Patellar mechanics during simulated kneeling in the natural and implanted knee

Kneeling is required during daily living for many patients after total knee replacement (TKR), yet many patients have reported that they cannot kneel due to pain, or avoid kneeling due to discomfort, which critically impacts quality of life and perceived success of the TKR procedure. The objective of this study was to evaluate the effect of component design on patellofemoral (PF) mechanics during a kneeling activity. A computational model to predict natural and implanted PF kinematics and bone strains after kneeling was developed and kinematics were validated with experimental cadaveric studies. PF joint kinematics and patellar bone strains were compared for implants with dome, medialized dome, and anatomic components. Due to the less conforming nature of the designs, change in sagittal plane tilt as a result of kneeling at 90° knee flexion was approximately twice as large for the medialized-dome and dome implants as the natural case or anatomic implant, which may result in additional stretching of the quadriceps. All implanted cases resulted in substantial increases in bone strains compared with the natural knee, but increased strains in different regions. The anatomic patella demonstrated increased strains inferiorly, while the dome and medialized dome showed increases centrally. An understanding of the effect of implant design on patellar mechanics during kneeling may ultimately provide guidance to component designs that reduces the likelihood of knee pain and patellar fracture during kneeling.     

Isolating Potentiated Hsp104 Variants Using Yeast Proteinopathy Models

Many protein-misfolding disorders can be modeled in the budding yeast Saccharomyces cerevisiae. Proteins such as TDP-43 and FUS, implicated in amyotrophic lateral sclerosis, and α-synuclein, implicated in Parkinson’s disease, are toxic and form cytoplasmic aggregates in yeast. These features recapitulate protein pathologies observed in patients with these disorders. Thus, yeast are an ideal platform for isolating toxicity suppressors from libraries of protein variants. We are interested in applying protein disaggregases to eliminate misfolded toxic protein conformers. Specifically, we are engineering Hsp104, a hexameric AAA+ protein from yeast that is uniquely capable of solubilizing both disordered aggregates and amyloid and returning the proteins to their native conformations. While Hsp104 is highly conserved in eukaryotes and eubacteria, it has no known metazoan homologue. Hsp104 has only limited ability to eliminate disordered aggregates and amyloid fibers implicated in human disease. Thus, we aim to engineer Hsp104 variants to reverse the protein misfolding implicated in neurodegenerative disorders. We have developed methods to screen large libraries of Hsp104 variants for suppression of proteotoxicity in yeast. As yeast are prone to spontaneous nonspecific suppression of toxicity, a two-step screening process has been developed to eliminate false positives. Using these methods, we have identified a series of potentiated Hsp104 variants that potently suppress the toxicity and aggregation of TDP-43, FUS, and α-synuclein. Here, we describe this optimized protocol, which could be adapted to screen libraries constructed using any protein backbone for suppression of toxicity of any protein that is toxic in yeast.     

The Enhancement of Soil Fertility,Dry Matter Transport and Accumulation,Nitrogen Uptake and Yield in Rice via Green Manuring

Readily available chemical fertilizers have resulted in a decline in the use of organic manure (e.g., green manures), a traditionally sustainable source of nutrients. Based on this, we applied urea at the rate of 270 kg ha⁻¹ with and without green manure in order to assess nitrogen (N) productivity in a double rice cropping system in 2017. In particular, treatment combinations were as follows: winter fallow rice-rice (WF-R-R), milk vetch rice-rice (MV-R-R), oil-seed rape rice-rice (R-R-R) and potato crop rice-rice (P-R-R). Results revealed that green manure significantly (p ≤ 0.05) improved the soil chemical properties and net soil organic carbon content increased by an average 117.47%, total nitrogen (N) by 28.41%, available N by 26.64%, total phosphorus (P) by 37.77%, available P by 20.48% and available potassium (K) by 33.10% than WF-R-R, however pH was reduced by 3.30% across the seasons. Similarly, net dry matter accumulation rate enhanced in green manure applied treatments and ranked in order: P-R-R > R-R-R > MV-R-R > WF-R-R. Furthermore, the total leaf dry matter transport (t ha⁻¹ ) for the P-R-R in both seasons was significantly higher by an average 11.2%, 7.2% and 36 % than MV-R-R, R-R-R, and WF-R-R, respectively. In addition, net total nitrogen accumulation (kg ha⁻¹ ) was found higher in green manure applied plots compared to the control. Yield and yield attributed traits were observed maximum in green manure applied plots, with treatments ranking as follows: P-R-R > R-R-R > MV-R-R > WF-R-R. Thus, results obtained highlight ability of green manure to sustainably improve soil quality and rice yield.     

Impact of ivermectin on the ultrastructure of the testis of <Emphasis Type="Italic">Argas (Persicargas) persicus</Emphasis> (Ixodoidea: Argasidae)

Mated male Argas persicus were dissected 1 and 2 weeks after feeding on untreated and ivermectin (IVM)-treated pigeons. One week after feeding, testes of untreated ticks were filled with rounded spermatids with subplasmalemmal vesicles and cytoplasmic organelles, but lacking in treated ticks. Two weeks after feeding, testes were crowded with elongated spermatozoa supported by double-walled cisternal tubes. The tubes consisted of two opposite walls, each with outer-fringed processes and inner elongated cisternae. Both were supported with electron dense striated plates in the middle of the spermatozoon. Internally, the cisternal tubes contained mitochondria and vacuoles. The nuclei were elongated dense masses between the tubes and the cell membranes. Subcutaneous inoculation of IVM at the dose 400 μg/kg pigeon resulted in extensive alterations in the testis of A. persicus. IVM prevented the development of new spermatids. There was a break down of cell membranes and cytoplasmic organelles of spermatozoa. Multivesicular bodies and numerous vacuoles were noticed in their cytoplasm. Double membranes of elongated cisternae and striation of electron dense plates became indistinct. IVM caused granulation and vacuolization of the nucleus as well as injury of mitochondrial cristae. The results suggest that IVM may bind to the neurotransmitter or the hormone involved in the process of sperm development or may be toxic to the germinal cells of A. persicus testis.     

Appraisal of Transdermal Water-in-Oil Nanoemulgel of Selegiline HCl for the Effective Management of Parkinson’s Disease: Pharmacodynamic,Pharmacokinetic, and Biochemical Investigations

In the present study, the potential of transdermal nanoemulsion gel of selegiline hydrochloride for the treatment of Parkinson’s disease was investigated. Water-in-oil nanoemulsions were developed by comparing low- and high-energy methods and were subjected to thermodynamic stability tests, in vitro permeation, and characterization studies. In vitro studies indicated that components of nanoemulsion acted as permeation enhancers with highest flux of 3.531 ± 1.94 μg/cm²/h from nanoemulsion SB6 containing 0.5 mg selegiline hydrochloride, 3% distilled water, 21% S _mix (Span 85, Tween 80, PEG 400), and 76% isopropyl myristate by weight. SB6 with the least droplet size of 183.4 ± 0.35 nm, polydispersity index of 0.42 ± 0.06 with pH of 5.9 ± 0.32 and viscosity of 22.42 ± 0.14 cps was converted to nanoemulsion gel NEGS4 (viscosity = 22,200 ± 400 cps) by addition of Viscup160® for ease of application and evaluated for permeation, safety, and pharmacokinetic profile in Wistar rats. It provided enhancement ratio 3.69 times greater than conventional gel. NEGS4 showed 6.56 and 5.53 times increase in bioavailability in comparison to tablet and conventional gel, respectively, along with sustained effect. Therefore, the developed water-in-oil nanoemulsion gel promises to be an effective vehicle for transdermal delivery of selegiline hydrochloride.     

Optimisation and Assessment of Three Modern Touch Screen Tablet Computers for Clinical Vision Testing

Technological advances have led to the development of powerful yet portable tablet computers whose touch-screen resolutions now permit the presentation of targets small enough to test the limits of normal visual acuity. Such devices have become ubiquitous in daily life and are moving into the clinical space. However, in order to produce clinically valid tests, it is important to identify the limits imposed by the screen characteristics, such as resolution, brightness uniformity, contrast linearity and the effect of viewing angle. Previously we have conducted such tests on the iPad 3. Here we extend our investigations to 2 other devices and outline a protocol for calibrating such screens, using standardised methods to measure the gamma function, warm up time, screen uniformity and the effects of viewing angle and screen reflections. We demonstrate that all three devices manifest typical gamma functions for voltage and luminance with warm up times of approximately 15 minutes. However, there were differences in homogeneity and reflectance among the displays. We suggest practical means to optimise quality of display for vision testing including screen calibration.     

Temperature Gradient Measurements by Using Thermoelectric Effect in CNTs-Silicone Adhesive Composite

This work presents the fabrication and investigation of thermoelectric cells based on composite of carbon nanotubes (CNT) and silicone adhesive. The composite contains CNT and silicon adhesive 1∶1 by weight. The current-voltage characteristics and dependences of voltage, current and Seebeck coefficient on the temperature gradient of cell were studied. It was observed that with increase in temperature gradient the open circuit voltage, short circuit current and the Seebeck coefficient of the cells increase. Approximately 7 times increase in temperature gradient increases the open circuit voltage and short circuit current up to 40 and 5 times, respectively. The simulation of experimental results is also carried out; the simulated results are well matched with experimental results.