Response to ovarian stimulation is not impacted by a breast cancer diagnosis.

Abstract:
STUDY QUESTION
Does a breast cancer diagnosis impact ovarian function in the setting of fertility preservation?

SUMMARY ANSWER
Ovarian reserve and ovarian stimulation outcomes are similar in patients with a new diagnosis of breast cancer and patients undergoing elective fertility preservation.

WHAT IS KNOWN ALREADY
Prior studies, with small study populations, lack of controlling for individual differences in ovarian reserve and infertile controls, have reported conflicting outcomes for cancer patients undergoing ovarian stimulation for fertility preservation.

STUDY DESIGN, SIZE, DURATION
This retrospective cohort analysis included 589 patients undergoing ovarian stimulation for fertility preservation between 2009 and 2015.

PARTICIPANTS/MATERIALS, SETTING, METHODS
Women with a recent breast cancer diagnosis (n = 191) and women desiring elective fertility preservation (n = 398) underwent ovarian stimulation with an antagonist protocol at an academic medical center. The aromatase inhibitor letrozole was administered to breast cancer patients with estrogen-sensitive disease.

MAIN RESULTS AND THE ROLE OF CHANCE
Baseline antral follicle count (AFC) was not different between the breast cancer patients and controls (15.4 ± 10.4 [mean ± SD] vs 15.4 ± 10.0, P = NS), even after categorization by age. Total (19.4 ± 0.9 [mean ± SEM] vs 17.0 ± 0.5, P = NS) and mature (MII) oocytes retrieved (13.7 ± 0.7 vs 13.2 ± 0.4, P = NS), adjusted for age, BMI and total gonadotropin dose, were also similar between the two groups. Letrozole use was associated with a decreased maturity rate (MII/total oocytes retrieved) compared to elective cryopreservation (0.71 ± 0.01 vs 0.77 ± 0.01, P < 0.001), although the mature oocyte yield [MII/AFC] was comparable (1.01 ± 0.06 vs 0.93 ± 0.03, P = NS).

LIMITATIONS, REASONS FOR CAUTION
The single center design may impact generalizability. Additionally, the lack of subsequent embryo and pregnancy data is an inherent weakness.

WIDER IMPLICATIONS OF THE FINDINGS
In females, a breast cancer diagnosis does not impact gonadal function as measured by AFC or ovarian stimulation outcomes. Breast cancer patients should be counseled that their response to ovarian stimulation for fertility preservation is similar to that of patients undergoing elective oocyte cryopreservation.

STUDY FUNDING/COMPETING INTEREST(S)
None.

TRIAL REGISTRATION NUMBER
N/A.

Quinn|Molly M|MM|
Cakmak|Hakan|H|
Letourneau|Joseph M|JM|
Cedars|Marcelle I|MI|
Rosen|Mitchell P|MP|

breast cancer
fertility preservation
ovarian reserve
letrozole
elective cryopreservation
oocyte cryopreservation


Effect of Weight Reduction on Treatment Outcomes for Patients with Atopic Dermatitis.

Abstract:
Background
Several epidemiological studies have shown that the atopic tendency increases in the obese population.

Objective
The aim of this study was to confirm the effect of weight reduction on improvement of atopic dermatitis (AD) symptoms and to investigate the relationship between AD severity and the level of serum adipokines.

Methods
Forty subjects who were AD outpatients were recruited for this study. Obese patients were divided into a weight maintenance group and weight reduction group. During the study period, patient information was collected that included measured body mass index (BMI), Eczema Area and Severity Index (EASI), and visual analogue scale for pruritus. Adiponectin, leptin, eosinophil count, and total immunoglobulin E were also tested.

Results
In the weight reduction group, there was a significant improvement in the EASI score, however, no significant improvement was determined in the weight maintenance group. BMI and EASI showed positive correlation. The adiponectin level was lower in AD patients compared to healthy controls, and it was significantly lower in obese patients compared with normal weight patients. Serum levels of leptin were significantly different among control, obese patient group, and normal weight patient group. There was no statistically significant relationship between serum adipokine level and EASI.

Conclusion
In our study, weight reduction was associated with significant improvement of AD symptoms. Related adipokine levels were significantly different among the control, normal weight AD patient group, and obese AD patient group.

Atopic dermatitis
Body mass index
Adiponectin
Leptin
Weight loss


Three new alkaloids and three new phenolic glycosides from Liparis odorata.

Abstract: Three new alkaloids, liparis alkaloid A (1), B (2), C (3), and three new phenolic glycosides, liparis glycoside H (4), I (5), J (6), together with three known phenolic glycosides (7-9) were isolated from the whole plant of Liparis odorata. Their structures were characterized on the basis of extensive 1D-, 2D-NMR and HR-ESI-MS experiments. In addition, compounds 1-3 revealed hypolipidemic effects in the in vitro bioassays, and the ability to inhibit LPS-induced NO production of these isolated phenolic glycosides (4-9) was also evaluated.

Jiang|Piao|P| Liu|Hongdong|H| Xu|Xianghong|X| Liu|Bo|B| Zhang|Dongming|D| Lai|Xuewen|X| Zhu|Genghua|G| Xu|Peng|P| Li|Bin|B|

Alkaloids
Phenolic glycosides
Liparis odorata
Hypolipidemic effect
NO production inhibitory activities
Orchid family


The ARRIVE Trial: Interpretation from an Epidemiologic Perspective.

Abstract: The findings of the ARRIVE trial (A Randomized Trial of Induction Versus Expectant Management) were recently published. This multisite randomized trial was designed to provide evidence regarding whether labor induction or expectant management is associated with increased adverse perinatal outcomes and risk of cesarean birth among healthy nulliparous women at term. The trial reported that the primary outcome, a composite of adverse neonatal outcomes, was not significantly different between the 2 groups; the principal secondary outcome, cesarean birth, was significantly more common among women whose pregnancy was expectantly managed than among women whose labor was induced at 39 weeks. These results have the potential to change existing practice. Several aspects of the study design may influence its potential internal and external validity and should be considered in order to make sound causal inferences from this trial, which will in turn affect how its findings are translated to practice. Although chance and confounding are of minimal concern, given the sample size and randomization used in the study, selection bias may be a concern. Studies are vulnerable to selection bias when the sample population differs from eligible nonparticipants, including in randomized controlled trials. External validity is defined as the extent to which the study population and setting are representative of the larger source population the study intends to represent. External validity may be limited given the characteristics of the women enrolled in the ARRIVE trial and the practice settings where the study was conducted. This brief report provides concrete suggestions for further analyses that could help solidify conclusions from the trial, and for further research questions that will continue advancement toward answering this complex question of how best to manage labor and birth decisions at full term among low-risk women.

D016032:Randomized Controlled Trials as Topic

cesarean
causality
randomized controlled trials
induction of labor
labor onset
pragmatic randomized controlled trials


The ubiquitin ligase SCFFBXW7α promotes GATA3 degradation.

Abstract: GATA3 is a key transcription factor in cell fate determination and its dysregulation has been implicated in various types of malignancies. However, how the abundance and function of GATA3 are regulated remains unclear. Here, we report that GATA3 is physically associated with FBXW7α, and FBXW7α destabilizes GATA3 through assembly of a SKP1-CUL1-F-box E3 ligase complex. Importantly, we showed that FBXW7α promotes GATA3 ubiquitination and degradation in a GSK3 dependent manner. Furthermore, we demonstrated that FBXW7α inhibits breast cancer cells survival through destabilizing GATA3, and the expression level of FBXW7α is negatively correlated with that of GATA3 in breast cancer samples. This study indicated that FBXW7α is a critical negative regulator of GATA3 and revealed a pathway for the maintenance of GATA3 abundance in breast cancer cells.

Song|Nan|N| Cao|Cheng|C| Tang|Yiman|Y| Bi|Liyuan|L| Jiang|Yong|Y| Zhou|Yongsheng|Y| Song|Xin|X| Liu|Ling|L| Ge|Wenshu|W|

D000073979:F-Box-WD Repeat-Containing Protein 7

D044843:SKP Cullin F-Box Protein Ligases

ubiquitination
E3 ligase
breast cancer
protein stability


A Phase III, Randomized, Placebo-controlled Trial to Assess the Efficacy and Safety of Once-daily SPN-812 (Viloxazine Extended-release) in the Treatment of Attention-deficit/Hyperactivity Disorder in School-age Children.

Abstract:
PURPOSE
The limitations of current US Food and Drug Administration (FDA)-approved medications for the treatment of attention-deficit/hyperactivity disorder (ADHD) set the need for the development of novel, effective, and tolerable medications to treat this disorder. The purpose of this study was to evaluate whether treatment with SPN-812 (viloxazine extended-release) significantly reduces symptoms of ADHD in children.

METHODS
This study was a randomized, double-blind, placebo-controlled 6-week trial to assess the efficacy and safety of once-daily 100- and 200-mg SPN-812 in the treatment of ADHD in male and female children 6-11 years of age. Inclusion criteria required subjects to have a confirmed Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, ADHD diagnosis, an ADHD-Rating Scale-5 (ADHD-RS-5) score ≥28, a Clinical Global Impression-Severity score ≥4, and for subjects to be free of ADHD medication ≥1 week before randomization. The primary efficacy endpoint was the change from baseline (CFB) at end of study (EOS) in ADHD-RS-5 Total score. Key secondary endpoints included Clinical Global Impression-Improvement (CGI-I) scores at EOS and CFB at EOS in the Conners 3-Parent Short Form (Conners 3-PS) Composite T-score and the Weiss Functional Impairment Rating Scale-Parent (WFIRS-P) Total average score. Safety assessments included adverse events (AEs), laboratory tests, vital signs, physical examinations, ECGs, and the Columbia-Suicide Severity Rating Scale. The primary efficacy endpoint was analyzed by using a mixed model for repeated measures; all secondary measures were analyzed by using an ANCOVA model.

RESULTS
A total of 477 subjects were randomized to treatment (intent-to-treat population, n = 460). The majority of subjects were male (63%) and either White (51.3%) or African American (43.7%). The demographic and baseline characteristics between the groups were similar. Statistically significant improvements in ADHD-RS-5 Total score were observed in both the 100- and 200-mg/day SPN-812 treatment groups compared to placebo at week 1 of treatment (P = 0.0004 and P = 0.0244, respectively), which was maintained through EOS (P = 0.0004 and P < 0.0001). Significant improvements were also observed at EOS in the CGI-I scale (P = 0.0020 and P < 0.0001), Conners 3-PS Composite T-score (P = 0.0003 and P = 0.0002), and WFIRS-P Total average score (P = 0.0019 and P = 0.0002) versus placebo. Treatment-related AEs reported in ≥5% of subjects included somnolence, decreased appetite, and headache. The discontinuation rate due to AEs was <5%.

IMPLICATIONS
SPN-812 significantly reduced ADHD symptoms in children and was well tolerated. SPN-812 may prove to be an effective treatment for children with ADHD. ClinicalTrials.gov identifier: NCT03247530.

Nasser|Azmi|A|
Liranso|Tesfaye|T|
Adewole|Toyin|T|
Fry|Nicholas|N|
Hull|Joseph T|JT|
Chowdhry|Fatima|F|
Busse|Gregory D|GD|
Cutler|Andrew J|AJ|
Jones|Nandita Joshi|NJ|
Findling|Robert L|RL|
Schwabe|Stefan|S|

D001289:Attention Deficit Disorder with Hyperactivity

SPN-812
viloxazine
ADHD
ADHD-RS-5
Conners 3
WFIRS


Fabrication a controlled-release pesticide for improving UV-shielding properties and reducing toxicity via coating polydopamine.

Abstract: Controlled-release formulations (CRFs) have potential applications in modern agriculture, for it can not only prolong the duration of agrochemicals but also alleviate the adverse effect on non-target organism. In this study, we constructed pyraclostrobin@SiO2@polydopamine microcapsule (Pyr@SiO2@PDA MC). The resulting microcapsule is a near-rod shape (about 1.15 μm), which has a drug-loading efficiency of 55%. Fourier transform infrared (FTIR) and thermogravimetric analysis (TG) revealed the successful entrapment of the pesticide. The coating of polydopamine (PDA) endowing the microcapsule with superior UV-shielding properties than pyraclostrobin@SiO2 microcapsule (Pyr@SiO2 MC). Compared with pyraclostrobin emulsifiable concentrate (EC), the Pyr@SiO2@PDA MC exhibited 9.07-, 5.50-, 4.93- and 4.16-fold higher fungicidal activity against Rice blast fungus (Pyricularia oryzae) at concentrations of 0.5, 1, 2 and 4 mg/L. Moreover, acute toxicity tests demonstrated that the sample on zebrafish with lower toxicity on the first day. These results showed that the obtained microcapsule may process broader application potential in agriculture.

Wang|Ya|Y| Li|Chaonan|C| Zhang|Xin|X| Chen|Wei|W| Li|Xiaogang|X|

polydopamine
Pyraclostrobin
acute toxicity evaluation
bioactivity
sustained release


What is the cost burden of surgical implant waste? An analysis of surgical implant waste in an orthopedics and trauma surgery department of a French university hospital in 2016.

Abstract:
BACKGROUND
During an orthopedic or trauma surgery procedure, when an implantable medical device is unpackaged, not implanted and cannot be resterilized, it is considered "waste". The cost burden falls on the hospital. The French Social Security Code provides for add-on reimbursement for certain expensive or very specialized devices (supplementary list of costly implants). To allow its restocking without linking it to a patient or reimbursement request, the wasted implant is tracked in a computerized database. The economic impact of these wasted implants is not known in France. This led us to conduct a retrospective study: 1) to determine the percentage and number of wasted implants, 2) to identify elements related to the surgery that impact implant waste.

HYPOTHESIS
Various elements of the surgical environment (type of procedure, specialty, surgeon experience, time of year) can independently contribute to the non-implantation of a medical device.

METHODS
We carried out a retrospective observational study of data collected prospectively in the database of our teaching hospital in 2016. The primary outcome was the percentage of wasted implants. The secondary outcome was the mean cost of these wasted implants. These parameters were determined for all the implants used in orthopedics and trauma surgery and tracked in this department, then for each variable hypothesized to led to non-implantation. Our analysis was descriptive, then comparative.

RESULTS
In our database, 29,073 devices were tracked (€3,761,180), of which 1995 devices were wasted (6.9%). The total cost of the wasted implants was €179,193 (4.8% of the overall cost). The breakdown of the wasted implants was 430 (4.4%) from the add-on list (average cost of €293.10) versus 1565 implants associated with the hospital's diagnosis-related group payment system (average cost of €33.90). Trauma surgery procedures had significantly more wasted implants than orthopedic surgery (1135 vs. 860 (p<0.01)), although the individual cost was less (€59.20 vs. €130.10 (p<0.01)). Fracture fixation implants were more likely to be wasted than ligament reconstruction or arthroplasty implants, with a lower mean cost. More implants were wasted during hip arthroplasty than during other arthroplasty procedures. Less experienced surgeons wasted more implants than more experienced surgeons (1087 vs. 905 (p<0.01)) but these implants cost less (€69.20 vs. €114.80 (p<0.05)). The percentage of implants wasted was higher during the resident changeover period relative to the other months of the year (772 vs. 1223 (p<0.01)).

DISCUSSION
This study is the first attempt at quantifying the number and cost of wasted implants in the context of orthopedics and trauma surgery at a teaching hospital in France. While trauma surgery is associated with more wasted implants, the cost burden is higher in orthopedics. Surgeons, by virtue of their experience and teaching mandate, have a decisive role managing this cost burden.

TYPE OF STUDY
IV, Retrospective study.

Laurut|Théa|T| Duran|Chloé|C| Pages|Arnaud|A| Morin|Marie-Claire|MC| Cavaignac|Etienne|E|

D003365:Costs and Cost Analysis
D005602:France
D017048:Health Care Costs
D006785:Hospitals, University
D006801:Humans
D008506:Medical Waste
D009985:Orthopedics
D019736:Prostheses and Implants
D012189:Retrospective Studies
D014193:Trauma Centers

Orthopedics
Trauma surgery
Wasted implants
Healthcare costs


Scallop shell coated Fe2O3 nanocomposite as an eco-friendly adsorbent for tetracycline removal.

Abstract: ABSTRACTThe present study focused on the usability of scallop shell coated Fe2O3 nanoparticles as an eco-friendly new absorbent in the treatment of tetracycline (TC). The process performance in terms of TC removal was investigated at different operating conditions, i.e. at solution pH of 3-11, Fe2O3-scallop dosage of 0.4-2.4 g L-1, initial TC content of 20-120 mg L-1 and temperature of 25-55°C. Solution pH of 7 yielded the highest TC removal efficiency (99%). At this pH value, almost complete TC removal was achieved at a Fe2O3-scallop shell nanocomposite dose of 1.6 g L-1 and 25°C. The responsible TC removal mechanism is suggested as the non-electrical π-π dispersion interaction between the bulk π system on the absorbent surface and TC molecules bearing both benzene rings and double bonds at this solution pH. TC removal efficiency appreciably enhanced up to the Fe2O3-scallop dosage of 1.6 g L-1 being an optimum. Adsorption rate was found to be fast at lower initial TC concentrations than 40 mg L-1. The effect of temperature on TC removal efficiency was insignificant. Adsorption followed the pseudo-second-order kinetic model. Experimental data perfectly fitted by the Langmuir equation. The maximum adsorption capacity was calculated as 49.26 mg g-1. Thermodynamic analysis demonstrated that adsorption process was spontaneous process and endothermic. The results obtained from the present study proved the excellent performance of scallop shell coated Fe2O3 nanoparticles as an eco-friendly adsorbent in TC treatment.

scallop shell
Fe2O3
tetracycline
Adsorption
antibiotic


Circulating tumor DNA analysis of metastatic renal cell carcinoma.

Abstract: The genomic landscape of metastatic renal cell carcinoma (RCC) is not well understood, and currently available data suggest that it is functionally distinct from that of localized tumors. Additionally, the large number of approved and trial agents used to treat metastatic RCC likely cause selective adaptations in the tumors. Circulating tumor DNA (ctDNA) is a platform to non-invasively determine the genomic profiles of these tumors. The objectives of the present study were to corroborate previous ctDNA studies in metastatic RCC, to identify novel mutations in metastatic RCC, and to compare ctDNA profiles obtained from plasma and urine in patients with metastatic RCC. ctDNA sequencing using the plasma and urine of 50 patients with metastatic RCC who received ctDNA profiling as part of routine clinical care at a single institution was performed using an investigational 120-gene panel. Genomic alterations (GAs) were identified in all 50 patients. The genes with the most GAs were GNAS, PTEN, MYC, MET and HNF1A and novel mutations in additional genes were identified. A significant correlation between the number of GAs detected in matched urine and plasma samples was also identified, but only 28.1% of GAs detected in plasma samples were also detected in matched urine samples. The results of the present study were consistent with those of the largest previous study of ctDNA from patients with metastatic RCC and may help identify additional potential targets for the treatment of such patients.

Zhang|Jingbo|J|
Liu|Yunchao|Y|
Xu|Bing|B|
Li|Fuwei|F|
Wang|Yan|Y|
Li|Mengjian|M|
Du|Rong|R|
Zhou|Ye|Y|
Salgia|Meghan|M|
Yang|Lixin|L|
Jones|Jeremy O|JO|

circulating tumor DNA
renal cell carcinoma
metastasis


The ineffectiveness and unintended consequences of the public health war on obesity.

Abstract: The public health war on obesity has had little impact on obesity prevalence and has resulted in unintended consequences. Its ineffectiveness has been attributed to: 1) heavy focus on individual-based approaches and lack of scaled-up socio-environmental policies and programs, 2) modest effects of interventions in reducing and preventing obesity at the population level, and 3) inappropriate focus on weight rather than health. An unintended consequence of these policies and programs is excessive weight preoccupation among the population, which can lead to stigma, body dissatisfaction, dieting, disordered eating, and even death from effects of extreme dieting, anorexia, and obesity surgery complications, or from suicide that results from weight-based bullying. Future public health approaches should: a) avoid simplistic obesity messages that focus solely on individuals' responsibility for weight and health, b) focus on health outcomes rather than weight control, and c) address the complexity of obesity and target both individual-level and system-level determinants of health.

public health
Obesity
stigma
weight bias


Mortality, cancer incidence, and survival in parents after bereavement.

Abstract:
PURPOSE
The study objective was to investigate whether child loss is related to mortality, cancer incidence, and cancer survival in parents.

METHODS
We used a population-based birth cohort (1964-1976) in Jerusalem and ascertained mortality (average follow-up of 39.1 years) and any cancer (average follow-up of 35.6 years) among parents who lost a child (2838 mothers and 2532 fathers) and among nonbereaved parents (38,212 mothers and 36,433 fathers). We also assessed mortality among parents with cancer. Time-dependent Cox models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs).

RESULTS
Overall mortality rates among bereaved parents were modestly increased when compared with nonbereaved parents (HR = 1.18, 95% CI: 1.05-1.32 in mothers; HR = 1.10, 95% CI: 1.01-1.20 in fathers). Hazard models indicated a significant relationship between bereavement and deaths from coronary heart disease in mothers (HR = 1.90, 95% CI: 1.23-2.95) and circulatory causes in both parents (HR = 1.69; 95% CI: 1.22-2.34 in mothers and HR = 1.25; 95% CI: 1.02-1.54 in fathers). Bereavement was not associated with parental risk of cancer disease and with survival from cancer. The association between bereavement and parental overall mortality was similar in the different parental sociodemographic characteristics. We observed a decrease in HRs for parental mortality associated with bereavement, with increasing time since the death of the child (HRs = 9-10, 0-3 years; HRs = 0.9-1.0, 9+ years; P(heterogeneity) ≤ 3 × 10(-32)). A similar decrease in HRs was observed for parental survival from cancer (HRs = 6.7-8.7, 0-3 years; HRs = 0.9-1.0, 9+ years).

CONCLUSIONS
Our study suggests that child loss was associated with slightly increased risk of all-cause and circulatory mortality in parents but not with incidence of cancer and cancer survival. The considerable increased parental mortality during a short period after child loss support the involvement of pathways related to psychological stress.

Schorr|Limor|L|
Burger|Ayala|A|
Hochner|Hagit|H|
Calderon|Ronit|R|
Manor|Orly|O|
Friedlander|Yechiel|Y|
Lawrence|Gabriella M|GM|
Paltiel|Ora|O|


Iron-loaded carbon nanotube-microfibrous composite for catalytic wet peroxide oxidation of m-cresol in a fixed bed reactor.

Abstract: A kind of novel iron-loaded carbon nanotube-microfibrous composite (Fe2O3-CNT-MF) catalyst is prepared and tested for fixed bed m-cresol catalytic wet peroxide oxidation (CWPO) reaction. Results show that the Fe2O3-CNT-MF can significantly decline the pressure drop of the fixed bed. Higher temperature, lower feed flow rate, higher catalyst bed height, and higher H2O2 dosage are beneficial to m-cresol degradation. Lower pH can also improve m-cresol degradation, but it will cause severe iron leaching. The highest m-cresol removal (over 99.5%) and total organic carbon (TOC) removal (53.6%) can be observed under condition of 2 cm bed height, flow rate of 2 mL/min, reaction temperature of 70 °C, 6 g/L H2O2, and initial pH = 1. Meanwhile, the Fe2O3-CNT-MF catalyst shows good stability with less than 10% decrease in m-cresol conversion and 7% decrease in TOC conversion after 24-h reaction and less than 2 mg/L iron leaching is observed in all conditions except for strong acid condition. Two probable pathways of m-cresol degradation process are presented. Under most conditions, m-cresol will first be turned into methylhydroquinone, followed by oxidation to p-toluquinone. In basic condition, some m-cresol will first be changed into 4-methylpyrocatechol. These aromatic intermediates will then be oxidized into some small molecular acids and finally be mineralized to CO2 and H2O.

Catalytic wet peroxide oxidation
m-Cresol
Carbon nanotube
Mechanism
Microfibrous composite


Organ-specific regulatory T cells of thymic origin are expanded in murine prostate tumors.

Abstract: Little is known about the relative contributions of self-specific regulatory T cells (Tregs) of thymic origin and induced Tregs generated extrathymically to the pool of tumor-infiltrating Tregs. We have recently demonstrated that thymic-derived Tregs reactive to a prostate-associated self antigen are highly and recurrently enriched within oncogene-driven murine prostate cancers.

Malchow|Sven|S|
Leventhal|Daniel S|DS|
Savage|Peter A|PA|

tumor
cancer
AIRE
FOXP3
development
induced regulatory T cells
thymus


Association between Visceral Fat and Brain Structural Changes or Cognitive Function.

Abstract: Visceral fat accumulation is an independent risk factor for cardiovascular disease and mortality. Visceral fat is a causal risk factor for hypertension and type 2 diabetes, which was reported as one of the risk factors for dementia. Visceral fat areas (VFA) might be clinically important to prevent dementia; however, the association between VFA and cognitive function in the elderly remains unknown. We aimed to evaluate the association between brain structural abnormalities using magnetic resonance imaging (MRI) and VFA, and the association between cognitive function and VFA, in the elderly. A total of 2364 healthy individuals were enrolled, and we excluded those diagnosed with dementia. Participants were divided into a high-VFA and a low-VFA group based on median VFA. The high-VFA group had significantly lower cognitive function than the low-VFA group (p = 0.025), after adjustment for related factors using a linear regression model. Regarding brain structure in MRI, VFA remained significantly associated with white matter lesions (odds ratio (OR), 1.90; 95% confidence interval (1.33-2.70); adjusted p < 0.001) and perivascular space (OR, 1.28; 95% confidence interval (1.02-1.61); adjusted p = 0.033). Further follow-up studies are needed, but reducing visceral fat might be important, not only to prevent cardiovascular disease but also to prevent dementia.

Ozato|Naoki|N|0000-0002-2038-4705 Saitou|Shinnichiro|S| Yamaguchi|Tohru|T|0000-0002-5946-1042 Katashima|Mitsuhiro|M| Misawa|Mina|M| Jung|Songee|S| Mori|Kenta|K| Kawada|Hiromitsu|H| Katsuragi|Yoshihisa|Y| Mikami|Tatsuya|T| Nakaji|Shigeyuki|S|

cognitive function
risk
cardiovascular disease
dementia
visceral fat area
elderly


An intramolecular chaperone inserted in bacteriophage P22 coat protein mediates its chaperonin-independent folding.

Abstract: The bacteriophage P22 coat protein has the common HK97-like fold but with a genetically inserted domain (I-domain). The role of the I-domain, positioned at the outermost surface of the capsid, is unknown. We hypothesize that the I-domain may act as an intramolecular chaperone because the coat protein folds independently, and many folding mutants are localized to the I-domain. The function of the I-domain was investigated by generating the coat protein core without its I-domain and the isolated I-domain. The core coat protein shows a pronounced folding defect. The isolated I-domain folds autonomously and has a high thermodynamic stability and fast folding kinetics in the presence of a peptidyl prolyl isomerase. Thus, the I-domain provides thermodynamic stability to the full-length coat protein so that it can fold reasonably efficiently while still allowing the HK97-like core to retain the flexibility required for conformational switching during procapsid assembly and maturation.

Suhanovsky|Margaret M|MM|
Teschke|Carolyn M|CM|

D017100:Bacteriophage P22
D036022:Capsid Proteins
D007700:Kinetics
D018832:Molecular Chaperones
D019696:Peptidylprolyl Isomerase
D017510:Protein Folding
D055550:Protein Stability
D017434:Protein Structure, Tertiary
D012486:Salmonella typhimurium

Bacteriophage
Protein Folding
Protein Self-assembly
Protein Stability
Virus Assembly


On-line solid-phase extraction coupled to liquid chromatography tandem mass spectrometry for the analysis of cyanotoxins in algal blooms.

Abstract: An analytical method based on on-line SPE-LC-HESI-MS/MS has been developed for the detection and quantification of eight selected cyanotoxins in algal bloom waters that include mycrocystins, anatoxin-a and cylindrospermopsin. The injection volume was 2 mL according to the expected concentration of cyanotoxins in matrix. The method provides an analysis time of 7 min per sample, acceptable recovery values (91-101%), good precision (RSD < 13%) and method limits of detection at the sub-microgram per liter levels (0.01-0.02 μg L(-1)). A detailed discussion on optimization parameters that have an impact on the overall performance of the method are presented. In particular, method optimization permitted the chromatographic separation of anatoxin-a and phenylalanine, an isobaric interference with a similar chromatographic characteristics. All optimization and validation experiments for the on-line SPE method and chromatographic separation were performed in environmentally relevant algal bloom water matrices. The applicability of the method was tested on several algal bloom water samples from monitored lakes across the province of Québec (Québec, Canada) known to produce cyanotoxins. All of the targeted cyanotoxins were detected with the exception of cylindrospermopsin. In addition, it was found that total microcystin concentrations in several surface water samples exceeded the proposed guidelines established by the province of Québec in Canada of 1.5 μg L(-1) as well as the World Health Organization of 1 μg L(-1) for both free and cell-bound microcystin-LR equivalent.

Fayad|Paul B|PB|
Roy-Lachapelle|Audrey|A|
Duy|Sung Vo|SV|
Prévost|Michèle|M|
Sauvé|Sébastien|S|

Mass spectrometry
Cyanotoxins
Microcystin
ANA-a
Anatoxin
Bleu green algae
Online SPE


Neck Circumference Is Associated With Hyperuricemia in Women With Polycystic Ovary Syndrome.

Abstract:
Objective
To evaluate the association between neck circumference (NC) and hyperuricemia in women with polycystic ovary syndrome (PCOS).

Methods
This is a cross-sectional study that recruited 601 women with PCOS from January 2018 to January 2021. PCOS was diagnosed according to the Rotterdam definition. Hyperuricemia was defined as serum uric acid level of at least 357 μmol/L.

Results
PCOS females with hyperuricemia had significantly greater values of NC, body mass index (BMI), waist circumference (WC) and hip circumference (HC). NC was positively associated with serum uric acid levels, with a standardized regression coefficient of 0.34 after adjusting for confounding factors. Furthermore, logistic regression analysis showed that NC was significantly associated with an increased risk of hyperuricemia, with an adjusted odds ratio of 1.36. The associations between NC and serum uric acid levels were more considerable in those with medium/high BMI (BMI ≥ 21.63 kg/m2), all ranges of WC or medium/high HC (HC ≥ 90 cm). The optimal cut-off point of NC in predicting hyperuricemia was 32.0 cm (Youden index = 0.48), with the sensitivity and negative predictive value of 84.81% and 92.08%, respectively.

Conclusions
NC was positively correlated with serum uric acid levels and the prevalence of hyperuricemia in women with PCOS. Therefore, we suggest NC as a simple, novel, and reliable anthropometric measure to be used in the routine clinical assessment of women with PCOS to screen those at high risk of hyperuricemia.

Yang|Haiyan|H| Liu|Chang|C| Jin|Congcong|C| Yu|Rong|R| Ding|Lin|L| Mu|Liangshan|L|

neck circumference
hyperuricemia
polycystic ovary syndrome
uric acid
anthropometric measurement


Bias-Free Chemically Diverse Test Sets from Machine Learning.

Abstract: Current benchmarking methods in quantum chemistry rely on databases that are built using a chemist's intuition. It is not fully understood how diverse or representative these databases truly are. Multivariate statistical techniques like archetypal analysis and K-means clustering have previously been used to summarize large sets of nanoparticles however molecules are more diverse and not as easily characterized by descriptors. In this work, we compare three sets of descriptors based on the one-, two-, and three-dimensional structure of a molecule. Using data from the NIST Computational Chemistry Comparison and Benchmark Database and machine learning techniques, we demonstrate the functional relationship between these structural descriptors and the electronic energy of molecules. Archetypes and prototypes found with topological or Coulomb matrix descriptors can be used to identify smaller, statistically significant test sets that better capture the diversity of chemical space. We apply this same method to find a diverse subset of organic molecules to demonstrate how the methods can easily be reapplied to individual research projects. Finally, we use our bias-free test sets to assess the performance of density functional theory and quantum Monte Carlo methods.

Swann|Ellen T|ET|0000-0002-0465-0380
Fernandez|Michael|M|
Coote|Michelle L|ML|0000-0003-0828-7053
Barnard|Amanda S|AS|

D016000:Cluster Analysis
D062126:Databases, Chemical
D000069550:Machine Learning
D008956:Models, Chemical
D025341:Principal Component Analysis
D011789:Quantum Theory
D013329:Structure-Activity Relationship
D013816:Thermodynamics

machine learning
benchmarking
quantum chemistry
bias-free test sets


The Impact of Multimorbidity and Coronary Disease Comorbidity on Physical Function in Women Aged 80 Years and Older: The Women's Health Initiative.

Abstract:
BACKGROUND
A better understanding of medically centered outcomes, such as physical function, for older women with multiple chronic conditions is a national public health priority.

METHODS
The prevalence of multimorbidity (defined as having 2 chronic conditions from a list of 12) and comorbidity with coronary disease (CHD) were calculated for 33,386 women who were enrolled in the Women's Health Initiative since 1993-1998 and were ≥ 80 years old by mid-September 2012. Associations between multimorbidity and CHD comorbidity on RAND-36 physical function scores were estimated using linear regression models.

RESULTS
The prevalence of multimorbidity in this sample was 59%. Women with 0-1 chronic condition had a mean physical function score of 74 (95% confidence interval [CI]: 73, 74). Relative decrements in physical function scores were -8 (95% CI: -8, -7), -13 (95% CI: -14, -12) and -19 (95% CI: -20, -18) in women with 2, 3, and ≥ 4 chronic conditions, respectively. Women with CHD in combination with hip fractures or cognitive impairment had the largest adjusted decreases in physical function scores compared to the scores for women with CHD only. The impact of select characteristics on physical function scores between multimorbid and non-multimorbid women were similar; however, overall mean physical functions scores were lower for women with multmorbidity.

CONCLUSIONS
Multimorbidity profoundly impacted physical functioning in women aged more than 80 years. Modifiable risk factors, such as obesity and physical activity, were similar in older women regardless of multimorbidity status and provide targets for health interventions aimed at preventing loss of late-age physical functioning.

Rillamas-Sun|Eileen|E|
LaCroix|Andrea Z|AZ|
Bell|Christina L|CL|
Ryckman|Kelli|K|
Ockene|Judith K|JK|
Wallace|Robert B|RB|

Multimorbidities
Physical function
Cardiovascular


A new look at population health through the lenses of cognitive, functional and social disability clustering in eastern DR Congo: a community-based cross-sectional study.

Abstract:
BACKGROUND
The importance of viewing health from a broader perspective than the mere presence or absence of disease is critical at primary healthcare level. However, there is scanty evidence-based stratification of population health using other criteria than morbidity-related indicators in developing countries. We propose a novel stratification of population health based on cognitive, functional and social disability and its covariates at primary healthcare level in DR Congo.

METHOD
We conducted a community-based cross-sectional study in adults with diabetes or hypertension, mother-infant pairs with child malnutrition, their informal caregivers and randomly selected neighbours in rural and sub-urban health zones in South-Kivu Province, DR Congo. We used the WHO Disability Assessment Schedule 2.0 (WHODAS) to measure functional, cognitive and social disability. The study outcome was health status clustering derived from a principal component analysis with hierarchical clustering around the WHODAS domains scores. We calculated adjusted odds ratios (AOR) using mixed-effects ordinal logistic regression.

RESULTS
Of the 1609 respondents, 1266 had WHODAS data and an average age of 48.3 (SD: 18.7) years. Three hierarchical clusters were identified: 9.2% of the respondents were in cluster 3 of high dependency, 21.1% in cluster 2 of moderate dependency and 69.7% in cluster 1 of minor dependency. Associated factors with higher disability clustering were being a patient compared to being a neighbour (AOR: 3.44; 95% CI: 1.93-6.15), residency in rural Walungu health zone compared to semi-urban Bagira health zone (4.67; 2.07-10.58), female (2.1; 1.25-2.94), older (1.05; 1.04-1.07), poorest (2.60; 1.22-5.56), having had an acute illness 30 days prior to the interview (2.11; 1.24-3.58), and presenting with either diabetes or hypertension (2.73; 1.64-4.53) or both (6.37; 2.67-15.17). Factors associated with lower disability clustering were being informally employed (0.36; 0.17-0.78) or a petty trader/farmer (0.44; 0.22-0.85).

CONCLUSION
Health clustering derived from WHODAS domains has the potential to suitably classify individuals based on the level of health needs and dependency. It may be a powerful lever for targeting appropriate healthcare service provision and setting priorities based on vulnerability rather than solely presence of disease.

Malembaka|Espoir Bwenge|EB|
Karemere|Hermès|H|
Balaluka|Ghislain Bisimwa|GB|
Lambert|Anne-Sophie|AS|
Muneza|Fiston|F|
Deconinck|Hedwig|H|
Macq|Jean|J|

Disability
Eastern DR Congo
WHODAS
Health clustering
Community
Medico-psychosocial


Long-term oncologic outcomes of liver resection for hepatocellular carcinoma in adolescents and young adults: A multicenter study from a hepatitis B virus-endemic area.

Abstract:
BACKGROUND
Hepatocellular carcinoma (HCC) is common among adolescents and young adults (AYAs) in areas with endemic hepatitis B virus infection. We sought to characterize clinical features and long-term outcomes among AYAs versus older adults (OAs) who underwent HCC resection.

METHODS
From a Chinese multicenter database, patients were categorized as AYA (aged 13-39 years) versus OA (aged ≥40 years). Patient clinical features, perioperative outcomes, overall survival (OS) and time-to-recurrence (TTR) were compared. Multivariable Cox-regression analyses were performed to identify the impact of age on OS and TTR.

RESULTS
Among 1952 patients, 354(22.2%) were AYAs. AYAs were less likely to have cirrhosis yet were likely to have advanced tumor pathological characteristics than OAs. Postoperative morbidity and mortality were comparable. Compared with OAs, AYAs had a comparable OS but a decreased TTR. Multivariable analyses identified that young age (<40 years) was independently associated with poorer TTR.

CONCLUSIONS
Compared with OAs, AYAs had a higher incidence of recurrence following liver resection among patients with HCC, suggesting that enhanced surveillance for postoperative recurrence may be required among AYAs.

Diao|Yong-Kang|YK|
Liu|Jun-Wei|JW|
Wu|Han|H|
Wang|Ming-Da|MD|
Fan|Xin-Ping|XP|
Chen|Ting-Hao|TH|
Wang|Jian-Yu|JY|
Zhou|Ya-Hao|YH|
Gu|Wei-Min|WM|
Wang|Hong|H|
Li|Jie|J|
Liang|Ying-Jian|YJ|
Chen|Zhi-Yu|ZY|
Lau|Wan Yee|WY|
Liang|Lei|L|
Li|Chao|C|
Zhang|Cheng-Wu|CW|
Shen|Feng|F|
Huang|Dong-Sheng|DS|
Yang|Tian|T|

Hepatocellular carcinoma
Adolescents and young adults
Overall survival
Time-to-recurrence
Hepatectomy


"When I Take Drugs, I Don't Care": Insights into the Operational Dynamics of Male Violent Offenders in a Correctional Centre.

Abstract: This study investigated the operational dynamics of male violent offenders incarcerated in Abakaliki custodial center, Nigeria. A cross-sectional survey research design was adopted and purposive technique used to recruit 260 inmates charged with violent offenses. The data generated from structured questionnaire were analyzed using Predictive Analytic Software (PAS), with ordinary least regression, descriptive statistics and spearman rank order correlation techniques, employed in testing the variables explored. Findings revealed that this population use drugs to enhance criminal performance through being brutal; instilling fear in victims to secure their total compliance and submission; and suppressing regret for their criminal acts. Heroin, followed by, cocaine, cannabis, tramadol, and multiple drug use, were commonly used drugs in the population surveyed, with their offenses ranging from cultism, armed robbery, murder and burglary to kidnapping and assault and battery. Gaining insights into the changing operational knowledge, procedures and dynamics of violent offenders will (re)direct policy approach and action that are capable of increasing public and custodial safety. It will also orient and direct practical prison reforms for successful rehabilitation and reintegration of released inmates into the free world.

drugs
insights
operational dynamics
violent offenders
custodial center


Determination and analysis of the complete mitochondrial genome sequence of Taoyuan chicken.

Abstract: Taoyuan chicken is excellent native breeds in China. This study firstly determined the complete mitochondrial genome sequence of Taoyuan chicken using PCR-based amplification and Sanger sequencing. The characteristic of the entire mitochondrial genome was analyzed in detail, with the base composition of 30.26% A, 23.79% T, 32.44% C, 13.50% G in the Taoyuan chicken (16,784 bp in length). It contained 2 ribosomal RNA genes, 13 protein-coding genes, 22 transfer RNA genes and a major non-coding control region (D-loop region). The complete mitochondrial genome sequence of Taoyuan chicken will be useful for the phylogenetics of poultry, and be available as basic data for the genetics and breeding.

Liu|Li-Li|LL| Xie|Hong-Bing|HB| Yu|Qi-Fang|QF| He|Shao-Ping|SP| He|Jian-Hua|JH|

D000818:Animals
D001482:Base Composition
D002645:Chickens
D004272:DNA, Mitochondrial
D050259:Genes, Mitochondrial
D054629:Genome, Mitochondrial
D012335:RNA, Ribosomal
D012343:RNA, Transfer
D017422:Sequence Analysis, DNA

mitochondrial
Genome
Taoyuan chicken
PCR method


Factors affecting treatment outcome in patients with idiopathic nonspecific interstitial pneumonia: a nationwide cohort study.

Abstract:
BACKGROUND
The effects of corticosteroid-based therapy in patients with idiopathic nonspecific interstitial pneumonia (iNSIP), and factors affecting treatment outcome, are not fully understood. We aimed to investigate the long-term treatment response and factors affecting the treatment outcome in iNSIP patients from a multi-center study in Korea.

METHODS
The Korean interstitial lung disease (ILD) Study Group surveyed ILD patients from 2003 to 2007. Patients were divided into two groups to compare the treatment response: response group (forced vital capacity (FVC) improves ≥10% after 1 year) and non-response group (FVC <10%). Factors affecting treatment response were evaluated by multivariate logistic regression analysis.

RESULTS
A total of 261 patients with iNSIP were enrolled, and 95 patients were followed-up for more than 1 year. Corticosteroid treatment was performed in 86 patients. The treatment group showed a significant improvement in lung function after 1-year: FVC, 10.0%; forced expiratory volume (FEV1), 9.8%; diffusing capacity of the lung for carbon monoxide (DLco), 8.4% (p < 0.001). Sero-negative anti-nuclear antibody (ANA) was significantly related with lung function improvement. Sero-positivity ANA was significantly lower in the response group (p = 0.013), compared to that in the non-response group. A shorter duration of respiratory symptoms at diagnosis was significantly associated with a good response to treatment (p = 0.018).

CONCLUSION
Treatment with corticosteroids and/or immunosuppressants improved lung function in iNSIP patients, which was more pronounced in sero-negative ANA and shorter symptom duration patients. These findings suggest that early treatment should be considered in iNSIP patients, even in an early disease stage.

Lee|Sang Hoon|SH|
Park|Moo Suk|MS|
Kim|Song Yee|SY|
Kim|Dong Soon|DS|
Kim|Young Whan|YW|
Chung|Man Pyo|MP|
Uh|Soo Taek|ST|
Park|Choon Sik|CS|
Park|Sung Woo|SW|
Jeong|Sung Hwan|SH|
Park|Yong Bum|YB|
Lee|Hong Lyeol|HL|
Shin|Jong Wook|JW|
Lee|Eun Joo|EJ|
Lee|Jin Hwa|JH|
Jegal|Yangin|Y|
Lee|Hyun Kyung|HK|
Kim|Yong Hyun|YH|
Song|Jin Woo|JW|
Park|Jong Sun|JS|

Treatment
Non-specific interstitial pneumonia
Pulmonary lung function


Evolution and functional analysis of odorant-binding proteins in three rice planthoppers: Nilaparvata lugens, Sogatella furcifera, and Laodelphax striatellus.

Abstract:
BACKGROUND
The white-backed planthopper (WBPH) Sogatella furcifera, the brown planthopper (BPH) Nilaparvata lugens, and the small brown planthopper (SBPH) Laodelphax striatellus are three notorious rice pests that cause annual losses in rice yield through sap-sucking and virus transmission. Odorant-binding proteins (OBPs) are crucial olfactory genes involved in host-seeking behavior.

RESULTS
We discovered the presence of 12, 12, and 16 OBPs in WBPH, BPH, and SBPH, respectively, including two novel OBPs in BPH and seven novel OBPs in SBPH. Phylogenetic analysis indicated that most of these OBPs have homologous genes, and one group (SfurOBP11, NlugOBP8, and LstrOBP2) show a slower evolution rate and are more conserved. Further, in vitro binding studies demonstrated that the three OBPs have similar binding affinities for some rice plant volatiles. Finally, RNA interference (RNAi) successfully inhibited the mRNA expression of the three OBPs, and in vivo behavioral tests showed that the OBP-deficient rice planthoppers were partly anosmic and lost some of their ability to locate rice plants.

CONCLUSION
These results demonstrate the crucial role of the rice planthopper OBP genes in seeking rice plants. This information complements the current genetic resources for the development of RNAi-based transgenic rice and other pest management technologies. © 2018 Society of Chemical Industry.

D000595:Amino Acid Sequence
D000818:Animals
D019143:Evolution, Molecular
D006430:Hemiptera
D019476:Insect Proteins
D008958:Models, Molecular
D010802:Phylogeny
D011487:Protein Conformation
D018035:Receptors, Odorant
D013045:Species Specificity

odorant-binding protein
rice planthoppers
host-seeking behavior
RNAi
binding properties
olfaction


CD84 is a regulator of the immunosuppressive microenvironment in multiple myeloma.

Abstract: Multiple myeloma (MM) is characterized by an accumulation of malignant plasma cells (PCs) within the BM. The BM microenvironment supports survival of the malignant cells and is composed of cellular fractions that foster myeloma development and progression by suppression of the immune response. Despite major progress in understanding the biology and pathophysiology of MM, this disease is still incurable and requires aggressive treatment with significant side effects. CD84 is a self-binding immunoreceptor belonging to the signaling lymphocyte activation molecule (SLAM) family. Previously, we showed that CD84 bridges between chronic lymphocytic leukemia cells and their microenvironment, and it regulates T cell function. In the current study, we investigated the role of CD84 in MM. Our results show that MM cells express low levels of CD84. However, these cells secrete the cytokine macrophage migration inhibitory factor (MIF), which induces CD84 expression on cells in their microenvironment. Its activation leads to an elevation of expression of genes regulating differentiation to monocytic/granulocytic-myeloid-derived suppressor cells (M-MDSCs and G-MDSCs, respectively) and upregulation of PD-L1 expression on MDSCs, which together suppress T cell function. Downregulation of CD84 or its blocking reduce MDSC accumulation, resulting in elevated T cell activity and reduced tumor load. Our data suggest that CD84 might serve as a novel therapeutic target in MM.

Lewinsky|Hadas|H|
Gunes|Emine G|EG|
David|Keren|K|
Radomir|Lihi|L|
Kramer|Matthias P|MP|
Pellegrino|Bianca|B|
Perpinial|Michal|M|
Chen|Jing|J|
He|Ting-Fang|TF|
Mansour|Anthony G|AG|
Teng|Kun-Yu|KY|
Bhattacharya|Supriyo|S|
Caserta|Enrico|E|
Troadec|Estelle|E|
Lee|Peter|P|
Feng|Mingye|M|
Keats|Jonathan|J|
Krishnan|Amrita|A|
Rosenzweig|Michael|M|
Yu|Jianhua|J|
Caligiuri|Michael A|MA|
Cohen|Yosef|Y|
Shevetz|Olga|O|
Becker-Herman|Shirly|S|
Pichiorri|Flavia|F|
Rosen|Steven|S|
Shachar|Idit|I|

Cancer
Cancer immunotherapy
Cellular immune response
Hematology
Oncology


MicroRNA-335-5p modulates spatial memory and hippocampal synaptic plasticity.

Abstract: MicroRNAs are endogenous, noncoding RNAs crucial for the post-transcriptional regulation of gene expression. In this study, we investigated the role of miR-335-5p in spatial learning and synaptic plasticity. To this end we first showed spatial learning induced down-regulation of miR-335-5p. Next we found impairment in long-term memory and reduction in hippocampal long-term potentiation by exogenous administration of the miRNA. These findings demonstrate that miR-335-5p is a key coordinator of the intracellular pathways that mediate experience-dependent changes in the brain.

Capitano|F|F|
Camon|J|J|
Licursi|V|V|
Ferretti|V|V|
Maggi|L|L|
Scianni|M|M|
Del Vecchio|G|G|
Rinaldi|A|A|
Mannironi|C|C|
Limatola|C|C|
Presutti|C|C|
Mele|A|A|


β-TrCP-dependent degradation of ASK1 suppresses the induction of the apoptotic response by oxidative stress.

Abstract: Apoptosis signal-regulating kinase 1 (ASK1) is a key player in the homeostatic response of many organisms. Of the many functions of ASK1, it is most well-known for its ability to induce canonical caspase 3-dependent apoptosis through the MAPK pathways in response to reactive oxygen species (ROS). As ASK1 is a regulator of apoptosis, its proper regulation is critical for the well-being of an organism. To date, several E3 ubiquitin ligases have been identified that are capable of degrading ASK1, signifying the importance of maintaining ASK1 expression levels during stress responses. ASK1 protein regulation under unstimulated conditions, however, is still largely unknown. Using tandem mass spectrometry, we have identified beta-transducin repeat containing protein (β-TrCP), an E3 ubiquitin ligase, as a novel interacting partner of ASK1 that is capable of ubiquitinating and subsequently degrading ASK1 through the ubiquitin-proteasome system (UPS). This interaction requires the seven WD domains of β-TrCP and the C-terminus of ASK1. By silencing the β-TrCP genes, we observed a significant increase in caspase 3 activity in response to oxidative stress, which could subsequently be suppressed by silencing ASK1. These findings suggest that β-TrCP is capable of suppressing oxidative stress-induced caspase 3-dependent apoptosis through suppression of ASK1, assisting in the organism's ability to maintain homeostasis in an unstable environment.

Cheng|Ran|R| Takeda|Kohsuke|K| Naguro|Isao|I| Hatta|Tomohisa|T| Iemura|Shun-Ichiro|SI| Natsume|Tohru|T| Ichijo|Hidenori|H| Hattori|Kazuki|K|

ASK1
Oxidative stress
Apoptosis
E3 ubiquitin ligase
β-TrCP
Ubiquitin-proteasome system


Development of a Non-Destructive Method for Detection of the Juiciness of Pear via VIS/NIR Spectroscopy Combined with Chemometric Methods.

Abstract: Juiciness is a primary index of pear quality and freshness, which is also considered as important as sweetness for the consumers. Development of a non-destructive detection method for pear juiciness is meaningful for producers and sellers. In this study, visible-near-infrared (VIS/NIR) spectroscopy combined with different spectral preprocessing methods, including normalization (NOR), first derivative (FD), detrend (DET), standard normal variate (SNV), multiplicative scatter correction (MSC), probabilistic quotient normalization (PQN), modified optical path length estimation and correction (OPLECm), linear regression correction combined with spectral ratio (LRC-SR) and orthogonal spatial projection combined with spectral ratio (OPS-SR), was used for comparison in detection of pear juiciness. Partial least squares (PLS) regression was used to establish the calibration models between the preprocessing spectra (650-1100 nm) and juiciness measured by the texture analyzer. In addition, competitive adaptive reweighted sampling (CARS) was used to identify the characteristic wavelengths and simplify the PLS models. All obtained models were evaluated via Monte Carlo cross-validation (MCCV) and external validation. The PLS model established by 19 characteristic variables after LRC-SR preprocessing displayed the best prediction performance with external verification determination coefficient (R2v) of 0.93 and root mean square error (RMSEv) of 0.97%. The results demonstrate that VIS/NIR coupled with LRC-SR method can be a suitable strategy for the quick assessment of juiciness for pears.

juiciness
pear
VIS/NIR spectroscopy
preprocessing


Fixing the broken clock in adrenal disorders: focus on glucocorticoids and chronotherapy.

Abstract: The circadian rhythm derives from the integration of many signals that shape the expression of clock-related genes in a 24-h cycle. Biological tasks, including cell proliferation, differentiation, energy storage, and immune regulation, are preferentially confined to specific periods. A gating system, supervised by the central and peripheral clocks, coordinates the endogenous and exogenous signals and prepares for transition to activities confined to periods of light or darkness. The fluctuations of cortisol and its receptor are crucial in modulating these signals. Glucocorticoids and the autonomous nervous system act as a bridge between the suprachiasmatic master clock and almost all peripheral clocks. Additional peripheral synchronizing mechanisms including metabolic fluxes and cytokines stabilize the network. The pacemaker is amplified by peaks and troughs in cortisol and their response to food, activity, and inflammation. However, when the glucocorticoid exposure pattern becomes chronically flattened at high- (as in Cushing's syndrome) or low (as in adrenal insufficiency) levels, the system fails. While endocrinologists are well aware of cortisol rhythm, too little attention has been given to interventions aimed at restoring physiological cortisol fluctuations in adrenal disorders. However, acting on glucocorticoid levels may not be the only way to restore clock-related activities. First, a counterregulatory mechanism on the glucocorticoid receptor itself controls signal transduction, and second, melatonin and/or metabolically active drugs and nutrients could also be used to modulate the clock. All these aspects are described herein, providing some insights into the emerging role of chronopharmacology, focusing on glucocorticoid excess and deficiency disorders.

Minnetti|Marianna|M|
Hasenmajer|Valeria|V|
Pofi|Riccardo|R|
Venneri|Mary Anna|MA|
Alexandraki|Krystallenia I|KI|
Isidori|Andrea M|AM|0000-0002-9037-5417


Analysis and Comparison of Rad-Hard Ring and LC-Tank Controlled Oscillators in 65 nm for SpaceFibre Applications.

Abstract: This work presented a comparison between two Voltage Controlled Oscillators (VCOs) designed in 65 nm CMOS technology. The first architecture based on a Ring Oscillator (RO) was designed using three Current Mode Logic (CML) stages connected in a loop, while the second one was based on an LC-tank resonator. This analysis aimed to choose a VCO architecture able to be integrated into a rad-hard Phase Locked Loop. It had to meet the requirements of the SpaceFibre protocol, which supports frequencies up to 6.25 GHz, for space applications. The full custom schematic and layout designs are shown, and Single Event Effect simulations results, performed with a double exponential current pulses generator, are presented in detail for both VCOs. Although the RO-VCO performances in terms of technology scaling and high-integration density were attractive, the simulations on the process variations demonstrated its inability to generate the target frequency in harsh operating conditions. Instead, the LC-VCO highlighted a lower influence through Process-Voltage-Temperature simulations on the oscillation frequency. Both architectures were biased with a supply voltage of 1.2 V. The achieved results for the second architecture analyzed were attractive to address the requirements of the new SpaceFibre aerospace standard.

SpaceFibre
ring oscillator
LC-tank oscillator
high-speed data transfer
rad-hard circuits
radiation effects


Consumption of processed and pickled food and esophageal cancer risk: A systematic review and meta-analysis.

Abstract: Previous investigations yielded inconsistent results for association of esophageal cancer (EC) risk and intake of processed food (including pickled food) or pickled food alone. The aim of this study was to perform a systematic review and meta-analysis of data exploring association of EC risk and intake of processed food (including pickled food) or pickled food alone. We systematically searched on PubMed and Web of Science for association of EC risk and intake of processed and pickled food published from 1964 to April 2018. We computed the multivariate odd ratio (OR) or relative risk (RR) and 95% confidence intervals (CI), comparing the highest and the lowest categories of processed or pickled food intake. The present meta-analysis showed that the highest categories of processed food intake were associated with a 78% increase in EC risk compared with the lowest categories. In addition, meta-analysis results indicated that the combined OR/RRs (95%CI) of studies comparing the highest and lowest categories were 2.10 (1.64-2.69) for pickled food. Subgroup study indicated significant positive associations between EC risk and intake of processed food or pickled food in case-control studies (combined ORs: processed food: 1.93 (95%CI: 1.66-2.24), pickled food: 2.28 (95%CI: 1.93-2.70)), whereas no significant associations were detected between them in cohort studies (combined RRs: processed food: 1.24 (95%CI: 0.98-1.58), pickled food: 1.43 (95%CI: 0.85-2.42)). In conclusion, this study suggests that both a high consumption of processed and pickled food may increase the EC risk.

Pickled food
Esophageal cancer
Meta-analysis
Processed food
Aliments transformés
Cancer de l'oesophage
Méta-analyse
Nourriture marinée


InSb Nanowires with Built-In GaxIn1-xSb Tunnel Barriers for Majorana Devices.

Abstract: Majorana zero modes (MZMs), prime candidates for topological quantum bits, are detected as zero bias conductance peaks (ZBPs) in tunneling spectroscopy measurements. Implementation of a narrow and high tunnel barrier in the next generation of Majorana devices can help to achieve the theoretically predicted quantized height of the ZBP. We propose a material-oriented approach to engineer a sharp and narrow tunnel barrier by synthesizing a thin axial segment of GaxIn1-xSb within an InSb nanowire. By varying the precursor molar fraction and the growth time, we accurately control the composition and the length of the barriers. The height and the width of the GaxIn1-xSb tunnel barrier are extracted from the Wentzel-Kramers-Brillouin (WKB) fits to the experimental I-V traces.

Car|Diana|D|0000-0002-6371-8285
Conesa-Boj|Sonia|S|
Zhang|Hao|H|
Op Het Veld|Roy L M|RL|
de Moor|Michiel W A|MW|
Fadaly|Elham M T|EM|
Gül|Önder|Ö|
Kölling|Sebastian|S|
Plissard|Sebastien R|SR|
Toresen|Vigdis|V|
Wimmer|Michael T|MT|
Watanabe|Kenji|K|0000-0003-3701-8119
Taniguchi|Takashi|T|
Kouwenhoven|Leo P|LP|
Bakkers|Erik P A M|EP|

tunnel barrier
Semiconductor nanowire
axial heterostructure
band engineering
indium antimonide
strain mapping


Using a multidimensional prognostic index (MPI) based on comprehensive geriatric assessment (CGA) to predict mortality in elderly undergoing transcatheter aortic valve implantation.

Abstract:
BACKGROUND
Selection of appropriate elderly who can benefit from transcatheter aortic valve implantation (TAVI) is challenging. We evaluated the prognosis of this procedure according to the comprehensive geriatric assessment (CGA) based on the multidimensional prognostic index (MPI).

METHODS
Prospective observational monocentric study from January 2013 to December 2015. Consecutive patients aged ≥75 who underwent TAVI and a complete CGA were included. Baseline demographic, geriatric and cardiologic data were collected. CGA was used to calculate the MPI score that is divided in three groups according to the mortality risk. Follow up was performed until December 2016 and mortality rate was assessed at one, six and 12months.

RESULTS
116 patients were included. Mean age was 86.2±4.2years, mean European system for cardiac operative risk evaluation (EuroSCORE) was 19.2±11.3%, mean MPI score was 0.39±0.13. Forty-five (38.8%) patients belonged to MPI-1 group, 68 (58.6%) to MPI-2 group and three to MPI-3 group. MPI score and Euroscore were moderately correlated (Spearman correlation coefficient rs=0.27, p=0.0035). Mortality rate was significantly different between MPI groups at six and 12months (p=0.040 and p=0.022). Kaplan Meier survival estimates at one year stratified by MPI groups was significantly different (hazard ratio HR=2.83, 95%confidence interval (CI) 1.38-5.82, p=0.004). Among variables retained to perform logistic regression analysis, the score of instrumental activities of daily living appeared the most relevant (p<0.001).

CONCLUSION
This study indicates that CGA based on MPI tool is accurate to predict prognosis in elderly patients undergoing TAVI procedure.

Bureau|Marie-Laure|ML| Liuu|Evelyne|E| Christiaens|Luc|L| Pilotto|Alberto|A| Mergy|Jean|J| Bellarbre|Fabienne|F| Ingrand|Pierre|P| Paccalin|Marc|M| |||

D065467:Transcatheter Aortic Valve Replacement

Multidimensional prognostic index
Mortality
Elderly
Transcatheter aortic valve implantation
Prognosis


Strongyloides stercoralis colitis in a patient positive for human T-cell leukaemia virus with rheumatoid arthritis during an anti-rheumatic therapy: a case report.

Abstract: An elderly woman with rheumatoid arthritis (RA) presented with a chief complaint of abdominal pain and diarrhoea while undergoing treatment with low-dose corticosteroids and abatacept. Endoscopic and histopathological findings revealed manifestations of ulcerative colitis (UC). An intermediate dose of corticosteroids and 5-aminosalicylic acid were administered. Abatacept was discontinued; the anti-TNF biologic, golimumab, was administered for treatment of both RA and UC. However, colitis worsened in response to this therapeutic regimen. Colonoscopy revealed severe mucosal lesions; larvae were detected in samples taken from multiple shallow mucosal ulcers. The patient was diagnosed with Strongyloides stercoralis colitis based on the results of an anti-parasite antibody test and examination of the larval DNA. Furthermore, serology revealed a positive test for antibodies against human T-cell leukaemia virus type 1 (HTLV-1). Immunosuppressive treatment was terminated; ivermectin was administered, which resulted in improvements in colitis symptoms within a few weeks. There are several published reports describing S. stercoralis colitis as a lethal mimic of UC. Corticosteroid and anti-TNF therapies have been reported as among the major risk factors associated with strongyloidiasis in patients with HTLV-1 infection. Therefore, HTLV-1 and Strongyloides infections may be considered in cases of new-onset gastrointestinal symptoms during immunosuppressive therapy, particularly in HTLV-1-endemic regions.

Hashiba|Yayoi|Y| Umekita|Kunihiko|K| Minami|Hiroyuki|H| Kawano|Atsuko|A| Nagayasu|Eiji|E| Maruyama|Haruhiko|H| Hidaka|Toshihiko|T| Okayama|Akihiko|A|

D000079424:Tumor Necrosis Factor Inhibitors

rheumatoid arthritis
biologics
human T-cell leukaemia virus type 1
Strongyloidiasis
parasite infection


Safety of Ustekinumab in Inflammatory Bowel Disease: Pooled Safety Analysis of Results from Phase 2/3 Studies.

Abstract:
BACKGROUND
Ustekinumab is currently approved globally in Crohn's disease (CD) and psoriatic diseases. Recent phase 3 data demonstrate safety/efficacy in ulcerative colitis (UC). Crohn's disease and UC phase 3 programs had similar study designs, facilitating integrated safety analyses.

METHODS
Data from 6 ustekinumab phase 2/3 CD and UC studies were pooled, and safety was evaluated through 1 year. Patients received 1 placebo or ustekinumab (generally 130 mg or ~6 mg/kg) intravenous induction, then subcutaneous (90 mg) maintenance every 8/12 weeks. Analyses incorporated all patients who received ≥1 ustekinumab dose. Safety outcomes are presented as percentages of patients (induction) and as number of patients with events per 100 patient-years of follow-up (through 1 year). For key safety events, 95% confidence intervals (CIs) are provided, as appropriate. Hazard ratios with 95% CIs from time-to-event analyses for serious adverse events and serious infections were also performed.

RESULTS
Through 1 year, 2574 patients received ustekinumab (1733 patient-years of follow-up). The number of patients with adverse events per 100 patient-years (placebo 165.99 [95% CI, 155.81-176.67] vs ustekinumab 118.32 [95% CI, 113.25-123.55]), serious AEs (27.50 [95% CI, 23.45-32.04] vs 21.23 [95% CI, 19.12-23.51]), infections (80.31 [95% CI, 73.28-87.84] vs 64.32 [95% CI, 60.60-68.21]), serious infections (5.53 [95% CI, 3.81-7.77] vs 5.02 [95% CI, 4.02-6.19]), and malignancies excluding nonmelanoma skin cancer (0.17 [95% CI, 0.00-0.93] vs 0.40 [95% CI, 0.16-0.83]) were similar between placebo and ustekinumab.

CONCLUSIONS
The safety profile of ustekinumab across the pooled inflammatory bowel disease population through 1 year was favorable and generally comparable to placebo. These data are consistent with the established safety profile of ustekinumab across indications.

CLINICALTRIALS.GOV NUMBERS
NCT00265122; NCT00771667; NCT01369329; NCT01369342; NCT01369355; NCT02407236.

Sandborn|William J|WJ|
Feagan|Brian G|BG|
Danese|Silvio|S|
O'Brien|Christopher D|CD|
Ott|Elyssa|E|
Marano|Colleen|C|
Baker|Thomas|T|
Zhou|Yiying|Y|
Volger|Sheri|S|
Tikhonov|Ilia|I|
Gasink|Christopher|C|
Sands|Bruce E|BE|
Ghosh|Subrata|S|

safety
ustekinumab
inflammatory bowel disease


Effect of Polymers and Storage Relative Humidity on Amorphous Rebamipide and Its Solid Dispersion Transformation: Multiple Spectra Chemometrics of Powder X-Ray Diffraction and Near-Infrared Spectroscopy.

Abstract: This study aimed to investigate the effect of polymers and storage relative humidity on amorphous rebamipide (RB) and its solid dispersion phase transformation using chemometrics based on multiple datasets. The amorphous RB was prepared using particle mixture and grinding methods with hydroxypropyl cellulose, polyvinylpyrrolidone, and sodium dodecyl sulfate. Prepared amorphous RB and solid dispersion samples were stored under a relative humidity of 30% and 75% for four weeks. Infrared spectra of the dispersion samples suggested that the hydrogen bond network was constructed among quinolinone, carbonyl acid, and amide of RB and other polymers. The dataset combining near-infrared (NIR) spectra and powder X-ray diffractograms were applied to principal component analysis (PCA). The relationship between diffractograms and NIR spectra was evaluated using loadings and the PCA score. The multiple spectra analysis is useful for evaluating model amorphous active pharmaceutical ingredients without a standard sample.

rebamipide
X-ray diffraction
near-infrared spectroscopy
principal component analysis


Trending autoregulatory indices during treatment for traumatic brain injury.

Abstract: Our goal is to use automatic data monitoring for reliable prediction of episodes of intracranial hypertension in patients with traumatic brain injury. Here we test the validity of our method on retrospective patient data. We developed the Continuous Hemodynamic Autoregulatory Monitor (CHARM), that siphons and stores signals from existing monitors in the surgical intensive care unit (SICU), efficiently compresses them, and standardizes the search for statistical relationships between any proposed index and adverse events. CHARM uses an automated event detector to reliably locate episodes of elevated intracranial pressure (ICP), while eliminating artifacts within retrospective patient data. A graphical user interface allowed data scanning, selection of criteria for events, and calculating indices. The pressure reactivity index (PRx), defined as the least square linear regression slope of intracranial pressure versus arterial BP, was calculated for a single case that spanned 259 h. CHARM collected continuous records of ABP, ICP, ECG, SpO2, and ventilation from 29 patients with TBI over an 18-month period. Analysis of a single patient showed that PRx data distribution in the single hours immediately prior to all 16 intracranial hypertensive events, significantly differed from that in the 243 h that did not precede such events (p < 0.0001). The PRx index, however, lacked sufficient resolution as a real-time predictor of IH in this patient. CHARM streamlines the search for reliable predictors of intracranial hypertension. We report statistical evidence supporting the predictive potential of the pressure reactivity index.

Kim|Nam|N| Krasner|Alex|A| Kosinski|Colin|C| Wininger|Michael|M| Qadri|Maria|M| Kappus|Zachary|Z| Danish|Shabbar|S| Craelius|William|W|

Traumatic brain injury
ICP
PRx
ABP
TBI
Autoregulation
Informatics SICU


Supracerebellar-Infratrochlear Approach for Midbrain Cavernoma: 3-Dimensional Operative Video.

Abstract: Gravity retraction is an underutilized adjunct in neurosurgery. Gravity is gentler than retractor blades; it does not cause brain edema or injury, and it tends to open natural subarachnoidal plans to deep lesions.1-3 A good example of this is the supracerebellar infratrochlear approach4-7 in semisitting position for resection to a midbrain cavernous malformation. This approach was selected because the cavernous malformation was 1 mm under the lateral mesencephalic sulcus. The procedure was developed with the use of transesophageal ultrasound and physiological neuromonitoring. We present a 3-dimensional video of this surgery with all the tricks and details used in the procedure. The patient consented to the procedure and to publication of the photos and surgical video.

Campero|Alvaro|A|
Román|Guillermo|G|
Baldoncini|Matías|M|
Villalonga|Juan F|JF|

Supracerebellar-infratrochlear approach
Midbrain
Cavernoma
Semisitting position
Gravidity


Population access to reperfusion services for ST-segment elevation myocardial infarction in Kerala, India.

Abstract:
BACKGROUND
Population access to timely reperfusion is a decisive factor in determining the success and acceptability of any regional system of ST-segment elevation myocardial infarction (STEMI) care. We sought to determine the proportion of population of the southern Indian state of Kerala having timely access to STEMI reperfusion.

METHODS
We identified the STEMI reperfusion facilities available at all acute-care hospitals, in Kerala, by conducting a cross-sectional survey. We mapped the geographical catchment areas of these hospitals using historical travel speeds and appropriate Geospatial Information Systems (GIS) analyses. Subsequently, using block level population data, we estimated the proportion of the population residing within these geographies.

RESULTS
We estimated that 23.33 million people, forming 69.84% of the state population, resided in the green zone (within half-hour travel distance of a percutaneous coronary intervention [PCI]-capable hospital), which covered 47.94% of the geographical area of the state. Outside this green zone, 21.87% of the state population resided within 1hr travel distance of a thrombolysis-capable hospital. Finally, 8.28% of the state population resided in the red zone, where access to any reperfusion-capable hospital took >1hr, which covered 22.15% of the geographical area of the state.

CONCLUSIONS
A majority of the population of Kerala had timely access to PCI-capable hospitals. GIS-based mapping of Indian states, in terms of access to STEMI reperfusion, may help devise protocols to achieve seamless transfer of patients to reperfusion-capable hospitals. Such regionalization of STEMI care would enhance organizational synergies to achieve better access to reperfusion, especially in remote areas.

Mathew|Anoop|A|
Abdullakutty|Jabir|J|
Sebastian|Placid|P|
Viswanathan|Sunitha|S|
Mathew|Cibu|C|
Nair|Venugopalan|V|
Mohanan|Padinhare P|PP|
George Koshy|A|A|

D010043:Outcome and Process Assessment, Health Care


Homosalate aggravates the invasion of human trophoblast cells as well as regulates intracellular signaling pathways including PI3K/AKT and MAPK pathways.

Abstract: Homosalate is an organic ultraviolet filter used in most sunscreens but has been reported to be toxic to marine organisms. The estrogenic activity of homosalate has also been reported, but its endocrine-disrupting effect remains unclear. Although homosalate has been detected in human placental tissues, its effect on the survival of human trophoblast cells needs to be investigated. Therefore, in this study, we evaluated if HTR8/SVneo, a human trophoblast cell line, treated with homosalate showed decreasing proliferative activity in a dose-dependent manner. Homosalate promoted the death of HTR8/SVneo cells with elevated lipid peroxidation and intracellular Ca2+ concentration. It also induced endoplasmic reticulum stress and mitochondrial morphological disturbances associated with the differentiation of human trophoblast cells. However, when the intracellular Ca2+ or reactive oxygen species were removed using BAPTA-AM or N-acetyl-L-cysteine (NAC), the cell proliferation suppressed by homosalate was restored. Homosalate also significantly inhibited the invasion of HTR8/SVneo cells. Furthermore, it modulated phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) signaling pathways, which were involved in the cross-talk between both signaling pathways in HTR8/SVneo cells. Thus, homosalate adversely affects the survival, proliferation, and invasiveness of human trophoblast cells and therefore pregnant women should practice caution while using personal care products containing homosalate.

Yang|Changwon|C|
Lim|Whasun|W|
Bazer|Fuller W|FW|
Song|Gwonhwa|G|

Homosalate Invasion Trophoblasts Proliferation Apoptosis


Pollution at schools and children's aerobic capacity.

Abstract: Poor respiratory health is a major cause of mortality and morbidity worldwide, and children are especially vulnerable. Existing research in economics has documented the effect of pollution on severe health outcomes, such as hospitalizations for asthma and infant death. However, evidence on the effect of air pollution on less extreme measures of respiratory health is limited, because these effects are difficult to measure. Using a more sensitive measure, aerobic capacity (  ), I study the impact of air pollution on respiratory performance of children. I combine school-grade level data from the California Physical Fitness Test from 2009 to 2017 with local air pollution and weather data to estimate the impact on student aerobic capacity of fluctuations in air pollution levels on testing days. Ozone affects child aerobic capacity at levels even below the Environmental Protection Agency thresholds.

schools
aerobic capacity
air pollution
child health


Exploiting Distal Reactivity of Coumarins: A Rhodium-Catalyzed Vinylogous Asymmetric Ring-Opening Reaction.

Abstract: While the utility of vinylogous enolates is well established in the setting of vinylogous aldol, Mannich, and Michael chemistries, literature reports concerning γ-reactivity are scarce for other reaction classes. Presented herein is an unprecedented example of vinylogous reactivity exemplified by the rhodium-catalyzed asymmetric ring-opening reaction of oxabicycles. This strategy also provides a powerful route to incorporate the biologically useful coumarin motif into the hydronapthalene scaffold.

ring-opening reactions
enantioselectivity
heterocycles
rhodium
synthetic methods


First neuroinvasive human case of West Nile Disease in Southern Italy: Results of the 'One Health' approach.

Abstract:
BACKGROUND
West Nile Disease (WND) is a zoonotic mosquito-borne infection involving viral pathogens, human and animal hosts, vectors and environment. Cooperation among medical, veterinary and entomological fields has been promoted by the Italian Public Health Authorities, and an integrated West Nile Virus (WNV) Surveillance Plan has been in force in Italy since 2016 to prevent the transmission risk of WND to humans through an early detection of viral circulation by animal and entomological surveillance. This managing model is unique in Europe.

OBJECTIVES
This survey aimed at presenting the 'One Health' approach applied in 2016 to the first autochthonous human case of West Nile Neuroinvasive Disease (WNND) in Sicily (Southern Italy).

METHODS
Serological (anti-WNV IgM and IgG ELISA, anti-WNV neutralizing antibodies) and molecular tests were conducted on blood, liquor and urine of a 38-year-old man with encephalitis and meningitis. Overall, 2704 adult culicides from 160 mosquito catches were morphologically identified. Female mosquitoes were analysed in pools for WNV RNA detection. Serological (anti-WNV IgM and IgG ELISA) and molecular analyses for WNV were carried out in 11 horses, 271 chickens and two dogs sampled in farms around the man's residence.

RESULTS AND CONCLUSIONS
WNND was confirmed by serological analysis on patient's liquor and serum. Collected mosquito species included Culex pipiens (93.56%, CI95% 92.64%-94.49%), Aedes albopictus (5.25%, CI95% 4.41%-6.09%), Culex hortensis (0.59%, CI95% 0.30%-0.88%), Culiseta longiareolata (0.55%, CI95% 0.27%-0.83%) and Anopheles maculipennis s.l. (0.04%, CI95% -0.04% to 0.11%). Mosquito pools were negative for WNV RNA. Two dogs (100%) and two horses (18.18%, CI95% -4.61 to 40.97%) resulted positive for anti-WNV specific antibodies. The 'One Health' approach allowed to report the first human neuroinvasive WND in Sicily and to confirm the local circulation of WNV in animals of the same area where the clinical case occurred, defining the autochthonous origin of the infection.

Macaluso|Giusi|G|
Gucciardi|Francesca|F|
Guercio|Annalisa|A|
Blanda|Valeria|V|
La Russa|Francesco|F|
Torina|Alessandra|A|
Mira|Francesco|F|
Bella|Santina Di|SD|
Lastra|Antonio|A|
Giacchino|Ilenia|I|
Castronovo|Calogero|C|
Vitale|Giustina|G|
Purpari|Giuseppa|G|

human case
Italy
West Nile Virus
mosquito
Integrated Surveillance System
‘One Health’


The genotype distribution of hepatitis C in southeastern Taiwan: Clinical characteristics, racial difference, and therapeutic response.

Abstract: The genotypes of hepatitis C virus (HCV) are associated with the therapeutic response. The racial diversity of Taitung, Taiwan is heterogeneous and a distinguishing feature; how such racial differences influence the genotype distribution and treatment outcome has not been well studied. The objective of this study is to elucidate the HCV genotype distribution in southeastern Taiwan and to analyze the racial differences influencing genotypes and clinical implications. In this retrospective cohort study, we included 343 patients who had been treated with peginterferon-alpha plus ribavirin. The predominant HCV genotype in the southeastern area was type 1 (43.7%), followed by type 2 (37.0%). The proportion of patients mixed with genotype 1 was lower in indigenous vis-à-vis nonindigenous groups (46.1% and 60.2%, p = 0.02). The prevalence of genotype 6 (5.2%) seems higher than in the general population of Taiwan and showed no difference between indigenous and nonindigenous people. The sustained virological response rate was higher in patients without genotype 1, low baseline HCV RNA (≤ 400,000 IU/mL), and in patients who achieved rapid virological response. Racial differences did not influence the therapeutic response. In this retrospective study, the proportion of HCV genotype 6 appeared slightly higher in southeastern areas than in the general population in Taiwan. The prevalence of genotype 1 in indigenous people was statistically lower than in nonindigenous people. Sustained virological response rate did not show any significant difference between indigenous and nonindigenous people in the current study.

Cheng|Chun-Han|CH| Chen|Huan-Lin|HL| Lin|I-Tsung|IT| Wu|Chia-Hsien|CH| Lee|Yuan-Kai|YK| Wong|Ming-Wun|MW| Bair|Ming-Jong|MJ|

Genotype
Hepatitis C
Therapeutics
Austronesian
Ethnic group


Quantitative Nonlinear Contrast-Enhanced Ultrasound of the Breast.

Abstract:
OBJECTIVE
Breast cancer is the most frequent type of cancer among women (25% of all cancers). The angiogenic process that fuels the growth of tumors is a potential early indicator for differentiating between malignant and benign tumors. Recently, the use of microbubble-based contrast agents combined with ultrasound has allowed the development of contrast agent-specific imaging modes that provide visualization of tumor neovascularity.

CONCLUSION
Contrast-enhanced Doppler, harmonic, and subharmonic imaging are some of the imaging modes that have been investigated for visualizing and quantifying the vascularity in breast tumors.

Sridharan|Anush|A|
Eisenbrey|John R|JR|
Dave|Jaydev K|JK|
Forsberg|Flemming|F|

ultrasound
breast
subharmonic imaging
microbubble contrast agent


Profile of rheumatology patients willing to report adverse drug reactions: bias from selective reporting.

Abstract:
BACKGROUND
Adverse drug reactions (ADRs) have a significant impact on human health and health care costs. The aims of our study were to determine the profile of rheumatology patients willing to report ADRs and to identify bias in such a reporting system.

METHODS
Semi-intensive ADRs reporting system was used in our study. Patients willing to participate (N=261) completed the questionnaire designed for the purpose of the study at the hospital admission. They were subsequently classified into two groups according to their ability to identify whether they had experienced ADRs during the previous month. Group 1 included 214 out of 261 patients who were able to identify ADRs, and group 2 consisted of 43 out of 261 patients who were not able to identify ADRs in their recent medical history.

RESULTS
Group 1 patients were more significantly aware of their diagnosis than the patients from group 2. Marginal significance was found between rheumatology patients with and without neurological comorbidities regarding their awareness of ADRs. The majority of patients reported ADRs of cytotoxic drugs. The most reported ADRs were moderate gastrointestinal discomforts.

CONCLUSION
We may draw a profile of rheumatological patients willing to report ADRs: 1) The majority of them suffer from systemic inflammatory diseases and are slightly more prone to neurological comorbidities. 2) They are predominantly aware of their diagnosis but less able to identify the drugs that may cause their ADRs. 3) They tend to report mainly moderate gastrointestinal ADRs; that is, other cohorts of patients and other types of ADRs remain mainly undetected in such a reporting, which could represent a bias. Counseling and education of patients as well as developing a network for online communication might improve patients' reporting of potential ADRs.

Protić|Dragana|D| Vujasinović-Stupar|Nada|N| Bukumirić|Zoran|Z| Pavlov-Dolijanović|Slavica|S| Baltić|Snežana|S| Mutavdžin|Slavica|S| Marković-Denić|Ljiljana|L| Zdravković|Marija|M| Todorović|Zoran|Z|

rheumatology
adverse drug reactions
bias
patient reporting system


Comfort goal of care and end-of-life outcomes in dementia: A prospective study.

Abstract:
BACKGROUND
Many people with dementia die in a nursing home. A comfort care goal may be beneficial. Little research has examined the relationship between care goals and outcome.

AIM
To investigate whether family satisfaction with end-of-life care and quality of dying is associated with whether or not dementia patients have a comfort goal shortly after admission.

DESIGN AND SETTING
Prospective data collection from 28 long-term care facilities (the Dutch End of Life in Dementia study). We included 148 patients who died after prospective follow-up. Main outcomes were family satisfaction (End-of-Life in Dementia-Satisfaction with Care scale; range: 10-40) and quality of dying (End-of-Life in Dementia-Comfort Assessment in Dying; range: 14-42). We performed generalized estimating equations regression analyses to analyze whether these outcomes are associated with a comfort goal established shortly after admission compared with another or no care goal as reported by the physician.

RESULTS
Families of patients were more satisfied with end-of-life care when a comfort goal was established shortly after admission. We found this pattern only for patients who died within 6 months of admission (adjusted b: 4.5; confidence interval: 2.8, 6.3 vs -1.2; confidence interval: -3.0, 0.6 for longer stay). For quality of dying, no such association was found.

CONCLUSION
We found that family satisfaction with care is related to a comfort care goal shortly after admission, but quality of dying did not. Establishing a comfort goal at an early stage may be important to the family. Advance care planning interventions should be studied for their effects on patient and family outcome.

van Soest-Poortvliet|Mirjam C|MC|
van der Steen|Jenny T|JT|
de Vet|Henrica C W|HC|
Hertogh|Cees M P M|CM|
Deliens|Luc|L|
Onwuteaka-Philipsen|Bregje D|BD|

dementia
nursing homes
advance care planning
Palliative care
long-term-care


Genetic analysis of hereditary gingival fibromatosis using whole exome sequencing and bioinformatics.

Abstract:
OBJECTIVES
Our study aims to identify genetic variants associated with hereditary gingival fibromatosis (HGF) by applying whole-exome sequencing (WES) and bioinformatics analyses such as gene set enrichment analysis (GSEA) and protein functional network study.

SUBJECTS AND METHODS
Two affected siblings whose grandparents and parents have normal gingiva were chosen for our investigation. Saliva collected from the patients and their parents were used for WES. GSEA and protein functional network study were performed to find gene groups in a biological coordination which are associated with HGF.

RESULTS
Genetic variants for homozygotes and compound heterozygotes were analyzed and translated into 845 genes. The result from protein functional network study showed that these genetic variants were mainly observed in genes affecting fibronectin as well as the immune and autoimmune system. Additionally, three mutated genes in our HGF patients, TMCO1, RIN2, and INSR, were found through human phenotype ontology (HPO) to have potential to contribute to gingival hyperplasia.

CONCLUSIONS
Genetic analysis of HGF in this study implicated mutations in fibronectin and the immune system as triggering abnormal gingival fibromatosis.

Hwang|J|J|
Kim|Y-L|YL|
Kang|S|S|
Kim|S|S|
Kim|S-O|SO|
Lee|J H|JH|
Han|D-H|DH|

D020022:Genetic Predisposition to Disease

D020662:Guanine Nucleotide Exchange Factors

hereditary gingival fibromatosis
bioinformatics
whole-exome sequencing
fibronectin
gingival hyperplasia


Considerations of critical quality attributes in the analytical comparability assessment of biosimilar products.

Abstract: Based on experience in clinical trial approvals and marketing authorizations for biosimilar products in Korea, we suggest principles for the analytical comparability assessment of biosimilar products with respect to regulatory considerations. The composition and manufacturing processes of biosimilar products can differ from those of the reference product depending on the information available for the reference product and the time of product development; however, the analytical characteristics of biosimilar products should be highly similar to those of the reference product. Although manufacturing an identical product in terms of the quality profile is nearly impossible due to the high molecular weight and complex structure of biological products, the developer of the biosimilar product should attempt to establish a quality level as similar to that of the reference product as possible. When comparing the similarity of quality attributes, the criticality of the quality attributes and the characteristics of orthogonal quality attributes need to be considered carefully. Based on the results from the analytical comparability assessment, the comparability results of non-clinical and clinical studies should be evaluated before claiming biosimilarity to the reference product. In this review, we focus on quality attribute evaluation based on our regulatory experience.

Kwon|Ohseok|O|
Joung|Jeewon|J|
Park|Younjoo|Y|
Kim|Chan Wha|CW|
Hong|Seung Hwa|SH|

D000818:Animals
D059451:Biosimilar Pharmaceuticals
D004341:Drug Evaluation
D004345:Drug Industry
D006801:Humans
D056910:Republic of Korea

Criticality
Quality attribute
Analytical comparability
Biosimilar product
Biosimilarity
Monoclonal antibody


Improved methods for predicting peptide binding affinity to MHC class II molecules.

Abstract: Major histocompatibility complex class II (MHC-II) molecules are expressed on the surface of professional antigen-presenting cells where they display peptides to T helper cells, which orchestrate the onset and outcome of many host immune responses. Understanding which peptides will be presented by the MHC-II molecule is therefore important for understanding the activation of T helper cells and can be used to identify T-cell epitopes. We here present updated versions of two MHC-II-peptide binding affinity prediction methods, NetMHCII and NetMHCIIpan. These were constructed using an extended data set of quantitative MHC-peptide binding affinity data obtained from the Immune Epitope Database covering HLA-DR, HLA-DQ, HLA-DP and H-2 mouse molecules. We show that training with this extended data set improved the performance for peptide binding predictions for both methods. Both methods are publicly available at www.cbs.dtu.dk/services/NetMHCII-2.3 and www.cbs.dtu.dk/services/NetMHCIIpan-3.2.

D000949:Histocompatibility Antigens Class II

T-cell epitope
affinity predictions
MHC binding specificity
immunogenic peptides
peptide-MHC binding


Evidence of heterospecific referential communication from domestic horses (Equus caballus) to humans.

Abstract: Referential communication occurs when a sender elaborates its gestures to direct the attention of a recipient to its role in pursuit of the desired goal, e.g. by pointing or showing an object, thereby informing the recipient what it wants. If the gesture is successful, the sender and the recipient focus their attention simultaneously on a third entity, the target. Here we investigated the ability of domestic horses (Equus caballus) to communicate referentially with a human observer about the location of a desired target, a bucket of food out of reach. In order to test six operational criteria of referential communication, we manipulated the recipient's (experimenter) attentional state in four experimental conditions: frontally oriented, backward oriented, walking away from the arena and frontally oriented with other helpers present in the arena. The rate of gaze alternation was higher in the frontally oriented condition than in all the others. The horses appeared to use both indicative (pointing) and non-indicative (nods and shakes) head gestures in the relevant test conditions. Horses also elaborated their communication by switching from a visual to a tactile signal and demonstrated perseverance in their communication. The results of the tests revealed that horses used referential gestures to manipulate the attention of a human recipient so to obtain an unreachable resource. These are the first such findings in an ungulate species.

Referential communication
Domestic horse
Referential gesture
Human–animal communication
Intentional communication


Risk stratification in patients with frequent premature ventricular complexes in the absence of known heart disease.

Abstract:
BACKGROUND
Frequent premature ventricular complexes (PVCs) can be an indicator of structural heart disease.

OBJECTIVE
The purpose of this study was to determine the prevalence of scarring detected by delayed enhancement cardiac magnetic resonance (DE-CMR) imaging in patients with frequent PVCs without apparent structural heart disease and to determine the value of programmed ventricular stimulation (PVS) for risk stratification in patients with frequent PVCs and myocardial scarring.

METHODS
DE-CMR imaging was performed in patients without apparent heart disease who had frequent PVCs and were referred for ablation. In the presence of scarring, scar volume was measured and correlated with outcome variables. All patients underwent PVS and were monitored for the occurrence of ventricular arrhythmias. Logistic regression was used to compare imaging and procedural findings with long-term outcomes, with adjustment for postablation ejection fraction (EF).

RESULTS
The study consisted of 272 patients (135 men; mean age 52 ± 15 years; EF 52% ± 12%). DE-CMR scar was found in 67 patients (25%), and 7 (3%) were found to have inducible ventricular tachycardia (VT). The presence and amount of DE-CMR were related to the risk of long-term VT independent of EF (hazard ratio 18.8 [95% confidence interval] [2.0-176.6], P = .01; and hazard ratio 1.4 [1.1-1.7] per cm3 scar, P <.001, respectively). The positive predictive value and negative predictive value of PVS for VT during long-term follow-up were 71% and 100%, respectively.

CONCLUSION
Preprocedural cardiac DE-CMR and PVS can be used to identify patients with frequent PVCs without apparent heart disease who are at risk for VT.

Ghannam|Michael|M|
Siontis|Konstantinos C|KC|
Kim|Myra Hyungjin|MH|
Cochet|Hubert|H|
Jais|Pierre|P|
Eng|Mehdi Juhoor|MJ|
Attili|Anil|A|
Sharaf-Dabbagh|Ghaith|G|
Latchamsetty|Rakesh|R|
Jongnarangsin|Krit|K|
Morady|Fred|F|
Bogun|Frank|F|

D019028:Magnetic Resonance Imaging, Cine

Delayed enhancement cardiac magnetic resonance imaging


Casticin inhibits interleukin-1β-induced ICAM-1 and MUC5AC expression by blocking NF-κB, PI3K-Akt, and MAPK signaling in human lung epithelial cells.

Abstract: The compound casticin, isolated from Vitex rotundifolia, exerts anti-inflammatory effects and causes apoptosis of cancer cells. In this study, we explored the anti-inflammatory effects of casticin and modulation of cyclooxygenase (COX)-2, intercellular adhesion molecule 1 (ICAM-1), and mucin 5AC (MUC5AC) expression in interleukin-1β (IL-1β)-activated A549 human pulmonary epithelial cells. A549 cells were treated with various concentrations of casticin (5-20 μM), and an inflammatory response was triggered with interleukin (IL)-1β cytokines. Casticin decreased levels of IL-6, tumor necrosis factor α, and IL-8 and suppressed COX-2 expression and prostaglandin E2 production. It also reduced MUC5AC, proinflammatory cytokine, and chemokine gene expression and inhibited ICAM-1 expression for monocyte adhesion in IL-1β-stimulated A549 cells. In addition, casticin inhibited phosphorylation of Akt, phosphatidylinositol 3-kinase (PI3K), and mitogen-activated protein kinase (MAPK) and blocked nuclear transcription factor kappa-B (NF-κB) subunit p65 protein translocation into the nucleus. Co-culture of NF-κB, MAPK, and PI3K inhibitors with casticin also led to more significantly suppressed ICAM-1 expression in inflammatory A549 cells. These results provide evidence that casticin has an anti-inflammatory effect by blocking proinflammatory cytokine, chemokine, and ICAM-1 expression via suppression of the PI3K/Akt, NF-κB, and MAPK signaling pathways in IL-1β-stimulated inflammatory pulmonary epithelial cells.