A wirelessly programmable, skin-integrated thermo-haptic stimulator system for virtual reality.

Sensations of heat and touch produced by receptors in the skin are of essential importance for perceptions of the physical environment, with a particularly powerful role in interpersonal interactions. Advances in technologies for replicating these sensations in a programmable manner have the potential not only to enhance virtual/augmented reality environments but they also hold promise in medical applications for individuals with amputations or impaired sensory function. Engineering challenges are in achieving interfaces with precise spatial resolution, power-efficient operation, wide dynamic range, and fast temporal responses in both thermal and in physical modulation, with forms that can extend over large regions of the body. This paper introduces a wireless, skin-compatible interface for thermo-haptic modulation designed to address some of these challenges, with the ability to deliver programmable patterns of enhanced vibrational displacement and high-speed thermal stimulation. Experimental and computational investigations quantify the thermal and mechanical efficiency of a vertically stacked design layout in the thermo-haptic stimulators that also supports real-time, closed-loop control mechanisms. The platform is effective in conveying thermal and physical information through the skin, as demonstrated in the control of robotic prosthetics and in interactions with pressure/temperature-sensitive touch displays.

Wireless, soft electronics for rapid, multisensor measurements of hydration levels in healthy and diseased skin.

Precise, quantitative measurements of the hydration status of skin can yield important insights into dermatological health and skin structure and function, with additional relevance to essential processes of thermoregulation and other features of basic physiology. Existing tools for determining skin water content exploit surrogate electrical assessments performed with bulky, rigid, and expensive instruments that are difficult to use in a repeatable manner. Recent alternatives exploit thermal measurements using soft wireless devices that adhere gently and noninvasively to the surface of the skin, but with limited operating range (∼1 cm) and high sensitivity to subtle environmental fluctuations. This paper introduces a set of ideas and technologies that overcome these drawbacks to enable high-speed, robust, long-range automated measurements of thermal transport properties via a miniaturized, multisensor module controlled by a long-range (∼10 m) Bluetooth Low Energy system on a chip, with a graphical user interface to standard smartphones. Soft contact to the surface of the skin, with almost zero user burden, yields recordings that can be quantitatively connected to hydration levels of both the epidermis and dermis, using computational modeling techniques, with high levels of repeatability and insensitivity to ambient fluctuations in temperature. Systematic studies of polymers in layered configurations similar to those of human skin, of porcine skin with known levels of hydration, and of human subjects with benchmarks against clinical devices validate the measurement approach and associated sensor hardware. The results support capabilities in characterizing skin barrier function, assessing severity of skin diseases, and evaluating cosmetic and medication efficacy, for use in the clinic or in the home.

Automated, multiparametric monitoring of respiratory biomarkers and vital signs in clinical and home settings for COVID-19 patients.

Capabilities in continuous monitoring of key physiological parameters of disease have never been more important than in the context of the global COVID-19 pandemic. Soft, skin-mounted electronics that incorporate high-bandwidth, miniaturized motion sensors enable digital, wireless measurements of mechanoacoustic (MA) signatures of both core vital signs (heart rate, respiratory rate, and temperature) and underexplored biomarkers (coughing count) with high fidelity and immunity to ambient noises. This paper summarizes an effort that integrates such MA sensors with a cloud data infrastructure and a set of analytics approaches based on digital filtering and convolutional neural networks for monitoring of COVID-19 infections in sick and healthy individuals in the hospital and the home. Unique features are in quantitative measurements of coughing and other vocal events, as indicators of both disease and infectiousness. Systematic imaging studies demonstrate correlations between the time and intensity of coughing, speaking, and laughing and the total droplet production, as an approximate indicator of the probability for disease spread. The sensors, deployed on COVID-19 patients along with healthy controls in both inpatient and home settings, record coughing frequency and intensity continuously, along with a collection of other biometrics. The results indicate a decaying trend of coughing frequency and intensity through the course of disease recovery, but with wide variations across patient populations. The methodology creates opportunities to study patterns in biometrics across individuals and among different demographic groups.

The Potentiality of Natural Products and Herbal Medicine as Novel Medications for Parkinson's Disease: A Promising Therapeutic Approach.

As the global population ages, the prevalence of Parkinson's disease (PD) is steadily on the rise. PD demonstrates chronic and progressive characteristics, and many cases can transition into dementia. This increases societal and economic burdens, emphasizing the need to find effective treatments. Among the widely recognized causes of PD is the abnormal accumulation of proteins, and autophagy dysfunction accelerates this accumulation. The resultant Lewy bodies are also commonly found in Alzheimer's disease patients, suggesting an increased potential for the onset of dementia. Additionally, the production of free radicals due to mitochondrial dysfunction contributes to neuronal damage and degeneration. The activation of astrocytes and the M1 phenotype of microglia promote damage to dopamine neurons. The drugs currently used for PD only delay the clinical progression and exacerbation of the disease without targeting its root cause, and come with various side effects. Thus, there is a demand for treatments with fewer side effects, with much potential offered by natural products. In this study, we reviewed a total of 14 articles related to herbal medicines and natural products and investigated their relevance to possible PD treatment. The results showed that the reviewed herbal medicines and natural products are effective against lysosomal disorder, mitochondrial dysfunction, and inflammation, key mechanisms underlying PD. Therefore, natural products and herbal medicines can reduce neurotoxicity and might improve both motor and non-motor symptoms associated with PD. Furthermore, these products, with their multi-target effects, enhance bioavailability, inhibit antibiotic resistance, and might additionally eliminate side effects, making them good alternative therapies for PD treatment.

Natural Products as the Potential to Improve Alzheimer's and Parkinson's Disease.

Alzheimer's disease and Parkinson's disease are the two most common neurodegenerative diseases in the world, and their incidence rates are increasing as our society ages. This creates a significant social and economic burden. Although the exact cause and treatment methods for these diseases are not yet known, research suggests that Alzheimer's disease is caused by amyloid precursor protein, while α-synuclein acts as a causative agent in Parkinson's disease. The accumulation of abnormal proteins such as these can lead to symptoms such as loss of protein homeostasis, mitochondrial dysfunction, and neuroinflammation, which ultimately result in the death of nerve cells and the progression of neurodegenerative diseases. The medications currently available for these diseases only delay their progression and have many adverse effects, which has led to increased interest in developing natural products with fewer adverse effects. In this study, we selected specific keywords and thesis content to investigate natural products that are effective in treating Alzheimer's and Parkinson's diseases. We reviewed 16 papers on natural products and found that they showed promising mechanisms of action such as antioxidant, anti-inflammatory, and mitochondrial function improvement. Other natural products with similar properties could also be considered potential treatments for neurodegenerative diseases, and they can be consumed as part of a healthy diet rather than as medicine.

A Novel Treatment Strategy by Natural Products in NLRP3 Inflammasome-Mediated Neuroinflammation in Alzheimer's and Parkinson's Disease.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases. Many studies have demonstrated that the release of NLRP3 inflammasome-mediated proinflammatory cytokines by the excessive activation of microglia is associated with the pathogenesis of AD and PD and suggested that the NLRP3 inflammasome plays an important role in AD and PD development. In both diseases, various stimuli, such as Aß and α-synuclein, accelerate the formation of the NLRP3 inflammasome in microglia and induce pyroptosis through the expression of interleukin (IL)-1ß, caspase-1, etc., where neuroinflammation contributes to gradual progression and deterioration. However, despite intensive research, the exact function and regulation of the NLRP3 inflammasome has not yet been clearly identified. Moreover, there have not yet been any experiments of clinical use, although many studies have recently been conducted to improve treatment of inflammatory diseases using various inhibitors for NLRP3 inflammasome pathways. However, recent studies have reported that various natural products show improvement effects in the in vivo models of AD and PD through the regulation of NLRP3 inflammasome assembly. Therefore, the present review provides an overview of natural extraction studies aimed at the prevention or treatment of NLRP3 inflammasome-mediated neurological disorders. It is suggested that the discovery and development of these various natural products could be a potential strategy for NLRP3 inflammasome-mediated AD and PD treatment.

The association between paralytic side and health-related quality of life in facial palsy: a cross-sectional study of the Korea National Health and Nutrition Examination Survey (2008-2012).

BACKGROUND: Facial palsy is known to have correlations with low level of quality of life. However, little is known about the association between preference based health-related quality of life (HRQoL) and paralytic side of facial palsy. METHODS: This study used Korea National Health and Nutrition Examination Survey (KNHANES, 2008-2012) data, only when the facial palsy examination had been included in the survey contents. Hierarchical regression analyses were used to obtain optimal regression coefficients in the association between paralytic side of the facial palsy and HRQoL measured by EuroQoL-5 Dimension (EQ-5D). We also analyzed the association between the deteriorated domains of EQ-5D and facial palsy in both subgroups by using multiple logistic regression models. RESULTS: We included the data of 28,106 participants aged ≥19 years who were examined as facial palsy according to House-Brackmann score and completed EQ-5D questionnaire in KNHANES 2008-2012. The mean EQ-5D score was significantly low and percentages of deteriorated numbers in its domains were significantly high in facial palsy group. CONCLUSIONS: These results show that, after adjusting for confounding variables, left facial palsy is associated with impaired HRQoL compared with right-sided palsy. Among the domains of EQ-5D, only 'self-care' domain was directly affected by the disease in left facial palsy patients. These findings could be used in developing model and conducting analyses of economic evaluation about facial palsy interventions.

Transparent Fingerprint Sensor System for Large Flat Panel Display.

In this paper, we introduce a transparent fingerprint sensing system using a thin film transistor (TFT) sensor panel, based on a self-capacitive sensing scheme. An armorphousindium gallium zinc oxide (a-IGZO) TFT sensor array and associated custom Read-Out IC (ROIC) are implemented for the system. The sensor panel has a 200 × 200 pixel array and each pixel size is as small as 50 µm × 50 µm. The ROIC uses only eight analog front-end (AFE) amplifier stages along with a successive approximation analog-to-digital converter (SAR ADC). To get the fingerprint image data from the sensor array, the ROIC senses a capacitance, which is formed by a cover glass material between a human finger and an electrode of each pixel of the sensor array. Three methods are reviewed for estimating the self-capacitance. The measurement result demonstrates that the transparent fingerprint sensor system has an ability to differentiate a human finger's ridges and valleys through the fingerprint sensor array.

PhaR, a Negative Regulator of PhaP, Modulates the Colonization of a Burkholderia Gut Symbiont in the Midgut of the Host Insect, Riptortus pedestris.

Five genes encoding PhaP family proteins and one phaR gene have been identified in the genome of Burkholderia symbiont strain RPE75. PhaP proteins function as the surface proteins of polyhydroxyalkanoate (PHA) granules, and the PhaR protein acts as a negative regulator of PhaP biosynthesis. Recently, we characterized one phaP gene to understand the molecular cross talk between Riptortus insects and Burkholderia gut symbionts. In this study, we constructed four other phaP gene-depleted mutants (ΔphaP1, ΔphaP2, ΔphaP3, and ΔphaP4 mutants), one phaR gene-depleted mutant, and a phaR-complemented mutant (ΔphaR/phaR mutant). To address the biological roles of four phaP family genes and the phaR gene during insect-gut symbiont interaction, these Burkholderia mutants were fed to the second-instar nymphs, and colonization ability and fitness parameters were examined. In vitro, the ΔphaP3 and ΔphaR mutants cannot make a PHA granule normally in a stressful environment. Furthermore, the ΔphaR mutation decreased the colonization ability in the host midgut and negatively affected the host insect's fitness compared with wild-type Burkholderia-infected insects. However, other phaP family gene-depleted mutants colonized well in the midgut of the fifth-instar nymph insects. However, in the case of females, the colonization rate of the ΔphaP3 mutant was decreased and the host's fitness parameters were decreased compared with the wild-type-infected host, suggesting that the environment of the female midgut may be more hostile than that of the male midgut. These results demonstrate that PhaR plays an important role in the biosynthesis of PHA granules and that it is significantly related to the colonization of the Burkholderia gut symbiont in the host insects' midgut.IMPORTANCE Bacterial polyhydroxyalkanoate (PHA) biosynthesis is a complex process requiring several enzymes. The biological roles of PHA granule synthesis enzymes and the surface proteins of PHA granules during host-gut symbiont interactions are not fully understood. Here, we report the effects on colonization ability in the host midguts and the fitness of host insects after feeding Burkholderia mutant cells (four phaP-depleted mutants and one phaR-depleted mutant) to the host insects. Analyses of both synthesized PHA granule amounts and CFU numbers suggest that the phaR gene is closely related to synthesis of the PHA granule and the colonization of the Burkholderia gut symbiont in the host insect's midgut. Like our previous report, this study also supports the idea that the environment of the host midgut may not be favorable to symbiotic Burkholderia cells and that PHA granules may be required to adapt in the host midgut.

Controlling Singlet-Triplet Energy Splitting for Deep-Blue Thermally Activated Delayed Fluorescence Emitters.

The development of efficient metal-free organic emitters with thermally activated delayed fluorescence (TADF) properties for deep-blue emission is still challenging. A new family of deep-blue TADF emitters based on a donor-acceptor architecture has been developed. The electronic interaction between donor and acceptor plays a key role in the TADF mechanism. Deep-blue OLEDs fabricated with these TADF emitters achieved high external quantum efficiencies over 19.2 % with CIE coordinates of (0.148, 0.098).

Donor-σ-Acceptor Motifs: Thermally Activated Delayed Fluorescence Emitters with Dual Upconversion.

A family of organic emitters with a donor-σ-acceptor (D-σ-A) motif is presented. Owing to the weakly coupled D-σ-A intramolecular charge-transfer state, a transition from the localized excited triplet state (3 LE) and charge-transfer triplet state (3 CT) to the charge-transfer singlet state (1 CT) occurred with a small activation energy and high photoluminescence quantum efficiency. Two thermally activated delayed fluorescence (TADF) components were identified, one of which has a very short lifetime of 200-400 ns and the other a longer TADF lifetime of the order of microseconds. In particular, the two D-σ-A materials presented strong blue emission with TADF properties in toluene. These results will shed light on the molecular design of new TADF emitters with short delayed lifetimes.

Benzimidazobenzothiazole-Based Bipolar Hosts to Harvest Nearly All of the Excitons from Blue Delayed Fluorescence and Phosphorescent Organic Light-Emitting Diodes.

Much effort has been devoted to developing highly efficient organic light-emitting diodes (OLEDs) that function through phosphorescence or thermally activated delayed fluorescence (TADF). However, efficient host materials for blue TADF and phosphorescent guest emitters are limited because of their requirement of high triplet energy levels. Herein, we report the rigid acceptor unit benzimidazobenzothiazole (BID-BT), which is suitable for use in bipolar hosts in blue OLEDs. The designed host materials, based on BID-BT, possess high triplet energy and bipolar carrier transport ability. Both blue TADF and phosphorescent OLEDs containing BID-BT-based derivatives exhibit external quantum efficiencies as high as 20 %, indicating that these hosts allow efficient triplet exciton confinement appropriate for blue TADF and phosphorescent guest emitters.

Highly durable and unidirectionally stooped polymeric nanohairs for gecko-like dry adhesive.

Gecko-like dry adhesive using high aspect ratio polymeric nanohairs has insuperable limitations, although it has huge potential in many applications. Repeated harsh contacts on a target substrate lead to physical collapse of nanohairs and significant degradation of the adhesion property, because the polymeric nanohairs are quite fragile due to poor mechanical robustness. Herein, we demonstrate a highly robust gecko-like dry adhesive with unidirectionally stooped polymeric nanohairs (diameter 100 nm) with a high aspect ratio (∼9) using an ultrathin metal coating. 100 cycles of repeated adhesion tests with 1 N preloading force did not significantly degrade adhesion or cause collapse of nanohairs. We believe that this approach allows gecko-like dry adhesive to be utilized in many related applications and diverse industry interests.

The Ratio of Typical Clubbing in Pulled-Out Hairs as a Useful Marker in Predicting the Course of Alopecia Areata.

BACKGROUND: Analysis of hair microscopic morphology is a simple and less invasive method to differentiate alopecia areata (AA) from other alopecic diseases. However, there is limited information on the distribution of the microscopic characteristics. OBJECTIVE: This study evaluated the microscopic morphological characteristics of pulled-out hair and their correlation with disease course in AA. METHODS: Morphological characteristics of pulled-out hair were classified into 5 categories: the presence of typical clubbing, surface undulation, tapering, breakage, and depigmentation in proximal hair shaft. Clinical course of AA was investigated through assessment of Severity of Alopecia Tool (SALT) score (initial score, maximal score and difference of them [ΔSALT]). RESULTS: Among 1,272 pulled-out hairs (n=179) obtained at initial visit, depigmentation (59.5%) was the most common, followed by loss of typical clubbing (57.2%) and surface undulation (55.2%). The percentage of loss of typical clubbing and proximal tapering was significantly higher in severe type of AA, younger age of onset and shorter disease duration. The ratio of typical clubbing (<50% vs. ≥50%) was associated with difference in maximal score and ΔSALT (p<0.05). Strong activity group (pulled-out hair ≥10, n=33) showed difference in clinical course (maximal score, ΔSALT) as well as distribution of microscopic features (loss of typical clubbing) compared with those in non-strong activity group. The ratio of typical clubbing significantly increased at follow-up than initially in strong activity group (p<0.05). CONCLUSION: Microscopic hair morphology, especially loss of typical clubbing and proximal tapering, could be useful tool to predict the course of AA.

A Case Study of Stress-Induced Alopecia Areata Treated with Hominis Placenta Pharmacopunture.

The purpose of this study is to report the clinical application of Hominis Placenta Pharmacopunture for Alopecia areata. Patient was diagnosed as stress-induced Alopecia areata 1 years ago. To reduce symptom, we treated a patient 8 times using Hominis Placenta Pharmacopunture. Hominis Placenta was injected subcutaneously into the lesion of head scalp alopecia. According to photographs, the lesion had been replaced with new terminal hair and the size of the lesion had decreased. This case has shown that stress-induced Alopecia areata patient could be treated by Hominis Placenta Pharmacopunture.

Bionic artificial skin with a fully implantable wireless tactile sensory system for wound healing and restoring skin tactile function.

Tactile function is essential for human life as it enables us to recognize texture and respond to external stimuli, including potential threats with sharp objects that may result in punctures or lacerations. Severe skin damage caused by severe burns, skin cancer, chemical accidents, and industrial accidents damage the structure of the skin tissue as well as the nerve system, resulting in permanent tactile sensory dysfunction, which significantly impacts an individual's daily life. Here, we introduce a fully-implantable wireless powered tactile sensory system embedded artificial skin (WTSA), with stable operation, to restore permanently damaged tactile function and promote wound healing for regenerating severely damaged skin. The fabricated WTSA facilitates (i) replacement of severely damaged tactile sensory with broad biocompatibility, (ii) promoting of skin wound healing and regeneration through collagen and fibrin-based artificial skin (CFAS), and (iii) minimization of foreign body reaction via hydrogel coating on neural interface electrodes. Furthermore, the WTSA shows a stable operation as a sensory system as evidenced by the quantitative analysis of leg movement angle and electromyogram (EMG) signals in response to varying intensities of applied pressures.

Alteration of lipopolysaccharide O antigen leads to avirulence of gut-colonizing Serratia marcescens.

The reason why the potent entomopathogen Serratia marcescens fails to kill insects through oral infection is unknown. To compare effects of septic injection and oral administration of S. marcescens, we used a model bean bug, Riptortus pedestris. Most R. pedestris insects survived oral infections, but not septic infections. Although the number of S. marcescens cells in hemolymph after oral infection, which were originated from gut-colonizing S. marcescens, was higher than the fatal number of cells used in septic injection, they did not kill host insects, suggesting a loss of virulence in gut-colonizing S. marcescens cells. When gut-colonizing S. marcescens cells were septically injected into insects, they failed to kill R. pedestris and survive in hemolymph. To understand the avirulence mechanisms in gut-colonizing bacteria, lipopolysaccharides of S. marcescens were analyzed and revealed that the O antigen was lost during gut colonization. Gut-colonizing S. marcescens cells were resistant to humoral immune responses but susceptible to cellular immune responses, easily succumbing to phagocytosis of hemocytes. When cellular immunity was suppressed, the gut-colonizing S. marcescens cells recovered their virulence and killed insects through septic injection. These results suggest that a key mechanism of avirulence in orally infected S. marcescens is the loss of the O antigen, resulting in susceptibility to host's cellular immune responses.

A Case of Neutrophil-Rich Anaplastic Large-Cell Lymphoma with Relapse.

After anaplastic large-cell lymphoma (ALCL) was first described by Stain in 1985, there have been several histological variants of ALCL reported. There are classified histological subtypes of ALCL, such as lymphohistiocytic, small cell, Hodgkin-like, composite pattern, and other less common variants including neutrophil-rich ALCL. A 63-year-old male patient presented with erythematous exophytic mass on the left lower leg. In the past, his condition had been diagnosed as abdominal primary cutaneous ALCL (pcALCL), which recurred as systemic ALCL (sALCL) in the left bronchus. After treatment, he achieved complete remission. Histopathologic examination showed large-sized pleomorphic, anaplastic mitotic tumor cells, several neutrophils, and a few lymphocytes. Neutrophil-rich ALCL is a rare histological variant of ALCL. It is characterized by the presence of CD30-positive anaplastic tumor cells with numerous neutrophil infiltrations. Neutrophil-rich ALCL responds well to treatment but tends to recur. There were four cases reported to have recurrent neutrophil-rich ALCL. All cases were diagnosed with neutrophil-rich pcALCL prior to recurrence. Three cases had local recurrence, and only one case relapsed as sALCL. Herein, we present the first case of neutrophil-rich ALCL recurring as sALCL twice.

Evaluation of Sleep Disturbance in Alopecia Areata through Questionnaire: Pittsburgh Sleep Quality Index as a Reasonable Tool.

BACKGROUND: Alopecia areata (AA) is common non-scarring hair loss disease. Sleep distrubance has been regarded as a triggering or aggravating factor for AA. However, objective evaluation of sleep disturbance and its clinical effect on AA has not been clearly demonstrated. OBJECTIVE: This study investigated objective sleep evaluation tool for AA patients and their clinical correlation. METHODS: Patients presenting with new-onset AA or recurrences of pre-existing AA were included, and those who reported sleep disturbance in the preliminary survey were designated as the sleep disturbance group (SD group). Sleep quality was investigated for them using three self-administered questionnaires: Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Epworth Sleep Scale (ESS). Demographic information and clinical features of AA were analyzed according to sleep quality. RESULTS: A total of 400 participants were enrolled, and 53 were categorized into the SD group. The incidence of stressful events was significantly higher in the SD group (54.7%) than in the non-SD group (25.1%) (p<0.001). Based on the PSQI, 77.3% of participants were objective poor sleepers (score of 5 or more), and they showed a significantly higher incidence of stressful events compared to good sleepers (p=0.019). The proportion of poor sleepers was significantly lower in patients with mild AA (S1) than in those with moderate to severe AA (S2~S5) (p=0.045). CONCLUSION: This study demonstrated a positive correlation among stress, SD, and AA. The degree of SD was objectively represented by the PSQI score, showing different scores according to AA severity.