Effects of light on the sleep-wakefulness cycle of mice mediated by intrinsically photosensitive retinal ganglion cells.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) are able to synthesize the photosensitive protein melanopsin, which is involved in the regulation of circadian rhythms, the papillary light reflex and other nonimaging visual functions. To investigate whether ipRGCs are involved in mediating the light modulation of sleep-wakefulness in rodents, melanopsin knockout mice (MKO), melanopsin-only mice (MO) and coneless, rodless, melanopsin knockout mice (TKO) were used in this study to record electroencephalogram and electromyography variations in the normal 12:12 h light:dark cycle, and 1 h and 3 h light pulses were administered at 1 h after the light was turned off. In the normal 12:12 h light-dark cycle, the WT, MKO and MO mice had a regular day-night rhythm and no significant difference in wakefulness, rapid eye movement (REM) or nonrapid eye movement (NREM) sleep. However, TKO mice could not be entrained according to the light-dark cycle and exhibited a free-running rhythm. Extending the light pulse durations significantly changed the sleep and wakefulness activities of the WT and MO mice but did not have an effect on the MKO mice. These results indicate that melanopsin significantly affects REM and NREM sleep and that ipRGCs play an important role in light-induced sleep in mice.

Effects of mobile phone exposure (GSM 900 and WCDMA/UMTS) on polysomnography based sleep quality: An intra- and inter-individual perspective.

BACKGROUND: Studies on effects of radio frequency-electromagnetic fields (RF-EMF) on the macrostructure of sleep so far yielded inconsistent results. This study investigated whether possible effects of RF-EMF exposure differ between individuals. OBJECTIVE: In a double-blind, randomized, sham-controlled cross-over study possible effects of electromagnetic fields emitted by pulsed Global System for Mobile Communications (GSM) 900 and Wideband Code-Division Multiple Access (WCDMA)/Universal Mobile Telecommunications System (WCDMA/UMTS) devices on sleep were analysed. METHODS: Thirty healthy young men (range 18-30 years) were exposed three times per exposure condition while their sleep was recorded. Sleep was evaluated according to the American Academy of Sleep Medicine standard and eight basic sleep variables were considered. RESULTS: Data analyses at the individual level indicate that RF-EMF effects are observed in 90% of the individuals and that all sleep variables are affected in at least four subjects. While sleep of participants was affected in various numbers, combinations of sleep variables and in different directions, showing improvements but also deteriorations, the only consistent finding was an increase of stage R sleep under GSM 900MHz exposure (9 of 30 subjects) as well as under WCDMA/UMTS exposure (10 of 30 subjects). CONCLUSIONS: The results underline that sleep of individuals can be affected differently. The observations found here may indicate an underlying thermal mechanism of RF-EMF on human REM sleep. Nevertheless, the effect of an increase in stage R sleep in one third of the individuals does not necessarily indicate a disturbance of sleep.

The effects of low-intensity narrow-band blue-light treatment compared to bright white-light treatment in sub-syndromal seasonal affective disorder.

BACKGROUND: The discovery of a novel photoreceptor in the retinal ganglion cells with a highest sensitivity of 470-490 nm blue light has led to research on the effects of short-wavelength light in humans. Several studies have explored the efficacy of monochromatic blue or blue-enriched light in the treatment of SAD. In this study, a comparison has been made between the effects of broad-wavelength light without ultraviolet (UV) wavelengths compared to narrow-band blue light in the treatment of sub-syndromal seasonal affective disorder (Sub-SAD). METHOD: In a 15-day design, 48 participants suffering from Sub-SAD completed 20-minute sessions of light treatment on five consecutive days. 22 participants were given bright white-light treatment (BLT, broad-wavelength light without UV 10 000 lux, irradiance 31.7 Watt/m(2)) and 26 participants received narrow-band blue light (BLUE, 100 lux, irradiance 1.0 Watt/m(2)). All participants completed daily and weekly questionnaires concerning mood, activation, sleep quality, sleepiness and energy. Also, mood and energy levels were assessed by means of the SIGH-SAD, the primary outcome measure. RESULTS: On day 15, SIGH-SAD ratings were significantly lower than on day 1 (BLT 54.8 %, effect size 1.7 and BLUE 50.7 %, effect size 1.9). No statistically significant differences were found on the main outcome measures. CONCLUSION: Light treatment is an effective treatment for Sub-SAD. The use of narrow-band blue-light treatment is equally effective as bright white-light treatment. TRIAL REGISTRATION: This study was registered in the Dutch Trial Register (Nederlands Trial Register TC = 4342 ) (20-12-2013).

Length polymorphism in the Period 3 gene is associated with sleepiness and maladaptive circadian phase in night-shift workers.

The objective of the current study was to determine if night-shift workers carrying the five-repeat variant of the Period 3 gene show elevated levels of nocturnal sleepiness and earlier circadian phase compared with homozygotes for the four-repeat allele. Twenty-four permanent night-shift workers were randomly selected from a larger study. Participants took part in an observational laboratory protocol including an overnight multiple sleep latency test and half-hourly saliva collection for calculation of dim-light melatonin onset. Period 3(-/5) shift workers had significantly lower multiple sleep latency test during overnight work hours compared with Period 3(4/4) workers (3.52 ± 23.44 min versus 10.39 ± 6.41 min, P = 0.003). We observed no significant difference in sleepiness during early morning hours following acute sleep deprivation. Long-allele carriers indicated significantly higher sleepiness on the Epworth Sleepiness Scale administered at 17:00 hours (12.08 ± 2.55 versus 8.00 ± 1.94, P < 0.001). We observed a significantly earlier melatonin onset in Period 3(-/5) individuals compared with Period 3(4/4) shift workers (20:44 ± 6:37 versus 02:46 ± 4:58, P = 0.021). Regression analysis suggests that Period 3 genotype independently predicts sleepiness even after controlling for variations in circadian phase, but we were unable to link Period 3 to circadian phase when controlling for sleepiness. Period 3(-/5) shift workers showed both subjective and objective sleepiness in the pathological range, while their Period 3(4/4) counterparts showed sleepiness within normal limits. Period 3(-/5) night workers also show a mean circadian phase 6 h earlier (i.e. less adapted) than Period 3(4/4) workers. Because Period 3(-/5) workers have maladaptive circadian phase as well as pathological levels of sleepiness, they may be at greater risk for occupational and automotive accidents. We interpret these findings as a call for future research on the role of Period 3 in sleepiness and circadian phase, especially as they relate to night work.

Increased physical activity improves sleep and mood outcomes in inactive people with insomnia: a randomized controlled trial.

While high levels of activity and exercise training have been associated with improvements in sleep quality, minimum levels of activity likely to improve sleep outcomes have not been explored. A two-armed parallel randomized controlled trial (N=41; 30 females) was designed to assess whether increasing physical activity to the level recommended in public health guidelines can improve sleep quality among inactive adults meeting research diagnostic criteria for insomnia. The intervention consisted of a monitored program of ≥150 min of moderate- to vigorous-intensity physical activity per week, for 6 months. The principal end-point was the Insomnia Severity Index at 6 months post-baseline. Secondary outcomes included measures of mood, fatigue and daytime sleepiness. Activity and light exposure were monitored throughout the trial using accelerometry and actigraphy. At 6 months post-baseline, the physical activity group showed significantly reduced insomnia symptom severity (F(8,26) = 5.16, P = 0.03), with an average reduction of four points on the Insomnia Severity Index; and significantly reduced depression and anxiety scores (F(6,28) = 5.61, P = 0.02; and F(6,28) = 4.41, P = 0.05, respectively). All of the changes were independent of daily light exposure. Daytime fatigue showed no significant effect of the intervention (F(8,26) = 1.84, P = 0.18). Adherence and retention were high. Internationally recommended minimum levels of physical activity improve daytime and night-time symptoms of chronic insomnia independent of daily light exposure levels.

Patterns of symptom burden during radiotherapy or concurrent chemoradiotherapy for head and neck cancer: a prospective analysis using the University of Texas MD Anderson Cancer Center Symptom Inventory-Head and Neck Module.

BACKGROUND: A prospective longitudinal study to profile patient-reported symptoms during radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) for head and neck cancer was performed. The goals were to understand the onset and trajectory of specific symptoms and their severity, identify clusters, and facilitate symptom interventions and clinical trial design. METHODS: Participants in this questionnaire-based study received RT or CCRT. They completed the University of Texas MD Anderson Cancer Center Symptom Inventory-Head and Neck Module before and weekly during treatment. Symptom scores were compared between treatment groups, and hierarchical cluster analysis was used to depict clustering of symptoms at treatment end. Variables believed to predict symptom severity were assessed using a multivariate mixed model. RESULTS: Among the 149 patients studied, the majority (47%) had oropharyngeal tumors, and nearly one-half received CCRT. Overall symptom severity (P < .001) and symptom interference (P < .0001) became progressively more severe and were more severe for those receiving CCRT. On multivariate analysis, baseline Eastern Cooperative Oncology Group performance status (P < .001) and receipt of CCRT (P < .04) correlated with higher symptom severity. Fatigue, drowsiness, lack of appetite, problem with mouth/throat mucus, and problem tasting food were more severe for those receiving CCRT. Both local and systemic symptom clusters were identified. CONCLUSIONS: The findings from this prospective longitudinal study identified a pattern of local and systemic symptoms, symptom clusters, and symptom interference that was temporally distinct and marked by increased magnitude and a shift in individual symptom rank order during the treatment course. These inform clinicians about symptom intervention needs, and are a benchmark for future symptom intervention clinical trials.

Acute exposure to evening blue-enriched light impacts on human sleep.

Light in the short wavelength range (blue light: 446-483 nm) elicits direct effects on human melatonin secretion, alertness and cognitive performance via non-image-forming photoreceptors. However, the impact of blue-enriched polychromatic light on human sleep architecture and sleep electroencephalographic activity remains fairly unknown. In this study we investigated sleep structure and sleep electroencephalographic characteristics of 30 healthy young participants (16 men, 14 women; age range 20-31 years) following 2 h of evening light exposure to polychromatic light at 6500 K, 2500 K and 3000 K. Sleep structure across the first three non-rapid eye movement non-rapid eye movement - rapid eye movement sleep cycles did not differ significantly with respect to the light conditions. All-night non-rapid eye movement sleep electroencephalographic power density indicated that exposure to light at 6500 K resulted in a tendency for less frontal non-rapid eye movement electroencephalographic power density, compared to light at 2500 K and 3000 K. The dynamics of non-rapid eye movement electroencephalographic slow wave activity (2.0-4.0 Hz), a functional index of homeostatic sleep pressure, were such that slow wave activity was reduced significantly during the first sleep cycle after light at 6500 K compared to light at 2500 K and 3000 K, particularly in the frontal derivation. Our data suggest that exposure to blue-enriched polychromatic light at relatively low room light levels impacts upon homeostatic sleep regulation, as indexed by reduction in frontal slow wave activity during the first non-rapid eye movement episode.

Sleep EEG alterations: effects of pulsed magnetic fields versus pulse-modulated radio frequency electromagnetic fields.

Studies have repeatedly shown that electroencephalographic power during sleep is enhanced in the spindle frequency range following radio frequency electromagnetic field exposures pulse-modulated with fundamental frequency components of 2, 8, 14 or 217 Hz and combinations of these. However, signals used in previous studies also had significant harmonic components above 20 Hz. The current study aimed: (i) to determine if modulation components above 20 Hz, in combination with radio frequency, are necessary to alter the electroencephalogram; and (ii) to test the demodulation hypothesis, if the same effects occur after magnetic field exposure with the same pulse sequence used in the pulse-modulated radio frequency exposure. In a randomized double-blind crossover design, 25 young healthy men were exposed at weekly intervals to three different conditions for 30 min before sleep. Cognitive tasks were also performed during exposure. The conditions were a 2-Hz pulse-modulated radio frequency field, a 2-Hz pulsed magnetic field, and sham. Radio frequency exposure increased electroencephalogram power in the spindle frequency range. Furthermore, delta and theta activity (non-rapid eye movement sleep), and alpha and delta activity (rapid eye movement sleep) were affected following both exposure conditions. No effect on sleep architecture and no clear impact of exposure on cognition was observed. These results demonstrate that both pulse-modulated radio frequency and pulsed magnetic fields affect brain physiology, and the presence of significant frequency components above 20 Hz are not fundamental for these effects to occur. Because responses were not identical for all exposures, the study does not support the hypothesis that effects of radio frequency exposure are based on demodulation of the signal only.

Sleep EEG alterations: effects of different pulse-modulated radio frequency electromagnetic fields.

Previous studies have observed increases in electroencephalographic power during sleep in the spindle frequency range (approximately 11-15 Hz) after exposure to mobile phone-like radio frequency electromagnetic fields (RF EMF). Results also suggest that pulse modulation of the signal is crucial to induce these effects. Nevertheless, it remains unclear which specific elements of the field are responsible for the observed changes. We investigated whether pulse-modulation frequency components in the range of sleep spindles may be involved in mediating these effects. Thirty young healthy men were exposed, at weekly intervals, to three different conditions for 30 min directly prior to an 8-h sleep period. Exposure consisted of a 900-MHz RF EMF, pulse modulated at 14 Hz or 217 Hz, and a sham control condition. Both active conditions had a peak spatial specific absorption rate of 2 W kg(-1) . During exposure subjects performed three different cognitive tasks (measuring attention, reaction speed and working memory), which were presented in a fixed order. Electroencephalographic power in the spindle frequency range was increased during non-rapid eye movement sleep (2nd episode) following the 14-Hz pulse-modulated condition. A similar but non-significant increase was also observed following the 217-Hz pulse-modulated condition. Importantly, this exposure-induced effect showed considerable individual variability. Regarding cognitive performance, no clear exposure-related effects were seen. Consistent with previous findings, our results provide further evidence that pulse-modulated RF EMF alter brain physiology, although the time-course of the effect remains variable across studies. Additionally, we demonstrated that modulation frequency components within a physiological range may be sufficient to induce these effects.

Effects of electromagnetic fields emitted by mobile phones (GSM 900 and WCDMA/UMTS) on the macrostructure of sleep.

In the present double-blind, randomized, sham-controlled cross-over study, possible effects of electromagnetic fields emitted by Global System for Mobile Communications (GSM) 900 and Wideband Code-Division Multiple Access (WCDMA)/Universal Mobile Telecommunications System (UMTS) cell-phones on the macrostructure of sleep were investigated in a laboratory environment. An adaptation night, which served as screening night for sleep disorders and as an adjustment night to the laboratory environment, was followed by 9 study nights (separated by a 2-week interval) in which subjects were exposed to three exposure conditions (sham, GSM 900 and WCDMA/UMTS). The sample comprised 30 healthy male subjects within the age range 18-30 years (mean ± standard deviation: 25.3 ± 2.6 years). A cell-phone usage at maximum radio frequency (RF) output power was simulated and the transmitted power was adjusted in order to approach, but not to exceed, the specific absorption rate (SAR) limits of the International Commission on Non-Ionizing Radiation Protection (ICNIRP) guidelines for general public exposure (SAR(10g) = 2.0 W kg(-1)). In this study, possible effects of long-term (8 h) continuous RF exposure on the central nervous system were analysed during sleep, because sleep is a state in which many confounding intrinsic and extrinsic factors (e.g. motivation, personality, attitude) are eliminated or controlled. Thirteen of 177 variables characterizing the initiation and maintenance of sleep in the GSM 900 and three in the WCDMA exposure condition differed from the sham condition. The few significant results are not indicative of a negative impact on sleep architecture. From the present results there is no evidence for a sleep-disturbing effect of GSM 900 and WCDMA exposure.

Night Photostimulation of Clearance of Beta-Amyloid from Mouse Brain: New Strategies in Preventing Alzheimer's Disease.

The deposition of amyloid-ß (Aß) in the brain is a risk factor for Alzheimer's disease (AD). Therefore, new strategies for the stimulation of Aß clearance from the brain can be useful in preventing AD. Transcranial photostimulation (PS) is considered a promising method for AD therapy. In our previous studies, we clearly demonstrated the PS-mediated stimulation of lymphatic clearing functions, including Aß removal from the brain. There is increasing evidence that sleep plays an important role in Aß clearance. Here, we tested our hypothesis that PS at night can stimulate Aß clearance from the brain more effectively than PS during the day. Our results on healthy mice show that Aß clearance from the brain occurs faster at night than during wakefulness. The PS course at night improves memory and reduces Aß accumulation in the brain of AD mice more effectively than the PS course during the day. Our results suggest that night PS is a more promising candidate as an effective method in preventing AD than daytime PS. These data are an important informative platform for the development of new noninvasive and nonpharmacological technologies for AD therapy as well as for preventing Aß accumulation in the brain of people with disorder of Aß metabolism, sleep deficit, elderly age, and jet lag.

Mobile phone 'talk-mode' signal delays EEG-determined sleep onset.

Mobile phones signals are pulse-modulated microwaves, and EEG studies suggest that the extremely low-frequency (ELF) pulse modulation has sleep effects. However, 'talk', 'listen' and 'standby' modes differ in the ELF (2, 8, and 217Hz) spectral components and specific absorption rates, but no sleep study has differentiated these modes. We used a GSM900 mobile phone controlled by a base-station simulator and a test SIM card to simulate these three specific modes, transmitted at 12.5% (23dBm) of maximum power. At weekly intervals, 10 healthy young adults, sleep restricted to 6h, were randomly and single-blind exposed to one of: talk, listen, standby and sham (nil signal) modes, for 30 min, at 13:30 h, whilst lying in a sound-proof, lit bedroom, with a thermally insulated silent phone beside the right ear. Bipolar EEGs were recorded continuously, and subjective ratings of sleepiness obtained every 3 min (before, during and after exposure). After exposure the phone and base-station were switched off, the bedroom darkened, and a 90 min sleep opportunity followed. We report on sleep onset using: (i) visually scored latency to onset of stage 2 sleep, (ii) EEG power spectral analysis. There was no condition effect for subjective sleepiness. Post-exposure, sleep latency after talk mode was markedly and significantly delayed beyond listen and sham modes. This condition effect over time was also quite evident in 1-4Hz EEG frontal power, which is a frequency range particularly sensitive to sleep onset. It is possible that 2, 8, 217Hz modulation may differentially affect sleep onset.

Modeling Neurocognitive Decline and Recovery During Repeated Cycles of Extended Sleep and Chronic Sleep Deficiency.

Study Objectives: Intraindividual night-to-night sleep duration is often insufficient and variable. Here we report the effects of such chronic variable sleep deficiency on neurobehavioral performance and the ability of state-of-the-art models to predict these changes. Methods: Eight healthy males (mean age ± SD: 23.9 ± 2.4 years) studied at our inpatient intensive physiologic monitoring unit completed an 11-day protocol with a baseline 10-hour sleep opportunity and three cycles of two 3-hour time-in-bed (TIB) and one 10-hour TIB sleep opportunities. Participants received one of three polychromatic white light interventions (200 lux 4100K, 200 or 400 lux 17000K) for 3.5 hours on the morning following the second 3-hour TIB opportunity each cycle. Neurocognitive performance was assessed using the psychomotor vigilance test (PVT) administered every 1-2 hours. PVT data were compared to predictions of five group-average mathematical models that incorporate chronic sleep loss functions. Results: While PVT performance deteriorated cumulatively following each cycle of two 3-hour sleep opportunities, and improved following each 10-hour sleep opportunity, performance declined cumulatively throughout the protocol at a more accelerated rate than predicted by state-of-the-art group-average mathematical models. Subjective sleepiness did not reflect performance. The light interventions had minimal effect. Conclusions: Despite apparent recovery following each extended sleep opportunity, residual performance impairment remained and deteriorated rapidly when rechallenged with subsequent sleep loss. None of the group-average models were capable of predicting both the build-up in impairment and recovery profile of performance observed at the group or individual level, raising concerns regarding their use in real-world settings to predict performance and improve safety.

High sensitivity of human melatonin, alertness, thermoregulation, and heart rate to short wavelength light.

Light can elicit acute physiological and alerting responses in humans, the magnitude of which depends on the timing, intensity, and duration of light exposure. Here, we report that the alerting response of light as well as its effects on thermoregulation and heart rate are also wavelength dependent. Exposure to 2 h of monochromatic light at 460 nm in the late evening induced a significantly greater melatonin suppression than occurred with 550-nm monochromatic light, concomitant with a significantly greater alerting response and increased core body temperature and heart rate ( approximately 2.8 x 10(13) photons/cm(2)/sec for each light treatment). Light diminished the distal-proximal skin temperature gradient, a measure of the degree of vasoconstriction, independent of wavelength. Nonclassical ocular photoreceptors with peak sensitivity around 460 nm have been found to regulate circadian rhythm function as measured by melatonin suppression and phase shifting. Our findings-that the sensitivity of the human alerting response to light and its thermoregulatory sequelae are blue-shifted relative to the three-cone visual photopic system-indicate an additional role for these novel photoreceptors in modifying human alertness, thermophysiology, and heart rate.

Long-term results in combined-modality treatment of small cell carcinoma of the lung.

Fifty eight patients with small cell carcinoma of the lung were treated with a combined-modality regimen: chemotherapy with adriamycin, cyclophosphamide, and vincristine; BCG immunotherapy; radiotherapy to the lung primary and prophylactic cranial irradiation. Ninteen patients had limited disease, and 39 had extensive disease. There were 27 (48%) partial remissions and 23 (41%) complete remissions, and median survival was 51 wk. Initial performance status and extent of disease had a definite effect on survival. Only 1 patient developed CNS metastases on prophylactic cranial irradiation. Five of 19 patients (26%) with limited disease remain alive and in complete remission at 26-45+ mo. It is becoming clear from this and other recent studies that we can significantly prolong median survival in small cell lung cancer. However, even more important is the fact that limited-extent small cell lung cancer may be a potentially curable disease.

Pulsed high-frequency electromagnetic field affects human sleep and sleep electroencephalogram.

To investigate whether the electromagnetic field (EMF) emitted by digital radiotelephone handsets affects the brain, healthy, young subjects were exposed during an entire night-time sleep episode to an intermittent radiation schedule (900 MHz; maximum specific absorption rate 1 W/kg) consisting of alternating 15-min on-15-min off intervals. Compared with a control night with sham exposure, the amount of waking after sleep onset was reduced from 18 to 12 min. Spectral power of the electroencephalogram in non-rapid eye movement sleep was increased. The maximum rise occurred in the 10-11 Hz and 13.5-14 Hz bands during the initial part of sleep and then subsided. The results demonstrate that pulsed high-frequency EMF in the range of radiotelephones may promote sleep and modify the sleep EEG.

The temporal onset of individual symptoms in winter depression: differentiating underlying mechanisms.

The transition from well to depressed offers a window to the mechanisms which underlie depressive symptoms. We examined the onset of each of 15 symptoms in 53 patients with winter depression. Three symptoms had a risk of onset closely associated with the onset of the episode itself and may represent a core syndrome. The risk of onset for the remaining symptoms was unrelated to the onset and the course of the episode. The symptoms were equally likely to begin at any time during the episode and suggest a different pathological mechanism. A dual vulnerability hypothesis is proposed; research and treatment implications are discussed.

Prediction of intellectual deficits in children with acute lymphoblastic leukemia.

Possible predictors of reported lower cognitive functioning in irradiated children with acute lymphoblastic leukemia (ALL) were investigated. Thirty-four subjects, 5-14 years old, with ALL in continuous complete remission and without evidence of current or past central nervous system disease, were examined 9-110 months after diagnosis, using standard measures of intelligence and academic achievement. Subjects with a history of post-irradiation somnolence syndrome were significantly older at diagnosis than nonsomnolent subjects. Intelligence (IQ) was found to be unrelated to history of somnolence syndrome. IQ and achievement were unrelated to age at irradiation, irradiation-examination interval, and radiation dosages. The strongest predictor of IQ by far is parental social class. The importance of controlling for social class differences when searching for treatment effects on IQ and achievement is stressed.

Complications of radiation therapy for head and neck cancers. The patient's perspective.

Newer treatments for head and neck cancers, including altered fractionation and the use of concomitant radiotherapy and chemotherapy, may provide better local-regional tumor control rates; however, patients may experience more frequent and more severe acute toxicities that result in considerable suffering. Through this study, we sought a better understanding of patients' experiences when undergoing radiotherapy. Personal interviews were conducted with 33 individuals who had received radiotherapy for head and neck cancers. These individuals described their treatment experiences and identified the most troublesome and debilitating side effects of radiotherapy. Overall, lethargy and weakness, dry mouth, mouth sores and pain, taste changes, and sore throat were the most frequently reported troublesome or debilitating side effects. The single most debilitating side effect was oropharyngeal mucositis that was characterized by patients as sore throat, and mouth sores and pain; both negatively affected the patient's ability to eat and drink, causing many patients to experience significant weight loss. Trends toward more aggressive management of head and neck cancers underscore the need for new and effective therapies for oropharyngeal mucositis occurring in patients receiving radiotherapy.