Organic Nanopatch Device Improves Sleep and Enhances Vital Organ Function

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1 Organic Nanopatch Device Improves Sleep and Enhances Vital Organ Function Homer Nazeran * PhD, CPEng (Biomed.), Sherry Blake-Greenberg MA, HMD * Department of Electrical and Computer Engineering, University of Texas at El Paso, El Paso, Texas, USA Health Integration Therapy, Palos Verdes Estates, Los Angeles, California, USA Abstract Actigraphic measurements depicting movement during sleep, tissue bioimpedance images of different organs reflecting their physiological functional status, Leeds Sleep Evaluation Questionnaire as well as sleep diary data reflecting subjective self-evaluation of sleep were collected from 20 volunteers [5 males and 15 females, (55 12) years of age, lbs (158 36) in weight, and ft ( ) in height] over a period of 3 weeks at baseline and at the end of each week afterwards. Baseline data were acquired from all subjects at the beginning of the study period before wearing an organic nanopatch device: the Silent Nights patch. After one week of accommodation to wearing the Actiwatches, Silent Nights patch was applied to the right temple 1 hour before sleep each night and worn throughout the night for 2 weeks. Subjects were instructed to keep well hydrated during the study period. All subjects served as their own control. The effects of Silent Nights patch on qualitative and quantitative measures of sleep were evaluated and the impact of quality of sleep on organ function was analyzed. The hypothesis to be tested was: The Silent Nights patch worn throughout the night for 2 weeks improves cellular physiologic functional status of different parts of the brain, cardiac ventricles, adrenal glands, and thyroid gland. The overall data in this pilot investigation demonstrated that this intervention produced considerable improvements in the objective and subjective measures of sleep and resulted in enhancement of physiological functional status of the brain, adrenal glands, cardiac ventricles, and thyroid gland. Keywords: Organic nanotpatch devices; Sleep, Silent Nights patch; Actigrapy; Bioimpedance Imagining; EIS; Organ function. 1. Introduction Quality sleep is essential for body systems rejuvenation and regeneration. Many factors in the physiological and psychological function of a person can affect quality of sleep. One of the factors, which decreases the quality and quantity of sleep is an overfunction and under-function of the nervous system and brain activity. The level of toxicity in the vital organs is also an important consideration. Stress is a main causative factor of all identifiable malfunctions of the body. There are currently increasing numbers of people who have disturbed sleep. Lack of quantity and quality of sleep majorly affects how a person can function in the daily life. Imbalanced body function leads to imbalanced brain and neurological performance, which in turn leads to imbalance in functional life performance. Due to the incidence of sleep depravation in the USA, a growing number of sleep clinics are established to study sleep issues with the aim to develop solutions for this serious ailment. Many other solutions and remedies are surfacing as sleep aids and are attempting to solve this growing problem of sleep. The Silent Nights patch is a non-invasive, natural solution to improve sleep. The aim of this study was to monitor quality and quantity of sleep, using markers of the nervous system, brain activity, and organ toxicity when the Silent Nights patch was introduced as an intervention. The qualitative tools used in the study were the Leeds Sleep Evaluation Questionnaire and a daily sleep questionnaire/log. The quantitative tools in the study were the Actiwatch and a Bioimpedance Imaging Device called the Electro Interstitial Scan (EIS) system, which measure the level of activity and organ function (tissue conductivity), respectively. Sleep research has demonstrated that objective sleep assessment do not always validate a selfreported sleep disturbance. Some individuals report subjective insomnia, but have no actigraphic (or polysomnographic) evidence of long latency to sleep onset or loss in total sleep time. Thus it is standard practice in the field to perform an evaluation of both self-reports and objective measures of sleep. Accordingly, the specific aims of this study were: 1. Primary Outcome Variable: To assess the effectiveness of the Silent Nights patch on improving quality of sleep in a sample population of subjects with varying degrees of sleep difficulties through self-assessments using the Leeds Sleep Evaluation Questionnaire and a daily sleep diary and by analyzing objective actigraphy data. The Leeds Sleep Evaluation Questionnaire is a wellestablished subjective evaluation tool in the sleep literature /12/$ IEEE 28

2 2. Secondary Outcome Variable: To evaluate the impact of using the Silent Nights patches on subjects physiological status in different organs. 3. Evaluate the safety and effectiveness of the application of Silent Nights patch as an aid for improving sleep in a mixed sample of subjects with varying degrees of self-assessed sleep difficulties when compared to baseline measurements. This is the first study of its kind to investigate the effect of the Silent Nights patch on quantitative and qualitative measures of sleep and vital organ physiologic function. 2. Materials and Methods 2.1. Subjects For this investigation actigraphy depicting movement during sleep, tissue bioimpedance images or Electro Interstitial Scans (EIS) indicative of physiological functional status of organs, Leeds Sleep Evaluation Questionnaire and sleep diary data reflecting on subjective self-assessment of quality of sleep were acquired from 20 volunteers [5 males and 15 females, (55 12) years of age, lbs (158 36) in weight, ft ( ) in height]. The Independent Institutional Review Board (IRB) approved the research protocol. After giving informed consent, the research data were collected from study participants and were used to create a digital database. Subjects were selfreporting as having no sleep concerns to sleeping disorders of varying severity. Subjects were recruited from the local area of Palos Verdes, in Los Angeles California in Inclusion criteria for participation in this study were functional individuals of any race, between 18 and 80 years of age exhibiting varying degrees of sleep difficulties, including those with no self-assessed sleep difficulties, who were willing to wear the Actiwatch devices for 3 weeks and the Silent Nights patch every night for 2 weeks and undergo bioimpedance imaging or Electro Interstitial Scanning at baseline and once a week for three weeks afterwards. These criteria also included the following: 1. Able to understand the requirements of the study and sign Informed Consent/HIPAA Authorization forms and willing to sign. 2. Willing to refrain from using any prescribed or over-the-counter sleeping aids during the course of the study. 3. Willing to refrain from drugs, antihistamines, and any other agent, which may affect sleep. Exclusion criteria for participation in this study involved the following: 1. Allergy or sensitivity to medical adhesives. 2. Medical condition that, in the opinion of the investigator(s), contraindicates the subject s participation in the clinical study. 3. Pacemaker. Dependence or unwillingness to refrain from any agents, which could interfere with study Data Collection The Independent Institutional Review Board (IRB) approved the study protocols for this investigation. After giving informed consent, baseline data were acquired from all subjects at the beginning of the study period before wearing the Silent Nights patch. After one week of accommodation to wearing the Actiwatches [1], Silent Nights patch was applied to the right temple 1 hour before sleep each night and worn throughout the night for 2 weeks. Subjects were instructed to keep well hydrated during the study period. All subjects served as their own control. The effects of Silent Nights patch on qualitative and quantitative measures of sleep were evaluated and the impact of quality of sleep on vital organ function was analyzed Organic Nanopatch Devices - Silent Nights Patch For this research, the Silent Nights patches (LifeWave Inc, San Diego, California, USA) were used. The Silent Nights patch is a member of the LifeWave patch family that uses organic nanotechnology to mildly stimulate acupuncture points in the body. It is designed to stimulate the release of melatonin upon stimulation of designated acupuncture points. Organic nanopatch technology employs localized absorption of infrared radiation produced by the body. These patches both trap and absorb infrared radiation. In addition, they are composed of nontoxic materials that promote reflection back of specific wavelengths of infrared radiation. These patches are designed to deliver infrared wavelengths to enhance the electrical conductivity of the tissue. They work by reflecting energy back into the body and they do not generate energy. The materials in the patches act like frequency specific mirrors or reflectors (narrow-band) as compared to the ceramic fibers found in infrared products, which are broadband reflectors. Placing a patch on the skin will allow the materials to passively absorb wide-band energy and reemit narrow-band energy back into the body. Infrared wraps contain inorganic ceramic fibers. These inorganic fibers absorb infrared energy from the body and then reemit the energy across a wide energy band. The difference between these patches and infrared products is that they only mirror back a very narrow band of frequencies. In this context these patches are not significantly different in mechanism of action from infrared wraps. Figure 1 shows the placement of a Silent Nights patch on the right temple [2]. Currently, organic nanotechnology is a novel method to mildly and continuously stimulate acupuncture points. The effectiveness of this technology has been shown in a number of studies [3-5]. Organic nanotechnology is used to balance the body s special form of electromagnetic (EM) energy at specific frequencies (known as Qi) conducted by the acupuncture meridians in the same way that metal needles, qigong energy needles, moxibustion, etc. modulate EM frequencies /12/$ IEEE 29

3 Litscher performed a comprehensive bioengineering assessment of needle (laser) acupuncture as a popular complimentary method to medical treatment, and highlighted the milestones of acupuncture research within a 30 years period [6,7]. In these reviews, Litscher carefully described a variety of advanced and wellestablished medical diagnostic methodologies that have been used to prove and validate the quantifiable effects of acupuncture stimulation in the brain in a non-invasive and reproducible fashion in real time [8-16]. In a recent paper Komori et al, documented the improvements in microcirculation responses due to acupuncture stimulation and phototherapy [17]. Figure 1. Silent Nights patch placed on the right temple [2] Actiwatch Device Actiwatch devices were used to monitor the levels of activity during sleep. The Actiwatch is an ambulatory actigraphy device made by Philips Respironics that is worn on the wrist. The Actiwatch software uses a polysomongraphy (PSG) validated sleep scoring algorithm, and is an FDA 510k approved Medical Device. The Actiwatch is equipped with a highly sensitive accelerometer and records levels of activity. The Actiwatch uses actigraphy principles to provide sleep schedule variability, sleep quantity and quality statistics and daytime activity patterns to better identify therapeutic options and understand responses to treatment for subjects in a study. Objective, multiday recordings in the home environment provide insight into a subject s sleep/wake behavior by recording activity levels during selected periods of time. Activity level is recognized as a valuable indicator for medical problems and can provide answers to many research questions [18]. Activity levels correlate with sleep/wake patterns, pain level, mood, energy expenditure, fatigue/alertness and other quantifiable parameters. In addition to sleep/wake activity recording, Actiwatch has the ability to record information about the amount and duration of ambient white light illuminance, in units of lux. Figure 2 shows an image of an Actiwatch Eletrco Insterstitial Scan (EIS) System An EIS system (LD Technology, Coral Gables, Florida, USA), a programmable electromedical device, was deployed to acquire bioelectrical impedance (related to tissue conductivity) measurements indicative of cellular physiologic functional status in different parts of the brain (frontal, temporal, hippocampus, hypothalamus, and pituitary gland) and different organs (thyroid gland-t, adrenal glands -AG, cardiac ventricles -CV, kidneys - K, liver-l, small intestine-si, and large intestine-li). The EIS is an integrated hardware/software system that applies precise algorithms and proprietary formulas to generate on-screen, 3-D modeling representations of the human body's systems; with specific intended uses. The EIS system is a French device, classified as a Biofeedback Class 2 device in the United States (FDA product Code: HCC). Recently the FDA has approved a number of alternating current (ac) bioelectric impedance (BIM) devices for use in cardiology and oncology [20-24]. Before EIS measurements were made on subjects, four operational tests were carried out automatically by the device: power supply test, channel test, volume and conductivity measurement and correspondence tests, as well as cable and precision control tests. Electrodes and their application sites were prepared following manufacturer s instructions. Under software control the hardware delivers a sequence of three 1.28V pulses: 22 ac pulses, 1 second each, at 50KHz (at 0.6 ma, energy/pulse = 0.77 mj); 22 dc pulses, 1 second each (at 0.6 ma, energy/pulse = 0.77 mj); and another set of 22 dc pulses, 3 second in duration for each pulse (at 0.6 ma, energy/pulse = 0.77 mj) to 6 electrodes. These electrodes (2 disposable Ag/AgCl applied to the forehead, 2 reusable polished stainless steel hand electrodes, and 2 reusable polished stainless steel foot electrodes) form 22 different electrode pair (sensing) configurations and measure the intensity of interstitial fluid conductivity (by applying Maxwell s equation) from which on-screen 3-D models of the human body organs are generated. The measurements are scaled on a scale of -100 to As DC current only passes through the interstitial fluid (16% of the body s total water), the device could measure electrical conductivity and the composition of interstitial fluid as well as other biochemical parameters and detect ionic abnormalities [EIS Manual]. Figure 3 shows the image of an EIS system. Figure 2. Actiwatch Device [19]. Figure 3. An EIS System [25] /12/$ IEEE 30

4 3. Results 3.1. Quantitative Actigraphy - In this investigation Actiwatches were used to monitor the levels of activity during sleep. Figure 4 shows a typical screen shot of the Actigraphic software used in the analysis of activity data acquired by the Actiwatches. Table I. Typical parameters for a female and a male subject at baseline and 2 weeks after wearing the Silent Nights patch. Female Male Actigraphic Parameter Total activity between markers Baseline 2 wks post patch Baseline 2 wks post patch Total awake time (in min) Ratio of time in bed over awake time Activity per min in bed(restless) Table II. Actigraphic parameters and % overal average change compared to baseline after wearing the Silent Nights patch for 2 weeks. Total activity between markers Total activity time (in min) 2 weeks post Baseline 2 weeks post Baseline sleep patch sleep patch % Reduction in activity 22% Reduction in total awake time Figure 4. A computer screen shot of actigraphic data analysis software. Table I shows typical actigraphic parameter values for a 49-year old female subject (weight 150 lbs, height 5.6 ft) and for a 41-year old male subject (weight 175 lbs, height 5.1 ft) at baseline and after 2 weeks of wearing the Silent Nights patch as examples. Table II shows the mean values in all subjects at baseline and after wearing the Silent Nights patch for 2 weeks as well as the % overall average change for the following 4 parameters: total activity between markers, total awake time in minutes, ratio of time in bed over awake time, and activity per minute in bed (restlessness) Electro Interstitial Scans- An Electro Interstitial Scan (EIS) System was used in this investigation to measure cellular physiologic function on a scale of -100 to -20 for under-function and +20 to +100 for overfunction. A reading in the -20 to + 20 range was indicative of normal values for organ function. Table II shows typical parameters Δ T represents the average total physiologic change after wearing the Silent Nights patch nightly for 2 weeks and Δ T-base is indicative of total change at the end of the 2-week period with respect to baseline (Base) measurements. Ratio of time in bed over awake time 2 weeks post Baseline sleep patch Activity per minute in bed (restlessness) Baseline 2 weeks post sleep patch Table IIIa shows the overall mean values and standard deviations for baseline (Base) and total change 2 weeks post patch with respect to baseline (Δ T-base ) in the physiologic status of different parts of the brain (n = 20). Table 3b shows the overall mean values and standard deviations for baseline (Base) and total change 2 weeks post patch with respect to baseline (Δ T-base ) in physiologic status for different organs (n = 20). The p- values and levels of significance are shown as well. Table IIIA. mean and standard deviation values of Δ T-base and baseline (base) calculated from EIS readouts for different parts of the brain. Frontal Lobe Temporal Lobe Hippocampus Hypothalamus Mean Δ T-base Mean Base Stdev Δ T-base Stdev Base p-value <0.001 <0.001 <0.001 Significance Very Highly Highly Highly Table IIIB. Mean and standard deviation values of Δ T-base and baseline (base) calculated from EIS readouts for different organs. T CV K AG L SI LI Mean Std Δ T-base Mean Std Base p- value Sig. Yes Yes No Highly No No No /12/$ IEEE 31

5 3.2. Qualitative Leeds Sleep Evaluation Questionnaire - The Leeds Sleep Evaluation Questionnaire has ten self-rating 100-mm-line analog questions (each 10 mm marking representing a score of 1 point, therefore the full line represents a score from 0 to 10) related to 4 areas of sleep: getting to sleep (GTS questions 1-3), quality of sleep (QOS questions 4,5), awake following sleep (AFS - questions 6,7), and behavior following wakening (BFW questions 8-10). The questionnaire has been used to monitor subjectively perceived changes in sleep during a variety of experiments [26]. Table IV shows the Leeds sleep score (the total score obtained by adding the markings of the 10 questions) for all the subjects participating in this investigation. Table V shows the mean and standard deviation values for the cumulative Leeds scores. The analysis of the Leeds scores over the study period revealed the there was a very significant (p = ) improvement in sleep attributes indicating that after wearing the Silent Nights patch nightly for 2 weeks, overall the following observations could be made: * It was easier and quicker than usual for subjects to get to sleep, * The subjects felt calmer with less wakeful periods than usual during sleep (better sleep quality), * It was easier and requiring less time to wake up than usual in the mornings, and the subjects felt more alert than usual, experiencing less disrupted balance and coordination upon awakening Self-Reported Sleep Diary - A sleep diary was created specifically for this study with the purpose of providing a secondary way of confirming that sleep markers were set correctly to capture actigraphy data and additional information about daily sleep activities. It comprised of 11 questions such as total hours slept last night, estimate of time to sleep, how easy was it to fall to sleep at night on a scale of 1-5, how many times did you wake up during the night, hour and length of time of each waking episode, did you have any dreams last night, time of waking up in the morning, on a scale of 1 to 5 how refreshed did you feel, how many naps did you take toady and how long did each one last, did you find yourself dozing off during the day, and what time did you go to bed. The analysis of the sleep diary data revealed that on average there were considerable qualitative improvements at the end of the study period in different sleep attributes. Overall the subjects felt that compared to usual it was easier to fall to sleep, woke up less number of times during the night with less time during each waking period, waking up later than usual in the mornings, feeling more refreshed requiring less naps with shorter duration during the day. Table IV. Leeds sleep scores at baseline, week 1, one week and two weeks post-patch application. Subject No. Baseline Week 1 1-week post-patch 2-week post-patch Table V. Mean and standard deviation values for the cumulative Leeds scores over the study period. Leeds Score Baseline Week1 Week2 Week3 Mean Std Discussion and Conclusions Actigraphic data analysis demonstrated that compared to baseline on average there was 29% reduction in activity level during sleep, 22% reduction in total awake time, 28% increase in ratio of time in bed over awake time, and 28% reduction in restlessness after applying the Silent Nights patch 1 hour before sleep each night wearing it nightly for 2 weeks. The analysis of the Leeds sleep evaluation scores over the study period revealed that there was a very significant (p < 0.01) improvement in sleep attributes indicating that after wearing the Silent Nights patch for 2 weeks, overall: it was easier and quicker than usual for subjects to get to sleep; the subjects felt calmer with less wakeful periods than usual during sleep (better sleep quality); it was easier and requiring less time to wake up than usual in the mornings; and the subjects felt more alert than usual, experiencing less disrupted balance and coordination upon awakening. The sleep diary data on average also confirmed considerable qualitative improvements at the end of the study period in different sleep attributes. Overall the subjects felt that compared to usual it was easier to fall to sleep, woke up less number of times during the night with less time during each waking period, waking up later in the mornings, feeling more refreshed requiring less naps with shorter duration during the day. Statistical analysis of the EIS data revealed that there were significant improvements in cellular physiologic functional status of the brain (frontal lobe, temporal lobe, hippocampus, hypothalamus), cardiac ventricles, adrenals, and thyroid gland at the end of the study period with respect to the corresponding baseline data. The results showed a highly significant (p < 0.001) improvement in the physiologic functional status of the temporal lobe, hippocampus, hypothalamus (average statistical power = 100%) and adrenal glands (statistical power = 96%) with a very significant improvement (p /12/$ IEEE 32

6 <0.01) in the functioning of the frontal lobe (statistical power = 75%). There was a significant (p < 0.05) improvement with an average statistical power of at least 72% in the functional status of the thyroid gland and cardiac ventricles. The liver, kidneys, and intestines did not achieve statistical significance over this period. In summary, the overall data in this pilot investigation demonstrated that the Silent Nights patch worn on the right temple nightly 1 hour before sleep for 2 weeks produced considerable improvements in the objective and subjective measures of sleep and caused an impressive improvement in the physiologic functional status of different parts of the brain and adrenal glands with significant enhancement on the functioning of the cardiac ventricles and thyroid gland. Therefore, the hypothesis was accepted as true. In future studies double-blind placebo-controlled protocols will be used to further investigate the efficacy of these organic nanopatch devices on improvement of sleep. ACKNOWLEDGMENT The support of Ms Sylvia Benitez in tallying the Leeds sleep scores is gratefully acknowledged. References [1] /actiwatch/default.wpd. Retrieved June [2] Retrieved June [3] H. Nazeran, and E. Haltiwanger, Nanoscale wearable devices reduce quantitative and qualitative measures of neuromuscular pain, Journal of Medical Implants and Devices, 5 (2), 103, [4] H. Nazeran, and S. Greenberg, Nanoscale carnosine patches improve organ function, SBEC International Federation of Medical and Biological Engineering Proceedings 32, pp , [3] [5] H. Nazeran, and S. Greenberg, Nanoscale glutathione patches improve organ function, SBEC International Federation of Medical and Biological Engineering Proceedings 32, , [4] T. Budzynski, H. Budzynski, K. Maret, and H. Tang, Heart Rate Variability Enhancement Through Nanotechnology: A Double Blind Randomized-Control Pilot Study. Journal of Neurotherapy: Investigations in Neuromodulation, Neurofeedback and Applied Neuroscience. 12 (1), 45-55, [5] H. Nazeran, Heart rate variability signal parameters quantify skin cooling effect of energy patches during rest and exercise in young healthy individuals, Biomedical Engineering Recent Developments. Wilson, Tran, Vossoughi, Editors, 13-19, [6] G. Litscher, L. Wang, D. Schiora, D. Rachbauer, et al, Biological effects of painless laser needle acupuncture, Medical Acupuncture, 16(1), 24-29, [7] G. Litscher and L. Wang, Biomedical engineering meets acupuncture, development of a miniaturized 48-channel skin impedance measurement system for needle and laser acupuncture, Biomedical Engineering Online, 9:78, [8] G. Litscher, Bioengineering assessment of acupuncture. part 1: thermography, Crit Rev Biomed Eng. 2006; 34(1):1 22. [9] G. Litscher and L. Wang, Biomedical engineering meets acupuncture, development of a miniaturized 48-channel skin impedance measurement system for needle and laser acupuncture, Biomedical Engineering Online, 9:78, [10] G. Litscher, Bioengineering assessment of acupuncture. part 1: thermography, Crit Rev Biomed Eng. 2006; 34(1):1 22. [11] G. Litscher, Bioengineering assessment of acupuncture. part 2: monitoring of microcirculation, Crit Rev Biomed Eng. 2006; 34(4): [12] G. Litscher, Bioengineering assessment of acupuncture. part 3: ultrasound, Crit Rev Biomed Eng. 2006; 34(4): [13] G. Litscher, Bioengineering assessment of acupuncture. part 4: functional magnetic resonance imaging, Crit Rev Biomed Eng. 2006; 34(4): [14] G. Litscher, Bioengineering assessment of acupuncture. part 5: cerebral near-infrared spectroscopy, Crit Rev Biomed Eng. 2006; 34(6): [15] G. Litscher, Bioengineering assessment of acupuncture. part 6: monitoring neurophysiology., Crit Rev Biomed Eng. 2007; 35(1):1 38. [16] G. Litscher, Bioengineering assessment of acupuncture. part 7: heart rate variability, Crit Rev Biomed Eng. 2007; 35(3-4): [17] Komori M, Takada K, Tomizawa Y, Nishiyama K, et al. Microcirculation responses to acupuncture stimulation and phototherapy. Anesthesia and Analgesia, 108(2), , [18] Ancoli-Israel S, Cole R, Alessi C, Chambers M, et al., The Role of Actigraphy in the Study of Sleep and Circadian Rhythms, Sleep, 26 (3): , [19] minimitter-philips.html. Retrieved June [20] J. M. Van De Water, T. W. Miller, R. L. Vogel, et al., Impedance cardiography: the next vital sign technology?, Chest, 123: , [21] L. A. H. Critchley, Impedance cardiography. The impact of new technology, Anaesthesia, 53:677-8, [22] G. Cotter, A. Schachner, L. Sasson L, et al (2006). Impedance cardiography revisited. Physiol Meas. 27:817-27, [23] Retrieved June [24] T. Morimoto, Y. Kinouchi, T. Iritani, S. Kimura S et al., Measurement of the electrical bioimpedance of breast tumors, Eur Surg Res, 22:86-92, [25] Retrieved September [26] A. C. Parrott, and I. Hindmarch, The Leeds Sleep Evaluation Questionnaire in psychopharmacological investigations - a review, Psychopharmacology (Berl)., 71(2): 173-9, /12/$ IEEE 33