Reliability, Validity, and Performance Characteristics of Elite Adolescent Athletes at Different Stages of Maturity in the 10 to 5 Repeated Jump Test.

PURPOSE: To examine the reliability, validity, and performance characteristics of the 10 to 5 repeated jump test (10-5 RJT) in adolescent male athletes. The 10-5 RJT has been shown to be a valid and reliable test of reactive strength index (RSI) in older adolescents (age 17-19 y), but less is known in younger adolescent athletes at different stages of maturity. METHODS: Athletes (age 11-17 y) completed the 10-5 RJT on 2 days, 1 week apart, to examine the reliability (n = 41), validity (n = 18) of the test. Athletes were classified as pre, circa, or post peak height velocity (PHV) height velocity using maturity offset to examine the effect of maturation status on RSI, flight time (FT), ground contact time (GCT), and jump height (JH) (n = 68) using a cross-sectional design. RESULTS: Paired samples t tests showed no significant differences (P ≥ .05), and Bland-Altman analysis showed no bias and close limits of agreement for RSI, JH, FT, and GCT between the contact mat and force plate. Interday reliability was rated excellent for RSI (intraclass correlation coefficient = .91) and good for GCT, FT, and JH (intraclass correlation coefficient = .81-.85). All variables had a coefficient of variation ≤ 10%. RSI increased across maturation groups, with significant differences between pre-PHV and post-PHV groups (P = .014, d = 1.00). CONCLUSION: The 10-5 RJT is a valid and reliable test for adolescent male athletes. Greater RSI with advancing maturity was primarily due to increased FT and JH, with GCT remaining similar.

Kinetics and thermodynamics of thermal inactivation for recombinant Escherichia coli cellulases, cel12B, cel8C, and polygalacturonase, peh28; biocatalysts for biofuel precursor production.

Lignocellulosic biomass conversion using cellulases/polygalacturonases is a process that can be progressively influenced by several determinants involved in cellulose microfibril degradation. This article focuses on the kinetics and thermodynamics of thermal inactivation of recombinant Escherichia coli cellulases, cel12B, cel8C and a polygalacturonase, peh 28, derived from Pectobacterium carotovorum sub sp. carotovorum. Several consensus motifs conferring the enzymes' thermal stability in both cel12B and peh28 model structures have been detailed earlier, which were confirmed for the three enzymes through the current study of their thermal inactivation profiles over the 20-80°C range using the respective activities on carboxymethylcellulose and polygalacturonic acid. Kinetic constants and half-lives of thermal inactivation, inactivation energy, plus inactivation entropies, enthalpies and Gibbs free energies, revealed high stability, less conformational change and protein unfolding for cel12B and peh28 due to thermal denaturation compared to cel8C. The apparent thermal stability of peh28 and cel12B, along with their hydrolytic efficiency on a lignocellulosic biomass conversion as reported previously, makes these enzymes candidates for various industrial applications. Analysis of the Gibbs free energy values suggests that the thermal stabilities of cel12B and peh28 are entropy-controlled over the tested temperature range.

Single oral dose for HIV pre or post-exposure prophylaxis: user desirability and biological efficacy in macaques.

BACKGROUND: Daily oral pre- or post-exposure prophylaxis (PrEP or PEP) is highly effective in preventing HIV infection. However, many people find it challenging to adhere to a daily oral regimen. Chemoprophylaxis with single oral doses of antiretroviral drugs taken before or after sex may better adapt to changing or unanticipated sexual practices and be a desirable alternative to daily PrEP or PEP. We investigated willingness to use a single oral pill before or after sex among men who have sex with men (MSM) and assessed the biological efficacy of a potent antiretroviral combination containing elvitegravir (EVG), emtricitabine (FTC), and tenofovir alafenamide (TAF). METHODS: Data on willingness to use single-dose PrEP or PEP were obtained from the 2017 cycle of the American Men's Internet Survey (AMIS), an annual online behavioral surveillance survey of MSM in the United States. Antiretroviral drug levels were measured in humans and macaques to define drug distribution in rectal tissue and identify clinically relevant doses for macaque modeling studies. The biological efficacy of a single dose of FTC/TAF/EVG as PrEP or PEP was investigated using a repeat-challenge macaque model of rectal HIV infection. FINDINGS: Through pharmacokinetic assessment in humans and macaques we found that EVG penetrates and concentrates in rectal tissues supporting its addition to FTC/TAF to boost and extend chemoprophylactic activity. Efficacy estimates for a single oral dose given to macaques 4h before or 2h after SHIV exposure was 91•7%[35•7%-98•9%] and 100%, respectively, compared to 80•1%[13•9%-95•4%] and 64•6%[-19•4%-89•5%] when single doses were given 6 and 24h post challenge, respectively. A two-dose regimen at 24h and 48h after exposure was also protective [77•1%[1•7%-94•7%]. INTERPRETATION: Informed by user willingness, human and macaque pharmacokinetic data, and preclinical efficacy we show that single-dose prophylaxis before or after sex is a promising HIV prevention strategy. Carefully designed clinical trials are needed to determine if any of these strategies will be effective in humans. FUNDING: Funded by CDC intramural funds, CDC contract HCVJCG2-2016-03948 (to CFK), and a grant from the MAC AIDS Fund and by the National Institutes of Health [P30AI050409] - the Emory Center for AIDS Research (to MZ and TS).

Pharmacokinetic Profiles of Gabapentin after Oral and Subcutaneous Administration in Black-tailed Prairie Dogs (Cynomys ludovicianus).

In veterinary and human medicine, gabapentin (a chemical analog of γ-aminobutyric acid) is commonly prescribed to treat postoperative and chronic neuropathic pain. This study explored the pharmacokinetics of oral and subcutaneous administration of gabapentin at high (80 mg/kg) and low (30 mg/kg) doses as a potential analgesic in black-tailed prairie dogs (Cynomys ludovicianus; n = 24). The doses (30 and 80 mg/kg) and half maximal effective concentration (1.4 to 16.7 ng/mL) for this study were extrapolated from pharmacokinetic efficacy studies in rats, rabbits, and cats. Gabapentin in plasma was measured by using an immunoassay, and data were evaluated using noncompartmental analysis. The peak plasma concentrations (mean ±1 SD) were 42.6 ±14.8 and 115.5 ±15.2 ng/mL, respectively, after 30 and 80 mg/kg SC and 14.5 ±3.5 and 20.7 ±6.1 ng/mL after the low and high oral dosages, respectively. All peak plasma concentrations of gabapentin occurred within 5 h of administration. Disappearance half-lives for the low and high oral doses were 7.4 ± 6.0 h and 5.0 ± 0.8 h, respectively. The results of this study demonstrate that oral administration of gabapentin at low (30 mg/kg) doses likely would achieve and maintain plasma concentrations at half maximum effective concentration for 12 h, making it a viable option for an every 12-h treatment.

Successful isolation of Treponema pallidum strains from patients' cryopreserved ulcer exudate using the rabbit model.

Clinical isolates of Treponema pallidum subspecies pallidum (T. pallidum) would facilitate study of prevalent strains. We describe the first successful rabbit propagation of T. pallidum from cryopreserved ulcer specimens. Fresh ulcer exudates were collected and cryopreserved with consent from syphilis-diagnosed patients (N = 8). Each of eight age-matched adult male rabbits were later inoculated with a thawed specimen, with two rabbits receiving 1.3 ml intratesticularly (IT), and six receiving 0.6 ml intravenously (IV) and IT. Monitoring of serology, blood PCR and orchitis showed that T. pallidum grew in 2/8 rabbits that were inoculated IV and IT with either a penile primary lesion specimen (CDC-SF003) or a perianal secondary lesion specimen (CDC-SF007). Rabbit CDC-SF003 was seroreactive by T. pallidum Particle Agglutination (TP-PA) and Rapid Plasma Reagin (RPR) testing, PCR+, and showed orchitis by week 6. Euthanasia was performed in week 7, with treponemal growth in the testes confirmed and quantified by qPCR and darkfield microscopy (DF). Serial passage of the extract in a second age-matched rabbit also yielded treponemes. Similarly, rabbit CDC-SF007 showed negligible orchitis, but was seroreactive and PCR+ by week 4 and euthanized in week 6 to yield T. pallidum, which was further propagated by second passage. Using the 4-component molecular typing system for syphilis, 3 propagated strains (CDC-SF003, CDC-SF007, CDC-SF008) were typed as 14d9f, 14d9g, and 14d10c, respectively. All 3 isolates including strain CDC-SF011, which was not successfully propagated, had the A2058G mutation associated with azithromycin resistance. Our results show that immediate cryopreservation of syphilitic ulcer exudate can maintain T. pallidum viability for rabbit propagation.

Medical 3D Printing Cost-Savings in Orthopedic and Maxillofacial Surgery: Cost Analysis of Operating Room Time Saved with 3D Printed Anatomic Models and Surgical Guides.

RATIONALE AND OBJECTIVE: Three-dimensional (3D) printed anatomic models and surgical guides have been shown to reduce operative time. The purpose of this study was to generate an economic analysis of the cost-saving potential of 3D printed anatomic models and surgical guides in orthopedic and maxillofacial surgical applications. MATERIALS AND METHODS: A targeted literature search identified operating room cost-per-minute and studies that quantified time saved using 3D printed constructs. Studies that reported operative time differences due to 3D printed anatomic models or surgical guides were reviewed and cataloged. A mean of $62 per operating room minute (range of $22-$133 per minute) was used as the reference standard for operating room time cost. Different financial scenarios were modeled with the provided cost-per-minute of operating room time (using high, mean, and low values) and mean time saved using 3D printed constructs. RESULTS: Seven studies using 3D printed anatomic models in surgical care demonstrated a mean 62 minutes ($3720/case saved from reduced time) of time saved, and 25 studies of 3D printed surgical guides demonstrated a mean 23 minutes time saved ($1488/case saved from reduced time). An estimated 63 models or guides per year (or 1.2/week) were predicted to be the minimum number to breakeven and account for annual fixed costs. CONCLUSION: Based on the literature-based financial analyses, medical 3D printing appears to reduce operating room costs secondary to shortening procedure times. While resource-intensive, 3D printed constructs used in patients' operative care provides considerable downstream value to health systems.

The Generation of Time in the Hippocampal Memory System.

We propose that ramping time cells in the lateral entorhinal cortex can be produced by synaptic adaptation and demonstrate this in an integrate-and-fire attractor network model. We propose that competitive networks in the hippocampal system can convert these entorhinal ramping cells into hippocampal time cells and demonstrate this in a competitive network. We propose that this conversion is necessary to provide orthogonal hippocampal time representations to encode the temporal sequence of events in hippocampal episodic memory, and we support that with analytic arguments. We demonstrate that this processing can produce hippocampal neuronal ensembles that not only show replay of the sequence later on, but can also do this in reverse order in reverse replay. This research addresses a major issue in neuroscience: the mechanisms by which time is encoded in the brain and how the time representations are then useful in the hippocampal memory of events and their order.

Molecular and biochemical characterization of recombinant cel12B, cel8C, and peh28 overexpressed in Escherichia coli and their potential in biofuel production.

BACKGROUND: The high crystallinity of cellulosic biomass myofibrils as well as the complexity of their intermolecular structure is a significant impediment for biofuel production. Cloning of celB-, celC-encoded cellulases (cel12B and cel8C) and peh-encoded polygalacturonase (peh28) from Pectobacterium carotovorum subsp. carotovorum (Pcc) was carried out in our previous study using Escherichia coli as a host vector. The current study partially characterizes the enzymes' molecular structures as well as their catalytic performance on different substrates which can be used to improve their potential for lignocellulosic biomass conversion. RESULTS: ß-Jelly roll topology, (α/α)6 antiparallel helices and right-handed ß-helices were the folds identified for cel12B, cel8C, and peh28, respectively, in their corresponding protein model structures. Purifications of 17.4-, 6.2-, and 6.0-fold, compared to crude extract, were achieved for cel12B and cel8C, and peh28, respectively, using specific membrane ultrafiltrations and size-exclusion chromatography. Avicel and carboxymethyl cellulose (CMC) were substrates for cel12B, whereas for cel8C catalytic activity was only shown on CMC. The enzymes displayed significant synergy on CMC but not on Avicel when tested for 3 h at 45 °C. No observed ß-glucosidase activities were identified for cel8C and cel12B when tested on p-nitrophenyl-ß-d-glucopyranoside. Activity stimulation of 130% was observed when a recombinant ß-glucosidase from Pcc was added to cel8C and cel12B as tested for 3 h at 45 °C. Optimum temperature and pH of 45 °C and 5.4, respectively, were identified for all three enzymes using various substrates. Catalytic efficiencies (kcat/Km) were calculated for cel12B and cel8C on CMC as 0.141 and 2.45 ml/mg/s respectively, at 45 °C and pH 5.0 and for peh28 on polygalacturonic acid as 4.87 ml/mg/s, at 40 °C and pH 5.0. Glucose and cellobiose were the end-products identified for cel8C, cel12B, and ß-glucosidase acting together on Avicel or CMC, while galacturonic acid and other minor co-products were identified for peh28 action on pectin. CONCLUSIONS: This study provides some insight into which parameters should be optimized when application of cel8C, cel12B, and peh28 to biomass conversion is the goal.

3D simulation of an audible ultrasonic electrolarynx using difference waves.

A total laryngectomy removes the vocal folds which are fundamental in forming voiced sounds that make speech possible. Although implanted prosthetics are commonly used in developed countries, simple handheld vibrating electrolarynxes are still common worldwide. These devices are easy to use but suffer from many drawbacks including dedication of a hand, mechanical sounding voice, and sound leakage. To address some of these drawbacks, we introduce a novel electrolarynx that uses vibro-acoustic interference of dual ultrasonic waves to generate an audible fundamental frequency. A 3D simulation of the principles of the device is presented in this paper.

A citrus waste-based biorefinery as a source of renewable energy: technical advances and analysis of engineering challenges.

An assessment of recent technical advances on pretreatment processes and its effects on enzymatic hydrolysis as the main steps of a proposed citrus processing waste (CPW) biorefinery is presented. Engineering challenges and relevant gaps in scientific and technical information for reliable design, modeling and scale up of a CPW biorefinery are also discussed. Some integrated physico-chemical pretreatments are proposed for testing for CPW, including high speed knife-grinding and simultaneous caustic addition. These new proposed processes and the effect of parameters such as particle size, surface area and morphology, pore volume and chemical composition of the diverse fractions resulting from pretreatment and enzymatic hydrolysis need to be evaluated and compared for pretreated and untreated samples of grapefruit processing waste. This assessment suggests the potential for filling the data gaps, and preliminary results demonstrate that the reduction of particle size and the increased surface area for the CPW will result in higher reaction rates and monosaccharide yields for the pretreated waste material.