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During the non-breeding season, Ossimi rams have testicular regression, including reductions in blood flow, size and spermatogenesis. The objective was to determine the effect of pentoxifylline (PTX) on Ossimi rams during the non-breeding season. Fifteen sexually mature Ossimi rams were allotted to three groups: (1) G0 (n = 5) control group (basic diet, no PTX); (2) G1 (n = 5) 10 mg/kg BW PTX; and (3) G2 (n = 5) 20 mg/kg BW PTX. The PTX was given orally once daily for 7 weeks (wk1 to wk7), whereas ultrasonographic assessment of testes, and collection of semen and blood started 1 week before PTX and were done weekly for 8 weeks (wk0 to wk7). In G2, there was a decrease(P < 0.05) in both Doppler indices (resistive index, pulsatility index) in G2 from wk2 to wk4 and an increase(P < 0.05) in ultrasonographic testicular coloration from wk2 to wk7. Moreover, G2 had the highest (P < 0.05) testicular volume (wk5 to wk7), individual motility, sperm viability and acrosome integrity (wk4 to wk7) and sperm cell concentration (wk6 and wk7). Blood concentrations of testosterone and nitric oxide were increased (P < 0.05) concurrent with decreased Doppler indices. In conclusion, PTX enhanced testicular blood flow and volume, semen quality, and concentrations of testosterone and nitric oxide potential in Ossimi rams during the non-breeding season, with potential to ameliorate deleterious effects of heat stress and perhaps enhance ram fertility. • Pentoxifylline improved testicular hemodynamics via reducing the resistance of supratesticular artery. • Pentoxifylline mitigated the effects of HS on individual motility, sperm cell viability from Weeks 4–7. • Pentoxifylline at dose of 20 mg/kg b.w has potential for enhancement testicular volume and sperm cell concentrations at wk6 and wk7 of treatment. • Pentoxifylline increases testosterone and nitric oxide levels from Weeks 2–7. • Pentoxifylline (especially at dose of 20 mg/kg bw) could be used during non-breeding season to mitigate the harmful effect of heat stress on TBF, semen quality. [ABSTRACT FROM AUTHOR]

Background: Due to recurrent shortages of aminophylline, intravenous caffeine has emerged as a commonly used, safe and reliable method to treat adverse effects of vasodilator stress agents. We sought to evaluate the safety and effectiveness of buccal caffeine strips which are rapidly absorbed, inexpensive, readily available, and simplify caffeine administration. Methods: Consecutive patients undergoing regadenoson stress SPECT MPI were assessed for the occurrence of symptoms during testing over an 11-week period at a single metropolitan hospital. Adverse symptoms, including their severity and duration, were recorded at the time of testing. Patient satisfaction was rated on a scale of 1 to 5 (5 being the most satisfied). Patients received reversal with caffeine if symptoms were felt to be significant enough by the patient and physician performing the test. The treatment received alternated week to week between IV caffeine (60 mg) or 100 mg buccal caffeine strips. Caffeine was given at least 3 minutes after tracer injection. A rescue dose of IV caffeine was offered 10 minutes later if indicated. Results: Of the 122 patients enrolled in the study, 70 (57%) were included during buccal caffeine weeks and 52 (43%) during IV caffeine weeks, and only 28 (24%) received reversal with a caffeine agent. Seven (6%) received IV caffeine and 21 (17%) received buccal caffeine. There was no significant difference in symptom duration between IV and buccal caffeine after treatment (152.8 vs 163.4 seconds, P = 0.87). There was no significant difference in initial and final symptom severity between groups. Only 2 patients in the buccal group required rescue IV caffeine for ongoing symptoms and emesis. None of the IV group required a rescue dose. There was no significant difference in patient satisfaction between the groups (2.8 vs 3.2, P = 0.38). Conclusion: Buccal caffeine strips are a safe, well tolerated, and effective initial strategy to reverse adverse effects of vasodilator stress in the minority of patients who request it. Buccal caffeine alone or with IV rescue caffeine was highly effective in reversing adverse effects and was free of major adverse clinical events. [ABSTRACT FROM AUTHOR]

Radial head replacement is the main line of treating complex unstable elbow injuries. Radial head prostheses are either monopolar or bipolar. The difference between both designs in patients' clinical outcomes and postoperative complications is not yet clear. So, a systematic review and meta-analysis was conducted to evaluate the efficacy and safety of monopolar vs. bipolar implants. PubMed, EMBASE, Cochrane, and Scopus were searched to identify studies comparing monopolar and bipolar implants. Data on clinical outcomes, postoperative complications, revision, and removal rates were extracted. Nine studies met our inclusion criteria, with a total of 591 patients (365 monopolar and 226 bipolar). Both prostheses achieved similar ranges of motion; Mayo Elbow Performance Score; Disabilities of the Arm, Shoulder, and Hand score; and visual analog scale for pain. Incidence of postoperative complications was also similar between both designs. Revision and removal rates were 24%, 8% and 29%, 14% for monopolar and bipolar implants, respectively, but no statistically significant difference could be detected. No significant difference was found between monopolar and bipolar radial head prostheses in terms of efficacy and safety. Therefore, high-quality randomized controlled trials are required to determine the superiority of one design over the other. [ABSTRACT FROM AUTHOR]

In this work, a three-dimensional viscoplasticity formulation with progressive damage is developed and used to investigate the complex time-dependent constituent load transfer and progressive damage behavior in ceramic matrix composites (CMCs) subjected to creep. The viscoplasticity formulation is based on Hill's orthotropic plastic potential, an associative flow rule, and the Norton-Bailey creep power law with Arrhenius temperature dependence. A fracture mechanics-informed isotropic matrix damage model is used to account for CMC brittle matrix damage initiation and propagation, in which two scalar damage variables capture the effects of matrix porosity as well as matrix property degradation due to matrix crack initiation and propagation. The Curtin progressive fiber damage model is utilized to simulate progressive fiber failure. The creep-damage formulation is subsequently implemented as a constitutive model in the generalized method of cells (GMC) micromechanics formulation to simulate time-dependent deformation and material damage under creep loading conditions. The developed framework is used to simulate creep of single fiber SiC/SiC microcomposites. Simulation results are in excellent agreement with experimental and numerical data available in the literature. [ABSTRACT FROM AUTHOR]

[Display omitted] For proportionally formulated intermediate strengths of a topical product, the relationship of drug release across multiple strengths of a given product is not always well understood. The current study aims to assess the proportionality of tretinoin release rates across multiple strengths of tretinoin topical gels when manufactured using two different methods to understand the impact of formulation design on drug product microstructure and tretinoin release rate. Two groups of tretinoin gels of 0.04 %, 0.06 %, 0.08 % and 0.1 % strengths were manufactured. Gels in Group I were prepared by incorporating 4–10 % g/g of 1 % w/w tretinoin-loaded microparticles into a gel base. Gels in Group II were manufactured using 10 % g/g of the microparticles that were loaded with increasing amounts (0.4–1 % w/w) of tretinoin. The two groups of gels were characterized by evaluating microstructure using a polarized microscope, rheology using an oscillatory rheometer, and drug release using Vison® Microette™ Hanson vertical diffusion cells. The microscopic images were used to discriminate between the two groups of gels based on the abundance of microparticles in the gel matrix observed in the images. This abundance increased across gels of Group I and was similar across gels of Group II. The rheology parameters, namely viscosity at a shear rate of 10 s−1, shear thinning rate, storage, and loss modulus, increased across gels of Group I, and were not significantly different across gels of Group II. The release rate of tretinoin from the drug products was proportional to the nominal strength of the drug product in both Group I and Group II, with a correlation coefficient of 0.95 in each case, although the absolute release rates differed. Overall, changing the formulation design of tretinoin topical gels containing porous microparticles may change the physicochemical and structural properties, as well as the drug release rate of the product. Further, keeping the formulation design consistent across all strengths of microparticle-based topical gels is important to achieve proportional release rates across multiple strengths of a given drug product. [ABSTRACT FROM AUTHOR]

In Alzheimer’s disease (AD) the blood–brain barrier (BBB) is compromised, thus therapeutic targeting of the BBB to enhance its integrity and function could be a unique approach to treat, slow or hold the progression of AD. Recently, we have developed an in vitro high-throughput screening assay to screen for compounds that increase the integrity of a cell-based BBB model. Results from primary screen identified multiple hit compounds that enhanced the monolayer integrity. Herein, further characterization of selected hit compounds, namely 8-bromoguanosine cyclic monophosphate, JW74, 1,10-phenanthroline monohydrate, SB216763 and α-tocopherol was performed. Compounds were subjected to concentration-dependent studies to determine their EC50 and potency to enhance the cell-based model integrity by the Lucifer Yellow permeability and amyloid-beta (Aβ) transport across the monolayer. The compounds demonstrated different EC50s to enhance the monolayer integrity ranging from 0.4 to 12.8 µM, and different effect on enhancing Aβ transport with highest transport observed for α-tocopherol (2.2-fold increase). Such effects were associated with increased levels of tight junction proteins such as claudin-5 and/or ZO-1, and Aβ major transport proteins LRP1 and P-glycoprotein. In vivo studies for α-tocopherol were performed in AD mouse model; consistent with the in vitro results α-tocopherol significantly increased BBB integrity measured by IgG extravasation, and reduced brain Aβ levels. In conclusion, findings support our developed cell-based BBB model as a functional predictive in vivo tool to select hit compounds, and suggest that enhancing BBB tightness and function has the potential to reduce Aβ pathology associated with AD. [ABSTRACT FROM AUTHOR]

In former cohort most of the applications that are designed for examining the effect of underground water for naval operations follows a specific path for all types of mission operations. But the development and success of such process is usually carried out using specification in score type maneuvers. However the effect of naval operation can only be examined in real time by using a well-defined bi-conditional statement system that integrates the communication device for choosing intelligent route. Therefore a fuzzy logic system is implemented for observing the effect of underwater applications using a defined system model. But unlike in existing models the sonar type model with data handling technique is not used but a secured data transfer approach is created using the constraint statements. Further to prove the effectiveness of the developed system with fuzzy logic five scenarios are described with performance analysis where the outcomes proves that projected method provides high effectiveness for about 67% as compared to existing method. • This is a real-time prototype work with a unique design model. • We have designed a core segment consisting of the entire navy model representing the number of changes in the system. • The outcome of the proposed method is to integrate the design with analytical equations and fuzzy logic system that checks whether the objective function is minimised or maximised. • Another highlight of this work is scenario-wise assessments. Based on different scenarios, the parametric evaluations of navy applications are meticulously made. • Performance measurement is done through MATLAB coding, and relevant results are simulated. • More than all, this work is mathematically justified. [ABSTRACT FROM AUTHOR]

Q fever, a commonly reported zoonosis worldwide, is caused by infection with Coxiella burnetii , an obligate intracellular bacterium. The infection is often asymptomatic in ruminants, but it can lead to reproductive disorders with bacterial shedding into the environment. Between 2011 and 2013, a study was undertaken in small ruminant flocks in different regions of Algeria. A total of 35 flocks were visited and 227 sera and 267 genital swabs were collected from females after abortions or the lambing period to investigate Q fever infection. Indirect ELISA was used to detect specific antibodies against C. burnetii and real-time PCR for detecting bacterial DNA. Our survey indicated that 58% (95% CI = 40–76%) of flocks had at least one positive animal (17 seropositive flocks) and individual seroprevalence was estimated at 14.1% (95% CI = 11.8–16.4%) (32 seropositive animals). Bacterial excretion was observed in 21 flocks (60%), and 57 females showed evidence of C. burnetii shedding (21.3%). These results suggest that C. burnetii distribution is high at the flock level and that seropositive and infected (shedder) animals can be found all over the country. Further studies are needed in other regions and on different animal species to better understand the distribution and incidence of Q fever, as well as human exposure, and to develop an adequate prophylaxis program. [ABSTRACT FROM AUTHOR]

This paper presents an experimental investigation into the thermomechanical properties and failure modes of toughened epoxy adhesives and composite-to-aluminum bonded joints in high and low temperature conditions. First, nondestructive evaluation techniques were utilized to characterize the inherent defect morphology of bulk adhesives and the bonded joint interface. This was followed by quasi-static tensile testing conducted over a temperature range of −37 °C to 57 °C. The damage mechanisms and failure modes were investigated using in-situ digital image correlation (DIC) and high-resolution camera. The information from the morphology characterization studies was also used to reconstruct high-fidelity geometries of the test specimens for finite element (FE) analysis. The elastic properties and tensile strength of bulk adhesive test specimens showed significant deterioration while exhibiting considerable ductility at higher temperatures. DIC and FE analysis revealed the strong influence of size and distribution of defects on the material properties and damage localization. In addition, post-fracture surface characterization of the adhesively bonded specimens revealed failure modes ranging between adherent-dominant to adhesive-dominant modes at low and high-temperature conditions. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this 2-arm parallel randomized controlled trial was to evaluate patient acceptance of the mini-implant anchored Forsus Fatigue Resistant Device (FFRD) (3M Unitek, Monrovia, Calif).Methods: The study included 32 skeletal Class II girls. The eligibility criteria included a deficient mandible, a horizontal or neutral growth pattern, an increased overjet, and a full set of erupted permanent teeth. After the leveling and alignment stage, FFRDs and mini-implants were inserted; they were removed after the teeth reached an edge-to-edge incisor relationship. The patients were afterward asked to fill out assessment questionnaires regarding their experience with the FFRD.Outcomes: The primary outcome of this study was to assess patient acceptance of the appliance and satisfaction with the results. The secondary outcomes were interference with functional activities, noticeability by others, pain, swelling, gum problems caused by the appliance, and appliance breakage.Randomization: Computer random sequence generation was done using block sizes of 6 and 4. Allocation concealment was achieved with sequentially numbered opaque sealed envelopes.Blinding: Blinding of the clinicians and the patients to the intervention was impossible, but it was done for the outcome assessment and the statistician.Results: The 32 patients were randomly allocated in a 1:1 ratio into 2 groups: 16 patients (mean age, 13.25 ± 1.12 years) received the FFRD alone (FFRD group), and 16 patients (mean age, 13.07 ± 1.41 years) had mini-implants in conjunction with FFRDs (FMI group). No statistically significant differences were reported between the 2 groups regarding ease of appliance insertion, noticeability by others, pain, swelling, effects on eating and speech, and gum bleeding; 100% and 87.5% were satisfied with the results in the FFRD and FMI groups, respectively, with a ridit value of 0.57 (95% confidence interval, 0.43-0.71; P = 0.36). No serious harm was observed other than swelling of the cheeks, which occurred in 4 patients.Conclusions: There were no significant differences between the patients' acceptance of the FFRD and the mini-implant anchored FFRD. They were highly satisfied with the results. Neither group reported significant functional limitations.Registration: This trial was not registered.Protocol: The protocol was not published before trial commencement.Funding: The study was self-funded by the authors. [ABSTRACT FROM AUTHOR]

Background & Aims Serrated lesions are an important contributor to colorectal cancer (CRC), notably in the proximal colon. Findings in the distal colorectum are markers of advanced proximal adenomatous neoplasia. However, it is not known whether they affect the odds of advanced proximal serrated lesions. Methods We performed a retrospective cross-sectional study of data from 1910 patients (59.3 ± 8.0 years, 53.8% female) who underwent an average-risk screening colonoscopy from August 2005 through April 2012 at Indiana University Hospital and an associated ambulatory surgery center. Colonoscopies were performed by an endoscopist with high rates of detection of adenomas and serrated polyps. Tissue samples of all serrated polyps (hyperplastic, sessile serrated adenoma/polyp [SSA/P], or traditional serrated adenoma) proximal to the sigmoid colon and serrated polyps >5 mm in the rectum or sigmoid colon were reviewed by a gastrointestinal pathologist and reclassified on the basis of World Health Organization criteria. Advanced serrated lesion (ASL) was defined as SSA/P with cytologic dysplasia, SSA/P ≥10 mm, or traditional serrated adenoma. Advanced conventional adenomatous neoplasia (ACN) was defined as tubular adenoma ≥10 mm, villous histology, high-grade dysplasia, or cancer. The prevalence of proximal ASL and ACN was calculated on the basis of distal colorectal findings. Multivariable logistic regression analysis was performed to determine the age-adjusted and sex-adjusted odds of advanced proximal adenomatous and serrated lesions. Secondary analyses were performed to examine the effect of variable ASL definitions. Results Fifty-two patients (2.7%) had proximal ASL, and 99 (5.2%) had proximal ACN. Of the 52 patients with proximal ASL, 27 (52%) had no distal polyps. Of the 99 patients with proximal ACN, 40 (40%) had no distal polyps. Age and type of distal adenomas were significantly associated with proximal ACN. There were no significant associations between distal polyp type and proximal ASL. In secondary analyses, distal SSA/Ps ( P = .008) but not distal hyperplastic polyps or conventional adenomas were associated with any proximal SSA/P. Conclusions The findings at flexible sigmoidoscopy that traditionally serve as indications for colonoscopy (conventional adenomas) are likely to be ineffective for detection of proximal ASL. This finding, plus the observation that most patients with proximal ASL have no distal polyps, favors screening colonoscopy over sigmoidoscopy, especially in the elderly. The observation that non-advanced distal SSA/Ps are associated with any proximal SSA/P warrants further study. [ABSTRACT FROM AUTHOR]

Acquired cardiac long QT syndrome (LQTS) is a frequent drug-induced toxic event that is often caused through blocking of the human ether-á-go-go-related (hERG) K + ion channel. This has led to the removal of several major drugs post-approval and is a frequent cause of termination of clinical trials. We report here a computational atomistic model derived using long molecular dynamics that allows sensitive prediction of hERG blockage. It identified drug-mediated hERG blocking activity of a test panel of 18 compounds with high sensitivity and specificity and was experimentally validated using hERG binding assays and patch clamp electrophysiological assays. The model discriminates between potent, weak, and non-hERG blockers and is superior to previous computational methods. This computational model serves as a powerful new tool to predict hERG blocking thus rendering drug development safer and more efficient. As an example, we show that a drug that was halted recently in clinical development because of severe cardiotoxicity is a potent inhibitor of hERG in two different biological assays which could have been predicted using our new computational model. [ABSTRACT FROM AUTHOR]