Therapeutic Properties of PDMS Nanoparticles: A Promising New Drug Delivery Vehicle against Inflammatory Conditions.

BACKGROUND: Over the last few decades, there has been a stupendous change in the area of drug delivery using particulate delivery systems, with increasing focus on nanoparticles in recent times. Nanoparticles help to improve and alter the pharmacodynamic properties and pharmacokinetics of various types of drug molecules. These features help to protect the drug entity in the systemic circulation, access of the drug to the chosen sites, and to deliver the drug in a controlled and sustained rate at the site of action. OBJECTIVE: Nanoparticle based targeted delivery of anti-inflammatory drugs/signal modulatory agents to the cytoplasm or nuclei of the targeted cell can significantly enhance the precision and efficacy of intended therapeutic activity. To this end, we report ligand free, enhanced intra-nuclear delivery model of anti-inflammatory therapeutics via PDMS nanoparticles. METHODS: PDMS nanoparticles were prepared by sacrificial silica template-based approach and details of their characterization for suitability as a nanoparticle-based delivery material are detailed herein. RESULTS: Biological evaluation for compatibility was carried out and the results showed that the PDMS nanoparticle has no toxicity on RAW 264.7 cells in the concentration range of 10, 20, 40, 60, 80, 100 and 120 µg/mL in culture. Biocompatibility and absence of toxicity were determined by morphological examination and cell viability assays. Drug loading and release kinetics were carried out with the anti-inflammatory drug Diclofenac. CONCLUSION: In this paper, we clearly demonstrate the various aspects of nanoparticle articulation, characterization, effect of their characteristics and their applications as a non-toxic drug delivery molecule for its potential applications in therapeutic delivery of drugs for sustained release.

Correlation of Mast Cell and Angiogenesis in Oral Lichen Planus, Dysplasia (Leukoplakia), and Oral Squamous Cell Carcinoma.

OBJECTIVE: The aim of this study was to compare and correlate mast cell density (MCD) and microvessel density (MVD) between normal oral mucosa, oral lichen planus, various grades of dysplasia, and oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: The study comprised a total of 75 samples, of which 65 were archival tissue blocks of histopathologically confirmed cases, which included 10 cases of oral lichen planus, 25 cases of dysplasia (mild [n=10], moderate [n=10], and severe [n=5]), and 30 cases of OSCC (well differentiated [n=10], moderately differentiated [n=10], and poorly differentiated [n=10]), and 10 samples of normal oral mucosa. All the sections were immunohistochemically stained with anti-CD34 and counterstained with toluidine blue stain. Mean MCD and MVD were determined and analyzed using ANOVA test and compared between the lesions using Tukey HSD test. Pearson's correlation coefficient test was used to correlate these two factors between various lesions. RESULTS: Mean MCD and mean MVD were found to be increased in all the lesions compared to normal oral mucosa, and the values were statically significant. Overall, MCD and MVD showed a significant positive correlation (r=0.640). CONCLUSION: Increase of MCD and MVD and their positive correlation in all the lesions have emphasized their role in the pathogenesis and disease progression.

Hidden polymorphism of FAPbI3 discovered by Raman spectroscopy.

Formamidinium lead iodide (FAPbI3) can be used in its cubic, black form as a light absorber material in single-junction solar cells. It has a band-gap (1.5 eV) close to the maximum of the Shockley-Queisser limit, and reveals a high absorption coefficient. Its high thermal stability up to 320 °C has also a downside, which is the instability of the photo-active form at room temperature (RT). Thus, the black α-phase transforms at RT with time into a yellow non-photo-active δ-phase. The black phase can be recovered by annealing of the yellow state. In this work, a polymorphism of the α-phase at room temperature was found: as-synthesized (αi), degraded (αδ) and thermally recovered (αrec). They differ in the Raman spectra and PL signal, but not in the XRD patterns. Using temperature-dependent Raman spectroscopy, we identified a structural change in the αi-polymorph at ca. 110 °C. Above 110 °C, the FAPbI3 structure has undoubtedly cubic Pm3[combining macron]m symmetry (high-temperature phase: αHT). Below that temperature, the αi-phase was suggested to have a distorted perovskite structure with Im3[combining macron] symmetry. Thermally recovered FAPbI3 (αrec) also demonstrated the structural transition to αHT at the same temperature (ca. 110 °C) during its heating. The understanding of hybrid perovskites may bring additional assets in the development of new and stable structures.

Plasma Assisted Reduction of Graphene Oxide Films.

The past decade has seen enormous efforts in the investigation and development of reduced graphene oxide (GO) and its applications. Reduced graphene oxide (rGO) derived from GO is known to have relatively inferior electronic characteristics when compared to pristine graphene. Yet, it has its significance attributed to high-yield production from inexpensive graphite, ease of fabrication with solution processing, and thus a high potential for large-scale applications and commercialization. Amongst several available approaches for GO reduction, the mature use of plasma technologies is noteworthy. Plasma technologies credited with unique merits are well established in the field of nanotechnology and find applications across several fields. The use of plasma techniques for GO development could speed up the pathway to commercialization. In this report, we review the state-of-the-art status of plasma techniques used for the reduction of GO-films. The strength of various techniques is highlighted with a summary of the main findings in the literature. An analysis is included through the prism of chemistry and plasma physics.

Ten-Year Results of FAST: A Randomized Controlled Trial of 5-Fraction Whole-Breast Radiotherapy for Early Breast Cancer.

PURPOSE: Previous studies of hypofractionated adjuvant whole-breast radiotherapy for early breast cancer established a 15- or 16-fraction (fr) regimen as standard. The FAST Trial (CRUKE/04/015) evaluated normal tissue effects (NTE) and disease outcomes after 5-fr regimens. Ten-year results are presented. METHODS: Women ≥ 50 years of age with low-risk invasive breast carcinoma (pT1-2 pN0) were randomly assigned to 50 Gy/25 fr (5 weeks) or 30 or 28.5 Gy in 5 once-weekly fr of 6.0 or 5.7 Gy. The primary end point was change in photographic breast appearance at 2 and 5 years; secondary end points were physician assessments of NTE and local tumor control. Odds ratios (ORs) from longitudinal analyses compared regimens. RESULTS: A total of 915 women were recruited from 18 UK centers (2004-2007). Five-year photographs were available for 615/862 (71%) eligible patients. ORs for change in photographic breast appearance were 1.64 (95% CI, 1.08 to 2.49; P = .019) for 30 Gy and 1.10 (95% CI, 0.70 to 1.71; P = .686) for 28.5 Gy versus 50 Gy. α/ß estimate for photographic end point was 2.7 Gy (95% CI, 1.5 to 3.9 Gy), giving a 5-fr schedule of 28 Gy (95% CI, 26 to 30 Gy) estimated to be isoeffective with 50 Gy/25 fr. ORs for any moderate/marked physician-assessed breast NTE (shrinkage, induration, telangiectasia, edema) were 2.12 (95% CI, 1.55 to 2.89; P < .001) for 30 Gy and 1.22 (95% CI, 0.87 to 1.72; P = .248) for 28.5 Gy versus 50 Gy. With 9.9 years median follow-up, 11 ipsilateral breast cancer events (50 Gy: 3; 30 Gy: 4; 28.5 Gy: 4) and 96 deaths (50 Gy: 30; 30 Gy: 33; 28.5 Gy: 33) have occurred. CONCLUSION: At 10 years, there was no significant difference in NTE rates after 28.5 Gy/5 fr compared with 50 Gy/25 fr, but NTE were higher after 30 Gy/5 fr. Results confirm the published 3-year findings that a once-weekly 5-fr schedule of whole-breast radiotherapy can be identified that appears to be radiobiologically comparable for NTE to a conventionally fractionated regimen.

Anesthetic management of parturient with thoracic kyphoscoliosis, malaria and acute respiratory distress syndrome for urgent cesarean section.

The management of cesarean section in kyphoscoliotic patient is challenging. The respiratory changes and increased metabolic demands due to pregnancy may compromise the limited respiratory reserves in such patients. Presence of other comorbidities like malaria and respiratory tract infection will further compromise the effective oxygenation. We report a case of kyphoscoliosis along with malaria and acute respiratory distress syndrome for urgent cesarean section.

Biomechanical analysis of pediatric injuries and child restraint system.

Airbag related injuries to infants in rear facing child seats are common in frontal crashes. Several vehicular modifications such as deactivated passenger airbags, manual cut-off switches, depowered airbags and smart airbags have been advanced to mitigate the effect of airbag deployment on child seats. However, there is limited research effort to address the biomechanics of airbag injuries due to modification in child restraint systems. The purpose of this research is to evaluate the biomechanical effects of a protective barrier between the rear facing child restraint and the frontal passenger airbag of the vehicle. An experimental study was conducted using an Anthropometric Test Dummy (ATD) in a vehicular partial structure (buck). The rear facing child seat was placed in the right front passenger seat of the vehicle. The child seat was restrained using the three-point restraint in the vehicle. The six-month-old instrumented ATD was restrained in the child seat. The ATD was instrumented with the head tri-axial and two uni-axial linear accelerometers. The uni-axial linear acceleration was used to calculate the angular acceleration. Two different rear facing child seats, the standard rear facing infant seat and the rear facing infant seat inside the protective barrier structure were tested. In each test, the Head Injury Criteria (HIC) and angular head acceleration were measured. Results show that the HIC was reduced by 95% and the angular head acceleration was reduced by 85% by the protective barrier. The head injury values were well below the tolerance limit for the child with the barrier. The protective barrier deflected the airbag away from the ATD’s head and also acted as a shield to minimize airbag force on the child seat. In the typical infant seat, the airbag contacted the ATD’s head and exerted significant force on the child seat which rotated the seat rearward. These kinematic responses may explain the clinical observation of severe head injuries by infants in rear facing seats due to forces transmitted through the child seat and downward force from the top of the head. The present study is a first step in better understanding the injury mitigating aspects of the safety protective structure in child restraints.

Experimental biomechanical study of head injuries in lateral falls with skateboard helmet.

Traumatic brain injuries (TBI) are common in sports accidents. Helmets are generally known to provide protection to the head. However, the effectiveness of helmets in mitigating a TBI may be compromised due to the impact location and impact speed. Although it is known that the helmet decreases the linear head accelerations and the resulting head injury potential, to the best of our knowledge, limited research effort has been devoted to the study of the biomechanics of TBI in side impact conditions. The present work is designed to delineate the biomechanics of TBI in a fall impacting the parietal/temporal regions. A standing Hybrid III male dummy with pedestrian pelvis was used. The dummy was placed on a swinging platform for the fall simulation. The drop was achieved by stopping the platform with a block. The platform was swung from a predetermined height and stopped to allow the free fall of the dummy. The test was conducted with and without a skate board helmet. The impact on the dummy’s head was in the parietal and temporal regions. The head impact speed with the floor was approximately 24 kph (6.7 m/sec) The dummy was instrumented with tri-axial linear and tri-axial angular head accelerometers to measure the biomechanical injury responses. Results from three tests were compared. The linear head CG acceleration, Head Injury Criteria (HIC) and angular head accelerations were compared. Results suggest that the helmet reduced the linear head acceleration, HIC and angular head acceleration compared to the impact without a helmet. Although the linear head accelerations and HIC were reduced, the angular head accelerations even with the helmet were above nearly all proposed rotational head injury threshold in the literature. The higher angular head accelerations indicate a higher probability of concussion, acute subdural hematoma and diffuse axonal injuries. The present study is an additional step to better understand the biomechanics of TBI and the role of protective headgear systems in sports and recreational accidents.

Biomechanical analysis and injury prevention in off-highway vehicular crashes - biomed 2010.

Traffic safety has significantly improved over the past several decades reducing injury and fatality rates. However, there is a paucity of research effort directed to address the safety issues in off-highway vehicular crashes, specifically the all terrain/utility vehicular crashes. Rollover crashes are severe accidents leading to the increase in fatalities and injuries. The appropriate safety measures to contain occupants in vehicular compartments are crucial in mitigating injuries in rollover crashes. The purpose of this study is to delineate the occupant kinematics in simulated rollover conditions and to evaluate the injury prevention aspects. Two utility/all terrain vehicles were used. Each vehicle was placed on the motorized test equipment in the laboratory. The motorized dynamic rollover test equipment simulated the rollover environment in a controlled manner. Human surrogate models representing 1th percentile female, 50th percentile male and 96th percentile male were utilized in the testing. The multi-phase dynamic testing was conducted to quantify the occupant kinematic responses in foreseeable real world conditions. A total of 39 tests were conducted. The vehicle with belted surrogates was rolled 90 degrees at a roll rate up to 45 degrees/second. The excursion of the head, upper extremity and lower extremities beyond the plane of the vehicular structure was measured and compared between the two vehicles using two onboard cameras and three off-board cameras. Results show that the advanced restraint system with the occupant containment feature significantly reduced the occupant excursion. Such a significant reduction of occupant movement will better protect occupants in rollover off-highway accidents.

Biomechanical analysis of protective countermeasures in underride motor vehicle accidents - biomed 2009.

Traffic safety has been significantly improved over the past several decades reducing injury and fatality rates. However, there is a paucity of research effort to address the safety issues in underride accidents, specifically the side underride crashes. It is well known that the compromise of occupant space in the vehicle leads to a higher probability of serious or fatal injuries. A better understanding of occupant protection and mechanism of injuries involved in side underride accidents assists in the advancement of safety measures. The present work evaluates the injury potential to occupants during side underride crashes using the car-to-trailer crash methodology. Four crash tests were conducted into the side of a stationary trailer fitted with the side underride guard system (SURG). The SURG used in these tests is 25% lighter than the previous design. A 5th percentile hybrid III female dummy was placed in the driver seat and restrained with the three-point lap and shoulder harness. The anthropometric dummy was instrumented with a head triaxial accelerometer, a chest triaxal accelerometer, a load cell to measure neck force and moment, and a load cell to measure the femur force. The vehicle acceleration was measured using a traxial accelerometer in the rear center tunnel. High speed, standard video and still photos were taken. In all tests, the intrusion was limited to the front structure of the vehicle without any significant compromise to the occupant space. Results indicate that the resultant head and chest accelerations, head injury criterion (HIC), neck force and moment, and femur force were well below the injury tolerance. The present findings support the hypothesis that the SURG not only limits or eliminates the intrusion into the occupant space but also results in biomechanical injury values well below the tolerance limit in motor vehicle crashes.

Biomechanical analysis of child restraint system - biomed 2009.

The purpose of the study is to test the hypothesis that potential for the head injury to child occupants is reduced with energy absorbing foam in a rear facing restraint system. The traffic safety of the pediatric population is improved with the child restraint system. However, the child restraint is effective only if advanced protective features are incorporated. One of the protective features is the energy absorbing padding on the side wings of the child seat wherein the child would interact during the crash. A hybrid computer model of the child restraint system was developed using the commercially available MADYMO and LS-DYNA software. A rear facing child seat in the rear compartment of the vehicle was simulated. The 9 months old anthropometric dummy was modeled. The dummy was restrained in the child seat and the child seat was restrained using the lap and shoulder harness. Two computer models with and without the padding on the side wing were simulated. The input included the acceleration at the center of gravity of the vehicle and the door intrusion into the vehicular interior and the child restraint system. Results indicate that the lack of padding allowed the child's head to interact with the side wing in a concentrated manner while the padding allowed distributed contact to the head area. The padding also retained the head within the confines of the child seat with no exposure to outside environment. The head injury parameters (Head Injury Criteria and Angular Acceleration) were reduced two to three times due to padding on the extended side wing. The present study is an additional step towards a better understanding of the injury biomechanics of pediatric population involved in motor vehicle crashes.

Biomechanics of under ride motor vehicle crashes.

The present study evaluates the biomechanical aspects of injuries sustained by occupants of passenger cars during collisions with the trailer portion of a tractor/trailer rig. In such collisions, the occupants of the passenger car often sustain serious injuries when the passenger car passes beneath the trailer. This process by which the car "underrides" the trailer occurs due to the mismatch in height between the lowermost edge of the trailer and the crash mitigation structures in the vehicle. The study outlines a car-to-trailer crash testing methodology used to determine the effectiveness of one potential trailer underride guard in preventing serious injuries to occupants of passenger cars. The results from initial crash tests suggest that occupants of cars that collide with the unguarded sides of trailers are at a high risk of serious injury to the head, neck, and chest due the large intrusion of the roof and roof support structures into the occupant compartment. Testing of a trailer fitted with an underride guard showed that occupants of vehicles that collide with the sides of trailers that have been modified to engage the energy absorbing structures of passenger cars are exposed to a smaller risk of injury.

Effect of roof strength in injury mitigation during pole impact.

Motor vehicle accidents involving pole impacts often result in serious head and neck injuries to occupants. Pole impacts are typically associated with rollover and side collisions. During such events, the roof structure is often deformed into the occupant survival space. The existence of a strengthened roof structure would reduce roof deformation and accordingly provide better protection to occupants. The present study examines the effect of reinforced (strengthened) roofs using experimental crash study and computer model simulation. The experimental study includes the production cab structure of a pickup truck. The cab structure was loaded using an actual telephone pole under controlled laboratory conditions. The cab structure was subjected to two separate load conditions at the A-pillar and door frame. The contact force and deformation were measured using a force gauge and potentiometer, respectively. A computer finite element model was created to simulate the experimental studies. The results of finite element model matched well with experimental data during two different load conditions. The validated finite element model was then used to simulate a reinforced roof structure. The reinforced roof significantly reduced the structural deformations compared to those observed in the production roof. The peak deformation was reduced by approximately 75% and peak velocity was reduced by approximately 50%. Such a reduction in the deformation of the roof structure helps to maintain a safe occupant survival space.

Biomechanical evaluation of occupant anthropometry during frontal collisions.

The present study examines the biomechanical implications of 3-point lap/shoulder seat belts and frontal air bags to the injury probabilities for occupants of varying anthropometry, during frontal collisions. Using Mathematical Dynamic Modeling (MADYMO) software, a variety of simulated frontal crash tests were conducted to evaluate the effectiveness of seat belts and air bags in reducing probability of injury to different sized occupants. The simulations included virtual models of the 5th percentile female, 50th percentile male, and 95th percentile male to represent three occupant size classes. The test matrix paired each of these dummy sizes with four restraint system configurations. The configurations examined were seat belt only, air bag only, both seat belt and air bag, and none. Each of the simulated crashes was modeled to replicate a direct (12 O'clock) frontal collision with a total change in velocity of 56.3kph. Likelihood of serious injury was determined through the calculation of Head Injury Criteria (HIC,36ms), angular acceleration of the head center of gravity, and the Nij neck injury criteria. The results generally suggested that air bags produce a more significant reduction in HIC for larger belted occupants than they do for smaller belted occupants, and that whether belted or not, smaller occupants received the largest reduction in head CG angular acceleration due to the existence of an air bag. Though clear trends were not noted in the neck injury values, it was noted that the simulations with out air bags produced two results that failed the injury criterion, while no serious neck injuries would be expected based on the values produced in the simulations with air bags. The study suggested that a properly timed air bag deployment can reduce injury potential for all occupants of all sizes, but that the magnitude of this benefit is dependent on anthropometry.