Bench Press Range-of-Motion and Velocity-based Repetition Control: Effects on Ballistic Push-up Performance in Males.

The purpose of this study was to investigate whether the ballistic push-up (BPU) is responsive to post-activation performance enhancement (PAPE) after a bench press conditioning exercise using velocity-based repetition control. Additionally, we aimed to evaluate the effects of range of motion (ROM) conditions on subsequent BPU performance. In a randomized crossover design, 18 males performed two conditions (full ROM and self-selected partial ROM) of bench press at 80% of their 1RM until mean concentric velocity dropped 10%. Each participant performed two pre- and six post-test BPUs to assess the PAPE effect. Paired sample t-tests assessed bench press performance measures. Multiple two-way repeated measures ANOVAs assessed differences in flight time, impulse, and peak power for the pre- and post-test BPUs. No significant differences existed between ROM conditions for total repetitions, volume load, or peak velocity. Compared to partial ROM, full ROM showed greater displacement (0.42 ± 0.05 vs. 0.34 ± 0.05 m), work (331.99 ± 67.72 vs. 270.92 ± 61.42 J), and mean velocity (0.46 ± 0.09 vs. 0.44 ± 0.08 m/s). Neither bench press ROM condition enhanced the BPU and were detrimental in some cases. Several time points showed partial ROM (flight time: 2 min post, impulse: 12 min post, peak power: 12 min post) significantly greater than full ROM, possibly indicating less fatigue accumulation. The BPU may require a different stimulus or may not be practical for PAPE effects in college-aged males. Partial ROM can be an alternative that achieves similar peak velocities while requiring less overall work.

Fragment-Based Design, Synthesis, and Characterization of Aminoisoindole-Derived Furin Inhibitors.

A 1H-isoindol-3-amine was identified as suitable P1 group for the proprotein convertase furin using a crystallographic screening with a set of 20 fragments known to occupy the S1 pocket of trypsin-like serine proteases. Its binding mode is very similar to that observed for the P1 group of benzamidine-derived peptidic furin inhibitors suggesting an aminomethyl substitution of this fragment to obtain a couplable P1 residue for the synthesis of substrate-analogue furin inhibitors. The obtained inhibitors possess a slightly improved picomolar inhibitory potency compared to their benzamidine-derived analogues. The crystal structures of two inhibitors in complex with furin revealed that the new P1 group is perfectly suited for incorporation in peptidic furin inhibitors. Selected inhibitors were tested for antiviral activity against respiratory syncytial virus (RSV) and a furin-dependent influenza A virus (SC35M/H7N7) in A549 human lung cells and demonstrated an efficient inhibition of virus activation and replication at low micromolar or even submicromolar concentrations. First results suggest that the Mas-related G-protein coupled receptor GPCR-X2 could be a potential off-target for certain benzamidine-derived furin inhibitors.

Exploitation of Engineered Light-Switchable Myosin XI for Nanotechnological Applications.

For certain nanotechnological applications of the contractile proteins actin and myosin, e.g., in biosensing and network-based biocomputation, it would be desirable to temporarily switch on/off motile function in parts of nanostructured devices, e.g., for sorting or programming. Myosin XI motor constructs, engineered with a light-switchable domain for switching actin motility between high and low velocities (light-sensitive motors (LSMs) below), are promising in this regard. However, they were not designed for use in nanotechnology, where longevity of operation, long shelf life, and selectivity of function in specific regions of a nanofabricated network are important. Here, we tested if these criteria can be fulfilled using existing LSM constructs or if additional developments will be required. We demonstrated extended shelf life as well as longevity of the actin-propelling function compared to those in previous studies. We also evaluated several approaches for selective immobilization with a maintained actin propelling function in dedicated nanochannels only. Whereas selectivity was feasible using certain nanopatterning combinations, the reproducibility was not satisfactory. In summary, the study demonstrates the feasibility of using engineered light-controlled myosin XI motors for myosin-driven actin transport in nanotechnological applications. Before use for, e.g., sorting or programming, additional work is however needed to achieve reproducibility of the nanofabrication and, further, optimize the motor properties.

A latent class analysis of patterns of tobacco and cannabis use in Australia and their health-related correlates.

INTRODUCTION: The shifting landscape in Australia's tobacco and cannabis policies and emerging new products and modes of administration may increase experimentation and the risks of addiction to these drugs. METHODS: We analysed cross-sectional data from the 2019 National Drug Strategy and Household Survey (n = 22,015) of Australians aged 14 and above. Latent class analysis was used to identify distinct groups based on types of tobacco and cannabis products used. The socio-demographic, health-rated correlates and past-year substance use of each latent class was examined. RESULTS: A four-class solution was identified: co-use of tobacco and cannabis (2.4%), cannabis-only (5.5%), tobacco-only (8.0%) and non-user (84.0%). Males (odds ratio [OR] range 1.5-2.9), younger age (OR range 2.4-8.4), moderate to high psychological distress (OR range 1.3-3.0), using illicit substances in the last year (OR range 1.41-22.87) and high risk of alcohol use disorder (OR range 2.0-21.7) were more likely to be in the tobacco/cannabis use classes than non-users. Within the co-use class, 78.4% mixed tobacco with cannabis and 89.4% had used alcohol with cannabis at least once. DISCUSSION AND CONCLUSIONS: Approximately 16% of respondents used tobacco or cannabis, or both substances, and no major distinct subgroups were identified by the use of different product types. Mental health issues and the poly-substance use were more common in the class who were co-users of cannabis and tobacco. Existing policies need to minimise cannabis and tobacco-related harms to reduce the societal burden associated with both substances.

Dive Performance and Aquatic Thermoregulation of the World's Smallest Mammalian Diver, the American Water Shrew (Sorex palustris).

Allometry predicts that the 12-17-g American water shrew (Sorex palustris)-the world's smallest mammalian diver-will have the highest diving metabolic rate coupled with the lowest total body oxygen storage capacity, skeletal muscle buffering capacity, and glycolytic potential of any endothermic diver. Consistent with expectations, and potentially owing to their low thermal inertia, water shrews had a significantly higher diving metabolic rate in 10°C water (8.77 mL O2 g-1 h-1) compared with 30°C water (6.57 mL O2 g-1 h-1). Unlike larger-bodied divers, muscle myoglobin contributed minimally (7.7%-12.4%) to total onboard O2 stores of juvenile and adult water shrews, respectively, but was offset by high blood O2 carrying capacities (26.4%-26.9% v/v). Diving was predominantly aerobic, as only 1.2%-2.3% of dives in 10°C and 30°C water, respectively, exceeded the calculated aerobic dive limits at these temperatures (10.8-14.4 s). The mean voluntary dive time of water shrews during 20-min trials in 3°C-30°C water was 5.0±0.1 s (N=25, n=1,628), with a mean maximum dive time of 10.1±0.4 s. However, the average dive duration (6.9±0.2 s, n=257) of radio-telemetered shrews exclusively foraging in a simulated riparian environment (3°C water) for 12-28 h suggests that mean (but not maximum) dive times of water shrews in the wild may be longer. Mean dive duration, duration of the longest dive, and total time in water all decreased significantly as water temperature declined, suggesting that shrews employed behavioral thermoregulation to defend against immersion hypothermia. Additionally, free-diving shrews in the 24-h trials consistently elevated core body temperature by ∼1°C immediately before initiating aquatic foraging bouts and ended these bouts when body temperature was still at or above normal resting levels (∼37.8°C). We suggest that this observed predive hyperthermia aids to heighten the impressive somatosensory physiology, and hence foraging efficiency, of this diminutive predator while submerged.

Differences in Muscle Activity and Kinetics Between the Goblet Squat and Landmine Squat in Men and Women.

ABSTRACT: Collins, KS, Klawitter, LA, Waldera, RW, Mahoney, SJ, and Christensen, BK. Differences in muscle activity and kinetics between the goblet squat and landmine squat in men and women. J Strength Cond Res 35(10): 2661-2668, 2021-Squat exercise variations are widely used and extensively researched. However, little information exists on the goblet squat (GBS) and landmine squat (LMS) and differences between men and women. This study investigated the differences in muscle activity and kinetics between the GBS and the LMS in 16 men and 16 women. Five repetitions of each squat type were performed loaded at 30% of their body mass. Vertical and anteroposterior ground reaction forces for the eccentric and concentric phases and peak vertical force were recorded with a force plate. Electromyographic (EMG) signals were recorded for the vastus medialis (VM), vastus lateralis (VL), semitendinosus (ST), and biceps femoris (BF). Normalized mean EMG values and ground reaction forces were analyzed with repeated measures analysis of variance (p < 0.05). Significant main effects for squat condition and sex were found. The LMS reduced activity in the quadriceps (VM and VL) muscles and vertical forces, while increasing posterior horizontal forces. In the LMS, men showed decreased ST activity, whereas women had decreased BF activity. Women exhibited greater quadriceps activity in both the GBS and LMS and greater ST in the LMS. Women also produced greater eccentric vertical force in both the GBS and LMS and less posterior horizontal forces in the LMS. The LMS may be useful to balance hamstring to quadriceps activity, increase horizontal loading, and reduce vertical loading. Conversely, the GBS can better target quadriceps activity and increase vertical loading. Sex differences should be considered for training programs that include the GBS and LMS.

Availability of substances for use in personal vaporisers on three online cryptomarkets.

BACKGROUND: Personal vaporisers are gaining popularity as an alternative route of administration for a range of substances. Online cryptomarkets are becoming increasingly popular among people who use substances due to their perceived anonymity, ease of use, and reduced risk of violence compared to traditional face-to-face dealers. We examined the diversity of substances marketed for use in a personal vaporiser on these marketplaces. METHODS: Vaping related listings were extracted from three online cryptomarkets ('Agartha', 'Cryptonia', and 'Tochka') using The Onion Router browser. Data collection occurred between October and November 2019. RESULTS: We identified 1929 listings from 201 unique sellers. The top product on Agartha, Cryptonia, and Tochka were vape cartridges prefilled with the e-liquid (70.4 %, 39.4 %, 52.3 % respectively). The most common substance in these products was cannabis oil (96.1 %, 82.1 %, 87.8 %), followed by synthetic cannabinoids (3.7 %, 9.7 %, 9.8 %) and psychedelic substances (0.2 %, 6.4 %, 1.2 %). Vendors were primarily from the USA. Many products offered worldwide shipping (96.3 %, 42.4 %, 51.2 %). CONCLUSION: Vaping products listed on online cryptomarkets in 2019 primarily contained cannabis oils. Future studies should continue to examine cryptomarkets to identify emerging trends of substances that can be used in personal vaporisers.

CYP2C9 genotype vs. metabolic phenotype for individual drug dosing--a correlation analysis using flurbiprofen as probe drug.

Currently, genotyping of patients for polymorphic enzymes responsible for metabolic elimination is considered a possibility to adjust drug dose levels. For a patient to profit from this procedure, the interindividual differences in drug metabolism within one genotype should be smaller than those between different genotypes. We studied a large cohort of healthy young adults (283 subjects), correlating their CYP2C9 genotype to a simple phenotyping metric, using flurbiprofen as probe drug. Genotyping was conducted for CYP2C9*1, *2, *3. The urinary metabolic ratio MR (concentration of CYP2C9-dependent metabolite divided by concentration of flurbiprofen) determined two hours after flurbiprofen (8.75 mg) administration served as phenotyping metric. Linear statistical models correlating genotype and phenotype provided highly significant allele-specific MR estimates of 0.596 for the wild type allele CYP2C9*1, 0.405 for CYP2C9*2 (68 % of wild type), and 0.113 for CYP2C9*3 (19 % of wild type). If these estimates were used for flurbiprofen dose adjustment, taking 100 % for genotype *1/*1, an average reduction to 84 %, 60 %, 68 %, 43 %, and 19 % would result for genotype *1/*2, *1/*3, *2/*2, *2/*3, and *3/*3, respectively. Due to the large individual variation within genotypes with coefficients of variation ≥ 20 % and supposing the normal distribution, one in three individuals would be out of the average optimum dose by more than 20 %, one in 20 would be 40 % off. Whether this problem also applies to other CYPs and other drugs has to be investigated case by case. Our data for the given example, however, puts the benefit of individual drug dosing to question, if it is exclusively based on genotype.

Developing a service platform definition to promote evidence-based planning and funding of the mental health service system.

Ensuring that a mental health system provides 'value for money' requires policy makers to allocate resources to the most cost-effective interventions. Organizing cost-effective interventions into a service delivery framework will require a concept that can guide the mapping of evidence regarding disorder-level interventions to aggregations of services that are meaningful for policy makers. The 'service platform' is an emerging concept that could be used to this end, however no explicit definition currently exists in the literature. The aim of this study was to develop a service platform definition that is consistent with how policy makers conceptualize the major elements of the mental health service system and to test the validity and utility of this definition through consultation with mental health policy makers. We derived a provisional definition informed by existing literature and consultation with experienced mental health researchers. Using a modified Delphi method, we obtained feedback from nine Australian policy makers. Respondents provided written answers to a questionnaire eliciting their views on the acceptability, comprehensibility and usefulness of a service platform definition which was subject to qualitative analysis. Overall, respondents understood the definition and found it both acceptable and useful, subject to certain conditions. They also provided suggestions for its improvement. Our findings suggest that the service platform concept could be a useful way of aggregating mental health services as a means for presenting priority setting evidence to policy makers in mental health. However, further development and testing of the concept is required.

Electron-beam patterning of polymer electrolyte films to make multiple nanoscale gates for nanowire transistors.

We report an electron-beam based method for the nanoscale patterning of the poly(ethylene oxide)/LiClO4 polymer electrolyte. We use the patterned polymer electrolyte as a high capacitance gate dielectric in single nanowire transistors and obtain subthreshold swings comparable to conventional metal/oxide wrap-gated nanowire transistors. Patterning eliminates gate/contact overlap, which reduces parasitic effects and enables multiple, independently controllable gates. The method's simplicity broadens the scope for using polymer electrolyte gating in studies of nanowires and other nanoscale devices.

Employee psychological distress and treated prevalence by indices of rurality.

OBJECTIVE: Although there is population data on the prevalence and treated prevalence of mental disorders by urban-rural indices, there is a lacuna of information pertaining to employees. This paper examines the prevalence and treated prevalence of psychological distress in employees by urban-rural indicators. METHODS: Cross-sectional employee Health and Performance at Work Questionnaire responses (n=78,726 from 58 large companies) are interrogated by indices of remoteness (Accessibility/Remoteness Index of Australia), psychological distress (Kessler 6) and treatment-seeking behaviours for mental health problems. RESULTS: The overall prevalence of moderate or high psychological distress in employees was 35.2%. The prevalence varied only slightly (maximum to minimum difference of 4.6%) by rural/remote indices. Overall treatment-seeking behaviour for psychological distress was low (22.5%). The percentage of employees seeking treatment for high levels of psychological distress was the lowest in very remote regions (15.1%). CONCLUSION: Very remote employees are less likely to access mental health treatments and may be an employee subgroup that would benefit from specific employer health interventions aimed to increase treatment-seeking behaviours. IMPLICATIONS: Employees in very remote Australia could benefit from specific interventions aimed to increase mental health awareness/literacy.

Substituted pyrazoles as novel sEH antagonist: investigation of key binding interactions within the catalytic domain.

A novel series of pyrazole sEH inhibitors is reported. Lead optimization efforts to replace the aniline core are also described. In particular, 2-pyridine, 3-pyridine and pyridazine analogs are potent sEH inhibitors with favorable CYP3A4 inhibitory and microsomal stability profiles.

Statistical model to estimate a threshold dose and its confidence limits for the analysis of sublinear dose-response relationships, exemplified for mutagenicity data.

Strongly sublinear dose-response relationships (slope increasing with dose) raise the question about a putative threshold dose below which no biologically relevant effect would be expected. A mathematical threshold with a break in the curve at the threshold dose is generally rejected for consequences of genotoxicity such as mutation, because proportionality between low dose and the rate of DNA-adduct formation is a reasonable hypothesis. In view of an increasing database for distinct deviation from linearity for mutagenicity, we offer a statistical model to analyze continuous response data and estimate a threshold dose together with its confidence limits, thereby taking data quality and degree of sublinearity into account. The simplest mathematical threshold model is a hockey stick defined by a low-dose part with slope zero at background level a to a theoretical break point at threshold dose td, followed by a linear increase above td with slope b. The function is y (dose d)=a+bx(d-td)x1([d>td]). Using the free statistics software package "R", we make a procedure available to estimate the parameters a, b, and td. Confidence intervals are calculated for all parameters at a significance level that can be defined by the user. If the lower limit of the confidence interval for td is >0, linearity is rejected. The procedure is illustrated by two examples. A small data set with three replicates per dose group, indicating a threshold for the induction of thymidine kinase mutants in L5178Y tk(+/-) mouse lymphoma cells treated with methyl methanesulfonate, did not achieve significance. On the other hand, the large data set reported in this issue (Gocke et al.) on lacZ mutants in bone marrow cells of transgenic mice treated with ethyl methanesulfonate strongly favoured the hockey stick model. The question of a theoretically expected linear dose-related increase below the threshold dose is addressed by linear regression of the data below the break point and estimation of an upper limit of the slope. The question of biological relevance of the resulting slope is discussed against the normal variation of background measures in the control group.

2-Aminobenzimidazoles as potent ITK antagonists: trans-stilbene-like moieties targeting the kinase specificity pocket.

Based on the information from molecular modeling and X-ray crystal structures, the kinase specificity pocket of ITK could be occupied upon extension of the right-hand-side of the 2-benzimidazole core of the inhibitors. 2-Aminobenzimidazoles with a trans-stilbene-like extension were designed and synthesized as novel ITK antagonists. Significant improvement on binding affinity and cellular activity were obtained through the trans-stilbene-like antagonists. Several compounds showed inhibitory activity in an IL-2 functional assay.

Metabolite profiling in human urine by LC-MS/MS: method optimization and application for glucuronides from dextromethorphan metabolism.

Analysis of human urine for specific compounds or metabolites is an established method for biomonitoring occupational or environmental exposures. Modern liquid chromatography-tandem mass spectrometry is not limited to single compounds but can simultaneously analyze whole classes of urine constituents with both high sensitivity and specificity. Individual differences in the composition of urine are very large in humans, which raises a number of problems that are not encountered in animal experimentation. In this report, we investigated whether analysis of glucuronides as a class could reflect differences between human individuals regarding the polymorphic activity of the cytochrome P450 enzyme CYP2D6. From a group of 152 students that had been classified for CYP2D6 activity, urine of 12 "poor metabolizers" and 35 "extensive metabolizers" was collected 90 min after ingestion of 10mg of the antitussive drug dextromethorphan (DEX) and analyzed for glucuronides. Methods development included the following aspects: adjustment of urine samples to equal creatinine concentration to avoid differences between samples in retention times and ion suppression; on-line enrichment of low-level analytes by column switching; precursor ion scan vs. theoretical multiple reaction monitoring; use of quality control samples to check for reproducibility in large sample series; peak extraction and handling of null entries to build the data matrix; logarithmic data transformation and different scaling procedures; principal component analysis (PCA) vs. discriminant analysis. Our results show that an optimized procedure not only identified the known DEX metabolites as predictors of CYP2D6-specific metabolic pathways but also indicated the presence of additional, so far unknown path-specific glucuronide metabolites. We conclude that metabolite profiling of urine and other biofluids by modern mass spectrometric methodology may help characterize individual differences and become useful in drug development and personalized pharmacotherapy.

Financial incentives and psychiatric services in Australia: an empirical analysis of three policy changes.

Australia has a national, compulsory and universal health insurance scheme, called Medicare. In 1996 the Government changed the Medicare Benefit Schedule Book in such a way as to create different financial incentives for consumers or producers of out-of-hospital private psychiatric services, once an individual consumer had received 50 such services in a 12-month period. The Australian Government introduced a new Item (319) to cover some special cases that were affected by the policy change. At the same time, the Commonwealth introduced a 'fee-freeze' for all medical services. The purpose of this study is two-fold. First, it is necessary to describe the three policy interventions (the constraints on utilization, the operation of the new Item and the general 'fee-freeze'.) The new Item policy was essentially a mechanism to 'dampen' the effect of the 'constraint' policy, and these two policy changes will be consequently analysed as a single intervention. The second objective is to evaluate the policy intervention in terms of the (stated) Australian purpose of reducing utilization of psychiatric services, and thus reducing financial outlays. Thus, it is important to separate out the different effects of the three policies that were introduced at much the same time in November 1996 and January 1997. The econometric results indicate that the composite policy change (constraining services and the new 319 Item) had a statistically significant effect. The analysis of the Medicare Benefit (in constant prices) indicates that the 'fee-freeze' policy also had a statistically significant effect. This enables separate determination of the several policy changes. In fact, the empirical results indicate that the Commonwealth Government underestimated the 'savings' that would arise from the 'constraint' policy.

Metabolic profiling of glucuronides in human urine by LC-MS/MS and partial least-squares discriminant analysis for classification and prediction of gender.

Mass spectrometry (MS) is increasingly being used for metabolic profiling, but detection modes such as constant neutral loss or multiple reaction monitoring have not often been reported. These modes allow focusing on structurally related compounds, which could be advantageous for situations in which the trait under investigation is associated with a particular class of metabolites. In this study, we analyzed endogenous glucuronides excreted in human urine by monitoring characteristic transitions of putative steroid glucuronides by LC-MS/MS for discrimination of females from males. Two methods for data extraction were used: (i) a manual procedure based on visual inspection of the chromatograms and selection of 23 peaks and (ii) a software-supported method (MarkerView) set to extract 100 peaks. Data from 10 female and 10 male students were analyzed by principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) using software SIMCA. With PCA, only the manual peak selection resulted in clustering males and females. With PLS-DA, the manual method provided full separation on the basis of one single discriminant; the software-supported approach required a two-component model for complete separation. Loading plots were analyzed for their ability to reveal peaks with high discriminating power, that is, potential biomarkers. The PLS-DA models were validated with urine samples collected from five new females and five new males. Gender was correctly assigned for all. Our results indicate that inclusion of biological criteria for variable selection coupled to class-specific MS analysis and data extraction by appropriate software may constitute a valuable addition to the methods available for metabolomics.

Changes in private sector electroconvulsive treatment in Australia.

OBJECTIVES: This paper reports on changes, over time and between states, in the use of electroconvulsive therapy (ECT) in the private psychiatric sector in Australia between 1984 and 2004. METHOD: Data for ECT services, and all specialist psychiatry services provided under the Medicare system, have been analysed in absolute numbers and as utilization rates. RESULTS: Changes in the use of ECT over time are different from other services provided by private psychiatrists. As in other countries, the use of ECT initially declined in period studied but has increased in recent years. In addition, there is a clear pattern of differential use of ECT between the states and territories. CONCLUSIONS: This descriptive study cannot 'explain' the results obtained: other data, incorporated into an explanatory model using regression analysis, are needed to determine the factors underlying the utilization patterns obtained in this study. Thus, further work is needed. Furthermore, it is important to analyse data at a lower level of geographical aggregation than that of the state/territory: this (state/territory) aggregation conceals differences in utilization between metropolitan, minor city, rural and remote regions of the country.