Eight weeks of high-intensity interval training versus stretching do not change the psychoneuroendocrine response to a social stress test in emotionally impulsive humans.

PURPOSE: Research supports physical activity as a method to heighten stress resistance and resilience through positive metabolic alterations mostly affecting the neuroendocrine system. High-intensity interval training (HIIT) has been proposed as a highly effective time-saving method to induce those changes. However, existing literature relies heavily on cross-sectional analyses, with few randomised controlled trials highlighting the necessity for more exercise interventions. Thus, this study aims to investigate the effects of HIIT versus an active control group on the stress response to an acute psychosocial stressor in emotionally impulsive humans (suggested as being strong stress responders). METHODS: The study protocol was registered online (DRKS00016589) before data collection. Sedentary, emotionally impulsive adults (30.69 ± 8.20 y) were recruited for a supervised intervention of 8 weeks and randomly allocated to either a HIIT (n = 25) or a stretching group (n = 19, acting as active controls). Participants were submitted to a test battery, including saliva samples, questionnaires (self-efficacy- and perceived stress-related), visual analogue scales (physical exercise- and stress-related), and resting electroencephalography and electrocardiography assessing their reaction to an acute psychological stressor (Trier Social Stress Test) before and after the exercise intervention. RESULTS: HIIT increased aerobic fitness in all participants, whereas stretching did not. Participants from the HIIT group reported perceiving exercising more intensively than those from the active control group (ƞp2 = 0.108, p = 0.038). No further group differences were detected. Both interventions largely increased levels of joy post-TSST (ƞp2 = 0.209, p = 0.003) whilst decreasing tension (ƞp2 = 0.262, p < 0.001) and worries (ƞp2 = 0.113, p = 0.037). Finally, both interventions largely increased perceived levels of general self-efficacy (ƞp2 = 0.120, p = 0.029). CONCLUSION: This study suggests that 8 weeks of HIIT does not change the psychoneuroendocrine response to an acute psychological stress test compared to an active control group in emotionally impulsive humans. Further replications of supervised exercise studies highly powered with active and passive controls are warranted.

Disruption of global hypothalamic microRNA (miR) profiles and associated behavioral changes in California mice (Peromyscus californicus) developmentally exposed to endocrine disrupting chemicals.

Developmental exposure to endocrine disrupting chemicals (EDCs), e.g., bisphenol A (BPA) or genistein (GEN), causes longstanding epigenome effects. MicroRNAs (miRs) regulate which mRNAs will be translated to proteins and thereby serve as the final checkpoint in epigenetic control. Scant amount is known, however, whether EDCs affect neural miRNA (miR) patterns. We aimed to test the hypothesis that developmental exposure of California mice (Peromyscus californicus) to GEN, BPA, or both chemicals influences hypothalamic miR/small RNA profiles and ascertain the extent such biomolecular alterations correlate with behavioral and metabolic changes. California mice were developmentally exposed to GEN (250 mg/kg feed weight, FW), GEN (250 mg/kg FW)+BPA (5 mg/kg FW), low dose (LD) BPA (5 mg/kg FW), or upper dose (UD) BPA (50 mg/kg FW). Adult offspring were tested in a battery of behavioral and metabolic tests; whereupon, mice were euthanized, brains were collected and frozen, small RNAs were isolated from hypothalamic punches, and subsequently sequenced. California mice exposed to one or both EDCs engaged in one or more repetitive behaviors. GEN, LD BPA, and UD BPA altered aspects of ultrasonic and audible vocalizations. Each EDC exposure led to sex-dependent differences in differentially expressed miR/small RNAs with miR7-2, miR146, and miR148a being increased in all female and male EDC exposed groups. Current findings reveal that developmental exposure to GEN and/or BPA affects hypothalamic miR/small RNA expression patterns, and such changes correlate with EDC-induced behavioral and metabolic alterations. miR146 is likely an important mediator and biomarker of EDC exposure in mammals, including humans.

Sensorimotor training and whole-body vibration training have the potential to reduce motor and sensory symptoms of chemotherapy-induced peripheral neuropathy-a randomized controlled pilot trial.

Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent and clinically relevant side effect of chemotherapy. The symptoms diminish patients' quality of life and represent a decisive limiting factor for medical therapy. To date, effective treatment options are lacking. Specific exercise interventions have proven promising to target relevant symptoms. We conducted a prospective, four-armed, randomized, controlled trial, to evaluate the effects of sensorimotor training (SMT) and whole-body vibration training (WBV) on patients with CIPN. Participants (N = 40) were randomized to either one of two intervention groups (SMT N = 10 or WBV N = 10) or oncological control group (N = 10) and matched by gender and age with a healthy control (N = 10). The intervention groups exercised twice a week for 6 weeks. Primary endpoint was the reduction of CIPN-related symptoms (improve peripheral deep sensitivity, Achilles tendon reflex (ASR) and patellar tendon reflex (PSR), light-touch perception, sense of position, and lower leg strength). Secondary endpoints were nerve conduction velocity and amplitude, balance control, quality of life, and CIPN-related pain. Patients exercising improved sensory and associated motor symptoms. Significant intergroup differences were found for the tendon reflexes (ASR P = .017 and PSR P = .020), peripheral deep sensitivity (P = .010), and pain (P = .043). Furthermore, tendencies were found regarding the subjective improvement of symptoms (P = .075) and two subscales of the EORTC-QLQ-C30 questionnaire: pain (P = .054) and dyspnea (P = .054). The results for the SMT group were superior regarding the tendon reflexes, and a tendency regarding the subjective report of symptoms, while WBV was superior regarding pain. SMT and WBV behold a large potential to reduce CIPN-related symptoms and can be considered feasible and safe for patients with CIPN (compliance 97.5%, no adverse events).Registration: DRKS00013027.

Effects of maternal or paternal bisphenol A exposure on offspring behavior.

Bisphenol A (BPA) is an endocrine disrupting chemical used in the production of polycarbonate plastics and resins. Exposure to BPA during gestation has been proposed as a risk factor for the development of neurobehavioral disorders, such as autism spectrum disorder. To address the behavioral impact of developmental exposure to BPA, we tested offspring of mice exposed to a daily low dose of BPA during pregnancy. We also asked if preconception exposure of the sire affected behaviors in offspring. Sires that consumed BPA for 50days prior to mating weighed less than controls, but no effects on any reproductive measures were noted. Juvenile offspring exposed to BPA maternally, but not paternally, spent less time in the open arms of the elevated plus maze than controls, indicating increased anxiety-like behavior. However, neither parental exposure group differed significantly from controls in the social recognition task. We also assessed the behaviors of maternally exposed offspring in two novel tasks: ultrasonic vocalizations (USVs) in pups and operant reversal learning in adults. Maternal BPA exposure increased the duration and median frequency of USVs emitted by pups during maternal separation. In the reversal learning task, females responded more accurately and earned more rewards than males. Additionally, control females received more rewards than BPA females during the acquisition phase of the task. These are among the first studies conducted to ask if BPA exposure via the sire affects offspring behavior and the first study to report effects of gestational BPA exposure on pup USVs and adult operant responding.

Manipulating Surface States of III-V Nanowires with Uniaxial Stress.

III-V compound semiconductors are indispensable materials for today's high-end electronic and optoelectronic devices and are being explored for next-generation transistor logic and quantum technologies. III-V surfaces and interfaces play the leading role in determining device performance, and therefore, methods to control their electronic properties have been developed. Typically, surface passivation studies demonstrated how to limit the density of surface states. Strain has been widely used to improve the electronic transport properties and optoelectronic properties of III-Vs, but the potential of this technology to modify the surface properties still remains to be explored. Here we show that uniaxial stress induces a shift in the energy of the surface states of III-V nanowires, modifying their electronic properties. We demonstrate this phenomenon by modulating the conductivity of InAs nanowires over 4 orders of magnitude with axial strain ranging between -2.5% in compression and 2.1% in tension. The band bending at the surface of the nanostructure is modified from accumulation to depletion reversibly and reproducibly. We provide evidence of this physical effect using a combination of electrical transport measurement, Raman spectroscopy, band-structure modeling, and technology computer aided design (TCAD) simulations. With this methodology, the deformation potentials for the surface states are quantified. These results reveal that strain technology can be used to shift surface states away from energy ranges in which device performance is negatively affected and represent a novel route to engineer the electronic properties of III-V devices.

Development of an adaptive, personalized, and scalable dementia care program: Early findings from the Care Ecosystem.

Katherine Possin and colleagues report on the implementation, development, and early findings of the Care Ecosystem, an adaptive, personalized, and scalable dementia care program.

Bowel function in patients with urinary diversion: a gender-matched comparison of continent urinary diversion with the ileocecal pouch and ileal conduit.

PURPOSE: To evaluate stool habits and associated quality of life (QoL) in a matched pair analysis of patients who underwent continent cutaneous diversion using the ileocecal segment [Mainz pouch I (MzPI)] with an intussuscepted ileal nipple as efferent segment with those receiving an ileal conduit (IC) after radical cystectomy. METHODS: We identified 250 patients who underwent radical cystectomy and urinary diversion (UD) with either MzPI with an ileal nipple or IC in our database. A detailed history of stool habits using the modified Wexner score was obtained, and questions addressing general lifestyle, comparison of symptom differences before and after surgery considering bowel function as well as bowel-associated QoL were assessed. RESULTS: Forty-five age- and sex-matched pairs could be compared. Overall, stool incontinence (p = 0.481) and the Wexner score (p = 0.464) revealed no differences between both groups. However, patients with MzPI as compared to those with IC had significant higher rates of stool frequency (53 vs 31 %), softer stool consistencies (60 vs 13 %), diarrhea (62 vs 20 %) and a lower rate of constipation (4 vs 22 %). Patients with MzPI had a trend toward lower bowel-associated QoL compared with patients with IC. Similarly, the MzPI group reported a significantly impaired overall postoperative QoL (51 %) compared to the IC group (29 %) (p = 0.024). CONCLUSIONS: Patients following UD by MzPI have an increased stool frequency and softer stool consistency. However, there is no difference between both groups in terms of de novo stool incontinence. Change in bowel habits should be part of preoperative informed consent in any kind of UD. Careful patient selection is of paramount importance.

The surface electronic structure of silicon terminated (100) diamond.

A combination of synchrotron-based x-ray spectroscopy and contact potential difference measurements have been used to examine the electronic structure of the (3 × 1) silicon terminated (100) diamond surface under ultra high vacuum conditions. An occupied surface state which sits 1.75 eV below the valence band maximum has been identified, and indications of mid-gap unoccupied surface states have been found. Additionally, the pristine silicon terminated surface is shown to possess a negative electron affinity of -0.86 ± 0.1 eV.

Increased water contamination and grow-out Pekin duck mortality when raised with water troughs compared to pin-metered water lines using a United States management system.

Controversy has developed as to whether or not pin-metered water lines or water troughs are more appropriate for Pekin ducks. We hypothesized that water troughs would show improved duck body conditions and environmental quality compared to pin-metered water lines. To test this hypothesis, we housed ducks in 2 barns, one with water lines and one with water troughs. Water troughs were constructed to meet RSPCA guidelines for number and density of ducks and with recently described verandas. Ducks were divided into 4 pens per barn (n=1,000 ducks/pen). The study was then repeated (n=8 pens per water source) in a cross-over design so the barns each contained the opposite water source to the first experiment. We scored the ducks' body condition using an established scoring rubric and analyzed using SAS Proc GLM-Mix as binomial data. Ducks housed with water troughs showed higher (thus worse condition; P<0.001) scores for eyes, nostrils, feather quality, feather cleanliness, and foot pads. We also compared water condition, water quality, and duck mortality using a Student t test for both water sources each week. We found that the water troughs showed higher iron (P<0.001), nitrites (P<0.001), pH (P<0.01), and bacterial growth (P<0.001). The bacterial growth was shown to have higher (P<0.001)E. coli, coliforms, and Staphylococcusin the water troughs. Water lines typically showed no bacterial growth in culture-based assays. Ducks housed with water troughs used greater (P=0.001) volumes of water compared to ducks housed with water lines. Ducks with water troughs also showed a greater percent (P=0.008) mortality at all ages compared to ducks with water lines. These data suggest that water troughs may not be beneficial for duck welfare and could adversely impact both environment and duck or human health.

Exercise-induced Natural Killer Cell Activation is Driven by Epigenetic Modifications.

Exercise has been proven to reduce the risk and progression of various diseases, such as cancer, diabetes and neurodegenerative disorders. Increasing evidence suggests that exercise affects the cytokine profile and changes distribution and function of tumor-competitive immune cells. Initial studies have shown that different exercise interventions are associated with epigenetic modifications in different tissues and cell types, such as muscle, fat, brain and blood. The present investigation examines the effect of an intense endurance run (half marathon) on global epigenetic modifications in natural killer (NK) cells in 14 cancer patients compared to 14 healthy controls. We were able to show that histone acetylation and NKG2D expression, a functional NK cell marker, were elevated for at least 24 h after the run. Thus, this is the first study to present a potential mechanism of how exercise may impact NK cell activity on the subcellular level. Further studies should focus on epigenetic mechanisms and dose-dependent effects of exercise.

Effects of different wavelengths of light on the biology, behavior, and production of grow-out Pekin ducks.

Previous research has shown that red light conditions may improve growth and decrease aggressive behaviors in chickens and turkeys; however, more recent studies suggest that blue-green light may improve production of broilers over red light. To date, no research has been conducted to examine whether different wavelengths of light have an impact on production in the Pekin duck. To determine this, we raised Pekin ducks under aviary conditions that were similar to standard commercial barns. The ducks were kept in 3 different pens: red light (approximately 625 nm), blue light (approximately 425 nm), and white light. Light sources in each pen were standardized to produce a peak energy at 1.6 × 10³ µM photons/m²/s at the level of the ducks' heads. Ducks were given ad libitum access to water and commercial duck diet, and were housed on pine shavings at a density of 0.43 m²/duck. Ducks were evaluated weekly for BW and condition and a subjective measure of the duck's anxiety levels was determined. We found that ducks housed under blue light had significantly (P < 0.01) reduced BW at every age until the end of the study (processing age; 35 d). Unlike ducks housed under red or white light, ducks housed in the blue pen showed a higher level of anxiety; while evaluators were in the pen a majority of them began panting, they were much less inquisitive than other ducks, they took longer to exhibit normal social behavior once evaluation was completed, and they frequently "swarmed" when no people were present. There were no differences in any measurements between the red and white-lighted pens. These data suggest that unlike the chicken, blue lights may be inappropriate for raising Pekin ducks in a commercial setting.

Charge transfer doping of silicon.

We demonstrate a novel doping mechanism of silicon, namely n-type transfer doping by adsorbed organic cobaltocene (CoCp2*) molecules. The amount of transferred charge as a function of coverage is monitored by following the ensuing band bending via surface sensitive core-level photoelectron spectroscopy. The concomitant loss of electrons in the CoCp2* adlayer is quantified by the relative intensities of chemically shifted Co2p components in core-level photoelectron spectroscopy which correspond to charged and neutral molecules. Using a previously developed model for transfer doping, the evolution in relative intensities of the two components as a function of coverage has been reproduced successfully. A single, molecule-specific parameter, the negative donor energy of -(0.50±0.15) eV suffices to describe the self-limiting doping process with a maximum areal density of transferred electrons of 2×1013 cm-2 in agreement with the measured downward band bending. The advantage of this doping mechanism over conventional doping for nanostructures is addressed.

OpenStructure: an integrated software framework for computational structural biology.

Research projects in structural biology increasingly rely on combinations of heterogeneous sources of information, e.g. evolutionary information from multiple sequence alignments, experimental evidence in the form of density maps and proximity constraints from proteomics experiments. The OpenStructure software framework, which allows the seamless integration of information of different origin, has previously been introduced. The software consists of C++ libraries which are fully accessible from the Python programming language. Additionally, the framework provides a sophisticated graphics module that interactively displays molecular structures and density maps in three dimensions. In this work, the latest developments in the OpenStructure framework are outlined. The extensive capabilities of the framework will be illustrated using short code examples that show how information from molecular-structure coordinates can be combined with sequence data and/or density maps. The framework has been released under the LGPL version 3 license and is available for download from http://www.openstructure.org.

Transient receptor potential ankyrin 1 mediates chronic pancreatitis pain in mice.

Chronic pancreatitis (CP) is a devastating disease characterized by persistent and uncontrolled abdominal pain. Our lack of understanding is partially due to the lack of experimental models that mimic the human disease and also to the lack of validated behavioral measures of visceral pain. The ligand-gated cation channel transient receptor potential ankyrin 1 (TRPA1) mediates inflammation and pain in early experimental pancreatitis. It is unknown if TRPA1 causes fibrosis and sustained pancreatic pain. We induced CP by injecting the chemical agent trinitrobenzene sulfonic acid (TNBS), which causes severe acute pancreatitis, into the pancreatic duct of C57BL/6 trpa1(+/+) and trpa1(-/-) mice. Chronic inflammatory changes and pain behaviors were assessed after 2-3 wk. TNBS injection caused marked pancreatic fibrosis with increased collagen-staining intensity, atrophy, fatty replacement, monocyte infiltration, and pancreatic stellate cell activation, and these changes were reflected by increased histological damage scores. TNBS-injected animals showed mechanical hypersensitivity during von Frey filament probing of the abdomen, decreased daily voluntary wheel-running activity, and increased immobility scores during open-field testing. Pancreatic TNBS also reduced the threshold to hindpaw withdrawal to von Frey filament probing, suggesting central sensitization. Inflammatory changes and pain indexes were significantly reduced in trpa1(-/-) mice. In conclusion, we have characterized in mice a model of CP that resembles the human condition, with marked histological changes and behavioral measures of pain. We have demonstrated, using novel and objective pain measurements, that TRPA1 mediates inflammation and visceral hypersensitivity in CP and could be a therapeutic target for the treatment of sustained inflammatory abdominal pain.

Altered ultrasonic vocalizations in a tuberous sclerosis mouse model of autism.

Tuberous sclerosis (TSC) is an autosomally dominant neurocutaneous disease notable for its high comorbidity with autism in human patients. Studies of murine models of tuberous sclerosis have found defects in cognition and learning, but thus far have not uncovered deficits in social behaviors relevant to autism. To explore social communication and interaction in TSC2 heterozygous mice, we recorded ultrasonic vocalizations (USV) and found that although both wild-type (WT) and heterozygous pups born to WT dams showed similar call rates and patterns, baseline vocalization rates were elevated in pups born to heterozygous dams. Further analysis revealed several robust features of maternal potentiation in all but WT pups born to heterozygous dams. This lack of potentiation is suggestive of defects in mother-pup social interaction during or before the reunion period between WT pups and heterozygous dams. Intriguingly, male pups of both genotypes born to heterozygous dams showed particularly heightened call rates and burst patterns. Because our maternal retrieval experiments revealed that TSC2(+/-) dams exhibited improved defensive reactions against intruders and highly efficient pup retrieval performance, the alterations in their pups' USVs and maternal potentiation do not appear to result from poor maternal care. These findings suggest that a pup's interaction with its mother strongly influences the pup's vocal communication, revealing an intriguing dependence of this social behavior on TSC2 gene dosage of both parties involved. Our study of this murine model thus uncovers social abnormalities that arise from TSC haploinsufficiency and are suggestive of autism.

Assessing Smart Phones for Generating Life-space Indicators.

Life-space is a promising method for estimating older adults' functional status. However, traditional life-space measures are costly and time consuming because they often rely on active subject participation. This study assesses the feasibility of using the global positioning system (GPS) function of smart phones to generate life-space indicators. We first evaluated the location accuracy of smart phone collected GPS points versus those acquired by a commercial GPS unit. We then assessed the specificity of the smart phone processed life-space information against the traditional diary method. Our results suggested comparable location accuracy between the smart phone and the standard GPS unit in most outdoor situations. In addition, the smart phone method revealed more comprehensive life-space information than the diary method, which leads to higher and more consistent life-space scores. We conclude that the smart phone method is more reliable than traditional methods for measuring life-space. Further improvements will be required to develop a robust application of this method that is suitable for health-related practices.

Surface transfer doping of hydrogen-terminated diamond by C60F48: energy level scheme and doping efficiency.

Surface sensitive C1s core level photoelectron spectroscopy was used to examine the electronic properties of C(60)F(48) molecules on the C(100):H surface. An upward band bending of 0.74 eV in response to surface transfer doping by fluorofullerene molecules is measured. Two distinct molecular charge states of C(60)F(48) are identified and their relative concentration determined as a function of coverage. One corresponds to ionized molecules that participate in surface charge transfer and the other to neutral molecules that do not. The position of the lowest unoccupied molecular orbital of neutral C(60)F(48) which is the relevant acceptor level for transfer doping lies initially 0.6 eV below the valence band maximum and shifts upwards in the course of transfer doping by up to 0.43 eV due to a doping induced surface dipole. This upward shift in conjunction with the band bending determines the occupation of the acceptor level and limits the ultimately achievable hole concentration with C(60)F(48) as a surface acceptor to values close to 10(13) cm(-2) as reported in the literature.

LFA-1 antagonism inhibits early infiltration of endogenous memory CD8 T cells into cardiac allografts and donor-reactive T cell priming.

Alloreactive memory T cells are present in virtually all transplant recipients due to prior sensitization or heterologous immunity and mediate injury undermining graft outcome. In mouse models, endogenous memory CD8 T cells infiltrate MHC-mismatched cardiac allografts and produce IFN-γ in response to donor class I MHC within 24 h posttransplant. The current studies analyzed the efficacy of anti-LFA-1 mAb to inhibit early CD8 T cell cardiac allograft infiltration and activation. Anti-LFA-1 mAb given to C57BL/6 6 (H-2(b)) recipients of A/J (H-2(a)) heart grafts on days -1 and 0 completely inhibited CD8 T cell allograft infiltration, markedly decreased neutrophil infiltration and significantly reduced intragraft expression levels of IFN-γ-induced genes. Donor-specific T cells producing IFN-γ were at low/undetectable numbers in spleens of anti-LFA-1 mAb treated recipients until day 21. These effects combined to promote substantial prolongation (from day 8 to 27) in allograft survival. Delaying anti-LFA-1 mAb treatment until days 3 and 4 posttransplant did not inhibit early memory CD8 T cell infiltration and proliferation within the allograft. These data indicate that peritransplant anti-LFA-1 mAb inhibits early donor-reactive memory CD8 T cell allograft infiltration and inflammation suggesting an effective strategy to attenuate the negative effects of heterologous immunity in transplant recipients.

A robust automated system elucidates mouse home cage behavioral structure.

Patterns of behavior exhibited by mice in their home cages reflect the function and interaction of numerous behavioral and physiological systems. Detailed assessment of these patterns thus has the potential to provide a powerful tool for understanding basic aspects of behavioral regulation and their perturbation by disease processes. However, the capacity to identify and examine these patterns in terms of their discrete levels of organization across diverse behaviors has been difficult to achieve and automate. Here, we describe an automated approach for the quantitative characterization of fundamental behavioral elements and their patterns in the freely behaving mouse. We demonstrate the utility of this approach by identifying unique features of home cage behavioral structure and changes in distinct levels of behavioral organization in mice with single gene mutations altering energy balance. The robust, automated, reproducible quantification of mouse home cage behavioral structure detailed here should have wide applicability for the study of mammalian physiology, behavior, and disease.