Mouse tetherin enhances moloney murine leukemia virus-induced syncytium formation.

Abstract: Tetherin (also referred to as BST-2 or CD317) is an antiviral cellular restriction factor that inhibits the release of many enveloped viruses. It is a 30-36 kDa type II transmembrane protein, expression of which is induced by type I interferon. Mouse tetherin inhibits nascent cell-free particle release. However, it is unclear whether mouse tetherin restricts cell-to-cell spread of moloney murine leukemia virus (Mo-MLV) or whether is the mouse tetherin involved in syncytium formation. To examine cell-to-cell spread and syncytium formation of Mo-MLV in the presence or absence of mouse tetherin, R peptide (the cytoplasmic tail of the transmembrane protein (TM); 16 amino acids) truncated Env expressing vector was constructed. It contained enhanced green fluorescent protein (EGFP) in the proline rich region (PRR) of Env. This R(-)Env full-length molecular clone could rule out virus-cell transmission due to the slightly reduced R(-)Env protein incorporation into the viral particles. When NIH3T3 cells stably expressing mouse tetherin were transfected with R(-)Env full-length molecular clone, syncytium formation was significantly enhanced in the tetherin-expressing cells. These data suggest that tetherin-mediated retention of R-defective virions on the cell surface could enhance syncytium formation. In addition, we found that the R(-)Env full-length molecular clone containing EGFP in the PRR of Env to be a useful tool allowing fast and convenient detection of syncytia by fluorescence microscopy.

D000818:Animals
D015703:Antigens, CD
D015726:Giant Cells
D008562:Membrane Glycoproteins
D051379:Mice
D008979:Moloney murine leukemia virus
D041681:NIH 3T3 Cells
D012192:Retroviridae Infections
D012376:Rodent Diseases
D014771:Virion
D057074:Virus Release

syncytium
cell-to-cell transmission
R(-)Env full-length clone
tetherin.


Stress oxidative and genotoxicity in Prochilodus lineatus (Valenciennes, 1836) exposed to commercial formulation of insecticide cypermethrin.

Abstract: The use of toxic pesticides has become a world problem because they can contaminate streams and rivers, producing an adverse impact on non-target aquatic biota, including fishes. Cypermethrin is one of the most important insecticides to control ectoparasites in wide-scale. The aim of this study was to evaluate the effect of commercial formulations of cypermethrin, SHERPA O (0.0, 0.075, 0.15, and 0.3 µg/L of cypermethrin) in fish Prochilodus lineatus for 96 h in semi-static condition, using biomarkers of genotoxicity: micronucleus frequency (MNF) in erythrocytes and biomarkers of oxidative damage: lipid peroxidation (TBARS) and antioxidant defenses, catalase (CAT) and glutathione (GSH) in liver tissue. Our results showed a significant decrease (p < 0.05) of CAT at pesticide concentrations of 0.150 and 0.300 μg/L, but no significant difference was observed in TBARS or GSH in any exposed group (p > 0.05) in comparison to the control. A significant increase was observed in the MNF in the group exposed to 0.3 μg/L of cypermethrin compared to negative control (p < 0.05). Finally, P. lineatus proved to be a sensitive species to the commercial formulations of cypermethrin and that CAT and MNF are effective indicators of these toxic effects.

Davico|C E|CE|
Loteste|A|A|
Parma|M J|MJ|
Poletta|G|G|
Simoniello|M F|MF|

Fish
biomarkers
micronucleus frequency
catalase
liver tissue


Term perinatal mortality audit in the Netherlands 2010-2012: a population-based cohort study.

Abstract:
OBJECTIVE
To assess the implementation and first results of a term perinatal internal audit by a standardised method.

DESIGN
Population-based cohort study.

SETTING
All 90 Dutch hospitals with obstetric/paediatric departments linked to community practices of midwives, general practitioners in their attachment areas, organised in perinatal cooperation groups (PCG).

POPULATION
The population consisted of 943 registered term perinatal deaths occurring in 2010-2012 with detailed information, including 707 cases with completed audit results.

MAIN OUTCOME MEASURES
Participation in the audit, perinatal death classification, identification of substandard factors (SSF), SSF in relation to death, conclusive recommendations for quality improvement in perinatal care and antepartum risk selection at the start of labour.

RESULTS
After the introduction of the perinatal audit in 2010, all PCGs participated. They organised 645 audit sessions, with an average of 31 healthcare professionals per session. Of all 1102 term perinatal deaths (2.3/1000) data were registered for 86% (943) and standardised anonymised audit results for 64% (707). In 53% of the cases at least one SSF was identified. Non-compliance to guidelines (35%) and deviation from usual professional care (41%) were the most frequent SSF. There was a (very) probable relation between the SSF and perinatal death for 8% of all cases. This declined over the years: from 10% (n=23) in 2010 to 5% (n=10) in 2012 (p=0.060). Simultaneously term perinatal mortality decreased from 2.3 to 2.0/1000 births (p<0.00001). Possibilities for improvement were identified in the organisation of care (35%), guidelines or usual care (19%) and in documentation (15%). More pregnancies were antepartum selected as high risk, 70% in 2010 and 84% in 2012 (p=0.0001).

CONCLUSIONS
The perinatal audit is implemented nationwide in all obstetrical units in the Netherlands in a short time period. It is possible that the audit contributed to the decrease in term perinatal mortality.

Eskes|Martine|M|
Waelput|Adja J M|AJM|
Erwich|Jan Jaap H M|JJHM|
Brouwers|Hens A A|HAA|
Ravelli|Anita C J|ACJ|
Achterberg|Peter W|PW|
Merkus|Hans J M W M|HJMWM|
Bruinse|Hein W|HW|

D002423:Cause of Death
D015331:Cohort Studies
D006801:Humans
D007231:Infant, Newborn
D008485:Medical Audit
D009426:Netherlands
D066087:Perinatal Death
D054238:Perinatal Mortality
D047929:Term Birth
D013997:Time Factors

OBSTETRICS
PERINATOLOGY
PRIMARY CARE
PUBLIC HEALTH


Intravenous contrast-free standardized exercise perfusion imaging in diabetic feet with ulcers.

Abstract:
BACKGROUND
Impaired foot perfusion is a primary contributor to foot ulcer formation. There is no existing device nor method that can be used to measure local foot perfusion during standardized foot muscle exercise in an MRI environment.

PURPOSE
To develop a new MRI-compatible foot dynamometer and MRI methods to characterize local perfusion in diabetic feet with ulcers.

STUDY TYPE
Prospective.

POPULATION/SUBJECTS
Seven participants without diabetes and 10 participants with diabetic foot ulcers.

FIELD STRENGTH/SEQUENCE
3.0T, arterial spin labeling (ASL).

ASSESSMENTS
Using a new MRI-compatible foot dynamometer, all participants underwent MRI ASL perfusion assessment at rest and during a standardized toe-flexion exercise. The participants without diabetes were scanned twice to assess the reproducibility of perfusion measurements. The absolute perfusion and perfusion reserve values were compared between two groups and between regions near ulcers (peri-ulcer) and away from ulcers (away-ulcer).

STATISTICAL TESTS
Bland-Altman methods for the calculation of coefficient of repeatability (CR) and two-sided and unpaired Student's t-test to compare multiple differences.

RESULTS
The perfusion reserves measured had the best reproducibility (CR in medial region: 1.6, lateral region: 0.9). The foot perfusion reserve was significantly lower in the participants with diabetes compared with the participants without diabetes (1.34 ± 0.32, 95% confidence interval [CI]: 1.1, 1.58 vs. 1.76 ± 0.31, 95% CI: 1.53, 1.98, P = 0.02). Both peri-ulcer exercise perfusion (8.7 ± 3.9 ml/min/100g) and perfusion reserve (1.07 ± 0.39, 95% CI: 0.78, 1.35) were significantly lower than away-ulcer exercise perfusion (12.7 ± 3.8 ml/min/100g, P = 0.02) and perfusion reserve (1.39 ± 0.37, 95% CI: 1.11, 1.66, P = 0.03), respectively.

DATA CONCLUSION
This study demonstrates intravenous contrast-free methods for local perfusion in feet with ulcers by standardized exercise-based MRI. Ischemia regions around foot ulcers can be quantitatively distinguished from normal perfused muscle regions.

LEVEL OF EVIDENCE
2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:474-480.

Edalati|Masoud|M|
Hastings|Mary K|MK|
Muccigrosso|David|D|
Sorensen|Christopher J|CJ|
Hildebolt|Charles|C|
Zayed|Mohamed A|MA|
Mueller|Michael J|MJ|
Zheng|Jie|J|

exercise
perfusion
foot ulcer
diabetes mellitus
magnetic resonance imaging


Is Pulse Pressure an Independent Risk Factor for Incident Stroke, REasons for Geographic And Racial Differences in Stroke.

Abstract:
BACKGROUND
Pulse pressure (PP) is a potential risk factor of stroke. The relationship of incident stroke with systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and PP was examined.

METHODS
Data were from the REasons for Geographic And Racial Differences in Stroke national cohort study of 30,239 black and white participants aged ≥45 years, enrolled between 2003 and 2007. PP (SBP-DBP) and MAP (MAP = DBP + 1/3*PP) were calculated. Telephone follow-up occurred every six months for self or proxy-reported suspected stroke events, confirmed using expert adjudication. Cox-proportional hazards models examined the association of incident stroke for the different BP measurements with multivariable adjustment for sociodemographic and clinical risk factors including gender and race.

RESULTS
Men and women without prevalent stroke at baseline were analyzed (n = 25,462). During follow-up (mean 6.3±2.3 years, maximum 10 years), 916 strokes occurred. Unadjusted PP (hazard ratio [HR] = 1.30; 95% confidence interval [CI] 1.24-1.35), SBP (HR = 1.22; 95% CI 1.18-1.32), MAP (HR = 1.24; 95% CI 1.16-1.32), and DBP (HR = 1.09; 95% CI 1.01-1.17) were associated with stroke risk; however, after adjustment for SBP and other risk factors, the association with PP was attenuated (HR = 0.98; 95% CI 0.90-1.07), whereas SBP persisted as a predictor (HR = 1.14; 95% CI 1.06-1.23). These associations were consistent across age (younger vs. older >70 years) and race (black vs. white).

CONCLUSIONS
PP is positively associated with incident stroke, but not independently from SBP; and, there were no significant gender, racial, or regional differences in that association.

Glasser|Stephen P|SP|
Halberg|Daniel L|DL|
Sands|Charles D|CD|
Mosher|Aleena|A|
Muntner|Paul M|PM|
Howard|George|G|

pulse pressure
blood pressure
hypertension
incident stroke.


Estimation of Energy Expenditure for Wheelchair Users Using a Physical Activity Monitoring System.

Abstract:
OBJECTIVE
To develop and evaluate energy expenditure (EE) estimation models for a physical activity monitoring system (PAMS) in manual wheelchair users with spinal cord injury (SCI).

DESIGN
Cross-sectional study.

SETTING
University-based laboratory environment, a semistructured environment at the National Veterans Wheelchair Games, and the participants' home environments.

PARTICIPANTS
Volunteer sample of manual wheelchair users with SCI (N=45).

INTERVENTION
Participants were asked to perform 10 physical activities (PAs) of various intensities from a list. The PAMS consists of a gyroscope-based wheel rotation monitor (G-WRM) and an accelerometer device worn on the upper arm or on the wrist. Criterion EE using a portable metabolic cart and raw sensor data from PAMS were collected during each of these activities.

MAIN OUTCOME MEASURES
Estimated EE using custom models for manual wheelchair users based on either the G-WRM and arm accelerometer (PAMS-Arm) or the G-WRM and wrist accelerometer (PAMS-Wrist).

RESULTS
EE estimation performance for the PAMS-Arm (average error ± SD: -9.82%±37.03%) and PAMS-Wrist (-5.65%±32.61%) on the validation dataset indicated that both PAMS-Arm and PAMS-Wrist were able to estimate EE for a range of PAs with <10% error. Moderate to high intraclass correlation coefficients (ICCs) indicated that the EE estimated by PAMS-Arm (ICC3,1=.82, P<.05) and PAMS-Wrist (ICC3,1=.89, P<.05) are consistent with the criterion EE.

CONCLUSIONS
Availability of PA monitors can assist wheelchair users to track PA levels, leading toward a healthier lifestyle. The new models we developed can estimate PA levels in manual wheelchair users with SCI in laboratory and community settings.

Hiremath|Shivayogi V|SV|
Intille|Stephen S|SS|
Kelleher|Annmarie|A|
Cooper|Rory A|RA|
Ding|Dan|D|

Estimation
Wheelchairs
Spinal cord injuries
Energy metabolism
Exercise test
Motor activity
Rehabilitation
Smartphone


Inhibition of melanoma metastasis by dual-peptide PLGA NPS.

Abstract: Despite the positive results observed in vitro and in vivo, clinical trials with bioactive peptides are generally hampered by their fast degradation in the biological system. Two bioactive peptides, P20 (CSSRTMHHC) and the combined peptide C (CVNHPAFACGYGHTMYYHHYQHHL) have been identified as anticancer therapeutics. Combined peptide C consists of peptide C (CVNHPAFAC), a tumor-homing peptide, conjugated to the antiangiogenic peptide HTMYYHHYQHHL with a GYG. In this work, PLGA NPs with peptide C were applied as a dual-peptide carrier for application in cancer therapy. Peptide P20 was loaded into the NPs and combined peptide C was conjugated to the NPs surface. These NPs were evaluated as a therapeutic system to treat metastatic melanoma. In vivo assays showed that P20 encapsulation in PLGA NPs enhanced its antitumor activity. The inhibitory activity of P20-PLGANPs was similar to the activity of non-encapsulated P20 in a dose fivefold higher. The inhibitory activity was even higher when P20PLGA NPs were functionalized with combined peptide C. P20PLGAPepC NPs reduced in 28% the number of lung nodules in a syngeneic model of metastatic melanoma as compared to untreated animals. Additionally to the better tumor targeting and the in situ release of P20, it is expected that the therapeutic efficiency of the dual-peptide PLGA NPs was further enhanced by a synergistic effect between P20 and combined peptide C. Our encouraging results showed that by enabling the co-delivery of two peptides and promoting tumor targeting, PLGA NPs coupled with peptide C is a promising platform for peptide-based cancer therapy.

D000077182:Polylactic Acid-Polyglycolic Acid Copolymer

PLGA
metastatic melanoma
antitumor peptides
nanoparticles


The Overlap Between Binge Eating Behaviors and Polycystic Ovarian Syndrome: An Etiological Integrative Model.

Abstract: Studies indicate that Polycystic Ovarian Syndrome (PCOS) features (e.g. insulin instability, food cravings, overproduction of androgens and menstrual irregularities) are associated with increased appetite, impaired impulse control and feelings of body dissatisfaction. Counter intuitively, binge eating behaviors have been shown to reinforce PCOS symptomatology, precipitating concurrently body dissatisfaction, weight gain, insulin instability and overproduction of androgens. The present systematic literature review aspires to investigate the relationship between binge eating, in the broader context of eating disorder behaviors, and Polycystic Ovarian Syndrome (PCOS), taking into account shared characteristics between EDs (Eating Disorders) and PCOS. To address this aim, the PRISMA guidelines are adopted. A total of 21 studies, which investigated the presence of binge eating in PCOS population and the presence of PCOS in EDs population, were synthesized. Findings suggested that an increased prevalence of binge eating has been reported in women with Polycystic Ovarian Syndrome (PCOS); and that women suffering from BN (Bulimia Nervosa) and BED (Binge Eating Disorder) are more likely to display polycystic ovaries. Further research on their shared liability is required in order to inform more efficient prevention and treatment initiatives for populations presenting with comorbid features.

Paganini|Chiara|C| Peterson|Gregory|G| Stavropoulos|Vasilis|V| Krug|Isabel|I|

menstrual irregularities
body dissatisfaction
eating disorders
Binge eating disorder
menstruation
polycystic ovarian syndrome.


The riddle of style changes in the visual arts after interference with the right brain.

Abstract: We here analyze the paintings and films of several visual artists, who suffered from a well-defined neuropsychological deficit, visuo-spatial hemineglect, following vascular stroke to the right brain. In our analysis we focus in particular on the oeuvre of Lovis Corinth and Luchino Visconti as both major artists continued to be highly productive over many years after their right brain damage. We analyzed their post-stroke paintings and films, indicate several aspects that differ from their pre-stroke work (omissions, use of color, perseveration, deformation), and propose-although both artists come from different times, countries, genres, and styles-that their post-stroke oeuvre reveals important similarities in style. We argue that these changes may be associated with visuo-spatial hemineglect and the right brain. We discuss future avenues of how the neuropsychological investigation of visual artists with and without neglect may allow us to investigate the relationship between brain and art.

visual arts
painting
film
neuropsychology
Lovis Corinth
Luchino Visconti
neurology


Age dependent in vitro metabolism of bifenthrin in rat and human hepatic microsomes.

Abstract: Bifenthrin, a pyrethroid insecticide, undergoes oxidative metabolism leading to the formation of 4'-hydroxy-bifenthrin (4'-OH-BIF) and hydrolysis leading to the formation of TFP acid in rat and human hepatic microsomes. In this study, age-dependent metabolism of bifenthrin in rats and humans were determined via the rates of formation of 4'-OH-BIF and TFP acid following incubation of bifenthrin in juvenile and adult rat (PND 15 and PND 90) and human (<5years and >18years) liver microsomes. Furthermore, in vitro hepatic intrinsic clearance (CLint) of bifenthrin was determined by substrate consumption method in a separate experiment. The mean Vmax(±SD) for the formation of 4'-OH-BIF in juvenile rat hepatic microsomes was 25.0±1.5pmol/min/mg which was significantly lower (p<0.01) compared to that of adult rats (86.0±17.7pmol/min/mg). However, the mean Km values for juvenile (19.9±6.6μM) and adult (23.9±0.4μM) rat liver microsomes were similar. On the other hand, in juvenile human hepatic microsomes, Vmax for the formation of 4'-OH-BIF (73.9±7.5pmol/min/mg) was significantly higher (p<0.05) than that of adults (21.6±0.6pmol/min/mg) albeit similar Km values (10.5±2.8μM and 8.9±0.6μM) between the two age groups. The trends in the formation kinetics of TFP acid were similar to those of 4'-OH-BIF between the species and age groups, although the differences between juveniles and adults were less pronounced. The data also show that metabolism of bifenthrin occurs primarily via oxidative pathway with relatively lesser contribution (~30%) from hydrolytic pathway in both rat and human liver microsomes. The CLint values for bifenthrin, determined by monitoring the consumption of substrate, in juvenile and adult rat liver microsomes fortified with NADPH were 42.0±7.2 and 166.7±20.5μl/min/mg, respectively, and the corresponding values for human liver microsomes were 76.0±4.0 and 21.3±1.2μl/min/mg, respectively. The data suggest a major species difference in the age dependent metabolism of bifenthrin. In human liver microsomes, bifenthrin is metabolized at a much higher rate in juveniles than in adults, while the opposite appears to be true in rat liver microsomes.

Nallani|Gopinath C|GC|
Chandrasekaran|Appavu|A|
Kassahun|Kelem|K|
Shen|Li|L|
ElNaggar|Shaaban F|SF|
Liu|Zhiwei|Z|

Bifenthrin
Liver microsomes
Intrinsic hepatic clearance
K(m)
V(max)


Contrast-enhanced ultrasound for screening hepatocellular carcinoma: an implemented program at a semi-rural academic center.

Abstract:
PURPOSE
To describe our early experience using a contrast-enhanced ultrasound (CEUS) protocol for surveillance of hepatocellular carcinoma (HCC) at a semi-rural academic medical center.

METHODS
Retrospective, longitudinal study of the first 100 patients who underwent CEUS liver screening imaging over 2 years. Each patient underwent a standard of care abdominal ultrasound, which was checked with the radiologist, who searched for a focal lesion on the cine clips to target specifically with contrast. If none was present, the HCC contrast-enhanced screening protocol consisting of individual sweeps of the right and left lobes was performed from 0 to 60 s and 3-4 min post contrast-Lumason was utilized. Images, report details, and patient demographics were analyzed.

RESULTS
66 men and 34 women (average age, 59 ± 13 years) were included. On average, the distance from patient's home to our institution was 39 miles (range 2-179 miles). The majority of our patients were covered under Private insurance (46%) with 43% covered by Medicare. CEUS exams on average took 35 min to complete. Lumason was administered in split doses for an average total of 5 mL per exam. Of the 10 lesions identified, there were five LI-RADS 3, two LI-RADS 4, one LI-RADS 5, two LI-RADS M, and one bland portal vein thrombus. There were no complications reported.

CONCLUSION
This semi-rural single-center study demonstrates the feasibility of starting a HCC CEUS screening program. CEUS can be performed in conjunction with routine ultrasound imaging with added benefit of identifying and characterizing lesions in one setting.

Motz|Victoria L|VL|0000-0001-8290-4369
White|Rachel|R|
Lee|Roland|R|
Vu|Tuan|T|
Shin|Benjamin|B|
McGillen|Kathryn L|KL|


Restoration of basic hand function following devastating hand injuries using a microsurgically fabricated chimeric iliac osteocutaneous flap.

Abstract: Reconstruction following devastating hand injuries, with amputations of the thumb plus multiple digits, is challenging. Double flap or combined flap transfers may be options in such cases. Between 2012 and 2014, 6 patients underwent hand reconstruction following devastating injuries with amputations of the thumb and multiple digits. Sensate anterolateral thigh free flaps and superficial circumflex iliac artery osteocutaneous flaps were microsurgically fabricated as sequential chimeric flaps. Basic hand function, including pulp-to-palm distance, pinch strength, sensation recovery and modified DASH scores, were evaluated. Anterolateral thigh flaps were used as "piggyback" flaps, and their size ranged from 8 cm × 16 cm to 10 cm × 25 cm. Cutaneous portions of superficial circumflex iliac artery osteocutaneous flaps ranged in size from 4 cm × 5 cm to 7 cm × 15 cm, and bone flap size ranged from 1 cm × 3 cm × 0.8 cm to 1 cm × 4 cm × 1 cm. All of the flaps survived uneventfully. All patients were able to perform basic hand functions after a median follow-up of 1.8 years. Microsurgically fabricated chimeric iliac osteocutaneous flaps may restore basic hand function to some extent. This procedure is an option worth considering for hand reconstruction following devastating injuries in carefully selected patients.

Pan|Zhao Hui|ZH|
Jiang|Ping Ping|PP|
Xue|Shan|S|
Li|Hongfei|H|
Wang|Jian Li|JL|

Superficial circumflex iliac artery osteocutaneous flap


Attitude towards problem-based learning and its relationship with locus of control and academic self-concept among medical students.

Abstract:
PURPOSE
This study aimed to assess the degree of acceptance of problem-based learning (PBL) among phase one medical students and its association with academic self-concept (ASC) and internal locus of control (ILOC).

METHODS
A 5-point Likert scale valid and reliable questionnaire assessing the attitude towards PBL, ASC, and ILOC was given to phase one medical students at MAHSA University. Data were analysed using IBM SPSS ver. 22.0 (IBM Corp., Armonk, USA).

RESULTS
Out of 255 participants, there were 84 males and 171 females, 175 Malaysians and 80 non-Malaysians. The results showed an overall acceptance of PBL with a mean of 3.7±0.07, ASC of 3.5±0.05 and ILOC of 2.9±0.05. Females showed a higher significant acceptance of PBL, ASC, and ILOC as compared with males. There was no difference between Malaysians and non-Malaysians in any of the variables measured. Simple regression analysis revealed a significant predictive effect of acceptance of PBL on ASC and ILOC (r=0.44 and r=0.88, respectively).

CONCLUSION
The higher the acceptance of PBL among students, the higher is the ASC and ILOC. This reflects the importance of PBL as a teaching method as well as the importance of increasing the level of appreciation of PBL amongst students.

Abdalla|Mona Mohamed Ibrahim|MMI|
Abdelal|Mahmoud Said|MS|
Soon|Siew Choo|SC|

Problem-based learning
Academic self-concept
Academic success
Active learning
Internal-external


Learning optimal eye movements to unusual faces.

Abstract: Eye movements, which guide the fovea's high resolution and computational power to relevant areas of the visual scene, are integral to efficient, successful completion of many visual tasks. How humans modify their eye movements through experience with their perceptual environments, and its functional role in learning new tasks, has not been fully investigated. Here, we used a face identification task where only the mouth discriminated exemplars to assess if, how, and when eye movement modulation may mediate learning. By interleaving trials of unconstrained eye movements with trials of forced fixation, we attempted to separate the contributions of eye movements and covert mechanisms to performance improvements. Without instruction, a majority of observers substantially increased accuracy and learned to direct their initial eye movements towards the optimal fixation point. The proximity of an observer's default face identification eye movement behavior to the new optimal fixation point and the observer's peripheral processing ability were predictive of performance gains and eye movement learning. After practice in a subsequent condition in which observers were directed to fixate different locations along the face, including the relevant mouth region, all observers learned to make eye movements to the optimal fixation point. In this fully learned state, augmented fixation strategy accounted for 43% of total efficiency improvements while covert mechanisms accounted for the remaining 57%. The findings suggest a critical role for eye movement planning to perceptual learning, and elucidate factors that can predict when and how well an observer can learn a new task with unusual exemplars.

Peterson|Matthew F|MF|
Eckstein|Miguel P|MP|

Eye movements
Perceptual learning
Face recognition
Ideal observer


Ultrasensitive Detection of Parathyroid Hormone through Fast Silver Deposition Induced by Enzymatic Nitroso Reduction and Redox Cycling.

Abstract: Enzymatically induced silver deposition and subsequent electrochemical oxidation have been widely used in electrochemical biosensors. However, this method is ineffective for producing highly enhanced silver deposition for use in ultrasensitive detection. Herein, we report a fast silver deposition method that simultaneously uses three signal amplification processes: (i) enzymatic amplification, (ii) chemical-chemical (CC) redox cycling, and (iii) chemical-enzymatic (CN) redox cycling. DT-diaphorase (DT-D) is used for enzymatic amplification to convert a nitroso compound, a species incapable of directly reducing Ag+ to an amine compound, which can directly reduce Ag+. NADH acts as a reducing agent for the indirect reduction of Ag+ via the two redox cycling processes. 4-Nitroso-1-naphthol is converted to 4-amino-1-naphthol (NH2-N) in the presence of DT-D. NH2-N initiates two redox cycling processes: NH2-N, along with Ag+ and NADH, are involved in the CC redox cycling, whereas NH2-N, along with Ag+, DT-D, and NADH, are involved in the CN redox cycling. Finally, the deposited silver is electrochemically oxidized to produce a signal. When this triple signal amplification strategy for fast silver deposition is applied to an electrochemical immunosensor for detecting parathyroid hormone (PTH), a detection limit as low as ∼100 fg/mL is obtained. The concentrations of PTH in clinical serum determined using the developed immunosensor are found to agree with those measured using a commercial instrument. Thus, the use of this strategy for fast silver deposition is highly promising for ultrasensitive electrochemical detection and biosensing applications.

Bhatia|Aman|A|
Nandhakumar|Ponnusamy|P|
Kim|Gyeongho|G|
Kim|Jihyeon|J|
Lee|Nam-Sihk|NS|
Yoon|Young Ho|YH|
Yang|Haesik|H|0000-0001-7450-5915

parathyroid hormone
silver deposition
redox cycling
DT-diaphorase
immunosensor


ADCC-Inducing Antibody Trastuzumab and Selection of KIR-HLA Ligand Mismatched Donors Enhance the NK Cell Anti-Breast Cancer Response.

Abstract: Natural killer (NK)-cell-based immunotherapies are an attractive treatment option for cancer. We previously showed that alloreactive mouse NK cells cured mice of 4T1 breast cancer. However, the tumor microenvironment can inhibit immune responses, and these suppressive factors must be overcome to unfold the NK cells' full anti-tumor potential. Here, we investigated the combination of antibody-dependent cellular cytotoxicity (ADDC) and the selection of KIR-HLA-ligand mismatched NK cells to enhance NK cell anti-breast cancer responses in clinically relevant settings. Donor-derived and IL-2-activated NK cells were co-cultured with patient-derived breast cancer cells or cell lines MCF7 or SKBR3 together with the anti-HER2 antibody trastuzumab. NK cells mediated anti-breast cancer cytotoxicity under normoxic and hypoxic conditions. Under both conditions, trastuzumab vigorously enhanced NK cell degranulation (CD107a) against HER2-overexpressing SKBR3 cells, but we observed a discrepancy between highly degranulating NK cells and a rather modest increase in cytotoxicity of SKBR3. Against patient-derived breast cancer cells, the anti-tumor efficacy was rather limited, and HLA class I expression seemed to contribute to inhibited NK cell functionality. KIR-ligand-mismatched NK cells degranulated stronger compared to the matched NK cells, further highlighting the role of HLA. In summary, trastuzumab and KIR-ligand-mismatched NK cells could be two strategies to potently enhance NK cell responses to breast cancer.


Integrating Beck's Cognitive Theory of Depression and the Hopelessness Model in an Adolescent Sample.

Abstract: Adolescence is a critical period in the development of depression. Hence, researching the applicability of cognitive theories in adolescents is crucial. Currently, much remains unknown about how cognitive variables proposed in different theories interplay with one another and whether gender differences in these associations exist. Attempting to integrate Beck's cognitive model and the hopelessness model in adolescents, we conducted a 4-wave study using self-report instruments with 499 adolescents (mean ageTime1 = 15.33 years; SD = 0.75; 63.3% female; 73.7% White, 13.8% Black, 5.4% Latina/o, 4.4% mixed race/ethnicity, and 2.6% other) from a high school where almost one third of the students were eligible for free or reduced lunch. Using AMOS and PROCESS to calculate and compare four different theory-driven models, we found support for an integrated model in which the inferential styles proposed in the hopelessness model are located between cognitive errors and the cognitive triad from Beck's cognitive theory. Further, the individual inferential styles and elements of the cognitive triad are associated differently with each other and other variables in the integrated cognitive model. The gender differences we found were limited and did not form a meaningful pattern. If replicated, the integrated model could be the basis to understand how therapeutic techniques developed to modify cognitive variables proposed in one model can impact cognitive constructs from a different theory. This might make cognitive psychotherapies for depression more effective, as it will allow clinicians to integrate therapeutic techniques based on either of the original theories in one theory-driven treatment approach.

Depression
Hopelessness model
Adolescents
Beck’s cognitive model


Can we identify older people most vulnerable to living in cold homes during winter?

Abstract:
PURPOSE
Living in a cold home increases the risk of dying in winter, especially in older people. However, it is unclear which individual factors predict whether older people are living in cold homes.

METHODS
Thousand four hundred two men aged 74-95 years from a U.K. population-based study reported difficulties in keeping warm during winter, answering four simple "yes/no" questions. Associations between individual's characteristics and each of the four self-reported measures of cold homes were estimated using logistic regression models. Next, we investigated whether measures of cold homes predict mortality over the subsequent 2.1 years.

RESULTS
Manual social class, difficulties making ends meet, and not being married were each associated (P < .05) with each of the four measures of cold homes (adjusted odds ratios ranged from 1.61 to 4.68). Social isolation, poor respiratory health, and grip strength were also associated with reports of cold homes. Hundred twenty-six men died; those who reported the presence of at least three measures cold homes had increased mortality (adjusted hazard ratios 2.85 [95% confidence interval, 1.11-7.30, P = .029]).

CONCLUSIONS
Older people who find it hard to keep warm in winter, and have an elevated mortality, could be identified using a self-report questionnaire.

Sartini|Claudio|C|
Tammes|Peter|P|
Hay|Alastair D|AD|
Preston|Ian|I|
Lasserson|Daniel|D|
Whincup|Peter H|PH|
Wannamethee|S Goya|SG|
Morris|Richard W|RW|

Cold
Homes
Winter
Mortality
United Kingdom


A Review of Cry Protein Detection with Enzyme-Linked Immunosorbent Assays.

Abstract: The widespread use of Cry proteins in insecticide formulations and transgenic crops for insect control has led to an increased interest in the environmental fate of these proteins. Although several detection methods are available to monitor the fate of Cry proteins in the environment, enzyme-linked immunosorbent assays (ELISAs) have emerged as the preferred detection method, due to their cost-effectiveness, ease of use, and rapid results. Validation of ELISAs is necessary to ensure accurate measurements of Cry protein concentrations in the environment. Validation methodology has been extensively researched and published for the areas of sensitivity, specificity, accuracy, and precision; however, cross validation of ELISA results has been studied to a lesser extent. This review discusses the use of ELISAs for detection of Cry proteins in environmental samples and validation of ELISAs and introduces cross validation. The state of Cry protein environmental fate research is considered through a critical review of published literature to identify areas where the use of validation protocols can be improved.

Albright|Vurtice C|VC|
Hellmich|Richard L|RL|
Coats|Joel R|JR|

Cry protein
transgenic crops
environmental fate
ELISA
cross validation
Bt proteins
bioassays


Survival of patients with acute myeloid leukemia relapsing after allogeneic hematopoietic cell transplantation: a center for international blood and marrow transplant research study.

Abstract: Acute myeloid leukemia (AML) relapse after allogeneic hematopoietic cell transplantation (alloHCT) remains a major therapeutic challenge. We studied outcomes of 1788 AML patients relapsing after alloHCT (1990 to 2010) during first or second complete remission (CR) to identify factors associated with longer postrelapse survival. Median time to post-HCT relapse was 7 months (range, 1 to 177). At relapse, 1231 patients (69%) received intensive therapy, including chemotherapy alone (n = 660), donor lymphocyte infusion (DLI) ± chemotherapy (n = 202), or second alloHCT ± chemotherapy ± DLI (n = 369), with subsequent CR rates of 29%. Median follow-up after relapse was 39 months (range, <1 to 193). Survival for all patients was 23% at 1 year after relapse; however, 3-year overall survival correlated with time from HCT to relapse (4% for relapse during the 1- to 6-month period, 12% during the 6-month to 2-year period, 26% during the 2- to 3-year period, and 38% for ≥3 years). In multivariable analysis, lower mortality was significantly associated with longer time from alloHCT to relapse (relative risk, .55 for 6 months to 2 years; relative risk, .39 for 2 to 3 years; and relative risk, .28 for ≥3 years; P < .0001) and a first HCT using reduced-intensity conditioning (relative risk, .77; 95% confidence interval [CI], .66 to .88; P = .0002). In contrast, inferior survival was associated with age >40 years (relative risk, 1.42; 95% CI, 1.24 to 1.64; P < .0001), active graft-versus-host disease at relapse (relative risk, 1.25; 95% CI, 1.13 to 1.39; P < .0001), adverse cytogenetics (relative risk, 1.37; 95% CI, 1.09 to 1.71; P = .0062), mismatched unrelated donor (relative risk, 1.61; 95% CI, 1.22 to 2.13; P = .0008), and use of cord blood for first HCT (relative risk, 1.23; 95% CI, 1.06 to 1.42; P = .0078). AML relapse after alloHCT predicted poor survival; however, patients who relapsed ≥6 months after their initial alloHCT had better survival and may benefit from intensive therapy, such as second alloHCT ± DLI.

Bejanyan|Nelli|N|
Weisdorf|Daniel J|DJ|
Logan|Brent R|BR|
Wang|Hai-Lin|HL|
Devine|Steven M|SM|
de Lima|Marcos|M|
Bunjes|Donald W|DW|
Zhang|Mei-Jie|MJ|

D018380:Hematopoietic Stem Cell Transplantation

Acute myeloid leukemia
Relapse
Donor lymphocyte infusion
Allogeneic transplantation
Second transplantation


The emerging role of dopamine-glutamate interaction and of the postsynaptic density in bipolar disorder pathophysiology: Implications for treatment.

Abstract: Aberrant synaptic plasticity, originating from abnormalities in dopamine and/or glutamate transduction pathways, may contribute to the complex clinical manifestations of bipolar disorder (BD). Dopamine and glutamate systems cross-talk at multiple levels, such as at the postsynaptic density (PSD). The PSD is a structural and functional protein mesh implicated in dopamine and glutamate-mediated synaptic plasticity. Proteins at PSD have been demonstrated to be involved in mood disorders pathophysiology and to be modulated by antipsychotics and mood stabilizers. On the other side, post-receptor effectors such as protein kinase B (Akt), glycogen synthase kinase-3 (GSK-3) and the extracellular signal-regulated kinase (Erk), which are implicated in both molecular abnormalities and treatment of BD, may interact with PSD proteins, and participate in the interplay of the dopamine-glutamate signalling pathway. In this review, we describe emerging evidence on the molecular cross-talk between dopamine and glutamate signalling in BD pathophysiology and pharmacological treatment, mainly focusing on dysfunctions in PSD molecules. We also aim to discuss future therapeutic strategies that could selectively target the PSD-mediated signalling cascade at the crossroads of dopamine-glutamate neurotransmission.

de Bartolomeis|Andrea|A|
Buonaguro|Elisabetta F|EF|
Iasevoli|Felice|F|
Tomasetti|Carmine|C|

synaptic plasticity
Antipsychotics
mood stabilizers
Akt
GSK-3
Erk
D2 receptor
Homer
NMDA receptor
PSD-95


Prosthetic Jamming Terminal Device: A Case Study of Untethered Soft Robotics.

Abstract: This article illuminates the major and often overlooked challenge of untethering soft robotic systems through the context of recent work, in which soft robotic gripper technology enabled by jamming of granular media was applied to a prosthetic jamming terminal device (PJTD). The PJTD's technical and market feasibility was evaluated in a pilot study with two upper-limb amputees. A PJTD prototype was tested against a commercial device (Motion Control electric terminal service with a one degree-of-freedom pinching mechanism) using two existing hand function tests: the first quantified the device's speed in picking and placing small blocks and the second evaluated a person's ability to perform activities of daily living (ADLs). The PJTD prototype performed slightly slower than its commercial counterpart in the first test. While both participants successfully completed all the ADLs with both devices in the second test, the commercial device scored marginally higher. Results suggested that PJTD can have potential benefits over existing terminal devices, such as providing the capability to firmly grasp tools due to the ability of PJTD to conform to arbitrary surfaces and reducing compensatory shoulder movements due to its axisymmetric design. Some downsides were that users reported fatigue while operating the PJTD, as most operations require pushing the PJTD against target objects to adequately conform to them. The greatest drawback for the PJTD is also a major roadblock preventing a number of soft robotic research projects from making an impact in real-world applications: pneumatic technology required for operating the PJTD is currently too large and heavy to enable compact untethered operation.

Cheng|Nadia|N| Amend|John|J| Farrell|Todd|T| Latour|Debra|D| Martinez|Carlos|C| Johansson|Jen|J| McNicoll|Anthony|A| Wartenberg|Marek|M| Naseef|Samuel|S| Hanson|William|W| Culley|William|W|

prosthetic soft gripper upper-limb amputee hand myoelectric


HDL endocytosis and resecretion.

Abstract: HDL removes excess cholesterol from peripheral tissues and delivers it to the liver and steroidogenic tissues via selective lipid uptake without catabolism of the HDL particle itself. In addition, endocytosis of HDL holo-particles has been debated for nearly 40years. However, neither the connection between HDL endocytosis and selective lipid uptake, nor the physiological relevance of HDL uptake has been delineated clearly. This review will focus on HDL endocytosis and resecretion and its relation to cholesterol transfer. We will discuss the role of HDL endocytosis in maintaining cholesterol homeostasis in tissues and cell types involved in atherosclerosis, focusing on liver, macrophages and endothelium. We will critically summarize the current knowledge on the receptors mediating HDL endocytosis including SR-BI, F1-ATPase and CD36 and on intracellular HDL transport routes. Dependent on the tissue, HDL is either resecreted (retro-endocytosis) or degraded after endocytosis. Finally, findings on HDL transcytosis across the endothelial barrier will be summarized. We suggest that HDL endocytosis and resecretion is a rather redundant pathway under physiologic conditions. In case of disturbed lipid metabolism, however, HDL retro-endocytosis represents an alternative pathway that enables tissues to maintain cellular cholesterol homeostasis.

Resecretion
Cholesterol
Degradation
Transcytosis
Holo-particle uptake
Lipoprotein


"I'll eat meat because that's what we do": The role of national norms and national social identification on meat eating.

Abstract: Through meat-eating choices, people are able to express their national social identification and adhere to broader cultural norms. The current research examines the relationship between people's perceptions of national descriptive and injunctive meat-eating norms and their national social identification, on the one hand, and their attitudes toward meat-eating and their intentions to eat meat, on the other hand. In a sample that includes American, British, and Australian participants, we observe that: (1) favorable attitudes toward meat eating are positively predicted by national injunctive but not descriptive norms, and (2) intentions to eat meat are positively predicted by national descriptive but not injunctive norms. National social identification positively predicts both attitudes and intentions. Intentions to eat meat were also predicted by a three-way interaction between descriptive and injunctive norms, and social identification. Alignment of relatively high descriptive and injunctive meat-eating norms predicted meat-eating intentions more than alignment of relatively low descriptive and injunctive norms. With normative misalignment, however, people began to rely on their national social identifications as a basis for meat-eating intentions. The data are discussed with reference to the impact of social factors in influencing meat consumption. Moreover, we consider the potential for national social identification to have a normative component of meat consumption independent of descriptive and injunctive norms. This work advances our understanding of meat consumption by revealing national-level normative and identity processes beyond more focused identities of, for example, an environmentalist, a health conscious person, or an animal rights activist.

Social identification
Descriptive norm
Injunctive norm
Meat-eating intentions
Meat-eating attitudes


Non-prescription sales of antimicrobial agents at community pharmacies in developing countries: a systematic review.

Abstract: Antimicrobial resistance (AMR) is a global challenge. Developing countries are more vulnerable to the consequences of AMR than developed nations because of complex issues pertaining to the nature of their healthcare systems. Inappropriate antimicrobial drug use and the unrestricted availability of antimicrobial agents in community pharmacies in developing countries can contribute to the emergence of resistant microbes. The aim of this systematic review was to explore the availability of antimicrobial agents without a doctor's prescription in developing countries and to investigate factors that contribute to inappropriate antimicrobial supply in developing countries. The EMBASE, MEDLINE and International Pharmaceutical Abstracts databases were searched for articles published between 1980 and November 2017 describing studies using simulated client (or pseudo-patient) methodology in community pharmacies supplying non-prescription antimicrobial agents. Overall, 50 studies were included in this systematic review. All of the studies involved supply of one or more antimicrobials without a prescription. These studies involved using a hypothetical case presentation or direct product request by a simulated client. The review found non-prescription supply of antimicrobials as reported in 28 developing countries across Asia, Africa, South America, Europe and Middle Eastern regions. Contributing factors for non-prescription antimicrobial supply were poor national medicines regulations, limited availability of qualified pharmacists, commercial pressure on pharmacy staff, consumer demand, inappropriate prescribing practices and lack of awareness of AMR.

Sakeena|M H F|MHF|
Bennett|Alexandra A|AA|
McLachlan|Andrew J|AJ|

Non-prescription
Antimicrobials
Pharmacy
Developing countries
Antimicrobial resistance
Simulated client


Coaxial flow-gating interface for capillary electrophoresis.

Abstract: A coaxial flow-gating interface is described in which the separation capillary passes through the sampling capillary. Continuous flow of the sample solution flowing out of the sampling capillary is directed away from the injection end of the separation capillary by counter-current flow of the gating solution. During the injection, the flow of the gating solution is interrupted, so that a plug of solution is formed at the inlet into the separation capillary, from which the sample is hydrodynamically injected. Flow-gating interfaces are originally designed for on-line connection of capillary electrophoresis with analytical flow-through methods. The basic properties of the described coaxial flow-gating interface were obtained in a simplified arrangement in which a syringe pump with sample solution has substituted analytical flow-through method. Under the optimized conditions, the properties of the tested interface were determined by separation of K+ , Ba2+ , Na+ , Mg2+ and Li+ ions in aqueous solution at equimolar concentrations of 50 μM. The repeatability of the migration times and peak areas evaluated for K+ , Ba2+ and Li+ ions and expressed as relative standard deviation did not exceed 1.4%. The interface was used to determine lithium in mineral water and taurine in an energy drink.

flow-gating interface
capillary electrophoresis
mineral water
energy drinks
coaxial capillary arrangement


The temptin gene of the clade Lophotrochozoa is involved in formation of the prismatic layer during biomineralization in molluscs.

Abstract: The biomineralization mechanism of mollusc shell has been studied for a long time, but there is a lack of understanding about the relationship between the shell formation in vitro and the signaling system in vivo. In this study, we cloned a novel shell matrix protein gene (hc-temptin), which only be characterized as a water-borne protein pheromone of molluscs in previous studies, from the freshwater mussel Hyriopsis cumingii. By bioinformatics analysis we found that temptin was a gene unique to the clade Lophotrochozoa, and it exists in all mollusc taxa except Cephalopoda. The current data supported the premise that temptin was generated in the early emergence of molluscs and that it maintained a high mutation rate to evolve relative independently. The specificity of hc-temptin expression in the mantle tissue suggests its potential to participate in biomineralization. Its sequence contained typical Ca2+ binding sites. Our experiments involving the pearl formation process, damaged shell repair process, and RNAi experiment showed that hc-temptin was a shell matrix protein that plays an important role in formation of the prismatic layer. The results of this study provided new insights about the origin of the temptin gene and its role in molluscs.

Peng|Maoxiao|M| Liu|Zhenming|Z| Li|Zhi|Z| Qian|Shanqin|S| Liu|Xiaojun|X| Li|Jiale|J|

Biomineralization
Shell matrix protein
Evolution


Protein adsorption through Chitosan-Alginate membranes for potential applications.

Abstract:
BACKGROUND
Chitosan and Alginate were used as biopolymers to prepare membranes for protein adsorption. The network requires a cross-linker able to form bridges between polymeric chains. Viscopearl-mini(®) (VM) was used as a support to synthesize them. Six different types of membranes were prepared using the main compounds of the matrix: VM, Chitosan of low and medium molecular weight, and Alginate.

RESULTS
Experiments were carried out to analyze the interactions within the matrix and improvements were found against porous cellulose beads. SEM characterization showed dispersion in the compounds. According to TGA, thermal behaviour remains similar for all compounds. Mechanical tests demonstrate the modulus of the composites increases for all samples, with major impact on materials containing VM. The adsorption capacity results showed that with the removal of globular protein, as the adsorbed amount increased, the adsorption percentage of Myoglobin from Horse Heart (MHH) decreased. Molecular electrostatic potential studies of Chitosan-Alginate have been performed by density functional theory (DFT) and ONIOM calculations (Our own N-layered integrated molecular orbital and molecular mechanics) which model large molecules by defining two or three layers within the structure that are treated at different levels of accuracy, at B3LYP/6-31G(d) and PM6/6-31G(d) level of theory, using PCM (polarizable continuum model) solvation model.

CONCLUSIONS
Finally, Viscopearl-mini(®) acts as a suitable support on the matrix for the synthesis of Chitosan-Alginate membranes instead of cross-linkers usage. Therefore, it suggests that it is a promise material for potential applications, such as: biomedical, wastewater treatment, among others.Graphical abstractChitosan, Alginate, and Cellulose beads-based membranes for protein adsorption. Special attention was given for preparation, charaterization, adsorption capacity, and molecular electrostatic potential studies calculation. Viscopearl-mini(®) gives support on the matrix of Chitosan-Alginate membranes instead of cross-linkers usage.

Murguía-Flores|Dennise A|DA|
Bonilla-Ríos|Jaime|J|
Canales-Fiscal|Martha R|MR|
Sánchez-Fernández|Antonio|A|

Adsorption
Membrane
Cellulose beads
Filtration
Sodium alginate
Chitosan


Novel pH-responsive dextrin nanogels for doxorubicin delivery to cancer cells with reduced cytotoxicity to cardiomyocytes and stem cells.

Abstract: The aim of this study was to develop pH-responsive dextrin nanogels (DNGs) capable of triggered intracellular DOX release at the lower pH of cancer cells. DNGs were prepared by an emulsion cross-linking method using glyoxal as cross-linker to create an acid-labile bond. A higher molecular weight of dextrin with increasing mole ratio of dextrin to glyoxal decreased the average diameter of DNGs. DNGs showed slightly negative surface charge and pH-responsive behavior. The in vitro drug release was slow at pH 7.4 and increased with decreasing pH (pH 5>6.8). The cytotoxicity of DOX-loaded DNGs in mesenchymal stem cells and cardiomyocytes was lower than that of free DOX. Moreover, DOX-loaded DNGs were efficiently internalized by tumor cells with rapid release of DOX into the nucleus. Thus, DOX-loaded DNGs were successful for intracellular targeted anti-tumor drug delivery and reducing side-effects to non-tumor cells such as cardiomyocytes and stem cells.

Manchun|Somkamol|S|
Cheewatanakornkool|Kamonrak|K|
Dass|Crispin R|CR|
Sriamornsak|Pornsak|P|

pH-responsive Dextrin Nanogels Doxorubicin Cancer


Transgenerational metabolomic fingerprints in mice ancestrally exposed to the obesogen TBT.

Abstract:
BACKGROUND
Endocrine disrupting chemicals (EDCs) contribute to the etiology of metabolic disorders such as obesity, insulin resistance and hepatic dysfunction. Concern is growing about the consequences of perinatal EDC exposure on disease predisposition later in life. Metabolomics are promising approaches for studying long-term consequences of early life EDC exposure. These approaches allow for the identification and characterization of biomarkers of direct or ancestral exposures that could be diagnostic for individual susceptibility to disease and help to understand mechanisms through which EDCs act.

OBJECTIVES
We sought to identify metabolomic fingerprints in mice ancestrally exposed to the model obesogen tributyltin (TBT), to assess whether metabolomics could discriminate potential trans-generational susceptibility to obesity and recognize metabolic pathways modulated by ancestral TBT exposure.

METHODS
We used non-targeted 1H NMR metabolomic analyses of plasma and liver samples collected from male and female mice ancestrally exposed to TBT in two independent transgenerational experiments in which F3 and F4 males became obese when challenged with increased dietary fat.

RESULTS
Metabolomics confirmed transgenerational obesogenic effects of environmentally relevant doses of TBT in F3 and F4 males, in two independent studies. Although females never became obese, their specific metabolomic fingerprint evidenced distinct transgenerational effects of TBT in female mice consistent with impaired capacity for liver biotransformation.

DISCUSSION
This study is the first application of metabolomics to unveil the transgenerational effects of EDC exposure. Very early, significant changes in the plasma metabolome were observed in animals ancestrally exposed to TBT. These changes preceded the onset of obesogenic effects elicited by increased dietary fat in the TBT groups, and which ultimately resulted in significant changes in the liver metabolome. Development of metabolomic fingerprints could facilitate the identification of individuals carrying the signature of ancestral obesogen exposure that might increase their susceptibility to other risk factor such as increased dietary fat.

Chamorro-García|Raquel|R|
Poupin|Nathalie|N|
Tremblay-Franco|Marie|M|
Canlet|Cécile|C|
Egusquiza|Riann|R|
Gautier|Roselyne|R|
Jouanin|Isabelle|I|
Shoucri|Bassem M|BM|
Blumberg|Bruce|B|
Zalko|Daniel|D|

Metabolomics
Obesogen
Tributyltin
Transgenerational effects
Endocrine disruptor
Metabolic disruptor


The Score Card Approach: A First Step Toward an Evidence-based Differentiation Assessment for Tablets.

Abstract:
BACKGROUND
The differentiation of tablets by their physical appearance is a contributing factor to the safe use of medications. In this study, a "score card" was developed to assess how well one tablet is differentiated from another tablet on the basis of the physical attributes of color, size, and shape.

METHODS
The score card was derived from a "2-out-of-5" difference test, in which participants were presented with groups of 5 tablets with varying color, size, and shape, and were asked to identify the 2 tablets that were different from the other 3 tablets.

RESULTS
Based on the study results (ie, recognition rate of the differences in the tablets, and confidence in such recognition), simplified metrics were derived to "score" a comparison of 2 tablets differing in color, size, and/or shape. The higher the score, the better the 2 tablets could be visually distinguished from each other. The scores were ranked as representing "strong," "moderate," or "weak" differentiation, with a corresponding stoplight color code, to create the final score card. The score card was internally verified by applying it to the tablets used in the study, then to the multiple strengths of Gilotrif® (afatinib) tablets, a Boehringer Ingelheim approved drug product.

CONCLUSION
The score card is a first step in the assessment of adequate differentiation of tablets and can be used for the design of tablets that promote safe use of medication.

Pekari|Klaus|K|
Fürst|Thomas|T|
Gössl|Rüdiger|R|
Dudhedia|Mayur S|MS|
Segretario|James|J|
Sommer|Florian|F|
Watson|Patricia|P|

drug product differentiation
medication error
physical differences
risk assessment tool


Audiological approaches to address the psychosocial needs of adults with hearing loss: perceived benefit and likelihood of use.

Abstract:
OBJECTIVE
To explore the perceived benefit and likely implementation of approaches used by audiologists to address their adult clients' psychosocial needs related to hearing loss.

DESIGN
Adults with hearing loss and audiologists completed separate, but related, surveys to rate their perceived benefit and also their likely use of 66 clinical approaches (divided over seven themes) that aim to address psychosocial needs related to hearing loss.

STUDY SAMPLE
A sample of 52 Australian adults with hearing loss, and an international sample of 19 audiologists.

RESULTS
Overall, participants rated all of the approaches highly on both benefit and likelihood of use; the highest ranked theme was Providing Emotional Support. Cohort comparisons showed that audiologists ranked the approaches significantly higher than did adults with hearing loss. Overall, participants ranked the themes higher on benefit than on the likelihood to use scales.

CONCLUSIONS
Adults with hearing loss and audiologists recognise the importance of approaches that address the psychosocial impacts of hearing loss in audiological rehabilitation. However, both groups placed slightly greater value on the internal-based approaches (the clients own emotional response, empowerment, and responsibility), and slightly less emphasis on the external-based approaches (being supported by communication partners, support groups or other health professionals).

D012048:Correction of Hearing Impairment

psychosocial
hearing loss
audiologist
emotional support
empowerment
support groups
Hearing healthcare professional
counselling
self-management
significant others


Suicide Attempt and Suicidal Drug Overdose in Chronic Obstructive Pulmonary Disease Patients With or Without Depression.

Abstract:
Background
To determine differences in the incidence and risks of suicide attempt (SA) and suicidal drug overdose (SDO) between chronic obstructive pulmonary disease (COPD) patients with and without comorbid depression by using data from Taiwan's National Health Insurance Research Database.

Methods
We analyzed the data of patients aged ≥20 years who had received a COPD diagnosis between 2000 and 2012. These COPD patients were divided into those with and without depression, and they were compared against a cohort from the general population. We calculated adjusted hazard ratios and the corresponding 95% confidence intervals for SA and SDO in the three cohorts after adjustment for age, sex, and comorbidities.

Results
Until the end of 2012, 5.81% of patients with COPD developed depression. The incidence of SA and SDO in COPD patients with and without depression was 29.7 and 4.69 per 10,000 person-years and 71.2 and 20.9 per 10,000 person-years, respectively. COPD patients with depression had 13.6- and 10.0-fold higher risks of SA and SDO, respectively, than did controls. Particularly, an increased risk of SA caused by the enhancement effects of depression on COPD was noted in patients aged less than 50 years.

Conclusion
SA and SDO risks are extremely high in Taiwanese COPD patients with depression. Our findings suggest that clinicians should be aware that for COPD patients with comorbid depression, prescribing a large amount of medications may be associated with SA risk through SDO.

Lin|Chi-Yu|CY| Harnod|Tomor|T| Lin|Cheng-Li|CL| Kao|Chia-Hung|CH|

suicide
suicidal drug overdose
chronic obstructive pulmonary disease
depression
National Health Insurance


How Does Emotion Regulation Strategy Use and Psychological Wellbeing Predict Mood in Adults With and Without Autism Spectrum Disorder? A Naturalistic Assessment.

Abstract: The aim of this study was to identify emotion regulation (ER) strategies that most strongly impact momentary mood in a sample of 23 adults with and 19 without autism spectrum disorder (ASD). Participants completed cognitive and behavioural assessments, online questionnaires, and experience sampling methodology questions. In the ASD group, the use of dampening and other-blame reduced mood while savouring and emotional acceptance improved mood. The use of self-blame and avoidance negatively impacted mood only in the non-ASD group, suggesting the use of these two strategies do not reduce mood in individuals with ASD. ER and mental health interventions should capture ER strategy use and aim to decrease maladaptive strategy use and increase adaptive strategy use.

Emotion regulation
Autism
Experience sampling methodology
Anxiety
Depression
Positive psychological wellbeing


Investigating the dynamics of recombinant protein secretion from a microalgal host.

Abstract: Production of recombinant proteins with microalgae represents an alternative platform over plant- or bacterial-based expression systems for certain target proteins. Secretion of recombinant proteins allows accumulation of the target product physically separate from the valuable algal biomass. To date, there has been little investigation into the dynamics of recombinant protein secretion from microalgal hosts-the culture parameters that encourage secreted product accumulation and stability, while encouraging biomass production. In this work, the efficiency of recombinant protein production was optimized by adjusting cultivation parameters for a strain of Chlamydomonas reinhardtii previously engineered to secrete a functional recombinant Lolium perenne ice binding protein (LpIBP), which has applications as a frozen food texturing and cryopreservation additive, into its culture medium. Three media and several cultivation styles were investigated for effects on secreted LpIBP titres and culture growth. A combination of acetate and carbon dioxide feeding with illumination resulted in the highest overall biomass and recombinant protein titres up to 10mgL(-1) in the culture medium. Pure photoautotrophic production was possible using two media types, with recombinant protein accumulation in all cultivations correlating to culture cell density. Two different cultivation systems were used for scale-up to 10L cultivations, one of which produced yields of secreted recombinant protein up to 12mgL(-1) within six cultivation days. Functional ice recrystallization inhibition (IRI) of the LpIBP from total concentrated extracellular protein extracts was demonstrated in a sucrose solution used as a simplified ice cream model. IRI lasted up to 7 days, demonstrating the potential of secreted products from microalgae for use as food additives.

Lauersen|Kyle J|KJ|
Huber|Isabel|I|
Wichmann|Julian|J|
Baier|Thomas|T|
Leiter|Andreas|A|
Gaukel|Volker|V|
Kartushin|Viktor|V|
Rattenholl|Anke|A|
Steinweg|Christian|C|
von Riesen|Lena|L|
Posten|Clemens|C|
Gudermann|Frank|F|
Lütkemeyer|Dirk|D|
Mussgnug|Jan H|JH|
Kruse|Olaf|O|

Recombinant protein secretion
Microalgae
Chlamydomonas reinhardtii
Flat-panel photobioreactor
Lolium perenne ice-binding protein
Wave-bag culture


"Rusticall chymistry": Alchemy, saltpeter projects, and experimental fertilizers in seventeenth-century English agriculture.

Abstract: As the primary ingredient in gunpowder, saltpeter was an extraordinarily important commodity in the early modern world. Historians of science and technology have long studied its military applications but have rarely focused on its uses outside of warfare. Due to its potential effectiveness as a fertilizer, saltpeter was also an integral component of experimental agricultural reform movements in the early modern period and particularly in seventeenth-century England. This became possible for several reasons: the creation of a thriving domestic saltpeter production industry in the second half of the sixteenth century; the development of vitalist alchemical theories that sought a unified explanation for the "growth" of minerals, metals, and plants; the rise of experimental natural philosophy; and the mid-seventeenth-century dominance of the English East India Company in the saltpeter trade, which allowed agricultural reformers to repurpose domestically produced saltpeter in agriculturally productive ways. This paper argues that the Hartlib Circle - a loose network of natural philosophers and social reformers - adopted vitalist matter theories and the practical, experimental techniques of alchemists to transform agriculture into a more productive enterprise. Though their grandiose plans never came to fruition, their experimental trials to develop artificial fertilizers played an early role in the origins and development of saline chemistry, agronomy, and the British Agricultural Revolution.

Alchemy
saltpeter
Hartlib Circle
artificial fertilizers
British Agricultural Revolution
vitalism


Differences in Falls between Older Adult Participants in Group Exercise and Those Who Exercise Alone: A Cross-Sectional Study Using Japan Gerontological Evaluation Study (JAGES) Data.

Abstract: This study examined the difference in falls between older adults who participated in group exercise and those who exercised alone. We used cross-sectional data from the Japan Gerontological Evaluation Study. Data were obtained from functionally independent residents aged 65 years or older across 30 municipalities in Japan (n = 19,257). Logistic regression analysis was performed with experience of multiple falls over the past year as the dependent variable and type of exercise as the independent variable. Respondents were divided into three groups according to how they performed exercise: (1) non-exercisers (NE, no exercise), (2) those who only exercised alone (IE, individual exercise), and (3) those whose exercise included participation in group exercise (GE, group exercise). In total, 887 (4.6%) respondents reported multiple falls. After adjustment for 10 possible confounders, the GE group had an odds ratio (OR) for falls of 0.75 (95% confidence intervals 0.60⁻0.95) compared with the IE group. After adjustment for physiological factors and a psychological factor, the OR for the GE group increased slightly; however, an association between falls and exercise type was indicated. Older adults who participate in group exercise may receive additional benefits related to falls prevention compared with those who exercise alone.

Hayashi|Takahiro|T|0000-0001-6887-4378 Kondo|Katsunori|K| Kanamori|Satoru|S| Tsuji|Taishi|T|0000-0002-8408-6619 Saito|Masashige|M| Ochi|Akira|A| Ota|Susumu|S|

older adults
group exercise
cross-sectional study
fall prevention


Protocols for Cryopreservation and Rederivation of Rat Gametes.

Abstract: New genome-editing tools, such as ZFNs, TALEN, and CRISPR/Cas9, have enabled the generation of gene-modified models effectively in mammals. These technologies are a powerful tool for studying gene function and creating animal models for human diseases. On the other hand, such gene-modified animals are raised in numerous experimental animal facilities, which puts pressure on breeding space and maintenance costs. Embryo and sperm cryopreservation is not only the most simple and cost-effective method available for most gene-modified strains but also the most reliable method to preserve strains to avoid breeding problems and contamination. We have established a reliable, high quality embryo and sperm cryopreservation system for rat strains, ensuring the longevity of these valuable resources for the scientific community. These cryopreserved resources have been successfully used to rederive next generation pups using embryo transfer and intracytoplasmic sperm injection (ICSI). In this chapter, we describe in detail protocols for rat embryo vitrification and sperm cryopreservation followed by pup rederivation using the ICSI procedure and embryo transfer.

Cryopreservation
Rederivation
Sperm
Embryo transfer
ICSI
Vitrification
Two-cell


High Quantum Efficiency Hot Electron Electrochemistry.

Abstract: Using hot electrons to drive electrochemical reactions has drawn considerable interest in driving high-barrier reactions and enabling efficient solar to fuel conversion. However, the conversion efficiency from hot electrons to electrochemical products is typically low due to high hot electron scattering rates. Here, it is shown that the hydrogen evolution reaction (HER) in an acidic solution can be efficiently modulated by hot electrons injected into a thin gold film by an Au-Al2O3-Si metal-insulator-semiconductor (MIS) junction. Despite the large scattering rates in gold, it is shown that the hot electron driven HER can reach quantum efficiencies as high as ∼85% with a shift in the onset of hydrogen evolution by ∼0.6 V. By simultaneously measuring the currents from the solution, gold, and silicon terminals during the experiments, we find that the HER rate can be decomposed into three components: (i) thermal electron, corresponding to the thermal electron distribution in gold; (ii) hot electron, corresponding to electrons injected from silicon into gold which drive the HER before fully thermalizing; and (iii) silicon direct injection, corresponding to electrons injected from Si into gold that drive the HER before electron-electron scattering occurs. Through a series of control experiments, we eliminate the possibility of the observed HER rate modulation coming from lateral resistivity of the thin gold film, pinholes in the gold, oxidation of the MIS device, and measurement circuit artifacts. Next, we theoretically evaluate the feasibility of hot electron injection modifying the available supply of electrons. Considering electron-electron and electron-phonon scattering, we track how hot electrons injected at different energies interact with the gold-solution interface as they scatter and thermalize. The simulator is first used to reproduce other published experimental pump-probe hot electron measurements, and then simulate the experimental conditions used here. These simulations predict that hot electron injection first increases the supply of electrons to the gold-solution interface at higher energies by several orders of magnitude and causes a peaked electron interaction with the gold-solution interface at the electron injection energy. The first prediction corresponds to the observed hot electron electrochemical current, while the second prediction corresponds to the observed silicon direct injection current. These results indicate that MIS devices offer a versatile platform for hot electron sources that can efficiently drive electrochemical reactions.

quantum efficiency
hot electron
hydrogen evolution reaction
MIS devices
Monte Carlo simulation
scattering mechanism


Using Methacryl-Polyhedral Oligomeric Silsesquioxane as the Thermal Stabilizer and Plasticizer in Poly(vinyl chloride) Nanocomposites.

Abstract: In this study, we investigated the influence of methacryl-functionalized polyhedral oligomeric silsesquioxane (MA-POSS) nanoparticles as a plasticizer and thermal stabilizer for a poly(vinyl chloride) (PVC) homopolymer and for a poly(vinyl chloride)/dissononyl cyclohexane-1,2-dicarboxylate (PVC/DINCH) binary blend system. The PVC and the PVC/DINCH blend both became flexible, with decreases in their glass transition temperatures and increases in their thermal decomposition temperatures, upon an increase in MA-POSS content, the result of hydrogen bonding between the C=O groups of MA-POSS and the H-CCl units of the PVC, as determined using infrared spectroscopy. Furthermore, the first thermal decomposition temperature of the pure PVC, due to the emission of HCl, increased from 290 to 306 °C, that is, the MA-POSS nanoparticles had a retarding effect on the decomposition of the PVC matrix. In tensile tests, all the PVC/DINCH/MA-POSS ternary blends were transparent and displayed flexibility, but their modulus and tensile strength both decreased, while their elongation properties increased, upon an increase in MA-POSS concentration, both before and after thermal annealing. In contrast, the elongation decreased, but the modulus and tensile strength increased, after thermal annealing at 100 °C for 7 days.

Wang|Yu-Kai|YK| Tsai|Fang-Chang|FC|0000-0002-3189-4620 Ma|Chao-Chen|CC| Wang|Min-Ling|ML| Kuo|Shiao-Wei|SW|

plasticizer
poly(vinyl chloride)
nanocomposites
POSS


Designing micellar nanocarriers with improved drug loading and stability based on solubility parameter.

Abstract: The objective of this study is to demonstrate the feasibility of using solubility parameter as guidance for the design and identification of a stable micellar system with a high drug loading capacity for oral drug delivery. Using hydroxycamptothecin (HCPT) as a model drug, the effect of three hydrophobic blocks (fatty glycerides) grafted onto chitosan on the drug loading and stability of HCPT-loaded micellar nanoparticles formed by pH precipitation method were studied systematically. The Flory-Huggins interaction parameter (χFH) calculated by the group contribution method (GCM) and molecular dynamics simulation (MDS) was used to assess the compatibility between HCPT and the copolymers. The predicted order of compatibility between three chitosan derivatives and HCPT was verified experimentally. A high drug loading and remarkably stable micellar system for oral administration based on succinylated glycerol monooleate-chitosan was discovered in this study. Our study suggests that the miscibility between drug and copolymer is crucial to drug loading and stability of the micellar system. Thus, the calculation of χFH using GCM and MDS methods is useful for guiding the design or screening of a suitable copolymer for preparing drug-loaded micellar nanocarrier systems.

Tian|Ye|Y|
Shi|Chenjun|C|
Sun|Yujiao|Y|
Zhu|Chengyun|C|
Sun|Changquan Calvin|CC|
Mao|Shirui|S|

micellar system
group contribution method
chitosan derivatives
Flory−Huggins interaction parameter
molecular simulation


Capillary Electrophoresis in Metabolomics.

Abstract: Metabolomics is an analytical toolbox to describe (all) low-molecular-weight compounds in a biological system, as cells, tissues, urine, and feces, as well as in serum and plasma. To analyze such complex biological samples, high requirements on the analytical technique are needed due to the high variation in compound physico-chemistry (cholesterol derivatives, amino acids, fatty acids as SCFA, MCFA, or LCFA, or pathway-related metabolites belonging to each individual organism) and concentration dynamic range. All main separation techniques (LC-MS, GC-MS) are applied in routine to metabolomics hyphenated or not to mass spectrometry, and capillary electrophoresis is a powerful high-resolving technique but still underused in this field of complex samples. Metabolomics can be performed in the non-targeted way to gain an overview on metabolite profiles in biological samples. Targeted metabolomics is applied to analyze quantitatively pre-selected metabolites. This chapter reviews the use of capillary electrophoresis in the field of metabolomics and exemplifies solutions in metabolite profiling and analysis in urine and plasma.

Capillary electrophoresis
Metabolomics
Fatty acids
Mass spectrometry
Non-targeted
Targeted


How Big is the Pinacol Boronic Ester as a Substituent?

Abstract: The synthetically versatile pinacol boronic ester group (Bpin) is generally thought of as a bulky moiety because of the two adjacent quaternary sp3 -hydribized carbon atoms in its diol backbone. However, recent diastereoselective reactions reported in the literature have cast doubt on this perception. Reported herein is a detailed experimental and computational analysis of Bpin and structurally related boronic esters which allows determination of three different steric parameters for the Bpin group: the A-value, ligand cone angle, and percent buried volume. All three parameters suggest that the Bpin moiety is remarkably small, with the planarity of the oxygen-boron-oxygen motif playing an important role in minimising steric interactions. Of the three steric parameters, percent buried volume provides the best correlation between steric size and diastereoselectivity in a Diels-Alder reaction.

boronic esters
A-values
conformational analysis
density-functional calculations
steric hinderance


Transcriptome Profiling Analysis of Wolf Spider Pardosa pseudoannulata (Araneae: Lycosidae) after Cadmium Exposure.

Abstract: Pardosa pseudoannulata is one of the most common wandering spiders in agricultural fields and a potentially good bioindicator for heavy metal contamination. However, little is known about the mechanisms by which spiders respond to heavy metals at the molecular level. In the present study, high-throughput transcriptome sequencing was employed to characterize the de novo transcriptome of the spiders and to identify differentially expressed genes (DEGs) after cadmium exposure. We obtained 60,489 assembled unigenes, 18,773 of which were annotated in the public databases. A total of 2939 and 2491 DEGs were detected between the libraries of two Cd-treated groups and the control. Functional enrichment analysis revealed that metabolism processes and digestive system function were predominately enriched in response to Cd stress. At the cellular and molecular levels, significantly enriched pathways in lysosomes and phagosomes as well as replication, recombination and repair demonstrated that oxidative damage resulted from Cd exposure. Based on the selected DEGs, certain critical genes involved in defence and detoxification were analysed. These results may elucidate the molecular mechanisms underlying spiders' responses to heavy metal stress.

Li|Chang-Chun|CC| Wang|Yong|Y| Li|Guo-Yuan|GY| Yun|Yue-Li|YL| Dai|Yu-Jun|YJ| Chen|Jian|J| Peng|Yu|Y|

D060888:Real-Time Polymerase Chain Reaction

transcriptome
cadmium
P. pseudoannulata
RT-qPCR


Less Than Ideal Cardiovascular Health Is Associated With Shorter Leukocyte Telomere Length: The National Health and Nutrition Examination Surveys, 1999-2002.

Abstract:
BACKGROUND
The associations between individual cardiovascular disease risk factors and leukocyte telomere length (LTL) have been inconclusive. We investigated the association between LTL and overall cardiovascular health (CVH) as defined by the American Heart Association and whether the association is modified by sex and race/ethnicity.

METHODS AND RESULTS
We included 5194 adults (aged ≥20) from the National Health and Nutrition Examination Survey 1999-2002. CVH was defined as a composite score of the 7 metrics (smoking, physical activity, diet, body mass index, blood pressure, total cholesterol, and fasting blood glucose) and categorized as "poor," "intermediate," and "ideal." LTL was assayed from whole blood using the quantitative polymerase chain reaction method relative to standard reference DNA. Multivariable linear regression models were used to estimate the association between CVH and log-transformed LTL. We found strong graded association between CVH and LTL in the overall sample, with evidence of dose-response relationship (P for trend=0.013). Individuals with poor and intermediate CVH had significantly shorter LTL than individuals with ideal CVH (-3.4% [95% CI=-6.0%, -0.8%] and -2.4% [-4.4%, -0.3%], respectively), after adjustment for demographic variables, socioeconomic status, and C-reactive protein. The association was stronger in women (-6.6% [-10.2%, -2.9%] for poor vs ideal CVH) and non-Hispanic whites (-4.3% [-7.1%, -1.4%] for poor vs ideal CVH).

CONCLUSIONS
The findings suggest that less-than-ideal CVH is associated with shorter LTL, but this association varies by sex and race/ethnicity. Future longitudinal research is needed to elucidate the mechanisms that underlie the association between CVH and LTL.

Gebreab|Samson Y|SY|
Manna|Zerai G|ZG|
Khan|Rumana J|RJ|
Riestra|Pia|P|
Xu|Ruihua|R|
Davis|Sharon K|SK|

cardiovascular health
leukocyte telomere length
cardiovascular disease risk factors
aging
AHA Scientific Statement
diverse populations
epidemiology
inflammation
telomere genetics


The effects of fatty acid composition on cardiac hypertrophy and function in mouse models of diet-induced obesity.

Abstract: High-fat diets (HFDs) are used frequently to study the development of cardiac dysfunction in animal models of obesity and diabetes. However, impairment in systolic function, often reported as declining ejection fraction, may not consistently occur in a given time frame which could be contributable to a variety of factors within the experimental design. One major factor may be the amounts of saturated and unsaturated fatty acids (FAs) that are present in the diet. To determine whether the FA content and composition were critical determinants in the development of cardiac dysfunction in response to high-fat feeding, we fed adult, male mice Western diet (45% fat, 60% saturated), Surwit diet (60% fat, 90% saturated), milk-fat-based diet (60% fat, 60% saturated) or high-fat Western diet (HFWD, 60% fat, 32% saturated) for 12 weeks. We report that neither the amount of total fat nor the ratio of saturated to unsaturated FAs in the diets differentially affects body weight and adiposity in mice. In addition, no evidence of systolic dysfunction is present after 12 weeks. Interestingly, the HFWD, with equal parts saturated, monounsaturated and polyunsaturated FAs, induces mild cardiac hypertrophy and diastolic dysfunction after 12 weeks, which coincides with elevated serum levels of arachidonic acid. Our results suggest that the dietary FA content and composition may be a primary determinant of diastolic, but not systolic, dysfunction in animal models of diet-induced obesity.

Nguyen|Son|S|
Shao|Dan|D|
Tomasi|Loreta C|LC|
Braun|Alyssa|A|
de Mattos|Ana Barbosa Marcondes|ABM|
Choi|Yong Seon|YS|
Villet|Outi|O|
Roe|Nathan|N|
Halterman|Carliana R|CR|
Tian|Rong|R|
Kolwicz|Stephen C|SC|

Cardiomyopathy
Fatty acid profiling
Lipid metabolism
Lipid overload
Mouse strain


Nuclear organization of catecholaminergic neurons in the brains of a lar gibbon and a chimpanzee.

Abstract: Using tyrosine hydroxylase immunohistochemistry, we describe the nuclear parcellation of the catecholaminergic system in the brains of a lar gibbon (Hylobates lar) and a chimpanzee (Pan troglodytes). The parcellation of catecholaminergic nuclei in the brains of both apes is virtually identical to that observed in humans and shows very strong similarities to that observed in mammals more generally, particularly other primates. Specific variations of this system in the apes studied include an unusual high-density cluster of A10dc neurons, an enlarged retrorubral nucleus (A8), and an expanded distribution of the neurons forming the dorsolateral division of the locus coeruleus (A4). The additional A10dc neurons may improve dopaminergic modulation of the extended amygdala, the enlarged A8 nucleus may be related to the increased use of communicative facial expressions in the hominoids compared to other primates, while the expansion of the A4 nucleus appears to be related to accelerated evolution of the cerebellum in the hominoids compared to other primates. In addition, we report the presence of a compact division of the locus coeruleus proper (A6c), as seen in other primates, that is not present in other mammals apart from megachiropteran bats. The presence of this nucleus in primates and megachiropteran bats may reflect homology or homoplasy, depending on the evolutionary scenario adopted. The fact that the complement of homologous catecholaminergic nuclei is mostly consistent across mammals, including primates, is advantageous for the selection of model animals for the study of specific dysfunctions of the catecholaminergic system in humans.

tyrosine hydroxylase
ape
primates
adrenalin
dopamine
noradrenalin


Venous thromboembolism and underutilisation of anticoagulant thromboprophylaxis in hospitalised patients with inflammatory bowel disease.

Abstract:
BACKGROUND
Venous thromboembolism (VTE) is a well-recognised extra-intestinal manifestation of inflammatory bowel disease (IBD). Despite the widespread support for anticoagulant prophylaxis in hospitalised IBD patients, the utilisation and efficacy in clinical practice are unknown.

AIMS
The aim of this study was to assess the prevalence and clinical features of VTE among hospitalised IBD patients and ascertain whether appropriate thromboprophylaxis had been administered.

METHODS
All patients with a discharge diagnosis of Crohn disease or ulcerative colitis and VTE were retrospectively identified using International Classification of Diseases, tenth revision codes from medical records at our institution from July 1998 to December 2009. Medical records were then reviewed for clinical history and utilisation of thromboprophylaxis. Statistical analysis was performed by Mann-Whitney test and either χ(2) tests or Fisher's exact tests.

RESULTS
Twenty-nine of 3758 (0.8%) IBD admissions suffered VTE, 13 preadmission and 16 during admission. Of these 29 admissions (in 25 patients), 24% required intensive care unit and 10% died. Of the 16 venous thrombotic events that occurred during an admission, eight (50%) did not receive anticoagulant thromboprophylaxis and eight (50%) occurred despite thromboprophylaxis. Most thromboembolism despite prophylaxis occurred post-intestinal resection (n = 5, 63%).

CONCLUSION
Thromboprophylaxis is underutilised in half of IBD patients suffering VTE. Prescription of thromboprophylaxis for all hospitalised IBD patients, including dual pharmacological and mechanical prophylaxis in postoperative patients, may lead to a reduction in this preventable complication of IBD.

Dwyer|J P|JP|
Javed|A|A|
Hair|C S|CS|
Moore|G T|GT|

venous thromboembolism
anticoagulant
inflammatory bowel disease
Crohn disease
ulcerative colitis


Establishment of drug-resistant cell lines under the treatment with chemicals acting through different mechanisms.

Abstract: The problem of chemoresistance development is an inescapable flipside of modern oncotherapy, in particular for сolorectal cancer patients. The search for or development of drugs effective against resistant tumors involves the use of model resistant cell lines in vitro. To obtain such lines, we reproduced the development of chemoresistance of human colon adenocarcinoma cells under the treatment with drugs of different mechanisms, a cytostatic (paclitaxel) and a targeted agent (Nutlin-3a, an inhibitor of p53-Mdm2 protein-protein interaction). In each case, we gradually increased the content of the substance in the medium, starting from effective concentrations that do not cause total cell death. When studying the lines resistant to the corresponding drug, we noted a reduced sensitivity to the drug of another mechanism of action. Analysis of the original and resistant lines showed that the cells use the universal efflux defense mechanism. The observed effect can be partially neutralized using inhibitors of the ABC transport proteins, including P-glycoprotein, known for its oncoprotective function. The role of the latter was confirmed by real-time RT-PCR and Western blotting.

Grigoreva|Tatyana|T| Sagaidak|Aleksandra|A| Romanova|Angelina|A| Novikova|Daria|D| Garabadzhiu|Aleksander|A| Tribulovich|Viacheslav|V|

D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1

Chemoresistance
Paclitaxel
Nutlin-3a
p53-Mdm2
P-glycoprotein
Multiple drug resistance


Numerical solutions of the semiclassical Boltzmann ellipsoidal-statistical kinetic model equation.

Abstract: Computations of rarefied gas dynamical flows governed by the semiclassical Boltzmann ellipsoidal-statistical (ES) kinetic model equation using an accurate numerical method are presented. The semiclassical ES model was derived through the maximum entropy principle and conserves not only the mass, momentum and energy, but also contains additional higher order moments that differ from the standard quantum distributions. A different decoding procedure to obtain the necessary parameters for determining the ES distribution is also devised. The numerical method in phase space combines the discrete-ordinate method in momentum space and the high-resolution shock capturing method in physical space. Numerical solutions of two-dimensional Riemann problems for two configurations covering various degrees of rarefaction are presented and various contours of the quantities unique to this new model are illustrated. When the relaxation time becomes very small, the main flow features a display similar to that of ideal quantum gas dynamics, and the present solutions are found to be consistent with existing calculations for classical gas. The effect of a parameter that permits an adjustable Prandtl number in the flow is also studied.

Yang|Jaw-Yen|JY| Yan|Chin-Yuan|CY| Huang|Juan-Chen|JC| Li|Zhihui|Z|


Microstructure evaluation of dermally applicable liquid crystals as a function of water content and temperature: Can electron paramagnetic resonance provide complementary data?

Abstract: Insight into the microstructure of lyotropic liquid crystals (LCs) is of crucial importance for development of novel dermal delivery systems. Our aim was to evaluate the phase behaviour of dermally applicable LCs composed of isopropyl myristate/Tween 80/lecithin/water, along the dilution line, where phase transitions are predominantly driven by increased water content. Additionally, identification of LC temperature dependence is of great importance for skin application. Selected LCs were evaluated using electron paramagnetic resonance (EPR) plus conventionally used methods of polarization microscopy, small-angle X-ray scattering, differential scanning calorimetry, and rheological measurements. Depending on water content, LCs formed diverse microstructures, from (pseudo)hexagonal (LC1) and lamellar (LC2-LC7) liquid crystalline phases that possibly co-exist with rod-like micelles (LC4-LC7), to a transitional micellar phase (LC8). Furthermore, the LCs microstructure remained unaltered within the tested temperature range. EPR was shown to detect microstructural transitions of LCs and to provide complementary data to other techniques. These data thus confirm the applicability of EPR as a complementary technique for better understanding of LC microstructural transitions that are expected to contribute greatly to studies oriented towards the drug release characteristics from such systems.

Matjaž|Mirjam Gosenca|MG|
Mravljak|Janez|J|
Rogač|Marija Bešter|MB|
Šentjurc|Marjeta|M|
Gašperlin|Mirjana|M|
Pobirk|Alenka Zvonar|AZ|

D004578:Electron Spin Resonance Spectroscopy

Microstructure
EPR
Rheology
DSC
Hexagonal and lamellar liquid crystal
SAXS


Work-Life Balance and Productivity Among Academic Faculty During the COVID-19 Pandemic: A Latent Class Analysis.

Abstract: For faculty in academic health sciences, the balance between research, education, and patient care has been impeded by the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to identify personal and professional characteristics of faculty to understand the impact of the pandemic on faculty and consequent policy implications.  A 93-question survey was sent to faculty at a large urban public university and medical center. Demographic, family, and academic characteristics, work distribution and productivity before and during the pandemic, stress, and self-care data information were collected. Latent class analysis (LCA) was performed to identify classes of faculty sharing similar characteristics. Comparisons between latent classes were performed using analysis of variance and chi-square analyses.  Of 497 respondents, 60% were women. Four latent classes of faculty emerged based on six significant indicator variables. Class 1 individuals were more likely women, assistant professors, nontenured with high work and home stress; Class 2 faculty were more likely associate professors, women, tenured, who reported high home and work stress; Class 3 faculty were more likely men, professors, tenured with moderate work, but low home stress; and Class 4 faculty were more likely adjunct professors, nontenured, and had low home and work stress. Class 2 reported significantly increased administrative and clinical duties, decreased scholarly productivity, and deferred self-care.  The pandemic has not affected faculty equally. Early and mid-career individuals were impacted negatively from increased workloads, stress, and decreased self-care. Academic leaders need to acknowledge these differences and be inclusive of faculty with different experiences when adjusting workplace or promotion policies.

academic faculty
COVID-19 pandemic
latent class analysis
health sciences
gender
work–life balance


Fetal Origins of Mental Disorders? An Answer Based on Mendelian Randomization.

Abstract: The Barker hypothesis states that low birth weight (BW) is associated with higher risk of adult onset diseases, including mental disorders like schizophrenia, major depressive disorder (MDD), and attention deficit hyperactivity disorder (ADHD). The main criticism of this hypothesis is that evidence for it comes from observational studies. Specifically, observational evidence does not suffice for inferring causality, because the associations might reflect the effects of confounders. Mendelian randomization (MR) - a novel method that tests causality on the basis of genetic data - creates the unprecedented opportunity to probe the causality in the association between BW and mental disorders in observation studies. We used MR and summary statistics from recent large genome-wide association studies to test whether the association between BW and MDD, schizophrenia and ADHD is causal. We employed the inverse variance weighted (IVW) method in conjunction with several other approaches that are robust to possible assumption violations. MR-Egger was used to rule out horizontal pleiotropy. IVW showed that the association between BW and MDD, schizophrenia and ADHD is not causal (all p > .05). The results of all the other MR methods were similar and highly consistent. MR-Egger provided no evidence for pleiotropic effects biasing the estimates of the effects of BW on MDD (intercept = -0.004, SE = 0.005, p = .372), schizophrenia (intercept = 0.003, SE = 0.01, p = .769), or ADHD (intercept = 0.009, SE = 0.01, p = .357). Based on the current evidence, we refute the Barker hypothesis concerning the fetal origins of adult mental disorders. The discrepancy between our results and the results from observational studies may be explained by the effects of confounders in the observational studies, or by the existence of a small causal effect not detected in our study due to weak instruments. Our power analyses suggested that the upper bound for a potential causal effect of BW on mental disorders would likely not exceed an odds ratio of 1.2.


Control of Rest:Activity by a Dopaminergic Ultradian Oscillator and the Circadian Clock.

Abstract: There is long-standing evidence for rhythms in locomotor activity, as well as various other aspects of physiology, with periods substantially shorter than 24 h in organisms ranging from fruit flies to humans. These ultradian oscillations, whose periods frequently fall between 2 and 6 h, are normally well integrated with circadian rhythms; however, they often lack the period stability and expression robustness of the latter. An adaptive advantage of ultradian rhythms has been clearly demonstrated for the common vole, suggesting that they may have evolved to confer social synchrony. The cellular substrate and mechanism of ultradian rhythm generation have remained elusive so far, however recent findings-the subject of this review-now indicate that ultradian locomotor rhythms rely on an oscillator based on dopamine, dubbed the dopaminergic ultradian oscillator (DUO). These findings also reveal that the DUO period can be lengthened from <4 to >48 h by methamphetamine treatment, suggesting that the previously described methamphetamine-sensitive (circadian) oscillator represents a long-period manifestation of the DUO.

rest:activity
dopaminergic ultradian oscillator
circadian clock
biological rhythms
dopamine transporter