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.

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.

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.

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.

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.

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.

Implantable, Bioresorbable Radio Frequency Resonant Circuits for Magnetic Resonance Imaging.

Magnetic resonance imaging (MRI) is widely used in clinical care and medical research. The signal-to-noise ratio (SNR) in the measurement affects parameters that determine the diagnostic value of the image, such as the spatial resolution, contrast, and scan time. Surgically implanted radiofrequency coils can increase SNR of subsequent MRI studies of adjacent tissues. The resulting benefits in SNR are, however, balanced by significant risks associated with surgically removing these coils or with leaving them in place permanently. As an alternative, here the authors report classes of implantable inductor-capacitor circuits made entirely of bioresorbable organic and inorganic materials. Engineering choices for the designs of an inductor and a capacitor provide the ability to select the resonant frequency of the devices to meet MRI specifications (e.g., 200 MHz at 4.7 T MRI). Such devices enhance the SNR and improve the associated imaging capabilities. These simple, small bioelectronic systems function over clinically relevant time frames (up to 1 month) at physiological conditions and then disappear completely by natural mechanisms of bioresorption, thereby eliminating the need for surgical extraction. Imaging demonstrations in a nerve phantom and a human cadaver suggest that this technology has broad potential for post-surgical monitoring/evaluation of recovery processes.

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 battery-less wireless implant for the continuous monitoring of vascular pressure, flow rate and temperature.

Devices for monitoring blood haemodynamics can guide the perioperative management of patients with cardiovascular disease. Current technologies for this purpose are constrained by wired connections to external electronics, and wireless alternatives are restricted to monitoring of either blood pressure or blood flow. Here we report the design aspects and performance parameters of an integrated wireless sensor capable of implantation in the heart or in a blood vessel for simultaneous measurements of pressure, flow rate and temperature in real time. The sensor is controlled via long-range communication through a subcutaneously implanted and wirelessly powered Bluetooth Low Energy system-on-a-chip. The device can be delivered via a minimally invasive transcatheter procedure or it can be mounted on a passive medical device such as a stent, as we show for the case of the pulmonary artery in a pig model and the aorta and left ventricle in a sheep model, where the device performs comparably to clinical tools for monitoring of blood flow and pressure. Battery-less and wireless devices such as these that integrate capabilities for flow, pressure and temperature sensing offer the potential for continuous monitoring of blood haemodynamics in patients.

A wireless and battery-less implant for multimodal closed-loop neuromodulation in small animals.

Fully implantable wireless systems for the recording and modulation of neural circuits that do not require physical tethers or batteries allow for studies that demand the use of unconstrained and freely behaving animals in isolation or in social groups. Moreover, feedback-control algorithms that can be executed within such devices without the need for remote computing eliminate virtual tethers and any associated latencies. Here we report a wireless and battery-less technology of this type, implanted subdermally along the back of freely moving small animals, for the autonomous recording of electroencephalograms, electromyograms and body temperature, and for closed-loop neuromodulation via optogenetics and pharmacology. The device incorporates a system-on-a-chip with Bluetooth Low Energy for data transmission and a compressed deep-learning module for autonomous operation, that offers neurorecording capabilities matching those of gold-standard wired systems. We also show the use of the implant in studies of sleep-wake regulation and for the programmable closed-loop pharmacological suppression of epileptic seizures via feedback from electroencephalography. The technology can support a broader range of applications in neuroscience and in biomedical research with small animals.

Solvent-Assisted Filling of Liquid Metal and Its Selective Dewetting for the Multilayered 3D Interconnect in Stretchable Electronics.

As stretchable electronics are rapidly developing and becoming complex, the requirement for stretchable, multilayered, and large-area printed circuit boards (PCBs) is emerging. This demands a stretchable electrode and its vertical interconnect access (via) for 3-dimensional (3D) connectivity between layers. Here, we demonstrate solvent-assisted liquid metal (LM) filling into the submicrometer channel (∼400 nm), including via-hole filling and selective dewetting of LM. We provide the theoretical background of solvent-assisted LM filling and selective dewetting and reveal the osmotic pressure arising from anomalous mass transport phenomena, case II diffusion, which drives negative pressure, the spontaneous pulling of LM into the open channel. Also, we suggest design criteria for the geometry and dimension of LM interconnects to obtain structural stability without dewetting, based on the theoretical and computational background. We demonstrate a simple stretchable near-field communication (NFC) device including transferred micrometer-size light-emitting diodes (LEDs) with only 230 µm to the stretchable liquid metal PCB, without any soldering process. The device operates stably under repetitive stretching and releasing (∼50% uniaxial strain) due to the stable connection through the LM via between the upper and lower layers. Finally, we propose a concept for modular-type stretchable electronics, based on the cohesive liquid nature of LM. As a building block, the functional module can be easily removed from a mainframe, and replaced by another functional module, to suit user demand.

Universal Metasurfaces for Complete Linear Control of Coherent Light Transmission.

Recent advances in metasurfaces and optical nanostructures have enabled complex control of incident light with optically thin devices. However, it has thus far been unclear whether it is possible to achieve complete linear control of coherent light transmission, that is, independent control of polarization, amplitude, and phase for both input polarization states, with just a single, thin nanostructure array. Here, it is proved possible, and a universal metasurface is proposed, a bilayer array of high-index elliptic cylinders that possesses a complete degree of optical freedom with fully designable chirality and anisotropy. The completeness of achievable light control is mathematically shown with corresponding Jones matrices, new types of 3D holographic schemes that were formerly impossible are experimentally demonstrated, and a systematic way of realizing any input-state-sensitive vector linear optical device is presented. The results unlock previously inaccessible degrees of freedom in light transmission control.

Cerebrospinal Fluid-philic and Biocompatibility-Enhanced Soft Cranial Window for Long-Term In Vivo Brain Imaging.

Soft, transparent poly(dimethyl siloxane) (PDMS)-based cranial windows in animal models have created many opportunities to investigate brain functions with multiple in vivo imaging modalities. However, due to the hydrophobic nature of PDMS, the wettability by cerebrospinal fluid (CSF) is poor, which may cause air bubble trapping beneath the window during implantation surgery, and favorable heterogeneous bubble nucleation at the interface between hydrophobic PDMS and CSF. This may result in excessive growth of the entrapped bubble under the soft cranial window. Herein, to yield biocompatibility-enhanced, trapped bubble-minimized, and soft cranial windows, this report introduces a CSF-philic PDMS window coated with hydroxyl-enriched poly(vinyl alcohol) (PVA) for long-term in vivo imaging. The PVA-coated PDMS (PVA/PDMS) film exhibits a low contact angle θACA (33.7 ± 1.9°) with artificial CSF solution and maintains sustained CSF-philicity. The presence of the PVA layer achieves air bubble-free implantation of the soft cranial window, as well as induces the formation of a thin wetting film that shows anti-biofouling performance through abundant water molecules on the surface, leading to long-term optical clarity. In vivo studies on the mice cortex verify that the soft and CSF-philic features of the PVA/PDMS film provide minimal damage to neuronal tissues and attenuate immune response. These advantages of the PVA/PDMS window are strongly correlated with the enhancement of cortical hemodynamic changes and the local field potential recorded through the PVA/PDMS film, respectively. This collection of results demonstrates the potential for future microfluidic platforms for minimally invasive CSF extraction utilizing a CSF-philic fluidic passage.

Palisaded encapsulated neuroma on the lower lip: a case report.

Palisading encapsulated neuroma is a rare, benign, cutaneous nerve sheath tumor. It usually occurs as an asymptomatic solitary skin-colored papule and commonly affects the nose and cheeks. Sometimes, it involves other sites, including the shoulder, upper arm, and trunk, but rarely involves the oral mucosa, including that of the lip. In our case, a 63-year-old female patient complained of a pinkish rubbery nodule on her lower lip. Histopathologic examination demonstrated a well-circumscribed nodule encapsulated by connective tissue stroma in the dermis. The nodule consisted of palisading spindle-shaped tumor cells with wavy and basophilic nuclei. The cells were arranged in streaming fascicles with multiple clefts and were strongly positive for S-100 proteins. To our knowledge, only three cases of palisading encapsulated neuroma on the lower lip have been reported in the Korean literature. Herein, we report a rare case of an oral palisaded encapsulated neuroma.

Wireless, battery-free, and fully implantable electrical neurostimulation in freely moving rodents.

Implantable deep brain stimulation (DBS) systems are utilized for clinical treatment of diseases such as Parkinson's disease and chronic pain. However, long-term efficacy of DBS is limited, and chronic neuroplastic changes and associated therapeutic mechanisms are not well understood. Fundamental and mechanistic investigation, typically accomplished in small animal models, is difficult because of the need for chronic stimulators that currently require either frequent handling of test subjects to charge battery-powered systems or specialized setups to manage tethers that restrict experimental paradigms and compromise insight. To overcome these challenges, we demonstrate a fully implantable, wireless, battery-free platform that allows for chronic DBS in rodents with the capability to control stimulation parameters digitally in real time. The devices are able to provide stimulation over a wide range of frequencies with biphasic pulses and constant voltage control via low-impedance, surface-engineered platinum electrodes. The devices utilize off-the-shelf components and feature the ability to customize electrodes to enable broad utility and rapid dissemination. Efficacy of the system is demonstrated with a readout of stimulation-evoked neural activity in vivo and chronic stimulation of the medial forebrain bundle in freely moving rats to evoke characteristic head motion for over 36 days.