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Autonomic neuropathies

A limited autonomic neuropathy may underlie some unusual clinical syndromes, including the postural tachycardia syndrome, pseudo-obstruction syndrome, heat intolerance, and perhaps chronic fatigue syndrome. Antibodies to autonomic structures are common in diabetes, but their specificity is unknown. The presence of autonomic failure worsens prognosis in the diabetic state. Some autonomic neuropathies are treatable. Familial amyloid polyneuropathy may respond to liver transplantation. There are anecdotal reports of acute panautonomic neuropathy responding to intravenous gamma globulin. Orthostatic hypotension may respond to erythropoietin or midodrine.

Non-NASA Center↗

Calibration Experiments Conducted for Noninvasive Blood Glucose Sensing Through the Eye

There are more than 16 million diabetics in the United States and more than 100 million worldwide. Diabetes can lead to severe complications over time such as blindness, renal and cardiovascular diseases, and peripheral neuropathy in the limbs. Poor blood circulation in diabetics can lead to gangrene and the subsequent amputation of extremities. In addition, this pathology is the fourth leading cause of death in the United States. The most effective way to manage diabetes is frequent blood glucose monitoring performed by the patients themselves. However, because of pain, inconvenience, and the fear of developing infections from finger-prick blood tests or implants, many patients monitor their blood glucose levels less frequently than is recommended by their physicians. Therefore, a noninvasive, painless, and convenient method to monitor blood glucose would greatly benefit diabetics. Likewise, detecting, preventing, and treating the untoward effects of prolonged space travel (e.g., a human mission to Mars) in real-time requires the development of noninvasive diagnostic technologies that are compact and powerful. As a "window to the body," the eye offers the opportunity to use light in various forms to detect ocular and systemic abnormalities long before clinical symptoms appear and to help develop preventative and therapeutic countermeasures early. The noninvasive feature of these technologies permits frequent repetition of tests, enabling an evaluation of the response to therapy.

Ansari, Rafat R.↗

Protein turnover in adipose tissue from fasted or diabetic rats

Protein synthesis and degradation in vitro were compared in epididymal fat pads from animals deprived of food for 48 h or treated 6 or 12 days prior with streptozotocin to induce diabetes. Although both fasting and diabetes led to depressed (-24 to -57 percent) protein synthesis, the diminution in protein degradation (-63 to -72 percent) was even greater, so that net in vitro protein balance improved dramatically. Insulin failed to inhibit protein degradation in fat pads of these rats as it does for fed animals. Although insulin stimulated protein synthesis in fat pads of fasted and 12 day diabetic rats, the absolute change was much smaller than that seen in the fed state. The inhibition of protein degradation by leucine also seems to be less in fasted animals, probably because leucine catabolism is slower in fasting. These results show that fasting and diabetes may improve protein balance in adipose tissue but diminish the regulatory effects of insulin.

Tischler, Marc E.↗

Obesity-related cardiovascular risk factors: intervention recommendations to decrease adolescent obesity

The incidence of adolescent obesity is increasing dramatically in the United States with associated risks of hypertension, adverse lipid profiles, and Type II diabetes. Unless reversed, this trend predicts an epidemic of adult cardiovascular disease. Interventions at home, at school, and in the community are required to empower teens to increase physical activity and to modify eating habits. This article describes assessment for obesity-related health problems as well as scientific guidelines and research-based intervention strategies to decrease obesity in adolescents.

Review↗

Ocular static and dynamic light scattering: a noninvasive diagnostic tool for eye research and clinical practice

The noninvasive techniques of static and dynamic light scattering are emerging as valuable diagnostic tools for the early detection of ocular and systemic diseases. These include corneal abnormalities, pigmentary dispersion syndrome, glaucoma, cataract, diabetic vitreopathy, and possibly macular degeneration. Systemic conditions such as diabetes and possibly Alzheimer's disease can potentially be detected early via ocular tissues. The current state of development of these techniques for application to ophthalmic research and ultimately clinical practice is reviewed. (c) 2004 Society of Photo-Optical Instrumentation Engineers.

Review↗

Dynamic Light Scattering of Diabetic Vitreopathy

Diabetes induces pathology throughout the body via nonenzymatic glycation of proteins. Vitreous, which is replete with type 11 collagen, undergoes significant changes in diabetes. The resultant diabetic vitreopathy plays an important role in diabetic retinopathy. Detecting these molecular changes could provide insight into diabetic eye disease as well as molecular effects elsewhere in the body. Human eyes were obtained at autopsy and studied in the fresh, unfixed state. Sclera, choroid, and retina were dissected off the vitreous for dark-field slit microscopy and dynamic light scattering (DLS). For the former, the entire vitreous was exposed. For the latter, only a window at the equator was dissected in some specimens, and the anterior segment was removed leaving the posterior lens capsule intact in others. DLS was performed to determine particle sizes at multiple sites 0.5 mm apart, spanning the globe at the equator (window dissections) and along the antero-posterior axis. Dark-field slit microscopy in diabetic subjects detected findings typical of age-related vitreous degeneration, but at much younger ages than nondiabetic controls. Noninvasive DLS measurements found a greater heterogeneity and larger particle sizes in vitreous of subjects with diabetes as compared to age-matched controls. DLS can detect and quantify the early molecular effects that cause vitreous collagen fibrils to cross-link and aggregate. This could provide valuable insight into ocular and systemic effects of hyperglycemia, because the molecular changes in diabetic vitreopathy could serve as an index of such effects throughout the body. In addition to the diagnostic implications, this methodology could provide a rapid, reproducible way to monitor the response to therapy with novel agents intended to prevent the complications of diabetes on a molecular level.

Sebag, J.↗

Correlated Changes in Retinal Thickness and Visuomotor Function in Asymptomatic Plaquenil Toxicity Patients

We have previously shown that a 5-minute eye-movement test can capture a number of largely independent “oculometric” parameters of human visual/visuomotor function (Liston & Stone, 2014). This test has been successfully used to characterize mild neural impairment due to traumatic brain injury, sleep and circadian disruption, and alcohol consumption (Liston et al., 2017; Stone et al, 2019; Tyson et al, 2021). Here, we extend this approach to study patients at risk of progressive posterior-segment illness to see how oculometrics relate to standard clinical ophthalmological measures. Five female patients (<20:40 BCVA, 34-60 years old) undergoing hydroxychloroquine treatment (2-7mg/kg/day for 10-23 years for rheumatologic illness) have participated thus far. Under monocular viewing conditions in randomized order, they tracked a moving spot undergoing radial step-ramp motion in one of 90 randomized directions, at one of 5 randomized speeds, starting at random times (for details, see Stone et al, 2019). We computed nine independent oculometrics (latency, initial acceleration, steady-state gain, proportion smooth, saccadic rate, saccadic amplitude, direction noise, speed responsiveness, and speed noise). Spectral-domain optical coherence tomography (Zeiss, Dublin, CA) was used to measure the average thickness of the nine Early Treatment Diabetic Retinopathy Study macular sectors from the internal limiting membrane to the retinal pigmented epithelium. We used Pearson’s correlation between retinal thickness and our oculometrics with t-statistics to test separate one-sided hypotheses across 10 retinae. Our preliminary analysis found significant changes in several different aspects of visuomotor performance. Most notably, latency increased, initial acceleration decreased, and steady-state pursuit gain decreased as retinal thickness decreased (r2 = 0.364, 0.579, and 0.692; one-tailed P = 0.032, 0.005, and 0.001, respectively). Speed responsiveness appeared to decrease, but this effect was marginal for our current sample (r2 = 0.253, P = 0.069). Lastly, direction discrimination and saccadic behavior appeared unchanged. We conclude that oculometrics may provide sensitive measures of changes in retinal thickness. More importantly, oculometrics have the potential to detect impairment before it becomes evident with standard clinical imaging tools, while also providing insight into the behavioral implications of any resulting deficits in visual/visuomotor function.

eye movements↗

New optical scheme for a polarimetric-based glucose sensor

A new optical scheme to detect glucose concentration in the aqueous humor of the eye is presented. The ultimate aim is to apply this technique in designing a new instrument for, routinely and frequently, noninvasively monitoring blood glucose levels in diabetic patients without contact (no index matching) between the eye and the instrument. The optical scheme exploits the Brewster reflection of circularly polarized light off of the lens of the eye. Theoretically, this reflected linearly polarized light on its way to the detector is expected to rotate its state of polarization, owing to the presence of glucose molecules in the aqueous humor of a patient's eye. An experimental laboratory setup based on this scheme was designed and tested by measuring a range of known concentrations of glucose solutions dissolved in water. (c) 2004 Society of Photo-Optical Instrumentation Engineers.

Evaluation Studies↗

A New Optical Scheme for a Polarimetric-Based Glucose Sensor

We describe a new optical scheme to perform polarimetric measurements to detect glucose concentration in the aqueous humor of a model eye. The ultimate aim is to apply this technique in designing a new instrument for measuring glucose levels in diabetic patients routinely, frequently, and non-invasively. The scheme exploits the Brewsterreflection of circularly polarized light off of the lens of the eye. Theoretically, this backreflected linearly polarized light on its way to the detector is expected to rotate its state of polarization due to the presence of glucose molecules in the aqueous humor of patients. An experimental laboratory setup based on this scheme was designed and tested by measuring a range of known concentration of glucose solutions dissolved in water.

Ansari, Rafat R.↗

Fine-Scale Comparison of TOMS Total Ozone Data with Model Analysis of an Intense Midwestern Cyclone

High-resolution (approx. 40 km) along-track total column ozone data from the Total Ozone Mapping Spectrometer (TOMS) instrument are compared with a high-resolution mesoscale numerical model analysis of an intense cyclone in the Midwestern United States. Total ozone increased by 100 DU (nearly 38%) as the TOMS instrument passed over the associated tropopause fold region. Complex structure is seen in the meteorological fields and compares well with the total ozone observations. Ozone data support the meteorological analysis showing that stratospheric descent was confined to levels above approx. 600 hPa; significant positive potential vorticity at lower levels is attributable to diabetic processes. Likewise, meteorological fields show that two pronounced ozone streamers extending north and northeastward into Canada at high levels are not bands of stratospheric air feeding into the cyclone; one is a channel of exhaust downstream from the system, and the other apparently previously connected the main cyclonic circulation to a southward intrusion of polar stratospheric air and advected eastward as the cut-off cyclone evolved. Good agreement between small-scale features in the model output and total ozone data underscores the latter's potential usefulness in diagnosing upper tropospheric/lower stratospheric dynamics and kinematics.

Olsen, Mark A.↗

Introduction

The 2014 SPIE Sensing Technologies for Global Health, Military Medicine and Environmental Monitoring conference embraced a wealth of state-of-the-art information in basic and applied science. This event covered the latest developments in the following areas: Non-invasive Disease Diagnostics for Global Health- This opening series of two consecutive sessions focused on oral biospecimen based rapid assays and point-of-care devices for the detection of pathogens causing infectious diseases, biomarkers for cancer, and analytes for noncommunicable diseases such as diabetes. They also covered presentations on the human proteasome and microbiome with linkage to human diseases and diagnostic approaches. The sessions were built on the past experience and expertise of the National Institutes of Health, National Institutes of Dental and Craniofacial Research. Military Medicine I: Traumatic Brain Injury and PTSD-This assembly covered oral-biomarker based diagnostics for brain damage and TBI as well as prevention and rehabilitation technologies. Neurorehabilitation and noninvasive neuromodulation were also discussed as critical approaches for effective functioning. Military Medicine II: Physiology and Medicine of Extreme Environments and Spaceflight-This scientific segment showcased physiological, pharmacological and diagnostic sensing methodologies during spaceflight per the National Aeronautics and Space Administration as well as military-relevant toxicans and future sensing trends per the Department of Defense. It also included latest technologies to determine hydration status in warfighters, eye surgery using the latest laser technologies, and sensing tools for blood analysis.  Sensing Technologies for Disease Diagnostics and Environmental Monitoring-This closing series of two consecutive sessions provided the venues to learn and discuss more results on the next generation of diagnostic tools and field technologies for diseases, including biomarker detection by digital imaging, multiplex technologies, capillary electrophoresis and molecular platforms serving as labs-on-chips. This conference allowed cross-fertilization of ideas, projects and collaborative work by a multidisciplinary audience of national and international colleagues from the academia, industry and federal government: The National Institutes of Health, National Aeronautics and Space Administration, and the Department of Defense.

Wotring, Virginia E.↗

Fatigue and Fatigue Countermeasures

Sleep can play an important role in alleviating health disparities, as inadequate sleep is associated with serious, adverse health conditions including cardiovascular disease, diabetes, obesity, cancer, and premature mortality. Nonetheless, dissemination of sleep health interventions targeted towards health disparities populations remains limited. Social workers and social work students serve populations designated as health disparities populations and are in an optimal position to promote sleep health among their underserved clients. However, social work students lack the specific training and resources necessary to promote healthy sleep practices among their clients. In fact, bachelors, master's, and doctoral social work programs in the United States do not incorporate any sleep health training as part of their curriculum. To improve public health through the promotion of healthy sleep practices among underserved populations, we propose to equip social work students, through an online learning module, with the knowledge and resources necessary to promote healthy sleep practices among their clients in underserved communities. In order to maximize effectiveness and reach, this proposal employs: (1) a collaborative team of sleep medicine and social work professionals; and (2) an ideal university environment with sophisticated eLearning capabilities that has one of the largest social work programs in the state of Florida.

fatigue countermeasure↗

Applications in Bioastronautics and Bioinformatics: Early Radiation Cataracts Detected by Noninvasive, Quantitative, and Remote Means

Human exploration of Mars is a key goal in NASA's exploration planning in the next 20 years. Maintaining crew health and good vision is certainly an important aspect of achieving a successful mission. Continuous radiation exposure is a risk factor for radiation-induced cataracts in astronauts because radiation exposure in space travel has the potential of accelerating the aging process (ref. 1). A patented compact device (ref. 2) based on the technique of dynamic light scattering (DLS) was designed for monitoring an astronaut's ocular health during long-duration space travel. This capability of early diagnosis, unmatched by any other clinical technique in use today, may enable prompt initiation of preventive/curative therapy. An Internet web-based system integrating photon correlation data and controlling the hardware to monitor cataract development in vivo at a remote site in real time (teleophthalmology) is currently being developed. The new technology detects cataracts very early (at the molecular level). Cataract studies onboard the International Space Station will be helpful in quantifying any adverse effect of radiation to ocular health. The normal lens in a human eye, situated behind the cornea, is a transparent tissue. It contains 35 wt % protein and 65 wt % water. Aging, disease (e.g., diabetes), smoking, dehydration, malnutrition, and exposure to ultraviolet light and ionizing radiation can cause agglomeration of the lens proteins. Protein aggregation can take place anywhere in the lens, causing lens opacity. The aggregation and opacification could produce nuclear (central portion of the lens) or cortical (peripheral) cataracts. Nuclear and posterior subcapsular (the membrane's capsule surrounds the whole lens) cataracts, being on the visual optical axis of the eye, cause visual impairment that can finally lead to blindness. The lens proteins, in their native state, are small in size. As a cataract develops, this size grows from a few nanometers (transparent) to several micrometers (cloudy). Ansari and Datiles have shown that DLS can detect cataracts at least two to three orders of magnitude earlier noninvasively and quantitatively than the best imaging (Scheimpflug) techniques in clinical use today (ref. 3).

Ansari, Rafat R.↗

What do we really know about the ubiquitin-proteasome pathway in muscle atrophy?

Studies of many different rodent models of muscle wasting have indicated that accelerated proteolysis via the ubiquitin-proteasome pathway is the principal cause of muscle atrophy induced by fasting, cancer cachexia, metabolic acidosis, denervation, disuse, diabetes, sepsis, burns, hyperthyroidism and excess glucocorticoids. However, our understanding about how muscle proteins are degraded, and how the ubiquitin-proteasome pathway is activated in muscle under these conditions, is still very limited. The identities of the important ubiquitin-protein ligases in skeletal muscle, and the ways in which they recognize substrates are still largely unknown. Recent in-vitro studies have suggested that one set of ubquitination enzymes, E2(14K) and E3(alpha), which are responsible for the 'N-end rule' system of ubiquitination, plays an important role in muscle, especially in catabolic states. However, their functional significance in degrading different muscle proteins is still unclear. This review focuses on the many gaps in our understanding of the functioning of the ubiquitin-proteasome pathway in muscle atrophy, and highlights the strengths and limitations of the different experimental approaches used in such studies.

Review↗

The Evolution of Tropospheric Temperature Field and its Relationship With The Onset of Asian Summer Monsoon

The mean state and year-to-year variations of the tropospheric temperature fields and their relationship with the establishment of the summertime East Asian monsoon (EAM) and the Indian monsoon (INM) are studied using the NCEP reanalysis data of 15 years (1982-1996). The results show that the seasonal shift of the South Asian High in the upper troposphere and the establishment of the EAM and the INM are closely related to the seasonal warming which causes a reversal of the meridional gradient of upper tropospheric mean temperature over the monsoon regions. On the average of 15 years, the reversal time of the temperature gradient in the EAM region (INM region) is concurrent with (one pentad earlier than) the onset time of the summer monsoon. In most years of the 15-year period, the reversal of temperature gradient coincides or precedes the onset time of the summer monsoon in both the EAM region and the INM region. The results suggest an important role of thermal processes on the establishment of the Asian monsoon. The contributors to the upper tropospheric warming over the EAM region are the strong horizontal warm advection and the diabetic heating against the adiabatic cooling due to upward motion. In the INM region, strong adiabatic heating by subsidence and the diabetic heating are major warming processes against the strong horizontal cold advection related to the persistent northwestlies to the southwestern periphery of the Tibetan Plateau. It appears that the early or late establishment of the Asian summer monsoon is not directly related to the differential warming near the surface.

He, H.↗