Temporal Interactions between Neural Proxies forMemory Recall, Negative Affect, and EmotionRegulation in Major Depression.

Dysfunction in emotion regulation (ER) and autobiographical memory are components of major depressive disorder (MDD). However, little is known about how they mechanistically interact with mood disturbances in real time. Using machine learning-based neural signatures, we can quantify negative affect (NA), ER, and memory continuously to evaluate how these processes dynamically interact in MDD. Unmedicated individuals with MDD (N=45) and healthy volunteers (HV; N=38) completed a negative autobiographical memory functional magnetic resonance imaging task wherein they recalled, distanced from (an ER strategy), and immersed into memories. We used a negative affect signature (PINES) and an emotion regulation signature (ERS) to quantify moment-to-moment NA and ER. We then examined whether memory engagement, indexed by hippocampal activity, predicted subsequent change in PINES and ERS over time. During memory recall and immersion, greater hippocampal activity predicted increased PINES across groups. During distancing, greater hippocampal activity in HVs predicted increased ERS but not PINES. In MDD, greater hippocampal activity predicted increased PINES but not ERS. Findings suggest abnormalities in the real-time relationship between memory, NA, and ER in MDD. During distancing, as predicted, HVs showed an attenuation of the linkage between memory engagement and NA, and they had subsequent increases in ER following memory reactivation. In contrast, MDD was characterized by continued linkage between memory engagement and NA, without subsequent increases in ER. Deficits in engagement of ER and ineffective modulation of NA following negative memory recall may contribute to the mood disturbances in MDD and are potential targets for clinical intervention.

[Job-related satisfaction and health perception of dance teachers]. / Berufsbezogene Zufriedenheit und Gesundheitswahrnehmung von Tanzpädagoginnen und -pädagogen.

BACKGROUND: The dance teacher's own body is considered to be the central working instrument within the movement mediation. Up to now there is a lack of knowledge about the subjective perception of one's own occupationally associated health and satisfaction as well as the identification of occupational characteristics that are detrimental to health. MATERIAL AND METHODS: Within the framework of a questionnaire-based cross-sectional survey, a cohort of dance teachers in Germany were investigated about dimensions of their own health and general job satisfaction in connection with their profession as a dance teacher. Likert scales were primarily used for these assessments. Additionally, general anthropometric and sociodemographic characteristics were recorded. Beside examining the overall cohort, gender-specific differences were tested. The statistical analysis included n = 232 dance teachers (male 51/female 181) aged 43.1 ± 11.0 years. RESULTS: The general state of health was rated as satisfactory (26.1%) to very good (14.7%) by 85.3% of those surveyed. Of the dance teachers 59.2% even rated their health as good (35.3%) to very good. There was a high degree of satisfaction with their own professional practice for 80% of the participants. Most of the dance teachers felt that they were able to deal with the physical (75.7%) and psychological demands of their profession (70.3%). In addition to fears about the future (51.5%), the main burdensome professional characteristics on dance teachers' self-perception were organizational aspects of work (lack of time for family and friends in 28.4%) and economic aspects (income insecurity in 61.0% and lack of old age security in 65.7%). CONCLUSION: The profession as a dance teacher is accompanied by a high level of general satisfaction and a positive perception of one's own state of health. A confirmation of these positive results by injury and illness statistics is still pending. In addition, an improvement in work organization and economic aspects would be desirable.

Fit to Teach?-Cardiorespiratory Capacity, Vitamin D3, and Ferritin in Physical Education Teachers With Specialization in Dance.

ABSTRACT: Schmidt, M, Ohlendorf, D, Groneberg, DA, and Wanke, EM. Fit to teach?-Cardiorespiratory capacity, vitamin D3, and ferritin in physical education teachers with specialization in dance. J Strength Cond Res 35(4): 1156-1164, 2021-Numerous studies have shown that good cardiorespiratory capacity is of great importance for a healthy and long-term professional career as a dancer. Although the cardiorespiratory demands during teaching can reach into the submaximal intensity range, current data on the objective physical fitness of this occupational group are still missing. The aim of this pilot project was to determine selected cardiorespiratory parameters. In addition, measurements of the vitamin D3 (25(OH)D3) and iron balance as well as a subjective assessment of dance teachers' (DTs) fitness were performed. Twenty-one DTs (f: n = 18, m: n = 3) aged 48.2 ± 9.3 years were examined for cardiorespiratory performance within the framework of maximum bicycle spiroergometry. In addition, the self-perception of DTs' fitness was examined as well as the serum vit D3 levels and ferritin concentration in the blood. The cardiorespiratory fitness of DTs can be assessed as average (maximal oxygen consumption, V̇o2max = 29.5 ± 7.1 ml·k-1·min-1; physical working capacity, PWCmax = 165.0 ± 44.4). The DTs seemed to underestimate or overestimate their own capacity. Laboratory diagnostics showed that the 25(OH)D3 levels (21.8 ± 8.5 ng·ml-1) and serum ferritin values (102.4 ± 35.0 g·dl-1) were not optimal for almost the entire sample. In view of the physical occupational requirements, an increase in aerobic cardiorespiratory fitness by endurance-oriented basic training for DTs seems advisable. In addition, the substitution of vit D3 is worth being discussed.

Impact of Hyperhomocysteinemia and Different Dietary Interventions on Cognitive Performance in a Knock-in Mouse Model for Alzheimer's Disease.

BACKGROUND: Hyperhomocysteinemia is considered a possible contributor to the complex pathology of Alzheimer's disease (AD). For years, researchers in this field have discussed the apparent detrimental effects of the endogenous amino acid homocysteine in the brain. In this study, the roles of hyperhomocysteinemia driven by vitamin B deficiency, as well as potentially beneficial dietary interventions, were investigated in the novel AppNL-G-F knock-in mouse model for AD, simulating an early stage of the disease. METHODS: Urine and serum samples were analyzed using a validated LC-MS/MS method and the impact of different experimental diets on cognitive performance was studied in a comprehensive behavioral test battery. Finally, we analyzed brain samples immunohistochemically in order to assess amyloid-ß (Aß) plaque deposition. RESULTS: Behavioral testing data indicated subtle cognitive deficits in AppNL-G-F compared to C57BL/6J wild type mice. Elevation of homocysteine and homocysteic acid, as well as counteracting dietary interventions, mostly did not result in significant effects on learning and memory performance, nor in a modified Aß plaque deposition in 35-week-old AppNL-G-F mice. CONCLUSION: Despite prominent Aß plaque deposition, the AppNL-G-F model merely displays a very mild AD-like phenotype at the investigated age. Older AppNL-G-F mice should be tested in order to further investigate potential effects of hyperhomocysteinemia and dietary interventions.

Toward Establishing Internal Validity for Correlated Gene Expression Measures in Imaging Genomics of Functional Networks: Why Distance Corrections and External Face Validity Alone Fall Short. Reply to "Distance Is Not Everything in Imaging Genomics of Functional Networks: Reply to a Commentary on Correlated Gene Expression Supports Synchronous Activity in Brain Networks".

The primary claim of the Richiardi et al. (2015) Science article is that a measure of correlated gene expression, significant strength fraction (SSF), is related to resting state fMRI (rsfMRI) networks. However, there is still debate about this claim and whether spatial proximity, in the form of contiguous clusters, accounts entirely, or only partially, for SSF (Pantazatos and Li, 2017; Richiardi et al., 2017). Here, 13 distributed networks were simulated by combining 34 contiguous clusters randomly placed throughout cortex, with resulting edge distance distributions similar to rsfMRI networks. Cluster size was modulated (6-15 mm radius) to test its influence on SSF false positive rate (SSF-FPR) among the simulated "noise" networks. The contribution of rsfMRI networks on SSF-FPR was examined by comparing simulated networks whose clusters were sampled from: (1) all 1,777 cortical tissue samples, (2) all samples, but with non-rsfMRI cluster centers, and (3) only 1,276 non-rsfMRI samples. Results show that SSF-FPR is influenced only by cluster size (r > 0.9, p < 0.001), not by rsfMRI samples. Simulations using 14 mm radius clusters most resembled rsfMRI networks. When thresholding at p < 10-4, the SSF-FPR was 0.47. Genes that maximize SF have high global spatial autocorrelation. In conclusion, SSF is unrelated to rsfMRI networks. The main conclusion of Richiardi et al. (2015) is based on a finding that is ∼50% likely to be a false positive, not <0.01% as originally reported in the article (Richiardi et al., 2015). We discuss why distance corrections alone and external face validity are insufficient to establish a trustworthy relationship between correlated gene expression measures and rsfMRI networks, and propose more rigorous approaches to preclude common pitfalls in related studies.

Work related cardiovascular load in professional dance teachers - a pilot study.

OBJECTIVE: There have been only a limited number of studies available on the physical requirements in dance teachers (DT), who are responsible for the training of recreational and/or professional dancers and/or dance students. First results provide indications that a consideration of physical work load (teaching load) of this occupational group is necessary. METHODS: HR measurements were done on a total of 21 DT (f: n = 18, m: n = 3) aged 48.2 ± 9.3 years during their lessons in three dance styles: ballet (B), jazz/modern dance (J/MD) and pre-school dance (CD). The HR data were objectified using the spiroergometrically measured maximum HR (HRmax). In addition, the rating of perceived exertion (RPE) was asked directly after the lesson using the Borg scale together with an additional questionnaire. RESULTS: Depending on the dance style, the average HR load during the lessons ranged between 56.7% ± 7.4%) (B) and 63.6% ± 9.8% (CD) of the individual HRmax. No significant differences could be found between the dance styles for the minimum, medium and maximum teaching loads. The DTs rated the average RPE of the teaching units according to BORG (11.4 ± 2.1). Correlations between the RPE and the mean and maximum cardiovascular loads (r = 0.376, p = 0.037 and r = 0.441, p = 0.013) could be shown for all dance units and for the mean loads in J/MD (r = 0.558, p = 0.044). CONCLUSION: Most dance units do not represent a load in the sense of a endurance training unit. An increase in aerobic fitness and possible positive effects in the context of injury prevention is not to be expected. In J/MD, the use of RPEs for the rough estimation of cardiovascular stress is conceivable. The assessment of cardiovascular load in dance lessons requires further investigations for more precise assessments.

Peripheral Vision Tests in Sports: Training Effects and Reliability of Peripheral Perception Test.

Various studies suggest the importance of peripheral vision (PV) in sports. Computer-based test systems provide objective methods to measure PV. Nevertheless, the reliability and training effects are not clarified in detail. The purpose of this investigation was to present a short narrative non-systematic review on computer-based PV tests and to determine the reliability and the training effects of peripheral perception sub-test (PP) of the Vienna test system (VTS) in a test-retest design. N = 21 male athletes aged between 20 and 30 years (M = 26.15; SD = 3.1) were included. The main outcome parameters were peripheral reaction (PR), PR left (PRL), PR right (PRR), field of vision (FOV), visual angle left (VAL), and visual angle right (VAR). Reliability was assessed using intraclass correlation coefficient (ICC) and Bland-Altman plots. Training effects were determined by students t-test. Good reliability was observed in PR, PRL, and PRR. Moderate reliability was found in FOV, VAL, and VAR. Significant improvements between T0 and T1 were found in PRL with a mean difference of 0.04 s (95% CI [0.00-0.07]) and in PR with a mean difference of 0.02 s (95% CI [0.00-0.05]). For PRR, FOV, VAL, VAR, no significant differences were detected. These results indicate that PP can be applied to asses PV abilities in sports. Future research is needed to clarify the influence of test repetitions on visuomotor learning in PP. Moreover, PV tests should be cross-validated with sport-specific measurements (e.g., on-field and/or 'virtual reality' approaches).

Health behaviors in dance teachers and their use of psychoactive substances.

BACKGROUND: Dance teachers (DTs) give lessons on various professional and amateur genres. Up to the present, little has been known on health-related behavior regarding the consumption of substances such as inhalant and synthetic substances, cocaine, cannabis/marijuana (c/m), anabolic steroids and naturally occurring hallucinogens in dance teachers. RELEVANCE: To analyze the consumption of these substances as well as to determine influencing variables due to their role model function (educational level, prevalence of injuries, BMI and income). METHODS: N = 236 (m: n = 53, f: n = 183) professional DTs participated in the single cross-sectional cohort study. RESULTS: The majority of DTs had a single or occasional use of the tested substances. This coincides with the results of the general population. C/m was the most frequently consumed substance with a prevalence of up to 40.1% (m). Only a few significant gender-specific differences were observed. There were weak gender-specific correlations between the consumption of substances and educational level (f) and income (m and f) or injuries (f). CONCLUSION: Due to the specific occupational stress DTs are exposed to, a use of substances would be conceivable. However, apart from cannabis/marijuana (c/m), the consumption of psychoactive substances in DTs seems to be negligible. However, attention should be paid to the significant proportion of dance teachers having tried out substances.

General perceptual-cognitive abilities: Age and position in soccer.

Various studies suggest the importance of sport-specific cognitive and perceptual abilities in soccer. However, the role of general perceptual-cognitive abilities and the relation of age respective to position have not been clarified for soccer in detail. Therefore, it was the objective of the present study to determine the relation of age and position to general perceptual-cognitive abilities. 178 highly talented male soccer players (mean age 16.2, age range 10 to 33 years) were involved. The participants performed computer-based sustained attention and anticipation (using Vienna Test System) tests. 139 subjects (mean age 16.6) took part in visual and acoustic reaction tests (using Talent Diagnostic System). The soccer players, subdivided into age and position groups, were recruited from a youth academy of a professional soccer club and played at the highest and 2nd highest national soccer competition for their age. Group differences were tested using analysis of variance. Correlations were analyzed for age and abilities. Significant correlations and group differences were found for age and sustained attention tasks. Significant differences for position groups were observed with regard to acoustic reaction time (ART). Further, we found statistical tendencies for group differences regarding the visual reaction time (VRT), indicating that midfielders outperform defenders and strikers in simple reaction tasks. Improved skills in sustained attention tasks resulted for defenders, who worked faster and more precisely in figural tasks. Regarding general anticipation tasks differences were not found. No group differences were found in basic anticipation tasks. Our study indicates that additional research is needed to further clarify the development of general perceptual-cognitive abilities and position-specific differences in the above abilities of highly talented soccer players.

Non-invasive bioluminescence imaging as a standardized assessment measure in mouse models of dermal inflammation.

BACKGROUND: Myeloperoxidase is used as a marker and diagnostic tool for inflammatory processes. Hypochlorous acid produced by myeloperoxidase oxidizes luminol to produce light. By injecting luminol into experimental animals, inflammatory processes can be tracked in real-time by bioluminescence imaging (BLI). OBJECTIVE: We aimed to establish BLI as a standardized assessment measure in three mouse models of dermal inflammation. METHODS: Oxazolone-induced delayed-type-hypersensitivity (DTH) (acute), a model for dermatitis, imiquimod (IMQ) (sub-chronic) model for psoriasis and the (chronic) bleomycin model for scleroderma were used. In the first two models, dexamethasone and clobetasol, respectively, were used as reference compounds. In all cases, classical readouts such as dermal swelling, severity scores and histological analyses were compared with in- vivo bioluminescence. RESULTS: In DTH, bioluminescence peaked earlier than ear swelling, reflecting early cell infiltration. Dexamethasone blocked both ear swelling and bioluminescence. In the IMQ model, bioluminescence closely reflected the psoriasis scores and histology and revealed a relapse-remitting course of the disease. Clobetasol partially decreased the disease severity. After stopping IMQ and clobetasol treatment, BLI adopted a rhythmic pattern during resolution. Bleomycin induced an increase in bioluminescence and in collagen thickness. BLI revealed a time-course of the effects of bleomycin that was not reflected by histology alone. CONCLUSION: For drug discovery and translational purposes, it is important that disease processes be tracked in vivo and possibly over a long period. We conclude that BLI is a valuable and reliable method for in-vivo measurement of dermal inflammation and potentially for inflammation resolution.

A comparison of manual tracing and FreeSurfer for estimating hippocampal volume over the adult lifespan.

MRI has become an indispensable tool for brain volumetric studies, with the hippocampus an important region of interest. Automation of the MRI segmentation process has helped advance the field by facilitating the volumetric analysis of larger cohorts and more studies. FreeSurfer has emerged as the de facto standard tool for these analyses, but studies validating its output are all based on older versions. To characterize FreeSurfer's validity, we compare several versions of FreeSurfer software with traditional hand-tracing. Using MRI images of 262 males and 402 females aged 38 to 84, we directly compare estimates of hippocampal volume from multiple versions of FreeSurfer, its hippocampal subfield routines, and our manual tracing protocol. We then use those estimates to assess asymmetry and atrophy, comparing performance of different estimators with each other and with brain atrophy measures. FreeSurfer consistently reports larger volumes than manual tracing. This difference is smaller in larger hippocampi or older people, with these biases weaker in version 6.0.0 than prior versions. All methods tested agree qualitatively on rightward asymmetry and increasing atrophy in older people. FreeSurfer saves time and money, and approximates the same atrophy measures as manual tracing, but it introduces biases that could require statistical adjustments in some studies.

Mutual inversion of flurbiprofen enantiomers in various rat and mouse strains.

Flurbiprofen (F) is a nonsteroidal anti-inflammatory drug (NSAID) used therapeutically as the racemate of (R)-enantiomer and (S)-enantiomer. The inversion of RF to SF and vice versa was investigated in C57Bl/6 and SJL mice and Dark Agouti and Lewis rats. The enzyme α-methylacyl-CoA racemase (AMACR) is involved in the chiral inversion pathway that converts members of the 2-arylpropionic acid NSAIDs from the R-enantiomer to the S-enantiomer. We studied C57Bl/6 mice deficient in AMACR postulating that they should show reduced inversion of RF to SF. In line with the data of others in mice, (R)-inversion to (S)-inversion was relatively high in both the C57Bl/6 and SJL mice (fraction inverted, FI  = 37.7% and 24.7%, respectively). In contrast, in AMACR deficient mice, there was no measurable peak for SF after administration of RF. The results in both rat strains (Dark Agouti and Lewis rats, FI  = 1.4% and 4.1%, respectively) confirm the low chiral inversion of the enantiomers of flurbiprofen in the rat, as observed by other authors in the Sprague-Dawley strain (<5%). From the present results, we conclude that for the study of flurbiprofen enantiomers, the rat is more suitable than the mouse as a model for the human in which (R)-inversion to (S)-inversion is negligible.

Work-related floors as injury hazards - a nationwide pilot project analyzing floors in theatres and education establishments in Germany.

BACKGROUND: An adequate dance floor is said to prevent injuries. On the basis of scientific research, numerous recommendations regarding an adequate dance floor have been developed. Up to the present, however, studies have still been lacking into how far these recommendations have already been implemented in theatres with regular dance productions and/or in-house dance ensembles. The aim of this study is to analyze a nationwide survey on dance floors of theatres and education establishments in Germany. METHODS: A questionnaire-based survey on existence and type of floors in the various dance-related working areas was carried out at theatres and education establishments institutions (n = 86 institutions (n = 76 theatres, n = 10 education establishments). References as to region, size of dance ensembles and dance styles performed were created. RESULTS: Of all education establishments, 75.3% were equipped with a sprung sub-floor in the ballet studios. In contrast, sprung sub-floors were only found in 29.7% of the working areas, the stage AND ballet studios in theatres. The percentage of theatres providing sprung sub-floors in all rooms used by dancers is even lower. Considering all dance-related work areas, larger ensembles (>30 dancers) were offered better conditions regarding floors than smaller ensembles (p > 0.001). No significant tendencies were found regarding regions or dance styles. CONCLUSION: Recommendations concerning an appropriate dance floor have only partly been realized. Besides secured finances for reinstallation, further education of responsible officials and artists is essential. However, accrediting dance as own genre in theatres is the indispensable prerequisite.

Targeting CYP2J to reduce paclitaxel-induced peripheral neuropathic pain.

Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a severe dose- and therapy-limiting side effect of widely used cytostatics that is particularly difficult to treat. Here, we report increased expression of the cytochrome-P450-epoxygenase CYP2J6 and increased concentrations of its linoleic acid metabolite 9,10-EpOME (9,10-epoxy-12Z-octadecenoic acid) in dorsal root ganglia (DRGs) of paclitaxel-treated mice as a model of CIPNP. The lipid sensitizes TRPV1 ion channels in primary sensory neurons and causes increased frequency of spontaneous excitatory postsynaptic currents in spinal cord nociceptive neurons, increased CGRP release from sciatic nerves and DRGs, and a reduction in mechanical and thermal pain hypersensitivity. In a drug repurposing screen targeting CYP2J2, the human ortholog of murine CYP2J6, we identified telmisartan, a widely used angiotensin II receptor antagonist, as a potent inhibitor. In a translational approach, administration of telmisartan reduces EpOME concentrations in DRGs and in plasma and reverses mechanical hypersensitivity in paclitaxel-treated mice. We therefore suggest inhibition of CYP2J isoforms with telmisartan as a treatment option for paclitaxel-induced neuropathic pain.

Associations Between Serum Inflammatory Markers and Hippocampal Volume in a Community Sample.

OBJECTIVES: To quantify associations between inflammatory biomarkers and hippocampal volume (HV) and to examine effect modification according to sex, race, and age. DESIGN: Cross-sectional analyses using generalized estimating equations to account for familial clustering; standardized ß-coefficients adjusted for age, sex, race, and education. SETTING: Community cohorts in Jackson, Mississippi and Rochester, Minnesota. PARTICIPANTS: The Genetic Epidemiology Network of Arteriopathy study. MEASUREMENTS: C-reactive protein (CRP), interleukin-6 (IL-6), and soluble tumor necrosis factor receptors 1 (sTNFR-1) and 2 (sTNFR-2) from peripheral blood were measured in a sample of 773 non-Hispanic whites (61% women, aged 60.2 ± 9.8) and 514 African Americans (70% women, aged 63.9 ± 8.1) who also underwent brain magnetic resonance imaging. Biomarkers were standardized and compared according to sex, race and age with HV. RESULTS: In the full sample, higher sTNFR-1 and sTNFR-2 were associated with smaller HV. Each standard deviation (SD) increase in sTNFR-1 was associated with 59.1 mm(3) (95% confidence interval (CI) = -101.4 to -16.7 mm(3) ) smaller HV and each SD increase in sTNFR-2 associated with 48.8 mm(3) (95% CI = -92.2 to -5.3 mm(3) ) smaller HV. Relationships were stronger for sTNFR-2 in men (HV = -116.6 mm(3) for each SD increase, 95% CI = -201.0 to -32.1) than women (HV = -26.0 per SD increase, 95% CI = -72.4-20.5) and sTNFR-1 in non-Hispanic whites (HV = -84.7 mm(3) per SD increase, 95% CI = -142.2 to -27.1) than African Americans (HV = -14.1 mm(3) per SD increase, 95% CI = -78.3-50.1). Associations between IL-6 or CRP and HV were not supported. CONCLUSION: Higher levels of sTNFRs were associated cross-sectionally with smaller hippocampi. Longitudinal data are needed to determine whether these biomarkers may help to identify risk of late-life cognitive impairment.

Optimizing novel implant formulations for the prolonged release of biopharmaceuticals using in vitro and in vivo imaging techniques.

As a rapidly growing class of therapeutics, biopharmaceuticals have conquered the global market. Despite the great potential from a therapeutic perspective, such formulations often require frequent injections due to their short half-life. Aiming to establish a parenteral dosage form with prolonged release properties, a biodegradable implant was developed, based on a combination of nanoencapsulation of protein-heparin complexes, creation of a slow release matrix by freeze-drying, and compression using hyaluronan and methylcellulose. In order to investigate this novel delivery system, formulations containing IFN-ß-1a and trypsinogen as model proteins were developed. No degradation of the proteins was observed at any stage of the formulation processing. The potential of the delivery system was evaluated in vivo and in vitro after fluorescence-labeling of the biopharmaceuticals. An optimized agarose gel was utilized as in vitro release medium to simulate the subcutaneous environment in a biorelevant manner. In addition, the formulations were administered to female SJL mice and release was innovatively tracked by fluorescence imaging, setting up an in vitro-in vivo correlation. A prolonged time of residence of approximately 12days was observed for the selected formulation design.

In Vivo Availability of Pro-Resolving Lipid Mediators in Oxazolone Induced Dermal Inflammation in the Mouse.

The activation and infiltration of polymorphonuclear neutrophils (PMN) are critical key steps in inflammation. PMN-mediated inflammation is limited by anti-inflammatory and pro-resolving mechanisms, including specialized pro-resolving lipid mediators (SPM). We examined the effects of 15-epi-LXA4 on inflammation and the biosynthesis of pro-inflammatory mediators, such as prostaglandins, leukotriene B4 and various hydroxyeicosatetraenoic acids and SPM, in an oxazolone (OXA)-induced hypersensitivity model for dermal inflammation. 15-epi-LXA4 (100 µM, 5 µL subcutaneously injected) significantly (P < 0.05) reduced inflammation in skin, 24 hours after the OXA challenge, as compared to skin treated with vehicle. No significant influence on the biosynthesis of prostaglandins or leukotriene B4 was observed, whereas the level of 15S-hydroxy-eicosatetraenoic acid was significantly (P < 0.05) lower in the skin areas treated with 15-epi-LXA4. In spite of the use of a fully validated analytical procedure, no SPM were detected in the biological samples. To investigate the reason for the lack of analytical signal, we tried to mimic the production of SPM (lipoxins, resolvins, maresin and protectin) by injecting them subcutaneously into the skin of mice and studying the in vivo availability and distribution of the compounds. All analytes showed very little lateral distribution in skin tissue and their levels were markedly decreased (> 95%) 2 hours after injection. However, docosahexaenoic acid derivatives were biologically more stable than SPM derived from arachidonic acid or eicosapentaenoic acid.

Nanocarriers for photodynamic therapy-rational formulation design and medium-scale manufacture.

The development and manufacture of novel nanocarriers for drug delivery has proved challenging with regards to scale-up and pharmaceutical quality. Polymeric nanocarriers composed of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-PEG) were prepared and the photosensitizer meso-tetrakis(3-hydroxyphenyl) chlorin (mTHPC) was effectively encapsulated. Furthermore, the interplay of various process and formulation parameters and their impact on the most important product specifications were investigated by using a factorial design and a central composite design in a microfluidic manufacturing process. These nanoparticles for intravenous administration with a size of 97 ± 0.13 nm, narrow size distribution, and an encapsulation efficiency of more than 80% were produced at high throughput. In vitro stability and in vitro drug release testing were applied for quality control purposes. Finally, the toxicity of the photosensitizer was tested in vitro. The cytotoxicity was successfully reduced while the efficacy of the formulation was maintained. First observations using in vivo imaging suggest effective distribution of the nanocarrier system after injection into rodents. Thus, further in vivo testing of the beneficial effects of nanoencapsulation into the matrix system and its formulation will be considered for the delivery of mTHPC to tumor tissues during photodynamic therapy.

Physical and mental workloads in professional dance teachers.

OBJECTIVE: The aim of this cross-sectional study was to investigate the level of mental and physical workloads in professional dance teachers depending on the trained students' age, technique level, or dance style. METHODS: A total number of 133 professional dance pedagogues responded to an online cross-sectional questionnaire survey on self-assessment of physical and mental workloads occurring during dance units. RESULTS: The majority of dance teachers estimated their level of physical and mental workload to be almost as high as that of their students, with differences in physical and mental workloads observed depending on dance style, age of students, and technical level. More than 60% of the teachers were convinced that their occupation implies positive effects on their own health in terms of self-realization (78.2%), musculoskeletal system (66.9%), and social relationships (61.7%). Of all respondents, 58.6% stated that their musculoskeletal system was jeopardized by the physically demanding activity. This is followed by the fear of financial insecurity (50.4%). The majority of all dance teachers (males 65.4%, females 63.9%) would like to obtain further education on prevention against or dealing with physical workload. CONCLUSION: Physical and mental workloads play an important role in dance teaching. Coping with or preventing these loads could be keys to a lifelong, healthy career as a professional dance teacher. Future trials should look at clinical parameters of physical and mental load.

Evaluation of copy number variations reveals novel candidate genes in autism spectrum disorder-associated pathways.

Autism spectrum disorders (ASDs) are highly heritable, yet relatively few associated genetic loci have been replicated. Copy number variations (CNVs) have been implicated in autism; however, the majority of loci contribute to <1% of the disease population. Therefore, independent studies are important to refine associated CNV regions and discover novel susceptibility genes. In this study, a genome-wide SNP array was utilized for CNV detection by two distinct algorithms in a European ancestry case-control data set. We identify a significantly higher burden in the number and size of deletions, and disrupting more genes in ASD cases. Moreover, 18 deletions larger than 1 Mb were detected exclusively in cases, implicating novel regions at 2q22.1, 3p26.3, 4q12 and 14q23. Case-specific CNVs provided further evidence for pathways previously implicated in ASDs, revealing new candidate genes within the GABAergic signaling and neural development pathways. These include DBI, an allosteric binder of GABA receptors, GABARAPL1, the GABA receptor-associated protein, and SLC6A11, a postsynaptic GABA transporter. We also identified CNVs in COBL, deletions of which cause defects in neuronal cytoskeleton morphogenesis in model vertebrates, and DNER, a neuron-specific Notch ligand required for cerebellar development. Moreover, we found evidence of genetic overlap between ASDs and other neurodevelopmental and neuropsychiatric diseases. These genes include glutamate receptors (GRID1, GRIK2 and GRIK4), synaptic regulators (NRXN3, SLC6A8 and SYN3), transcription factor (ZNF804A) and RNA-binding protein FMR1. Taken together, these CNVs may be a few of the missing pieces of ASD heritability and lead to discovering novel etiological mechanisms.