Prophylactic Use of Pentoxifylline and Tocopherol for Prevention of Osteoradionecrosis of the Jaw after Dental Extraction in Post-Radiated Oral and Oropharyngeal Cancer Patients: An Initial Case Series.

Osteoradionecrosis of the jaw is a morbid complication of radiotherapy in patients with oral and oropharyngeal cancers that may be precipitated by dental extractions. Pentoxifylline and tocopherol (PENTO) has been utilized in the management of osteoradionecrosis and as prophylaxis for post-radiated head and neck oncology patients requiring an invasive dental procedure. This observational study aims to report the outcome of the prophylactic use of PENTO in the prevention of osteoradionecrosis of the jaw after dental extractions in post-radiated oral and oropharyngeal cancer patients and to review the current literature on this topic. Four post-radiated oral and oropharyngeal oncology patients were referred to the dental oncology clinic of the University Dental Practice, University of Tennessee Health Sciences Center for dental extractions. All four patients were prescribed pentoxifylline 400 mg BID (twice a day) and tocopherol 400 IU BID (oral tablets) for 2 weeks before extraction(s) and for 6 weeks after extraction(s). All patients were followed up every week after the second week post-extraction if feasible until the extraction site(s) healed (covered by mucosa). The assessment endpoint was defined as 6 weeks post-extraction with the outcomes assessed as using four categories determined by the area of exposed bone: complete healing (complete mucosal coverage of extraction site); partial healing (reduction in size of extraction site); no change; and progression (increase in size of the extraction site). At the assessment endpoint, all patients had complete healing of all extraction sites. The ORN rate at the patient level (0/4) and individual tooth level (0/8) was 0%. All patients tolerated the PENTO medications and no adverse effects from the use of these medications were reported. This limited study in addition to the other reviewed studies estimates the rate of ORN at the patient level as 3.2% (14/436) for post-radiated head and neck oncology patients after dental extractions/invasive oral procedures. In conclusion, this PENTO regimen can reduce/prevent the incidence of ORN in post-radiated head and neck oncology patients. This safe and cost-effective protocol (PENTO regimen) should be further evaluated as prophylaxis for post-radiated head and neck oncology patients requiring an invasive dental procedure. We recommend large prospective studies to be carried out to further validate these findings.

Effect of whitening dentifrices on toothbrush abrasion on composites.

PURPOSE: To evaluate the laboratory long-term effect of various whitening dentifrices on the surface roughness of two brands of resin composite (TPH ST, Filtek Bulk Fill One) using a mechanical toothbrushing simulation. METHODS: Thirty-two samples each of Filtek and TPH were fabricated in ring molds 10 x 1 mm. Samples were randomly grouped (n=8; four groups), according to dentifrice used; Crest 3D, Optic White, Hello (charcoal), and Aim as control. Samples were brushed in mixed solutions containing deionized water and dentifrice at 150 gf for 10,000x with rotation to ensure uniform brushing. Surface roughness was measured both before (baseline) and after the mechanical toothbrushing simulation using a stylus profilometer. Data collected was compared independently for each treatment using two-way ANOVA and SNK with α< 0.05 for significance. RESULTS: The data showed that TPH was more susceptible to the abrasive nature of three of the whitening dentifrices tested [Crest 3D, Optic White, and Hello (charcoal) ]. Filtek also exhibited significant susceptibility to the abrasive nature of Hello. Aim showed the least or minimal amount of abrasion. CLINICAL SIGNIFICANCE: TPH ST composite was more susceptible to the abrasive nature of the three whitening dentifrices tested [Crest 3D, Optic White, and Hello (charcoal)]. Filtek also exhibited significant susceptibility to the abrasive nature of Hello. Aside from the data supporting the clinical efficacy of TPH compared to Filtek, clinicians should inform patients of the abrasive capacity of all whitening dentifrices, especially those that are charcoal based.

The Genetic Code Kit: An Open-Source Cell-Free Platform for Biochemical and Biotechnology Education.

Teaching the processes of transcription and translation is challenging due to the intangibility of these concepts and a lack of instructional, laboratory-based, active learning modules. Harnessing the genetic code in vitro with cell-free protein synthesis (CFPS) provides an open platform that allows for the direct manipulation of reaction conditions and biological machinery to enable inquiry-based learning. Here, we report our efforts to transform the research-based CFPS biotechnology into a hands-on module called the "Genetic Code Kit" for implementation into teaching laboratories. The Genetic Code Kit includes all reagents necessary for CFPS, as well as a laboratory manual, student worksheet, and augmented reality activity. This module allows students to actively explore transcription and translation while gaining exposure to an emerging research technology. In our testing of this module, undergraduate students who used the Genetic Code Kit in a teaching laboratory showed significant score increases on transcription and translation questions in a post-lab questionnaire compared with students who did not participate in the activity. Students also demonstrated an increase in self-reported confidence in laboratory methods and comfort with CFPS, indicating that this module helps prepare students for careers in laboratory research. Importantly, the Genetic Code Kit can accommodate a variety of learning objectives beyond transcription and translation and enables hypothesis-driven science. This opens the possibility of developing Course-Based Undergraduate Research Experiences (CUREs) based on the Genetic Code Kit, as well as supporting next-generation science standards in 8-12th grade science courses.

Unlocking Applications of Cell-Free Biotechnology through Enhanced Shelf Life and Productivity of E. coli Extracts.

Cell-free protein synthesis (CFPS) is a platform biotechnology that enables a breadth of applications. However, field applications remain limited due to the poor shelf-stability of aqueous cell extracts required for CFPS. Lyophilization of E. coli extracts improves shelf life but remains insufficient for extended storage at room temperature. To address this limitation, we mapped the chemical space of ten low-cost additives with four distinct mechanisms of action in a combinatorial manner to identify formulations capable of stabilizing lyophilized cell extract. We report three key findings: (1) unique additive formulations that maintain full productivity of cell extracts stored at 4 °C and 23 °C; (2) additive formulations that enhance extract productivity by nearly 2-fold; (3) a machine learning algorithm that provides predictive capacity for the stabilizing effects of additive formulations that were not tested experimentally. These findings provide a simple and low-cost advance toward making CFPS field-ready and cost-competitive for biomanufacturing.

Ultracompact Minihalos as Probes of Inflationary Cosmology.

Cosmological inflation generates primordial density perturbations on all scales, including those far too small to contribute to the cosmic microwave background. At these scales, isolated ultracompact minihalos of dark matter can form well before standard structure formation, if the perturbations have sufficient amplitude. Minihalos affect pulsar timing data and are potentially bright sources of gamma rays. The resulting constraints significantly extend the observable window of inflation in the presence of cold dark matter, coupling two of the key problems in modern cosmology.

Gravitational wave consistency relations for multifield inflation.

We study the tensor spectral index n(t) and the tensor-to-scalar ratio r in the simplest multifield extension to single-field, slow-roll inflation models. We show that multifield models with potentials V∼[under ∑]iλ_{i}|ϕ_{i}|^{p} have different predictions for n(t)/r than single-field models, even when all the couplings are equal λ_{i}=λ_{j}, due to the probabilistic nature of the fields' initial values. We analyze well-motivated prior probabilities for the λ_{i} and initial conditions to make detailed predictions for the marginalized probability distribution of n(t)/r. With O(100) fields and p>3/4, we find that n(t)/r differs from the single-field result of n(t)/r=-1/8 at the 5σ level. This gives a novel and testable prediction for the simplest multifield inflation models.

Simple predictions from multifield inflationary models.

We explore whether multifield inflationary models make unambiguous predictions for fundamental cosmological observables. Focusing on N-quadratic inflation, we numerically evaluate the full perturbation equations for models with 2, 3, and O(100) fields, using several distinct methods for specifying the initial values of the background fields. All scenarios are highly predictive, with the probability distribution functions of the cosmological observables becoming more sharply peaked as N increases. For N=100 fields, 95% of our Monte Carlo samples fall in the ranges ns∈(0.9455,0.9534), α∈(-9.741,-7.047)×10-4, r∈(0.1445,0.1449), and riso∈(0.02137,3.510)×10-3 for the spectral index, running, tensor-to-scalar ratio, and isocurvature-to-adiabatic ratio, respectively. The expected amplitude of isocurvature perturbations grows with N, raising the possibility that many-field models may be sensitive to postinflationary physics and suggesting new avenues for testing these scenarios.

Multidisciplinary management of placenta percreta complicated by embolic phenomena.

Hemorrhage and thrombosis are major causes of maternal mortality. This case discusses the management of a woman with placenta percreta complicated by intraoperative pulmonary embolism. A 39-year-old gravida 3 with two previous cesarean deliveries presented at 34 weeks of gestation with an antepartum hemorrhage. Magnetic resonance imaging confirmed placenta percreta. The multidisciplinary group including obstetricians, gynecological oncologists, interventional radiologists and anesthesiologists developed a delivery plan. Cesarean delivery was performed with internal iliac artery occlusion and embolization catheters in place. After the uterine incision our patient experienced acute hypotension and hypoxia associated with a drop in the end-tidal carbon dioxide and sinus tachycardia. She was resuscitated and the uterus closed with the placenta in situ. Postoperatively, uterine bleeding was arrested by immediate uterine artery embolization. With initiation of embolization, hypotension and hypoxia recurred. Oxygenation and hemodynamics slowly improved, the case continued and the patient was extubated uneventfully at the end of the procedure. Computed tomography revealed multiple pulmonary emboli. The patient was anticoagulated with low-molecular-weight heparin and returned six weeks later for hysterectomy. Placenta percreta with invasion into the bladder can be catastrophic if not recognized before delivery. The chronology of events suggests that this may have been amniotic fluid emboli. An intact placenta with abnormal architecture, such as placenta percreta, may increase the risk of amniotic fluid embolus. The clinical findings and co-existing filling defects on computed tomography may represent a spectrum of amniotic fluid embolism syndrome.

Management of a parturient with an acute exacerbation of idiopathic pulmonary haemosiderosis and posterior spinal instrumentation.

Idiopathic pulmonary haemosiderosis (IPH) is a rare condition associated with diffuse alveolar haemorrhage and pulmonary fibrosis. We describe the anaesthetic management of a parturient with a history of posterior spinal fusion presenting with an acute exacerbation of IPH necessitating vaginal delivery at 34 weeks gestation. We used a spinal catheter for labour analgesia and bilevel positive airway pressure (BIPAP) ventilation to improve oxygenation during labour. An arterial line sited to allow frequent arterial blood gas sampling also facilitated continuous cardiac output monitoring. The use of a carefully titrated neuraxial block for analgesia, in conjunction with BIPAP, was associated with minimal haemodynamic and respiratory compromise during labour in this patient.

Evaluation of the effect of endovascular options on infrarenal abdominal aortic aneurysm repair.

Endovascular devices designed to exclude flow to infrarenal abdominal aortic aneurysms (AAA) were approved by the Food and Drug Administration in the United States in 1999. This action allowed widespread use of this technology for AAA exclusion. The purpose of this report is to examine trends for use of these modalities, rates of rupture of AAA, and to compare results of open AAA repair with endovascular repair. Results were collected for all hospitals, except for Veterans Administration hospitals, by a state-wide repository. Data for the years 1996 through 1998 and 2001 through 2002 were evaluated, and data from 1999 through 2000 were excluded because no separate codes were available to distinguish between open and endovascular repair. The information gathered is based on the All Patient Refined Diagnostic Related Group (APRDRG; 3M, St. Paul, MN). An average of 718 open, elective AAA was performed between 1996 and 1998. This dropped to 503 open repairs from 2001 to 2002 (P < 0.005). During that same interval, 308 endovascular elective AAA repairs were performed, therefore the total rate of elective repair increased by 100. The average rate of ruptured AAA repairs from 1996 to 1998 was 121 per year, and this dropped to 89 from 2001 to 2002 (P < 0.005). The mortality of open AAA repair during the 1996 to 1998 and 2001 to 2002 intervals was unchanged (4.7%). Mortality from endovascular AAA repair between 2001 and 2002 was 1.9 per cent (P = 0.003). Major morbidity was 14.5 per cent for open, elective AAA repair and 6.3 per cent for endovascular elective repair from 2001 to 2002 (P < 0.001). These data suggest that the advent of endovascular AAA repair has contributed to a reduction in the rate of ruptured AAA repairs, an increase in total procedures performed, and a significant decrease in perioperative deaths and major complications when compared with open AAA repair.

The effect of perineural anesthesia on infrared thermographic images of the forelimb digits of normal horses.

Infrared thermography is an imaging modality gaining popularity as a diagnostic aid in the evaluation of equine lameness. Anecdotal reports of skin hyperthermia induced by local anesthesia, detected by thermography, have been made; however, no controlled studies have been reported. The purpose of this study was to examine the effects of perineural anesthesia on infrared thermographic images of the forelimb digits in normal horses. After environmental acclimation, infrared thermographs were made at intervals of 0, 5, 10, 15, 30, and 45 min from administration of mepivacaine hydrochloride or phosphate buffered saline in 6 adult horses with no clinical evidence of abnormality of the forelimb digits. The mean limb surface temperatures were compared by 2-factor ANOVA. Results indicated no significant difference between treatments, time after injection, or an interaction of time and treatment. Infrared thermographic imaging apparently can be performed within 45 min of perineural mepivacaine hydrochloride anesthesia without risk of artifactual changes in limb surface temperature.

Effect of long-duration spaceflight on postural control during self-generated perturbations.

This report is the first systematic evaluation of the effects of prolonged weightlessness on the bipedal postural control processes during self-generated perturbations produced by voluntary upper limb movements. Spaceflight impacts humans in a variety of ways, one of which is compromised postflight postural control. We examined the neuromuscular activation characteristics and center of pressure (COP) motion associated with arm movement of eight subjects who experienced long-duration spaceflight (3--6 mo) aboard the Mir space station. Surface electromyography, arm acceleration, and COP motion were collected while astronauts performed rapid unilateral shoulder flexions before and after spaceflight. Subjects generally displayed compromised postural control after flight, as evidenced by modified COP peak-to-peak anterior-posterior and mediolateral excursion, and pathlength relative to preflight values. These changes were associated with disrupted neuromuscular activation characteristics, particularly after the completion of arm acceleration (i.e., when subjects were attempting to maintain upright posture in response to self-generated perturbations). These findings suggest that, although the subjects were able to assemble coordination modes that enabled them to generate rapid arm movements, the subtle control necessary to maintain bipedal equilibrium evident in their preflight performance is compromised after long-duration spaceflight.

Sex and the Barnum effect: rationality versus helpfulness.

In 1998 Piper-Terry and Downey found that women accepted friends' bogus test interpretations more readily than did men and the researchers attributed this to women's helpfulness. Layne countered that women are more open and thus rationally expected their friends' interpretations to be more accurate. Later Downey asked participants how accurately they believed their friends could describe their personalities. Although this pilot study's sensitivity to differences was low, the women's accuracy ratings still tended to exceed those of men (p < .06) as Layne predicted. This may suggest that the rationality hypothesis is better supported than the female-helpfulness hypothesis.

Posture, locomotion, spatial orientation, and motion sickness as a function of space flight.

This article summarizes a variety of newly published findings obtained by the Neuroscience Laboratory, Johnson Space Center, and attempts to place this work within a historical framework of previous results on posture, locomotion, motion sickness, and perceptual responses that have been observed in conjunction with space flight. In this context, we have taken the view that correct transduction and integration of signals from all sensory systems is essential to maintaining stable vision, postural and locomotor control, and eye-hand coordination as components of spatial orientation. The plasticity of the human central nervous system allows individuals to adapt to altered stimulus conditions encountered in a microgravity environment. However, until some level of adaptation is achieved, astronauts and cosmonauts often experience space motion sickness, disturbances in motion control and eye-hand coordination, unstable vision, and illusory motion of the self, the visual scene, or both. Many of the same types of disturbances encountered in space flight reappear immediately after crew members return to earth. The magnitude of these neurosensory, sensory-motor and perceptual disturbances, and the time needed to recover from them, tend to vary as a function of mission duration and the space travelers prior experience with the stimulus rearrangement of space flight. To adequately chart the development of neurosensory changes associated with space flight, we recommend development of enhanced eye movement systems and body position measurement. We also advocate the use of a human small radius centrifuge as both a research tool and as a means of providing on-orbit countermeasures that will lessen the impact of living for long periods of time with out exposure to altering gravito-inertial forces.

Using factor analysis to identify neuromuscular synergies during treadmill walking.

Neuroscientists are often interested in grouping variables to facilitate understanding of a particular phenomenon. Factor analysis is a powerful statistical technique that groups variables into conceptually meaningful clusters, but remains underutilized by neuroscience researchers presumably due to its complicated concepts and procedures. This paper illustrates an application of factor analysis to identify coordinated patterns of whole-body muscle activation during treadmill walking. Ten male subjects walked on a treadmill (6.4 km/h) for 20 s during which surface electromyographic (EMG) activity was obtained from the left side sternocleidomastoid, neck extensors, erector spinae, and right side biceps femoris, rectus femoris, tibialis anterior, and medial gastrocnemius. Factor analysis revealed 65% of the variance of seven muscles sampled aligned with two orthogonal factors, labeled 'transition control' and 'loading'. These two factors describe coordinated patterns of muscular activity across body segments that would not be evident by evaluating individual muscle patterns. The results show that factor analysis can be effectively used to explore relationships among muscle patterns across all body segments to increase understanding of the complex coordination necessary for smooth and efficient locomotion. We encourage neuroscientists to consider using factor analysis to identify coordinated patterns of neuromuscular activation that would be obscured using more traditional EMG analyses.

The use of in-flight foot pressure as a countermeasure to neuromuscular degradation.

The purpose of this study was to determine whether applying foot pressure to unrestrained subjects during space flight could enhance the neuromuscular activation associated with rapid arm movements. Four men performed unilateral arm raises while wearing--or not wearing--specially designed boots during a 81- or 115-day space flight. Arm acceleration and surface EMG were obtained from selected lower limb and trunk muscles. Pearson r coefficients were used to evaluate similarity in phasic patterns between the two in-flight conditions. In-flight data also were magnitude normalized to the mean voltage value of the muscle activation waveforms obtained during the no-foot-pressure condition to facilitate comparison of activation amplitude between the two in-flight conditions. Foot pressure enhanced neuromuscular activation and somewhat modified the phasic features of the neuromuscular activation during the arm raises.

Adaptation of neuromuscular activation patterns during treadmill walking after long-duration space flight.

The precise neuromuscular control needed for optimal locomotion, particularly around heel strike and toe off, is known to he compromised after short duration (8- to 15-day) space flight. We hypothesized here that longer exposure to weightlessness would result in maladaptive neuromuscular activation during postflight treadmill walking. We also hypothesized that space flight would affect the ability of the sensory-motor control system to generate adaptive neuromuscular activation patterns in response to changes in visual target distance during postflight treadmill walking. Seven crewmembers, who completed 3- to 6-month missions, walked on a motorized treadmill while visually fixating on a target placed 30 cm (NEAR) or 2 m (FAR) from the subject's eyes. Electronic foot switch data and surface electromyography were collected from selected muscles of the right lower limb. Results indicate that the phasic features of neuromuscular activation were moderately affected and the relative amplitude of activity in the tibialis anterior and rectus femoris around toe off changed after space flight. Changes also were evident after space flight in how these muscles adapted to the shift in visual target distance.

Physical examination during space flight.

OBJECTIVE: To develop techniques for conducting a physical examination in microgravity and to describe and document the physiologic changes noted with use of a modified basic physical examination. DESIGN: On the basis of data gathered from physical examinations on KC-135 flights, three physical variables were assessed serially in astronauts during two shuttle missions (of 8- and 10-day duration, respectively). Preflight, in-flight, and postflight examinations were conducted by trained physician-astronauts or flight surgeons, who used this modified examination. MATERIAL AND METHODS: Five male and two female crewmembers participated in the "hands-on" physical examination of all physiologic systems except the genitourinary system. Level of edema, intensity of bowel sounds, and peripheral reflexes were assessed and graded. RESULTS: This investigation identified unique elements of a physical examination performed during space flight that will assist in the development of standard methods for conducting examinations of astronauts in weightlessness. In addition, demonstrable changes induced by microgravity were noted in most physiologic systems examined. CONCLUSION: The data support the hypothesis that the microgravity examination differs from that conducted on earth or in a 1g environment. In addition, alterations in the physiologic response can be detected with use of hands-on technique. These data are invaluable in the development of optimal medical care for humans in space.

A review of adaptive change in musculoskeletal impedance during space flight and associated implications for postflight head movement control.

We present a review of converging sources of evidence which suggest that the differences between loading histories experienced in 1-g and weightlessness are sufficient to stimulate adaptation in mechanical impedance of the musculoskeletal system. As a consequence of this adaptive change we argue that we should observe changes in the ability to attenuate force transmission through the musculoskeletal system both during and after space flight. By focusing attention on the relation between human sensorimotor activity and support surfaces, the importance of controlling mechanical energy flow through the musculoskeletal system is demonstrated. The implications of such control are discussed in light of visual-vestibular function in the specific context of head and gaze control during postflight locomotion. Evidence from locomotory biomechanics, visual-vestibular function, ergonomic evaluations of human vibration, and specific investigations of locomotion and head and gaze control after space flight, is considered.

Neuromuscular activation patterns during treadmill walking after space flight.

Astronauts adopt a variety of neuromuscular control strategies during space flight that are appropriate for locomoting in that unique environment, but are less than optimal upon return to Earth. We report here the first systematic investigation of potential adaptations in neuromuscular activity patterns associated with postflight locomotion. Astronaut-subjects were tasked with walking on a treadmill at 6.4 km/h while fixating a visual target 30 cm away from their eyes after space flights of 8-15 days. Surface electromyography was collected from selected lower limb muscles and normalized with regard to mean amplitude and temporal relation to heel strike. In general, high correlations (more than 0.80) were found between preflight and postflight activation waveforms for each muscle and each subject: however relative activation amplitude around heel strike and toe off was changed as a result of flight. The level of muscle cocontraction and activation variability, and the relationship between the phasic characteristics of the ankle musculature in preparation for toe off also were altered by space flight. Subjects also reported oscillopsia during treadmill walking after flight. These findings indicate that, after space flight, the sensory-motor system can generate neuromuscular-activation strategies that permit treadmill walking, but subtle changes in lower-limb neuromuscular activation are present that may contribute to increased lower limb kinematic variability and oscillopsia also present during postflight walking.