faced Role of PAPP-A in Post-Partum Breast Cancer: IGF-Signaling is Only the Beginning.

Abstract: Insulin-like growth factor (IGF) signaling and control of local bioavailability of free IGF by the IGF binding proteins (IGFBP) are important regulators of both mammary development and breast cancer. A recent genome-wide association study (GWAS) identified small nucleotide polymorphisms that reduce the expression of IGFBP-5 as a risk factor of developing breast cancer. This observation suggests that genetic alterations leading to a decreased level of IGFBP-5 may also contribute to breast cancer. In the current review, we focus on Pregnancy-Associated Plasma Protein A (PAPP-A), a protease involved in the degradation of IGFBP-5. PAPP-A is overexpressed in the majority of breast cancers but its role in cancer has only begun to be explored. More specifically, this review aims at highlighting the role of post-partum involution in the oncogenic function of PAPP-A. Notably, we summarize recent studies indicating that PAPP-A plays a role not only in the degradation of IGFBP-5 but also in the deposition of collagen and activation of the collagen receptor discoidin 2 (DDR2) during post-partum involution. Finally, considering the immunosuppressive microenvironment of post-partum involution, we also discuss the unexpected finding made in Ewing Sarcoma that PAPP-A plays a role in immune evasion. While the immunosuppressive role of PAPP-A in breast cancer remains to be determined, collectively these studies highlight the multifaced role of PAPP-A in cancer that extends well beyond its effect on IGF-signaling.

Jenkins|Edmund Charles|EC|
Brown|Samantha O|SO|
Germain|Doris|D|

D015972:Gene Expression Regulation, Neoplastic

D018975:Insulin-Like Growth Factor Binding Protein 5

Breast cancer
IGF
Involution
Collagen
Immune evasion
DDR
Pappalysin-1
Pregnancy


Parameter Identification of Fractional-Order Discrete Chaotic Systems.

Abstract: Research on fractional-order discrete chaotic systems has grown in recent years, and chaos synchronization of such systems is a new topic. To address the deficiencies of the extant chaos synchronization methods for fractional-order discrete chaotic systems, we proposed an improved particle swarm optimization algorithm for the parameter identification. Numerical simulations are carried out for the Hénon map, the Cat map, and their fractional-order form, as well as the fractional-order standard iterated map with hidden attractors. The problem of choosing the most appropriate sample size is discussed, and the parameter identification with noise interference is also considered. The experimental results demonstrate that the proposed algorithm has the best performance among the six existing algorithms and that it is effective even with random noise interference. In addition, using two samples offers the most efficient performance for the fractional-order discrete chaotic system, while the integer-order discrete chaotic system only needs one sample.

parameter identification
discrete chaotic system
particle swarm optimization
fractional difference


Downregulating circRNA_0044516 Inhibits Cell Proliferation in Gastric Cancer Through miR-149/Wnt1/β-catenin Pathway.

Abstract:
BACKGROUND
Circular RNAs (circRNAs) play important roles in the progression of gastric cancer (GC). The Wnt1/β-catenin pathway can promote the proliferation of GC cells. This study aimed to explore whether circRNA_0044516 can regulate the proliferation of GC cells by modulating the Wnt1/β-catenin pathway.

METHODS
The expression of circRNA_0044516, miR-149, Wnt1, and β-catenin in GC tissues or cells was detected by qRT-PCR and western blot. Cell viability and apoptosis were measured by CCK-8 and flow cytometry assays, respectively. The interaction between circRNA_0044516 and miR-149 was determined by luciferase reporter and RNA pull-down assays.

RESULTS
Upregulated circRNA_0044516 was found in GC tissues and cell lines. Downregulating circRNA_0044516 inhibited the viability and promoted apoptosis of GC cells. CircRNA_0044516 targeted miR-149, and its downregulation elevated miR-149 level in GC cells. Mechanistically, silencing circRNA_0044516 reduced the protein level of Wnt1 and β-catenin through miR-149, and finally suppressed viability and contributed to apoptosis of GC cells. Moreover, circRNA_0044516 knockdown inhibited the tumor growth of HGC-27 cells in nude mice.

CONCLUSIONS
Our results indicated an important role of circRNA_0044516 in GC and elucidated that downregulation of circRNA_0044516 inhibits the proliferation of GC cells through miR-149/Wnt1/β-catenin.


COVID-19 Associated Pneumonia: A review of chest radiograph and computed tomography findings.

Abstract: Medical imaging, including chest radiography and computed tomography, plays a major role in the diagnosis and follow-up of patients with COVID-19 associated pneumonia. This review aims to summarise current information on this topic based on the existing literature. A search of the Google Scholar (Google LLC, Mountain View, California, USA) and MEDLINE® (National Library of Medicine, Bethesda, Maryland, USA) databases was conducted for articles published until April 2020. A total of 30 articles involving 4,002 patients were identified. The most frequently reported imaging findings were bilateral ground glass and consolidative pulmonary opacities with a predominant lower lobe and peripheral subpleural distribution.

Al-Umairi|Rashid S|RS|
Al-Kalbani|Joukha|J|
Al-Tai|Saqar|S|
Al-Abri|Ahmed|A|
Al-Kindi|Faiza|F|
Kamona|Atheel|A|

COVID-19
Radiography
Diagnostic Imaging
Viral Pneumonia
X-Ray Computed Tomography


Predictive Factors Influencing Functional Results After Proximal Hamstring Tendon Avulsion Surgery: A Patient-Reported Outcome Study After 227 Operations From a Single Center.

Abstract:
Background
Although debilitating, proximal hamstring tendon avulsion injuries are rare and often overlooked or misdiagnosed. Consequently, delayed diagnosis and surgical treatment may result in poor outcomes. Studies investigating a correlation between postoperative functional outcomes and this delay in surgical treatment or other concomitant factors in large cohorts have not yet been performed to our knowledge.

Purpose/Hypothesis
The purpose of this study was to conduct an investigation in a large patient group regarding factors that could influence a patient's functional outcome after hamstring surgery. We hypothesized that this outcome would significantly correlate to the time between trauma and surgery.

Study Design
Case series; Level of evidence, 4.

Methods
Patients who received surgical treatment of proximal hamstring tendon avulsion injuries in our institution between the years 2010 and 2020 were asked to complete a validated, injury-specific outcome measurement, the Perth Hamstring Assessment Tool (PHAT; 0-100 points). In addition to calculating these outcomes, we evaluated the association of the obtained results with possible predictive factors such as age, sex, stump retraction shown on magnetic resonance imaging (MRI), and timing and duration of surgery.

Results
A total of 226 patients (227 operations) were eligible for the study, and 204 cases of hamstring tendon avulsion injury met our inclusion criteria. The return rate for the PHAT questionnaire was 85.3%. The mean PHAT score revealed good results (79.8 ± 19.1). Irrespective of concomitant factors, the scores of male patients were significantly higher compared with those of female patients (83.8 ± 16.9 vs 75.8 ± 20.6 respectively; P = .004). The mean time to surgery was 5.7 weeks after trauma, and more delayed surgery correlated significantly with lower PHAT scores (P = .003; r = -0.228). The mean degree of stump retraction on MRI (5 cm) did not significantly influence PHAT scores (P = .525; r = -0.06).

Conclusion
Delay of surgery and female sex were disadvantageous in terms of a good functional outcome measure (PHAT score) after hamstring tendon refixation surgery. By contrast, patient age as well as the retraction of the tendon stump on preoperative MRI did not influence PHAT scores in the present study.

Best|Raymond|R| Meister|Anorte|A| Meier|Malin|M| Huth|Jochen|J| Becker|Ulrich|U|

predictive factors
functional outcome
hamstring repair
proximal hamstring avulsion
time of surgery


Parallel chromatography and in situ scattering to interrogate competing protein aggregation pathways.

Abstract: Protein aggregation can follow different pathways, and these can result in different net aggregation rates and kinetic profiles. α-chymotypsinogen A (aCgn) was used as a model system to quantitatively and qualitatively assess an approach that combines ex situ size-exclusion chromatography (SEC) with in situ laser scattering (LS) to monitor aggregation vs. time. Aggregation was monitored for a series of temperatures and initial dimer (ID) levels for starting conditions that were primarily (> 97%) monomer, and under initial-rate conditions (limited to low monomer conversion-less than 20% monomer mass loss), as these conditions are of most to interest to many pharmaceutical and biotechnology applications. SEC results show that modest decreases of ID levels can greatly reduce monomer loss rates, but do not affect the effective activation energy for aggregation. The normalized aggregation rates determined from LS were typically ∼ 1 order of magnitude higher than the corresponding rates from SEC. Furthermore, LS signals vs. time became variable and highly nonlinear with decreasing ID level, temperature, and/or total protein concentration. Temperature-cycling LS experiments showed this corresponded to conditions where dimer/oligomer "seeding" was suppressed, and high levels of reversible oligomers ("prenuclei") were formed prior to "nucleation" and growth of stable aggregates. In those conditions, aggregation rates inferred from LS and SEC are greatly different, as the techniques monitor different stages of the aggregation process. Overall, the results illustrate an approach for interrogating non-native protein aggregation pathways, and potential pitfalls if one relies on a single method to monitor aggregation-this holds more generally than the particular methods here.

Gomes|Diana|D|
Kalman|Rebecca K|RK|
Pagels|Rebecca K|RK|
Rodrigues|Miguel A|MA|
Roberts|Christopher J|CJ|

D002850:Chromatography, Gel
D002919:Chymotrypsinogen
D002942:Circular Dichroism
D006863:Hydrogen-Ion Concentration
D007700:Kinetics
D008956:Models, Chemical
D066329:Protein Aggregates
D012542:Scattering, Radiation
D013696:Temperature

laser scattering
seeding
aggregation kinetics
folding intermediates
protein stability
self-association
size exclusion chromatography


Alteration in plasma free amino acid levels and its association with gout.

Abstract:
BACKGROUND
Studies on the association of plasma-free amino acids with gout are very limited and produced conflicting results. Therefore, we sought to explore and characterize the plasma-free amino acid (PFAA) profile in patients with gout and evaluate its association with the latter.

METHODS
Data from a total of 819 subjects (including 34 patients with gout) undergoing an annual health examination program in Shimane, Japan were considered for this study. Venous blood samples were collected from the subjects and concentrations of 19 plasma amino acids were determined by high-performance liquid chromatography-electrospray ionization-mass spectrometry. Student's t-test was applied for comparison of variables between patient and control groups. The relationships between the presence or absence of gout and individual amino acids were investigated by logistic regression analysis controlling for the effects of potential demographic confounders.

RESULTS
Among 19 amino acids, the levels of 10 amino acids (alanine, glycine, isoleucine, leucine, methionine, phenylalanine, proline, serine, tryptophan, valine) differed significantly (P < .001 to .05) between the patient and control groups. Univariate logistic regression analysis revealed that plasma levels of alanine, isoleucine, leucine, phenylalanine, tryptophan and valine had significant positive associations (P < .005 to .05) whereas glycine and serine had significant inverse association (P < .05) with gout.

CONCLUSIONS
The observed significant changes in PFAA profiles may have important implications for improving our understanding of pathophysiology, diagnosis and prevention of gout. The findings of this study need further confirmation in future large-scale studies involving a larger number of patients with gout.

D002851:Chromatography, High Pressure Liquid

D021241:Spectrometry, Mass, Electrospray Ionization

Plasma
Amino acids
Gout
Profile
Relationship


Tetherin antagonism by V proteins is a common trait among the genus Rubulavirus.

Abstract: Tetherin (BST-2/CD317/HM1.24) is an anti-viral factor that restricts the budding of several enveloped viruses. Most of these viruses have evolved to encode tetherin antagonists. Our previous study demonstrated that the growth of human parainfluenza virus type 2 (hPIV-2), a member of the genus Rubulavirus in the family Paramyxoviridae, was inhibited by tetherin, and its V protein decreases the amount of cell surface tetherin by the interaction. In the present study, we investigated whether tetherin inhibits the growth of other rubulaviruses including PIV-5, mumps virus (MuV), simian virus 41, and hPIV-4, and whether their V proteins act as tetherin antagonists. Plaque assay demonstrated that the growth of PIV-5 and MuV was inhibited by tetherin. Flow cytometry and immunoblot analyses revealed that the infection of PIV-5 and MuV caused reduction of cell surface tetherin without affecting total amount of tetherin. Immunoprecipitation analysis showed that all V proteins of rubulaviruses tested bound to tetherin. These results suggest that tetherin antagonism by V proteins is common among the genus Rubulavirus.

D000818:Animals
D015703:Antigens, CD
D019556:COS Cells
D002522:Chlorocebus aethiops
D005434:Flow Cytometry
D058851:GPI-Linked Proteins
D054884:Host-Pathogen Interactions
D006801:Humans
D057131:Immune Evasion
D015151:Immunoblotting
D047468:Immunoprecipitation
D050505:Mutant Proteins
D011485:Protein Binding
D019213:Rubulavirus
D014709:Vero Cells
D010948:Viral Plaque Assay
D014764:Viral Proteins

Tetherin
V protein
Rubulavirus
Paramyxovirus


Faecal shedding of pathogenic Yersinia enterocolitica determined by qPCR for yst virulence gene is associated with reduced live weight but not diarrhoea in prime lambs.

Abstract: Associations between faecal shedding of pathogenic Yersinia enterocolitica (based on the yst virulence gene) with growth, carcass weight and diarrhoea were investigated using an observational longitudinal study of 1200 crossbred prime (meat) lambs on eight Australian farms. Live weight, breech faecal soiling score (scale 1-5) and faecal consistency score (FCS; scale 1-5) were recorded, and faecal samples collected from each lamb on three sampling occasions; weaning (≈12 weeks of age), post-weaning (≈19 weeks) and pre-slaughter (≈29 weeks). Hot standard carcass weight was measured at slaughter. Faecal samples were screened for presence and concentration of pathogenic Y. enterocolitica using quantitative PCR. Associations of pathogenic Y. enterocolitica detection and shedding intensity with lamb health and production were assessed using general linear models (carcass weight), linear mixed effects models (live weight, FCS and breech soiling score) and non-parametric tests (FCS and breech soiling score). Prevalence for non-pelleted faeces (FCS ≥ 3.0) and diarrhoea (FCS ≥ 4.0) were compared with the two-tailed z-test, odds ratios and relative risk. Lambs shedding pathogenic Y. enterocolitica were 3.78 kg lighter post-weaning (P < 0.001) and 2.61 kg lighter pre-slaughter (P = 0.035) compared to lambs in which pathogenic Y. enterocolitica was not detected. Higher faecal concentration of pathogenic Y. enterocolitica was associated with lower live weight (P < 0.001). There was no association between pathogenic Y. enterocolitica detection and carcass weight. Overall, there was no evidence of association between pathogenic Y. enterocolitica detection and diarrhoea (higher FCS, higher risk for non-pelleted faeces or diarrhoea, or higher breech soiling score). Only one flock had increased relative risk for non-pelleted faeces associated with pathogenic Y. enterocolitica detection, and one other flock had increased relative risk for diarrhoea associated with pathogenic Y. enterocolitica detection. This is the first report of an association between reduced sheep live weight and pathogenic Y. enterocolitica based on the presence of the yst gene for heat stable enterotoxin determined by qPCR in sheep. Notably, impacts on live weight were observed in the absence of diarrhoea.

Jacobson|Caroline|C|
Yang|Rongchang|R|
Williams|Andrew|A|
Gardner|Graham E|GE|
Carmichael|Ian|I|
Campbell|Angus J D|AJD|
Ryan|Una|U|

Diarrhoea
Carcass
Productivity
Sheep
Carcase
Ill thrift
Yersiniosis


Association of vitamin D receptor gene polymorphisms with breast cancer risk in an Egyptian population.

Abstract: This study aimed to explore whether genetic polymorphisms in vitamin D receptor are correlated to the breast cancer prevalence in an Egyptian population. Polymerase chain reaction-restriction fragment polymorphism was used to genotype three frequently analyzed vitamin D receptor gene single-nucleotide polymorphisms (rs1544410, rs7975232, and rs731236) and were identified by sequencing analysis. This is the first study that recorded a new single-nucleotide polymorphism in ApaI genotype within an Egyptian population and was registered with the accession number KY859868. The authors found that TC in rs731236, and TG in KY859868 single-nucleotide polymorphism showed significant distribution differences with an increased risk of breast cancer ( p < 0.05, odds ratio = 3.71, 95% confidence interval: 1.04-13.28 and p < 0.001, odds ratio = 7.05, 95% confidence interval: 2.02-24, respectively) compared with the wild-type TT genotype carriers in both single-nucleotide polymorphisms. In addition, the distribution frequencies of haplotypes ACT, GTT, and ATT in the patients group were significant, where ATT haplotype was associated with the highest breast cancer risk among all other haplotypes in the patients group ( p = 0.0023, odds ratio = 1.72, 95% confidence interval: 1.24-2.437). In conclusion, vitamin D receptors ApaI and TaqI confer high breast cancer susceptibility, particularly in Egyptians females carrying haplotype ATT. However, further studies focusing on the vitamin D receptor variants and haplotypes effects on vitamin D and vitamin D receptor concentrations, activities, and functionalities are needed.

El-Shorbagy|Haidan M|HM|
Mahmoud|Nada H|NH|
Sabet|Salwa|S|

D020022:Genetic Predisposition to Disease

Vitamin D receptor
breast cancer
ApaI
TaqI
BsmI


The Mental Health Parity and Addiction Equity Act evaluation study: Impact on specialty behavioral health utilization and expenditures among "carve-out" enrollees.

Abstract: Interrupted time series with and without controls was used to evaluate whether the federal Mental Health Parity and Addiction Equity Act (MHPAEA) and its Interim Final Rule increased the probability of specialty behavioral health treatment and levels of utilization and expenditures among patients receiving treatment. Linked insurance claims, eligibility, plan and employer data from 2008 to 2013 were used to estimate segmented regression analyses, allowing for level and slope changes during the transition (2010) and post-MHPAEA (2011-2013) periods. The sample included 1,812,541 individuals ages 27-64 (49,968,367 person-months) in 10,010 Optum "carve-out" plans. Two-part regression models with Generalized Estimating Equations were used to estimate expenditures by payer and outpatient, intermediate and inpatient service use. We found little evidence that MHPAEA increased utilization significantly, but somewhat more robust evidence that costs shifted from patients to plans. Thus the primary impact of MHPAEA among carve-out enrollees may have been a reduction in patient financial burden.

Ettner|Susan L|SL|
M Harwood|Jessica|J|
Thalmayer|Amber|A|
Ong|Michael K|MK|
Xu|Haiyong|H|
Bresolin|Michael J|MJ|
Wells|Kenneth B|KB|
Tseng|Chi-Hong|CH|
Azocar|Francisca|F|

Parity
Behavioral health
Utilization
Expenditures
Insurance benefits


Delayed bipolar and ganglion cells neuroretinal processing in regular cannabis users: The retina as a relevant site to investigate brain synaptic transmission dysfunctions.

Abstract: Cannabis use is widespread worldwide, but the impact of smoking cannabis regularly on brain synaptic transmission has only been partially elucidated. The retina is considered as an easy means of determining dysfunction in brain synaptic transmission. The endocannabinoid system is involved in regulating retinal synaptic transmission, which might also be affected by tobacco. Previous preliminary results have shown impairments in retinal ganglion cell response in cannabis users. Here, we test the extent to which earlier retinal levels-bipolar cells and photoreceptors-are affected in cannabis users, i.e. by the association of tobacco and cannabis. We recorded pattern (PERG) and flash (fERG) ERG in 53 regular cannabis users and 29 healthy controls. Amplitude and peak time of P50 and N95 (PERG) and of a- and b-waves (fERG) were evaluated. Cannabis users showed a significant increase in PERG N95 peak time and in fERG light-adapted 3.0 b-wave peak time, compared with controls (p = 0.0001 and p = 0.002, respectively; Mann-Whitney U test). No significant difference was found between the groups in terms of wave amplitude (p = 0.525 and p = 0.767 for the N95 and light-adapted 3.0 b-wave amplitude respectively; Mann-Whitney U test). The results demonstrated delayed ganglion and bipolar cell responses in cannabis users. These results reflect a delay in the transmission of visual information from the retina to the brain. This retinal dysfunction may be explained by an effect of cannabis use on retinal synaptic transmission. Main limitations of these results concern tobacco and alcohol use that differed between groups. The consequences of these anomalies on visual perception along with the molecular mechanisms underlying this retinal dysfunction should be explored in future human and animal studies.

Schwitzer|Thomas|T| Schwan|Raymund|R| Angioi-Duprez|Karine|K| Giersch|Anne|A| Lalanne|Laurence|L| Albuisson|Eliane|E| Laprevote|Vincent|V|

Cannabis
Retina
Synaptic transmission
Endocannabinoid system
Electroretinogram
Retinal information processing


The development of an RDoC-based treatment program for adolescent depression: "Training for Awareness, Resilience, and Action" (TARA).

Abstract: Major depressive disorder (MDD) is one of the current leading causes of disability worldwide. Adolescence is a vulnerable period for the onset of depression, with MDD affecting 8-20% of all youth. Traditional treatment methods have not been sufficiently effective to slow the increasing prevalence of adolescent depression. We therefore propose a new model for the treatment of adolescent depression - Training for Awareness, Resilience, and Action (TARA) - that is based on current understanding of developmental and depression neurobiology. The TARA model is aligned with the Research Domain Criteria (RDoC) of the National Institute of Mental Health. In this article, we first address the relevance of RDoC to adolescent depression. Second, we identify the major RDoC domains of function involved in adolescent depression and organize them in a way that gives priority to domains thought to be driving the psychopathology. Third, we select therapeutic training strategies for TARA based on current scientific evidence of efficacy for the prioritized domains of function in a manner that maximizes time, resources, and feasibility. The TARA model takes into consideration the developmental limitation in top-down cognitive control in adolescence and promotes bottom-up strategies such as vagal afference to decrease limbic hyperactivation and its secondary effects. The program has been informed by mindfulness-based therapy and yoga, as well as modern psychotherapeutic techniques. The treatment program is semi-manualized, progressive, and applied in a module-based approach designed for a group setting that is to be conducted one session per week for 12 weeks. We hope that this work may form the basis for a novel and more effective treatment strategy for adolescent depression, as well as broaden the discussion on how to address this challenge.

Henje Blom|Eva|E|
Duncan|Larissa G|LG|
Ho|Tiffany C|TC|
Connolly|Colm G|CG|
LeWinn|Kaja Z|KZ|
Chesney|Margaret|M|
Hecht|Frederick M|FM|
Yang|Tony T|TT|

adolescent depression
RDoC
attention training
emotion regulation
mindfulness
treatment development
yoga-based movement


The Relationship Between Smoking and Delayed Cerebral Ischemia After Intracranial Aneurysm Rupture: A Systematic Review and Meta-Analysis.

Abstract: Background: Delayed cerebral ischemia (DCI) is the main cause of death and disability after intracranial aneurysm rupture. Previous studies have shown that smoking can lead to DCI after intracranial aneurysm rupture. However, some recent studies have shown that nicotine, as the main ingredient of tobacco, can cause cerebral vasodilation. This view has led to a debate about the relationship between smoking and DCI. This study aims to determine the relationship between smoking and DCI. Methods: A systematic literature search was performed according to PRISMA guidelines. The Cochrane Library, Web of Science, PubMed, and Embase online databases were searched for studies published up to September 2020. All studies related to smoking and DCI were included in the analysis. The R and RevMan software were used for data analysis, and random or fixed model analysis was selected depending on the degree of heterogeneity. Publication bias was examined by using the Begg-Mazumdar test and using contour-enhanced funnel plots with trim method. Results: A total of eight original articles (12 cohorts) with 10,722 patients were included in this meta-analysis. There were statistically significant higher rates of DCI in the smoking group than in the non-smoking group (RRtotal = 1.16, 95%CI: 1.05-1.27). After heterogeneity among cohorts was removed by sensitivity analysis, there was still a statistically significant difference in the incidence of DCI between the smoking and non-smoking groups (RRtotal = 1.13, 95%CI: 1.07-1.20). Conclusions: Although the effects of nicotine as the main component of tobacco are unclear in terms of cerebral vessels, the present study suggests that smoking is a risk factor for DCI in patients with ruptured aneurysm.

Ya|Xiaolong|X| Zhang|Chaoqi|C| Zhang|Shuo|S| Zhang|Qian|Q| Cao|Yong|Y| Wang|Shuo|S| Zhao|Jizong|J|

smoking
delayed cerebral ischemia
intracranial aneurysm
rupture
meta-analysis


Phenotype-Based Screening of Synthetic Cannabinoids in a Dravet Syndrome Zebrafish Model.

Abstract: Dravet syndrome is a catastrophic epilepsy of childhood, characterized by cognitive impairment, severe seizures, and increased risk for sudden unexplained death in epilepsy (SUDEP). Although refractory to conventional antiepileptic drugs, emerging preclinical and clinical evidence suggests that modulation of the endocannabinoid system could be therapeutic in these patients. Preclinical research on this topic is limited as cannabis, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are designated by United States Drug Enforcement Agency (DEA) as illegal substances. In this study, we used a validated zebrafish model of Dravet syndrome, scn1lab homozygous mutants, to screen for anti-seizure activity in a commercially available library containing 370 synthetic cannabinoid (SC) compounds. SCs are intended for experimental use and not restricted by DEA designations. Primary phenotype-based screening was performed using a locomotion-based assay in 96-well plates, and a secondary local field potential recording assay was then used to confirm suppression of electrographic epileptiform events. Identified SCs with anti-seizure activity, in both assays, included five SCs structurally classified as indole-based cannabinoids JWH 018 N-(5-chloropentyl) analog, JWH 018 N-(2-methylbutyl) isomer, 5-fluoro PB-22 5-hydroxyisoquinoline isomer, 5-fluoro ADBICA, and AB-FUBINACA 3-fluorobenzyl isomer. Our approach demonstrates that two-stage phenotype-based screening in a zebrafish model of Dravet syndrome successfully identifies SCs with anti-seizure activity.

Griffin|Aliesha|A|
Anvar|Mana|M|
Hamling|Kyla|K|
Baraban|Scott C|SC|

screen cannabinoid zebrafish epilepsy seizure locomotion


Heparin micropatterning onto fouling-release perfluoropolyether-based polymers via photobiotin activation.

Abstract: A simple method for constructing versatile ordered biotin/avidin arrays on UV-curable perfluoropolyethers (PFPEs) is presented. The goal is the realization of a versatile platform where any biotinylated biological ligands can be further linked to the underlying biotin/avidin array. To this end, microcontact arrayer and microcontact printing technologies were developed for photobiotin direct printing on PFPEs. As attested by fluorescence images, we demonstrate that this photoactive form of biotin is capable of grafting onto PFPEs surfaces during irradiation. Bioaffinity conjugation of the biotin/avidin system was subsequently exploited for further self-assembly avidin family proteins onto photobiotin arrays. The excellent fouling release PFPEs surface properties enable performing avidin assembly step simply by arrays incubation without PFPEs surface passivation or chemical modification to avoid unspecific biomolecule adsorption. Finally, as a proof of principle biotinylated heparin was successfully grafted onto photobiotin/avidin arrays.

Credi|Caterina|C|
De Marco|Carmela|C|
Molena|Elena|E|
Pla Roca|Mateu|M|
Samitier Martí|Josep|J|
Marques|Joana|J|
Fernàndez-Busquets|Xavier|X|
Levi|Marinella|M|
Turri|Stefano|S|

Heparin
Micropatterning
Polymers
Photobiotin
Perfluoropolyether
Microcontact arrayer
Microcontact printing
Antifouling
Malaria
Soft lithography


Expression of HLA-DQA1 and HLA-DQB1 genes in B lymphocytes, monocytes and whole blood.

Abstract: Differential expression of HLA-DQA1 and HLA-DQB1 gene alleles was analysed in three different cell populations isolated from peripheral blood-B lymphocytes, monocytes and whole-blood cells. Interallelic differences in mRNA levels were observed: DQA1*03 alleles were among the most expressed in all cell types, whereas DQA1*05 alleles were least expressed in whole blood and monocytes and among the most expressed in B cells. For DQB1 gene, DQB1*06 group of alleles were the most expressed, and DQB1*02 group the least expressed within all cell populations examined. In comparison with the rest alleles, DQB1*06 and DQB1*05:02 alleles have higher expression in monocytes than in B cells, professional antigen-presenting cells. Cell type-specific regulation of expression was observed as well, with higher and more balanced expression of alleles in B lymphocytes compared to monocytes.

HLA-DQA1
HLA-DQB1
HLA class II
antigen presentation
gene expression
genetic polymorphism


Attracting doctors to rural areas: a case study of the post-graduate seat reservation scheme in andhra pradesh.

Abstract:
BACKGROUND
Attracting doctors to rural posts is an ongoing challenge for health departments across different states in India. One strategy adopted by several states to make rural service attractive for medical graduates is to reserve post-graduate (PG) seats in medical colleges for doctors serving in the public sector.

OBJECTIVE
This study examines the PG reservation scheme in Andhra Pradesh to understand its role in improving rural recruitment of doctors and specialists, the challenges faced by the scheme and how it can be strengthened.

MATERIALS AND METHODS
Qualitative case study methodology was adopted in which a variety of stakeholders such as government officials, health systems managers and serving Medical Officers were interviewed. This was supplemented with quantitative data on the scheme obtained from the Health, Medical and Family Welfare Department in Andhra Pradesh.

RESULTS
The PG reservation scheme appears to have been one of the factors responsible in attracting doctors to the public sector and to rural posts, with a reduction in vacancies at both the Primary Health Centre and Community Health Centre levels. Expectedly, in-service candidates have a better chance of getting a PG seat than general candidates. However, problems such as the mismatch of the demand and supply of certain types of specialist doctors, poor academic performance of in-service candidates as well as quality of services and enforcement of the post-PG bond need to be resolved.

CONCLUSION
The PG reservation scheme is a powerful incentive to attract doctors to rural areas. However, better monitoring of service quality, strategically aligning PG training through the scheme with the demand for specialists as well as stricter enforcement of the financial bond are required to improve the scheme's effectiveness.

Shroff|Zubin C|ZC|
Murthy|Seema|S|
Rao|Krishna D|KD|

post-graduate
Andhra Pradesh
rural service
bond
medical education


Association between home availability and vegetable consumption in youth: a review.

Abstract:
OBJECTIVE
To systematically review literature examining the association between vegetable home availability and vegetable intake in youth.

DESIGN
Articles were identified through December 2012 using a search of PubMed, PsychINFO and OVID/Medline databases, using the following keywords in varying combinations: home, environment, availability, vegetable, intake, consumption, children. Quantitative studies examining home vegetable availability and vegetable intake in children and adolescents were included. Fifteen studies were included that met inclusion criteria.

SETTING
Studies were conducted in the USA (n 8), Australia (n 1), Greece (n 1), Iceland (n 1), Denmark (n 1), the UK (n 1), the Netherlands (n 1) and a combination of nine European countries (n 1).

SUBJECTS
Various populations of children and adolescents were examined.

RESULTS
Seven of the studies (47 %) found a positive association between vegetable availability and intake, with the others reporting null findings. There were no clear patterns of association by study design, age of subjects included, comprehensiveness of measures, or inclusion of covariates in analyses. Child report of home availability was associated with child vegetable intake (n 6, all found a positive association), while parent report of home availability was only minimally associated (n 9, one found a positive association; P=0.001 from post hoc Fisher's exact test comparing parent v. child report).

CONCLUSIONS
Parent perception of availability may be closer to truth, given the parental role in food shopping and preparation. Therefore, to impact child vegetable intake, absolute availability may not be as important as child perception of vegetables in the home. Child perception of availability may be altered by level of familiarity with vegetables.

Cook|Lauren T|LT|
O'Reilly|Gillian A|GA|
DeRosa|Christine J|CJ|
Rohrbach|Louise Ann|LA|
Spruijt-Metz|Donna|D|


Program evaluation of Sea Mar's Chronic Care Program for Latino and Caucasian patients with type 2 diabetes: providers and staff perspectives.

Abstract:
PROBLEM STATEMENT
Unprecedented consumption of health care resources in the USA coupled with increasing rates of chronic disease has fueled pursuit of improved models of health care delivery. The Chronic Care Model provides an organizational framework for chronic care management and practice improvement. Sea Mar, a community health care organization in Washington state, implemented the Chronic Care Model, but has not evaluated the outcomes related to provider and staff satisfaction. The specific aim of this project was to evaluate the effectiveness of the Chronic Care Model with the addition of the Chronic Care Coordinator role.

APPROACH
A descriptive method was used, which incorporated quantitative, and qualitative data from providers and clinic staff collected through a Web-based survey consisting of Likert-type questions sent via an electronic link.

RESULTS
This evaluation identified the strengths of and barriers to the chronic care model with a focus on provider and staff satisfaction regarding patient care since the addition of the Chronic Care Coordinator role. We found a high appreciation (94%) and acceptance of the role; 80% agreed that the Chronic Care Coordinator was well-integrated into clinic operations. Major strengths of the program included more patient education, better follow-up, and improved team communications. Barriers to success included limited provider access, confusion regarding role expectations of the Chronic Care Coordinator, inconsistent communications, and Chronic Care Coordinator turnover.

CONCLUSIONS/RECOMMENDATIONS
Our findings help to validate the importance of community health organizations such as Sea Mar, the utility of the chronic care model, and the potential value for specific roles such as the Chronic Care Coordinator to positively impact quality of care by helping to empower patients to improve self-management and ultimately impact patient outcomes. However, future studies involving larger samples are needed to further explore themes among staff and patients.

Bond|Gail E|GE|
Rechholtz|Laurie|L|
Bosa|Christina|C|
Impert|Celine|C|
Barker|Sara|S|

program evaluation
type 2 diabetes
chronic care model
Care Coordinator
case manager


Potential targets to reduce beryllium toxicity in plants: A review.

Abstract: Industrialization and inevitable mining has resulted in the release of some metals in environments, which have numerous industrial roles on one hand and also showed environmental toxicity on other hand. Beryllium is one of them, it has been used in number of industries however its excess use or inappropriate disposal of beryllium resulted in high beryllium accumulation in soil and ground water. This subsequently is affecting our environment and more potentially arable crop production. Beryllium has been extensively studied in humans and reported as toxic metal. In plants, only few studies have been documented toxic effects of beryllium in plants. Moreover, plant products (fruits, grains or other plant parts) could be major source of beryllium toxicity in our food chain therefore it is more imperative to understand how plant can be developed more tolerant to beryllium toxicity. In this short mini-review article, we primarily highlighted and speculated different beryllium uptake, translocation and beryllium storage mechanism in plants. This article provides considerable information for people who are working in identifying and developing heavy metal hyper accumulators plants.

Beryllium
Environmental pollution
Ion transport
Phytoremediation
Symplast


The E1B19K-deleted oncolytic adenovirus mutant AdΔ19K sensitizes pancreatic cancer cells to drug-induced DNA-damage by down-regulating Claspin and Mre11.

Abstract: Adenovirus-mediated sensitization of cancer cells to cytotoxic drugs depends on simultaneous interactions of early viral genes with cell death and survival pathways. It is unclear what cellular factors mediate these interactions in the presence of DNA-damaging drugs. We found that adenovirus prevents Chk1-mediated checkpoint activation through inactivation of Mre11 and downregulation of the pChk1 adaptor-protein, Claspin, in cells with high levels of DNA-damage induced by the cytotoxic drugs gemcitabine and irinotecan. The mechanisms for Claspin downregulation involve decreased transcription and increased degradation, further attenuating pChk1-mediated signalling. Live cell imaging demonstrated that low doses of gemcitabine caused multiple mitotic aberrations including multipolar spindles, micro- and multi-nucleation and cytokinesis failure. A mutant virus with the anti-apoptotic E1B19K-gene deleted (AdΔ19K) further enhanced cell killing, Claspin downregulation, and potentiated drug-induced DNA damage and mitotic aberrations. Decreased Claspin expression and inactivation of Mre11 contributed to the enhanced cell killing in combination with DNA-damaging drugs. These results reveal novel mechanisms that are utilised by adenovirus to ensure completion of its life cycle in the presence of cellular DNA damage. Taken together, our findings reveal novel cellular targets that may be exploited when developing improved anti-cancer therapeutics.

Pantelidou|Constantia|C|
Cherubini|Gioia|G|
Lemoine|Nick R|NR|
Halldén|Gunnel|G|

D048868:Adaptor Proteins, Signal Transducing

pancreatic cancer
cytotoxic drugs
mitotic aberrations
apoptosis
checkpoint-inactivation


Relative efficiency of Gafchromic EBT3 and MD-V3 films exposed to low-energy photons and its influence on the energy dependence.

Abstract: Energy-dependence of Gafchromic films exposed to low-energy photons has been reported to be a function of absorbed-dose. However, these studies are based on a relative-response, R, which considers the absorbed-dose in water and not within the film sensitive-volume. This work investigated the relative-efficiency, REfilm, (ratio of absorbed-dose required to produce the same net optical density (netOD) by 60Co gamma and by x-ray) of Gafchromic EBT3 and MD-V3 films exposed to five x-ray beams from 20 kV to 160 kV and 60Co gamma rays. A factor that accounts for the energy-dependence, fx,Q,med, based on REfilm, phantom-material and depth at which the films are placed during irradiation was used to remove the influence of absorbed dose. Values of REfilm indicated that the absorbed dose from 60Co gamma rays needs to be 4 and 3 times larger than those from 20 kV x-rays to produce the same netOD within the EBT3 and MD-V3 sensitive volumes, respectively. Thus, saturation could help explain why Gafchromic films show under-response to very low doses from low-energy photon beams, regardless of film model. Furthermore, REfilm, was found to be nearly independent of netOD and colour-channels. Consequently, fx,Q,med is independent of the absorbed dose and colour-channels. In contrast, besides the variation with the photon energy, fx,Q,med varied with film model, depth and phantom material used during the irradiation. Thus, the results suggest that fx,Q,med is a more reliable wide-ranging parameter for evaluating the degree of energy-dependence of the film rather than the relative-response method commonly considered.

D003037:Cobalt Radioisotopes
D005373:Film Dosimetry
D009010:Monte Carlo Method
D019047:Phantoms, Imaging
D017785:Photons
D014965:X-Rays

Relative efficiency
EBT3
MD-V3
Energy-dependence
Phantom material
(60)Co-gamma
Gafchromic-films
Intrinsic energy dependence
Ionisation-density
Low-energy-X-rays
Monte-Carlo
Relative response
Track-average LET


Trichloroethylene-mediated cytotoxicity in human epidermal keratinocytes is mediated by the rapid accumulation of intracellular calcium: Interception by naringenin.

Abstract: Industrial solvents pose a significant threat to the humankind. The mechanisms of their toxicity still remain in debate. Trichloroethylene (TCE) is a widespread industrial solvent responsible for severe liver dysfunction, cutaneous toxicity in occupationally exposed humans. We utilized an in vitro system of human epidermal keratinocyte (HaCaT) cells in this study to avoid complex cell and extracellular interactions. We report the cytotoxicity of organic solvent TCE in HaCaT and its reversal by a natural flavanone, naringenin (Nar). The cytotoxicity was attributed to the rapid intracellular free calcium (Ca(2+)) release, which might lead to the elevation of protein kinase C along with robust free radical generation, instability due to energy depletion, and sensitization of intracellular stress signal transducer nuclear factor κB. These effects were actually seen to induce significant amount of genomic DNA fragmentation. Furthermore, all these effects of TCE were effectively reversed by the treatment of Nar, a natural flavanone. Our studies identify intracellular Ca as a unique target used by organic solvents in the cytotoxicity and highlight the Ca(2+) ion stabilizer properties of Nar.

Ali|F|F|
Khan|A Q|AQ|
Khan|R|R|
Sultana|S|S|

naringenin
TCE
COX-2
NF-κB
PKC
calcium ions


Diagnostic performance of volume and limited oblique MRI of the anterior cruciate ligament compared to knee arthroscopy.

Abstract:
BACKGROUND
Many strategies have been used to improve the visualisation of the ACL including sagittal, coronal oblique sequences, and 3D volume imaging. Nevertheless, the ACL may not always be visualised.

METHODS
Two hundred and thirty-one consecutive patients (77 females; 154 males; average age 43.5, range 18 to 82 years; 205 with chronic, 20 acute, and 6 acute on chronic symptoms) underwent knee arthroscopy for mechanical symptoms within a week of MRI. After routine orthogonal sequences, if general MRI radiographers, with over four years experience, were not able to identify the presence of the ACL, then two 3D volume sequences and 2D limited sagittal oblique T1 sequences were performed. Patients requiring extra sequences, missed by the radiography technicians, were recalled. The MRI sequences were evaluated in a blinded fashion by three radiologists, and compared to the knee arthroscopy findings, with the normal ACL acting as internal controls. The radiography technicians performed additional ACL sequences in 63 patients (27%); of these, 10 patients had a partial and 12 patients had a complete ACL tear. Only 2 patients (0.6%) were recalled (one with a normal, and one with a full thickness ACL tear).

RESULTS
The filmed ACL evaluation for complete tears and a normal ACL had a sensitivity of 100%, specificity of 97.1% and accuracy of 97.3%, slightly higher than evaluating on the monitor. Volume sequences had specificities and accuracies over 95%, with good intraobserver reliability (Kappa 0.859, 95% CI 0.705-1.0). Experienced radiographers identified most cases requiring supplementary MRI ACL sequences. An additional volume sequence was beneficial when filmed. Use of the monitor can offer some benefits. Limited oblique T1 sequence of the intercondylar notch was unreliable.

Richards|Paula J|PJ|
McCall|Iain|I|
Kraus|Alexandra|A|
Jones|Mary|M|
Maffulli|Gayle|G|
Bridgman|Stephen|S|
Maffulli|Nicola|N|

MRI
anterior cruciate ligament
knee arthroscopy
volume sequences
ACL MRI


Estimated glomerular filtration rate changes in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors.

Abstract:
BACKGROUND
Chronic use of tyrosine kinase inhibitors (TKIs) may lead to previously unrecognized adverse events. This study evaluated the incidence of acute kidney injury (AKI) and chronic kidney disease (CKD) in chronic-phase (CP) chronic myeloid leukemia (CML) patients treated with imatinib, dasatinib, and nilotinib.

METHODS
Four hundred sixty-eight newly diagnosed CP CML patients treated with TKIs were analyzed. The molecular and cytogenetic response data, creatinine, and glomerular filtration rate (GFR) were followed from the start of therapy to the last follow-up (median, 52 months). GFR was estimated with the Modification of Diet in Renal Disease equation.

RESULTS
Nineteen patients (4%) had TKI-associated AKI. Imatinib was associated with a higher incidence of AKI in comparison with dasatinib and nilotinib (P = .014). Fifty-eight patients (14%) developed CKD while they were receiving a TKI; 49 of these patients (84%) did so while they were being treated with imatinib (P < .001). Besides imatinib, age, a history of hypertension, and diabetes mellitus were also associated with the development of CKD. In patients with no CKD at the baseline, imatinib was shown to reduce GFR over time. Interestingly, imatinib did not cause a significant decline in the GFRs of patients with a history of CKD. Imatinib, dasatinib, and nilotinib increased the mean GFR after 3 months of treatment, and nilotinib led with the most significant increase (P < .001). AKI or CKD had no significant impact on overall cytogenetic and molecular response rates or survival.

CONCLUSIONS
The administration of TKIs may be safe in the setting of CKD in CP CML patients, but close monitoring is still warranted.

Yilmaz|Musa|M|
Lahoti|Amit|A|
O'Brien|Susan|S|
Nogueras-González|Graciela M|GM|
Burger|Jan|J|
Ferrajoli|Alessandra|A|
Borthakur|Gautam|G|
Ravandi|Farhad|F|
Pierce|Sherry|S|
Jabbour|Elias|E|
Kantarjian|Hagop|H|
Cortes|Jorge E|JE|

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

glomerular filtration rate changes
tyrosine kinase inhibitor
kidney injury
chronic myeloid leukemia (CML)
imatinib
dasatinib
nilotinib
outcome


Developing reliable measures of the passive torque-angle relationship for shoulder internal and external rotation: Implications for overhead athletics.

Abstract:
OBJECTIVES
1) Thoroughly assess shoulder flexibility by establishing the passive torque-angle relationship for internal and external rotation with the arm in an overhead athletics position (abducted 90°) and 2) test the reliability of four passive torque-angle measures.

DESIGN
Reliability study.

SETTING
Data were collected in a university biomechanics laboratory.

PARTICIPANTS
Bilateral shoulder flexibility of 15 male college students (20.7 ± 1.1 y) was evaluated twice in two sessions over 7-10 days.

MAIN OUTCOME MEASURES
For both ER and IR, reliability was assessed bilaterally (intra-session, inter-session, and inter-tester) for the traditional range of motion measure and three novel kinetic measures: torque at end ROM, resistance onset angle, rotational stiffness. This resulted in 48 total assessments.

RESULTS
Thirty-four assessments had good to excellent reliability (ICC ≥ 0.8), 10 had fair reliability (0.7 ≤ ICC < 0.8), and 4 had poor reliability (ICC< 0.7). Three of the four flexibility measures had a good overall ICC score: ROM (0.83), torque at end ROM (0.84), and resistance onset angle (0.81). The fourth, stiffness, had a fair overall reliability score (0.74).

CONCLUSIONS
The passive torque-angle measures should be assimilated into clinical and research settings to determine the relevance to injury, rehabilitation, and performance.

Wight|Jeff T|JT|
Grover|Guy B|GB|
Chow|John W|JW|
Borsa|Paul A|PA|
Wikstrom|Erik A|EA|
Tillman|Mark D|MD|

Shoulder
External rotation
Flexibility
Internal rotation


Relevance of Imaging Examinations in the Surgical Planning of Patients with Bowel Endometriosis.

Abstract: Endometriosis is a benign gynecologic disease characterized by the presence of endometrial tissue outside the uterine cavity. The complexity of the disease results from its multiple clinical presentations, the multifocal pattern of distribution of the lesions, the presence of extra pelvic sites of the disease (mainly affecting the urinary and the intestinal tracts), and the difficulty in the preoperative diagnosis (by means of imaging studies) and in the surgical treatment. The preoperative mapping of the lesions, either by ultrasound or by magnetic resonance imaging, allows for an adequate surgical planning and a better preoperative patient counseling, especially in those women with deep infiltrating endometriosis affecting the bowel. Also, the choice of the surgical team that is going to perform the procedure may be based on the preoperative workup. In this paper, we highlight the important findings that should be described in the imaging examination reports for the preoperative workup of patients with deep infiltrating endometriosis of the intestine.

Trippia|Carlos H|CH|
Zomer|Monica T|MT|
Terazaki|Carlos R T|CR|
Martin|Rafael L S|RL|
Ribeiro|Reitan|R|
Kondo|William|W|

bowel
ultrasound
magnetic resonance imaging
deep infiltrating endometriosis
laparoscopy


Characterizing the culturable surface microbiomes of diverse marine animals.

Abstract: Biofilm-forming bacteria have the potential to contribute to the health, physiology, behavior and ecology of the host and serve as its first line of defense against adverse conditions in the environment. While metabarcoding and metagenomic information furthers our understanding of microbiome composition, fewer studies use cultured samples to study the diverse interactions among the host and its microbiome, as cultured representatives are often lacking. This study examines the surface microbiomes cultured from three shallow-water coral species and two whale species. These unique marine animals place strong selective pressures on their microbial symbionts and contain members under similar environmental and anthropogenic stress. We developed an intense cultivation procedure, utilizing a suite of culture conditions targeting a rich assortment of biofilm-forming microorganisms. We identified 592 microbial isolates contained within 15 bacterial orders representing 50 bacterial genera, and two fungal species. Culturable bacteria from coral and whale samples paralleled taxonomic groups identified in culture-independent surveys, including 29% of all bacterial genera identified in the Megaptera novaeangliae skin microbiome through culture-independent methods. This microbial repository provides raw material and biological input for more nuanced studies which can explore how members of the microbiome both shape their micro-niche and impact host fitness.

Keller|Abigail G|AG|
Apprill|Amy|A|
Lebaron|Philippe|P|
Robbins|Jooke|J|
Romano|Tracy A|TA|
Overton|Ellysia|E|
Rong|Yuying|Y|
Yuan|Ruiyi|R|
Pollara|Scott|S|
Whalen|Kristen E|KE|

microbiome
bacteria
coral
whale
skin
SSU rRNA


Heterologous expression and functional characterization of a GH10 endoxylanase from Aspergillus fumigatus var. niveus with potential biotechnological application.

Abstract: Xylanases decrease the xylan content in pretreated biomass releasing it from hemicellulose, thus improving the accessibility of cellulose for cellulases. In this work, an endo-β-1,4-xylanase from Aspergillus fumigatus var. niveus (AFUMN-GH10) was successfully expressed. The structural analysis and biochemical characterization showed this AFUMN-GH10 does not contain a carbohydrate-binding module. The enzyme retained its activity in a pH range from 4.5 to 7.0, with an optimal temperature at 60 °C. AFUMN-GH10 showed the highest activity in beechwood xylan. The mode of action of AFUMN-GH10 was investigated by hydrolysis of APTS-labeled xylohexaose, which resulted in xylotriose and xylobiose as the main products. AFUMN-GH10 released 27% of residual xylan from hydrothermally-pretreated corn stover and 14% of residual xylan from hydrothermally-pretreated sugarcane bagasse. The results showed that environmentally friendly pretreatment followed by enzymatic hydrolysis with AFUMN-GH10 in low concentration is a suitable method to remove part of residual and recalcitrant hemicellulose from biomass.

Velasco|Josman|J|
Oliva|Bianca|B|
Mulinari|Evandro José|EJ|
Quintero|Leidy Patricia|LP|
da Silva Lima|Awana|A|
Gonçalves|Aline Larissa|AL|
Gonçalves|Thiago Augusto|TA|
Damasio|André|A|
Squina|Fabio Marcio|FM|
Ferreira Milagres|Adriane Maria|AM|
Abdella|Asmaa|A|
Wilkins|Mark R|MR|
Segato|Fernando|F|

Endoxylanase
Corn stover
Sugarcane bagasse
Filamentous fungi
Xylooligosaccharides


Association between children's exposure to a violent event and objectively and subjectively measured sleep characteristics: a pilot longitudinal study.

Abstract: Although sleep disturbances are commonly reported among children exposed to violence, objective evidence of such disturbances is rare. This longitudinal, home-based study assessed the effects of a known community- or family-violence incident on both actigraphy-derived and subjectively reported sleep outcomes of an ethnically mixed, urban sample of children aged 8-16 years. We hypothesized that increased event severity (child physical assault, witnessed homicide) would be associated with lower sleep duration and poorer sleep quality both at baseline and at 3-month follow-up. Covariate-adjusted analyses based on a generalized estimating equations approach showed that children physically assaulted during the event showed lower sleep duration and sleep efficiency and greater wake after sleep onset than those not physically assaulted. Physically assaulted children were more likely to have a later bedtime than non-assaulted children, but this difference decreased at 3 months. Children witnessing a homicide showed greater wake after sleep onset at baseline and reported greater sleep problems than those witnessing a non-homicide event, but these differences decreased at 3 months. They were also somewhat more likely to have greater nightly variation in sleep duration. Collectively, results suggest that violence exposure influences children's sleep, but that specific dimensions of sleep may exhibit different susceptibility to different characteristics of violence, especially over time.

Spilsbury|James C|JC|
Babineau|Denise C|DC|
Frame|Jennifer|J|
Juhas|Kimberly|K|
Rork|Kristine|K|

children
violence
actigraphy
adolescents
traumatic stress


Tubular secretion of creatinine in autosomal dominant polycystic kidney disease: consequences for cross-sectional and longitudinal performance of kidney function estimating equations.

Abstract:
BACKGROUND
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by renal tubular cell proliferation and dedifferentiation, which may influence tubular secretion of creatinine (CCr[TS]).

STUDY DESIGN
Diagnostic test study.

SETTING & PARTICIPANTS
We therefore investigated CCr(TS) in patients with ADPKD and controls and studied consequences for the performance of glomerular filtration rate (GFR) estimating equations.

INDEX & REFERENCE TESTS
In patients with ADPKD and healthy controls, we measured GFR as (125)I-iothalamate clearance while simultaneously determining creatinine clearance.

OTHER MEASUREMENTS
24-hour urinary albumin excretion.

RESULTS
In 121 patients with ADPKD (56% men; mean age, 40 ± 11 [SD] years) and 215 controls (48% men; mean age, 53 ± 10 years), measured GFR (mGFR) was 78 ± 30 and 98 ± 17 mL/min/1.73 m(2), respectively, and CCr(TS) was 15.9 ± 10.8 and 10.9 ± 10.6 mL/min/1.73 m(2), respectively (P < 0.001). The higher CCr(TS) in patients with ADPKD remained significant after adjustment for covariates and appeared to be dependent on mGFR. Correlation and accuracy between mGFR and CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) estimated GFR (eGFR) were 0.95 and 99%, respectively; between mGFR and MDRD (Modification of Diet in Renal Disease) Study eGFR, they were 0.93 and 97%, respectively. Values for bias, precision, and accuracy were similar or slightly better than in controls. In addition, change in mGFR during 3 years of follow-up in 45 patients with ADPKD correlated well with change in eGFR.

LIMITATIONS
Cross-sectional, single center.

CONCLUSIONS
CCr(TS) in patients with ADPKD is higher than that in controls, but this effect is limited and observed at only high-normal mGFR. Consequently, the CKD-EPI and MDRD Study equations perform relatively well in estimating GFR and change in GFR in patients with ADPKD.

Spithoven|Edwin M|EM|
Meijer|Esther|E|
Boertien|Wendy E|WE|
Sinkeler|Steef J|SJ|
Tent|Hilde|H|
de Jong|Paul E|PE|
Navis|Gerjan|G|
Gansevoort|Ron T|RT|

D016891:Polycystic Kidney, Autosomal Dominant

estimated glomerular filtration rate (eGFR)


Validation Procedure for Multiplex Antibiotic Immunoassays Using Flow-Based Chemiluminescence Microarrays.

Abstract: Small molecules like antibiotics or other pharmaceuticals can be detected and quantified, among others, with indirect competitive immunoassays. With regard to multiplex quantification, these tests can be performed as chemiluminescence microarray immunoassays, in which, in principle, the analyte in the sample and the same substance immobilized on the chip surface compete for a limited number of specific antibody binding sites. The amount of the specific primary antibody that has been bound to the surface is visualized by means of a chemiluminescence reaction.Validated quantitative confirmatory methods for the detection of contaminants, for example drug residues, in food samples usually comprise chromatographic analysis and spectrometric detection, e.g., HPLC-MS, GC-MS, or GC with electron capture detection. Here, we describe a validation procedure (according to the Commission Decision of the European Communities 2002/657/EC) for multiplex immunoassays performed as flow-through chemiluminescence microarrays, using the example of a small molecule microarray for the simultaneous detection of 13 antibiotics in milk. By this means, we suggest to accept multianalyte immunoassays as confirmatory methods as well, to benefit from the advantages of a fast automated method that does not need any pretreatment of the sample. The presented microarray chip is regenerable, so an internal calibration is implemented. Therefore, the analytical results are highly precise, combined with low costs (the aim for commercialization is less than 1 € per analyte per sample, this is significantly less than HPLC-MS).

Meyer|Verena Katharina|VK|
Meloni|Daniela|D|
Olivo|Fabio|F|
Märtlbauer|Erwin|E|
Dietrich|Richard|R|
Niessner|Reinhard|R|
Seidel|Michael|M|

Antibiotics
Chemiluminescence
Microarrays
Competitive immunoassay
Regeneration
Flow-based analysis platform
Residue analysis
Screening methods
Veterinary drugs


Addressing antimicrobial resistance in Nigerian hospitals: exploring physicians prescribing behavior, knowledge, and perception of antimicrobial resistance and stewardship programs.

Abstract:
INTRODUCTION
We assessed the knowledge of, attitude toward antimicrobial resistance (AMR) and practice of antimicrobial stewardship (AMS) among physicians in Nigeria to provide future guidance to the Nigerian National Action Plan for AMR.

METHODS
A descriptive cross-sectional questionnaire-based study explored the physicians' self-reported practice of antibiotic prescribing, knowledge, attitude, and practice of AMR and components of ASPs.

RESULTS
The majority (217; 67.2%) of respondents prescribed antibiotics daily in their clinical practice AMR was recognized as a global and local problem by 308 (95.4%) and 262 (81.1%) respondents, respectively. Only 91 (28.2%) of respondents have ever heard of antibiotic stewardship. The median AMR knowledge score was 40 (19-45)out of 45while that for ASP was 46.0(32-57) out of 60. There was significant statistical difference between the ASP median scores among the medical specialties category (P value <0.0001) More respondents had good knowledge of AMR than ASPs (82.7% versus 36.5%; p < 0.0001).

CONCLUSION
Respondents in this study were more knowledgeable about AMR than AMS and its core components.

D007722:Health Knowledge, Attitudes, Practice

Nigeria
Antibiotic stewardship
antibiotic prescription
inappropriate use of antimicrobials
rational use of antimicrobials
tertiary healthcare facilities


A Runway Safety System Based on Vertically Oriented Stereovision.

Abstract: In 2020, over 10,000 bird strikes were reported in the USA, with average repair costs exceeding $200 million annually, rising to $1.2 billion worldwide. These collisions of avifauna with airplanes pose a significant threat to human safety and wildlife. This article presents a system dedicated to monitoring the space over an airport and is used to localize and identify moving objects. The solution is a stereovision based real-time bird protection system, which uses IoT and distributed computing concepts together with advanced HMI to provide the setup's flexibility and usability. To create a high degree of customization, a modified stereovision system with freely oriented optical axes is proposed. To provide a market tailored solution affordable for small and medium size airports, a user-driven design methodology is used. The mathematical model is implemented and optimized in MATLAB. The implemented system prototype is verified in a real environment. The quantitative validation of the system performance is carried out using fixed-wing drones with GPS recorders. The results obtained prove the system's high efficiency for detection and size classification in real-time, as well as a high degree of localization certainty.

Gradolewski|Dawid|D|
Dziak|Damian|D|
Kaniecki|Damian|D|
Jaworski|Adam|A|
Skakuj|Michal|M|
Kulesza|Wlodek J|WJ|

runway safety
safety system
stereovision
bird strike
localization
distributed computing
Internet of Things
bird monitoring
environmental sustainability
monitoring of avifauna
visual sensor network


Technophobia as emerging risk factor in aging: Investigation on computer anxiety dimension.

Abstract: Digital innovation changed the daily living impacting Quality of Life of individuals. Our study was focused on adult and elder behavioural approach to the technology. Out study aimed to investigate the impact of technology use in not digital native in order to investigate the behavioural degree of adaptation. An observational study was conducted on adult and old subjects (age range 50-67 years) measuring computer anxiety and technology use ability variables identifying the indexes for technophobia risk in digital living. Not digital native subjects and more older ones appeared being influenced by technophobia features because of feeling themselves as inadequate in the management of technology. Oneway ANOVA and then Bonferroni's post-hoc analysis showed that non-autonomous (p<0.01), low-frequency (p<0.01), and feelingneed- for-help users (p<0.01) had higher levels of computer anxiety. No significant effect was in gender distribution. Finally, social networking seems related better use of technology and lower anxiety for digital solutions. Our findings highlight technophobia as a possible new risk factor for not digital native because it can affect their daily life through lower adherence to digital solutions; rather than aging successfully, they could develop fragile ageing. More, they seemed inadequate to use the digital solutions for better living in aging.

Di Giacomo|Dina|D|
Guerra|Federica|F|
Perilli|Enrico|E|
Ranieri|Jessica|J|

computer anxiety
use of technology
Digital skills
adulthood


Cultural differences in human brain activity: a quantitative meta-analysis.

Abstract: Psychologists have been trying to understand differences in cognition and behavior between East Asian and Western cultures within a single cognitive framework such as holistic versus analytic or interdependent versus independent processes. However, it remains unclear whether cultural differences in multiple psychological processes correspond to the same or different neural networks. We conducted a quantitative meta-analysis of 35 functional MRI studies to examine cultural differences in brain activity engaged in social and non-social processes. We showed that social cognitive processes are characterized by stronger activity in the dorsal medial prefrontal cortex, lateral frontal cortex and temporoparietal junction in East Asians but stronger activity in the anterior cingulate, ventral medial prefrontal cortex and bilateral insula in Westerners. Social affective processes are associated with stronger activity in the right dorsal lateral frontal cortex in East Asians but greater activity in the left insula and right temporal pole in Westerners. Non-social processes induce stronger activity in the left inferior parietal cortex, left middle occipital and left superior parietal cortex in East Asians but greater activations in the right lingual gyrus, right inferior parietal cortex and precuneus in Westerners. The results suggest that cultural differences in social and non-social processes are mediated by distinct neural networks. Moreover, East Asian cultures are associated with increased neural activity in the brain regions related to inference of others' mind and emotion regulation whereas Western cultures are associated with enhanced neural activity in the brain areas related to self-relevance encoding and emotional responses during social cognitive/affective processes.

Culture
Meta-analysis
Social cognition
Neuroimaging


Identification of substrate-specific inhibitors of cathepsin K through high-throughput screening.

Abstract: Cathepsin K (CatK) is a cysteine protease and drug target for skeletal disorders that is known for its potent collagenase and elastase activity. The formation of oligomeric complexes of CatK in the presence of glycosaminoglycans has been associated with its collagenase activity. Inhibitors that disrupt these complexes can selectively block the collagenase activity without interfering with the other regulatory proteolytic activities of the enzyme. Here, we have developed a fluorescence polarization (FP) assay to screen 4761 compounds for substrate-specific ectosteric collagenase inhibitors of CatK. A total of 38 compounds were identified that block the collagenase activity without interfering with the hydrolysis of active site substrates such as the synthetic peptide substrate, benzyloxycarbonyl-Phe-Arg-7-amido-4-methylcoumarin, and gelatin. The identified inhibitors can be divided into two main classes, negatively charged and polyaromatic compounds which suggest the binding to different ectosteric sites. Two of the inhibitors were highly effective in preventing the bone-resorption activity of CatK in osteoclasts. Interestingly, some of the ectosteric inhibitors were capable of differentiating between the collagenase and elastase activity of CatK depending on the ectosteric site utilized by the compound. Owing to their substrate-specific selectivity, ectosteric inhibitors represent a viable alternative to side effect-prone active site-directed inhibitors.

Law|Simon|S|
Du|Xin|X|
Panwar|Preety|P|
Honson|Nicolette S|NS|
Pfeifer|Tom|T|
Roberge|Michel|M|
Brömme|Dieter|D|

cathepsin K
high-throughput screening
collagen
exosite inhibitor
osteoporosis
protease inhibitor


Association of ischemic stroke with ankylosing spondylitis: a nationwide longitudinal cohort study.

Abstract:
BACKGROUND
The purpose of this nationwide age- and sex-matched longitudinal follow-up study was to investigate the risk of developing ischemic stroke in ankylosing spondylitis (AS).

METHODS
The data in this study, spanning from January 1, 2010 to December 31, 2014, was obtained from a database maintained by the Korean National Health Insurance Service. A total of 12,988 patients with a diagnosis of AS were enrolled. The control group consisted of 64,940 age-sex-stratified matching subjects without AS. The 6year ischemic stroke incidence rate for each group was calculated using the Kaplan-Meier method. Cox proportional hazards regression analysis was used to estimate the hazard ratio of ischemic stroke.

RESULTS
During the follow-up period, 73 patients (0.56%) in the AS group and 250 patients (0.38%) in the control group developed ischemic stroke (p = 0.0041). The hazard ratio of ischemic stroke in the AS group was 1.46 (95% confidence interval [95% CI], 1.13-1.90) after adjusting for age and sex. The adjusted hazard ratio of ischemic stroke in the AS group was 1.35 (95% CI, 1.04-1.75) after controlling for demographics and comorbid medical disorders. According to subgroup analysis, in female and diabetes and non-hypertension and dyslipidemia subgroups, ischemic stroke incidence rates were significantly higher in AS patients than those in control group.

CONCLUSION
Our nationwide longitudinal study suggests an increased risk of ischemic stroke in AS patients.

Lee|Dong Hyun|DH|
Choi|Yoon Jin|YJ|
Han|In-Bo|IB|
Hong|Je Beom|JB|
Do Han|Kyung|K|
Choi|Jung Min|JM|
Sohn|Seil|S|0000-0001-5724-8099

Stroke
Ankylosing spondylitis
Epidemiology
Population


Effect of solid waste fermentation substrate on wheat (Triticum aestivum L.) growth in closed artificial ecosystem.

Abstract: Bioregenerative Life Support System (BLSS) is a closed artificial ecosystem and could provide oxygen, food, water and other substrates for long-term deep space survival. The treatment and recycle of the solid waste are crucial and rate-limiting steps in BLSS, and it's reported that the solid waste such as the inedible plants and human feces could be fermented aerobically and then reused as fertilizer for growing plants in BLSS, which may be an effective way to improve the solid waste recycling rate. However, the recycling performance and the effect on the system need to be evaluated. In this study, the fermented and decomposed solid waste product from the 365d BLSS experiment with human involved in Lunar Palace 1 was utilized, and was added to the Hoagland nutrient solution as a supplementary fertilizer in the weight proportion of 5% and 10%, respectively, for the cultivation of wheat (Group-5% and Group-10%). Then, the effects on wheat germination, morphology, photosynthesis, biomass, the conductivity of the cultured substrates and microorganisms were detected and compared with those of the CK group cultured using only Hoagland nutrient solution. The results showed that this planting method had no inhibitory effect on the wheat germination, root length and yield, and might even promote the vegetative growth of wheat in terms of Vigor index, plant height, leaf area and net photosynthesis rate to some extent. The added solid waste fermentation substrate as well as the planting environment in Lunar Palace 1 both had significant influences on the rhizosphere microorganisms of wheat. The bacteria diversity was more abundant than fungi at phylum level, and the relative abundance varied along with the wheat growth period. The relative abundance of the cellulose degrading microorganisms including Actinobacteria and Ascomycota increased in Group-5% and Group-10% compared with CK group along with the growth of wheat. Moreover, the proper reuse of the fermentation substrate could reduce the use of inorganic salts by 9.8%-11.9% and save 40L•m - 2 of water for wheat cultivation. This research has considerable application significance in future deep space exploration.

Liu|Dianlei|D| Xie|Beizhen|B| Liu|Hui|H| Yao|Zhikai|Z| Liu|Hong|H|

Bioregenerative life support system (BLSS)


Risk of Pancreatic Cancer in Patients With Pancreatic Cysts and Family History of Pancreatic Cancer.

Abstract:
BACKGROUND & AIMS
A diagnosis of pancreatic cancer in a first-degree relative increases an individuals' risk of this cancer. However, it is not clear whether this cancer risk increases in individuals with pancreatic cystic lesions who have a first-degree relative with pancreatic cancer. The Fukuoka criteria are used to estimate risk of pancreatic cancer for patients with pancreatic cystic lesions: individuals with cysts with high risk or worrisome features (Fukuoka positive) have a higher risk of pancreatic cancer than individuals without these features (Fukuoka negative). We aimed to compare the risk of pancreatic cancer and surgery based on presence or absence of pancreatic cystic lesions and a first-degree relative with pancreatic cancer.

METHODS
We performed a retrospective study of patients seen at the Mayo Clinic in Rochester, Minnesota, from January 1, 2000, through December 31, 2012. We identified individuals with: pancreatic cystic lesions and first-degree relative with pancreatic cancer (group 1, n = 269), individuals with pancreatic cystic lesions but no first-degree relative with pancreatic cancer (group 2, n = 1195), and individuals without pancreatic cystic lesions but with a first-degree relative with pancreatic cancer (group 3, n = 720). We compared, among groups, as well among patients with cysts classified according to Fukuoka criteria, proportions of individuals who developed pancreatic cancer or underwent pancreatic surgery within a 5-year period.

RESULTS
A significantly higher proportion of individuals in group 1 developed pancreatic cancer during the 5-year period than in group 3 (6.64% vs 1.69%; P = .03); there was no significant difference between the percentage of individuals in group 1 vs group 2 who developed pancreatic cancer (6.64% vs 4.05%; P = .41). There was no significant difference in pancreatic cancer development among individuals with Fukuoka-positive cysts with vs without a family history of pancreatic cancer (P = .39). There was no significant difference in the proportion of patients in group 1 vs group 2 who underwent pancreatic surgery for their pancreatic cyst over the 5-year period (14.37% vs 11.80%; P = .59). Among patients with Fukuoka-negative cysts, a significantly higher proportion underwent surgery in group 1 than in group 2 (10.90% vs 5.90%; P = .03). However, among patients with Fukuoka-positive cysts, there was no difference in proportions of patients who underwent surgery between groups 1 and 2 (P = .66).

CONCLUSIONS
In a retrospective study of patients with pancreatic cysts and/or cancer, we found that a family history of pancreatic cancer does not affect 5-year risk of pancreatic cancer in patients with pancreatic cystic lesions. Despite this, among patients with Fukuoka-negative cysts, a higher proportion of those with a family history of pancreatic cancer undergo surgery than patients without family history of pancreatic cancer.

Mukewar|Saurabh S|SS|
Sharma|Ayush|A|
Phillip|Nissy|N|
Gupta|Ridhi|R|
Aryal-Khanal|Anupama|A|
de Pretis|Nicolo|N|
Anani|Vincent|V|
Enders|Felicity T|FT|
Larson|Joseph J|JJ|
Takahashi|Naoki|N|
Levy|Michael J|MJ|
Topazian|Mark|M|
Pearson|Randall K|RK|
Vege|Santhi S|SS|
Chari|Suresh T|ST|

Family History
First-Degree Relative
Pancreatic Surgery
Pancreatic Tumors


The role of a sequencing-based clinical intestinal screening test in patients at high-risk for Clostridium difficile and other pathogens: a case report.

Abstract:
BACKGROUND
Hospitalization and antibiotic treatment can put patients at high risk for Clostridium difficile infection, where a disturbance of the gut microbiome allows for Clostridium difficile proliferation and associated symptoms, including mild, moderate, or severe diarrhea. Clostridium difficile infection is challenging to treat, often recurrent, and leads to almost 30,000 annual deaths in the USA alone. Here we present a case where SmartGut™, an at-home, self-administered sequencing-based clinical intestinal screening test, was used to identify the presence of Clostridium difficile in a patient with worsening diarrhea. Identification of this pathogen and subsequent treatment led to a significant improvement in symptoms.

CASE PRESENTATION
The patient is a 29-year-old white woman with a history of severe irritable bowel syndrome with diarrhea, hemorrhoidectomy, and anal sphincterotomy complicated by a perianal fistula and perirectal abscesses that required extended courses of broad-spectrum antibiotics. In June 2016, she developed intermittent Clostridium difficile infections, which required continued antibiotic use. Months later she used an at-home, self-administered, intestinal microbial test, the first of which was negative for the presence of Clostridium difficile, but it detected the relative abundance of microbes associated with irritable bowel syndrome outside the healthy reference ranges. In the subsequent 2 months after the negative Clostridium difficile result, her gastrointestinal symptoms worsened dramatically. A second microbiome test resulted in a positive Clostridium difficile finding and continued abnormal microbial parameters, which led the treating physician to refer her to a gastroenterologist. Additional testing confirmed the presence of Clostridium difficile with a toxin-positive strain. She received treatment immediately and her gastrointestinal symptoms improved significantly over the next week.

CONCLUSIONS
This case report suggests that more frequent DNA testing for Clostridium difficile infections may be indicated in patients that are at high-risk for Clostridium difficile infection, especially for patients with irritable bowel syndrome, and those who undergo gastrointestinal surgery and/or an extended antibiotic treatment. This report also shows that such testing could be effectively performed using at-home, self-administered sequencing-based clinical intestinal microbial screening tests. Further research is needed to investigate whether the observations reported here extrapolate to a larger cohort of patients.

D000038:Abscess
D000328:Adult
D000900:Anti-Bacterial Agents
D016360:Clostridioides difficile
D003015:Clostridium Infections
D005260:Female
D000069196:Gastrointestinal Microbiome
D041981:Gastrointestinal Tract
D006801:Humans
D043183:Irritable Bowel Syndrome
D012002:Rectal Diseases
D012648:Self Care
D013048:Specimen Handling

Screening test
Clostridium difficile
Irritable bowel syndrome
Gastrointestinal surgery
CDI
Comorbidity
IBS
Multimorbidity


Highly specific phosphopeptide enrichment by titanium(IV) cross-linked chitosan composite.

Abstract: Natural chitosan was applied as supporting material for Ti(IV) based immobilized metal ion affinity chromatographic (IMAC) material (Ti-CTS). Compared with other polymer based IMAC, Ti-CTS can save the cockamamie synthesis procedures and be easy to obtain. The morphology, surface area, pore volume and elemental composition of Ti-CTS were revealed by scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) method and X-ray photoelectron spectroscopy (XPS). Tryptic digest products from several standard proteins and two real samples (non-fat milk and serum) were enriched using Ti-CTS to demonstrate the efficiency of this method. The results showed that this composite enables high sensitive and selective phosphopeptide enrichment from casein variants, non-fat milk and human serum. Furthermore, multi-phosphorylated peptides with three serine phospholated sites (S*S*S*) demonstrated high affinity to Ti-CTS. Hence, this method had great potential for future studies of complex phosphoproteomes and especially multi-phosphorylated peptides.

Wu|Ting|T| Shi|Jiani|J| Zhang|Chuanjing|C| Zhang|Lingfan|L| Du|Yiping|Y|

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

Phosphopeptide enrichment
Chitosan
IMAC
MALDI TOF MS