Altered prefrontal beta oscillatory activity during removal of information from working memory in obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is related to working memory impairment. Since patients with OCD have difficulty controlling their obsessive thoughts, removal of irrelevant information might be important in the pathophysiology of OCD. However, little is known about brain activity during the removal of information from working memory in patients with OCD. Our goal was to explore potential deficits in inhibitory function related to working memory processes in patients with OCD. METHODS: Sixteen OCD patients and 20 healthy controls (HCs) were recruited. We compared in prefrontal alpha and beta band activity derived from magnetoencephalography (MEG) between patients with OCD and HCs during multiple phases of information processing associated with working memory, especially in post-trial period of the visuospatial working memory task (the delayed matching-to-sample task), which is presumed to be related to the information removal process of working memory. RESULTS: Prefrontal post-trial beta power change (presumed to occur at high levels during the post-trial period) exhibited significant reductions in patients with OCD compared to HCs. In addition, the post-trial beta power change was negatively correlated with Obsessive-Compulsive Inventory-Revised total scores in patients with OCD. CONCLUSIONS: These findings suggest that impairment in the removal of information from working memory might be a key mechanism underlying the inability of OCD patients to rid themselves of their obsessions.

Validation of Relationship between Patients' Descriptions of Pruritus and Patient-burden of Chronic Pruritus using Structural Equation Modelling.

Patients with chronic itch describe their pruritus in a wide variety of ways. However, these subjective descriptions are often not taken into consideration by physicians. This study aimed to validate patients' descriptions of pruritus, and to investigate the relationship between various descriptions of pruritus and the patient burden of chronic pruritus by examining the mediating effects of sleep disturbance and sexual dysfunction on patient's quality of life, as predicted by various descriptions of pruritus. Exploratory and confirmatory factor analyses were performed to identify the factor structure measured by 11 descriptions of pruritus. The study then analysed differences in the degree of sleep disturbance, sexual dysfunction, and quality of life deterioration factors using a structural equation modelling method. Using data from 419 patients with chronic pruritus, 11 descriptions of pruritus were classified into 2 groups: (i) sensory pruritus (i.e. stinging, stabbing, burning, painful, formication, throbbing, and cold) that are linked with descriptions of pruritus patterns; and (ii) affective pruritus (i.e. annoying, unbearable, worrisome, and warm) from patient reports of psychological or emotional distress. The study found that affective pruritus decreases patient's quality of life either directly or indirectly through sleep disturbance. In conclusion, clues about a patients' sleep disturbance or poor quality of life can be obtained through their descriptions of pruritus.

Optimal application of soft-palate webbing flap pharyngoplasty combined with nasal surgery for surgical treatment of primary snoring and obstructive sleep apnea.

BACKGROUND: Excessive collapse of the soft palate and lateral pharyngeal wall narrowing are established causes of loud snoring and sleep apnea in subjects with obstructive sleep apnea (OSA). Therefore, delicate surgical techniques are needed to reshape the soft palate and create sufficient tension in the lateral pharyngeal wall. This study aimed to determine the therapeutic outcome and favorable indications of soft-palate webbing flap pharyngoplasty in subjects with OSA and primary snoring. METHODS: A total of 174 subjects who underwent soft-palate webbing flap pharyngoplasty combined with uvulopalatal flap and septoturbinoplasty from August 2015 to February 2020 were included in this study. Medical records, including pre- and postoperative sleep parameters, were retrospectively reviewed. The primary outcome measure was the degree of improvement in AHI after surgery. Other outcomes were differences in surgical response rates, subjective visual analog score (VAS) for snoring, sleep quality, and complications. RESULTS: Polysomnographic results showed that apnea-hypopnea index (AHI) scores were significantly reduced from 39.6 ± 6.1 to 22.9 ± 3.6 following soft-palate webbing flap pharyngoplasty in 59 subjects, and overall success and response rates of this technique were analyzed with 71%. We found that the successful outcomes were observed in 50% of mild (n = 12) and 56% of moderate (n = 16) subjects with OSA subjects due to lateral pharyngeal wall collapse. The success rate of soft-palate webbing flap pharyngoplasty was relatively higher in subjects with mild and moderate OSA than those with severe OSA. Additionally, the mean VAS snoring scale was 4.7 and subjects' primary snoring intensity significantly improved to 2.9 after soft-palate webbing flap pharyngoplasty. Subjective symptoms such as daytime sleepiness and sleep quality also showed improvement. Most complications were found to be minimal and improved by 1 month after the operation. CONCLUSION: Our data demonstrate that soft-palate webbing flap pharyngoplasty is an effective treatment for OSA and primary snoring and may be a promising technique to reduce lateral pharyngeal wall collapse.

Smart Vitamin Micelles as Cancer Nanomedicines for Enhanced Intracellular Delivery of Doxorubicin.

Chemotherapy is one of the most effective treatments for cancer. However, intracellular delivery of many anticancer drugs is hindered by their hydrophobicity and low molecular weight. Here, we describe highly biocompatible and biodegradable amphiphilic vitamin conjugates comprising hydrophobic vitamin E and hydrophilic vitamin B labeled with dual pH and glutathione-responsive degradable linkages. Vitamin-based micelles (vitamicelles), formed by self-assembly in aqueous solutions, were optimized based on their stability after encapsulation of doxorubicin (DOX). The resulting vitamicelles have great potential as vehicles for anticancer drugs because they show excellent biocompatibility (>94% after 48 h of incubation) and rapid biodegradability (>90% after 2.5 h). Compared with free DOX, DOX-loaded vitamicelles showed a markedly enhanced anticancer effect as they released the drug rapidly and inhibited drug efflux out of cells efficiently. By exploiting these advantages, this study not only provides a promising strategy for circumventing existing challenges regarding the delivery of anticancer drugs but also extends the utility of current DOX-induced chemotherapy.

The Inhibitory Effects of Plant Derivate Polyphenols on the Main Protease of SARS Coronavirus 2 and Their Structure-Activity Relationship.

The main protease (Mpro) is a major protease having an important role in viral replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus that caused the pandemic of 2020. Here, active Mpro was obtained as a 34.5 kDa protein by overexpression in E. coli BL21 (DE3). The optimal pH and temperature of Mpro were 7.5 and 37 °C, respectively. Mpro displayed a Km value of 16 µM with Dabcyl-KTSAVLQ↓SGFRKME-Edans. Black garlic extract and 49 polyphenols were studied for their inhibitory effects on purified Mpro. The IC50 values were 137 µg/mL for black garlic extract and 9-197 µM for 15 polyphenols. The mixtures of tannic acid with puerarin, daidzein, and/or myricetin enhanced the inhibitory effects on Mpro. The structure-activity relationship of these polyphenols revealed that the hydroxyl group in C3', C4', C5' in the B-ring, C3 in the C-ring, C7 in A-ring, the double bond between C2 and C3 in the C-ring, and glycosylation at C8 in the A-ring contributed to inhibitory effects of flavonoids on Mpro.

Validity and reliability of itch assessment scales for chronic pruritus in adults: A prospective multicenter study.

BACKGROUND: Several tools can provide a reliable and accurate evaluation of pruritus, including the visual analog scale (VAS), numeric rating scale (NRS), verbal rating scale (VRS), and multidimensional questionnaires such as the Itch Severity Scale (ISS). However, no single method is considered a gold standard. OBJECTIVE: We evaluated the validity and reliability of VAS, NRS, VRS, and ISS and their correlation with a pruritus-specific quality of life instrument, ItchyQoL. METHODS: A total of 419 patients (215 men and 204 women) with chronic pruritus (mean age, 46.58 years) recorded their pruritus intensity on VAS, NRS, VRS, and ISS. Retest reliability was analyzed in a second assessment 3 hours after the initial assessment. All participants answered ItchyQoL. RESULTS: A strong correlation between VAS, NRS, and VRS was found. ISS showed a low intercorrelation validity with these tools. However, ISS was more strongly correlated with ItchyQoL. The retest reliability scores were similar for VAS, NRS, and VRS but lower than the scores obtained for ISS. LIMITATIONS: Limitations include patient heterogeneity and recall bias. CONCLUSION: The assessment of pruritus is challenging because of the subjective symptoms and the multifactorial nature. Therefore, more studies are needed to determine the best strategy to assess itch intensity.

Can Anodal Transcranial Direct Current Stimulation Increase Steady-State Visual Evoked Potential Responses?

BACKGROUND: It has been frequently reported that non-negligible numbers of individuals have steady-state visual evoked potential (SSVEP) responses of low signal-to-noise-ratio (SNR) to specific stimulation frequencies, which makes detection of the SSVEP difficult especially in brain-computer interface applications. We investigated whether SSVEP can be modulated by anodal transcranial direct-current stimulation (tDCS) of the visual cortex. METHODS: Each participant participated in two 20-min experiments-an actual tDCS experiment and a sham tDCS experiment-that were conducted on different days. Two representative electroencephalogram (EEG) features used for the SSVEP detection, SNR and amplitude, were tested for pre- and post-tDCS conditions to observe the effect of the anodal tDCS. RESULTS: The EEG features were significantly enhanced by the anodal tDCS for the electrodes with low pre-tDCS SNR values, whereas the effect was not significant for electrodes with relatively higher SNR values. CONCLUSION: Anodal tDCS of the visual cortex may be effective in enhancing the SNR and amplitude of the SSVEP response especially for individuals with low-SNR SSVEP.

Improvement of Information Transfer Rates Using a Hybrid EEG-NIRS Brain-Computer Interface with a Short Trial Length: Offline and Pseudo-Online Analyses.

Electroencephalography (EEG) and near-infrared spectroscopy (NIRS) are non-invasive neuroimaging methods that record the electrical and metabolic activity of the brain, respectively. Hybrid EEG-NIRS brain-computer interfaces (hBCIs) that use complementary EEG and NIRS information to enhance BCI performance have recently emerged to overcome the limitations of existing unimodal BCIs, such as vulnerability to motion artifacts for EEG-BCI or low temporal resolution for NIRS-BCI. However, with respect to NIRS-BCI, in order to fully induce a task-related brain activation, a relatively long trial length (≥10 s) is selected owing to the inherent hemodynamic delay that lowers the information transfer rate (ITR; bits/min). To alleviate the ITR degradation, we propose a more practical hBCI operated by intuitive mental tasks, such as mental arithmetic (MA) and word chain (WC) tasks, performed within a short trial length (5 s). In addition, the suitability of the WC as a BCI task was assessed, which has so far rarely been used in the BCI field. In this experiment, EEG and NIRS data were simultaneously recorded while participants performed MA and WC tasks without preliminary training and remained relaxed (baseline; BL). Each task was performed for 5 s, which was a shorter time than previous hBCI studies. Subsequently, a classification was performed to discriminate MA-related or WC-related brain activations from BL-related activations. By using hBCI in the offline/pseudo-online analyses, average classification accuracies of 90.0 ± 7.1/85.5 ± 8.1% and 85.8 ± 8.6/79.5 ± 13.4% for MA vs. BL and WC vs. BL, respectively, were achieved. These were significantly higher than those of the unimodal EEG- or NIRS-BCI in most cases. Given the short trial length and improved classification accuracy, the average ITRs were improved by more than 96.6% for MA vs. BL and 87.1% for WC vs. BL, respectively, compared to those reported in previous studies. The suitability of implementing a more practical hBCI based on intuitive mental tasks without preliminary training and with a shorter trial length was validated when compared to previous studies.

Brain Areas Responsible for Vigilance: An EEG Source Imaging Study.

Vigilance, sometimes referred to as sustained attention, is an important type of human attention as it is closely associated with cognitive activities required in various daily-life situations. Although many researchers have investigated which brain areas control the maintenance of vigilance, findings have been inconsistent. We hypothesized that this inconsistency might be due to the use of different experimental paradigms in the various studies. We found that most of the previous studies used paradigms that included specific cognitive tasks requiring a high cognitive load, which could complicate identification of brain areas associated only with vigilance. To minimize the influence of cognitive processes other than vigilance on the analysis results, we adopted the d2-test of attention, which is a well-known neuropsychological test of attention that does not require high cognitive load, and searched for brain areas at which EEG source activities were temporally correlated with fluctuation of vigilance over a prolonged period of time. EEG experiments conducted with 31 young adults showed that left prefrontal cortex activity was significantly correlated with vigilance variation in the delta, beta1, beta2, and gamma frequency bands, but not the theta and alpha frequency bands. Our study results suggest that the left prefrontal cortex plays a key role in vigilance modulation, and can therefore be used to monitor individual vigilance changes over time or serve as a potential target of noninvasive brain stimulation.

Long-Term Prognosis of Alopecia Totalis and Alopecia Universalis: A Longitudinal Study with More than 10 Years of Follow-Up: Better than Reported.

BACKGROUND: In alopecia totalis (AT) and alopecia universalis (AU), the chance of full hair regrowth is known to be less than 10%. However, this information is based on a few older studies conducted in the 1950s and 1960s. OBJECTIVE: We investigated the current long-term prognosis of individuals with AT/AU. METHODS: A retrospective chart review was performed in patients with AT/AU between 1994 and 2005. Outcome data were collected by reviewing outpatient clinical files or by phone interviews. Finally, the long-term assessment of 70 patients with valid outcome data was performed. RESULTS: Twelve out of 70 patients with AT/AU (17.1%) had complete hair regrowth. Five out of 24 patients with AT (20.8%) showed complete hair regrowth, and 7 of 46 patients with AU (15.2%) achieved complete regrowth. Seventeen out of 70 patients with AT/AU (24.2%) reported hair regrowth greater than or equal to 90%. Thirty patients with AU (65.2%) remained in an alopecic state without improvement, while 5 patients with AT (20.8%) showed no hair regrowth. CONCLUSION: Our results suggest that the long-term prognosis of AT/AU is more favorable than previously thought. However, the clinical burden of AT/AU is still substantial.

1,2,4,5-Tetramethoxybenzene Suppresses House Dust Mite-Induced Allergic Inflammation in BALB/c Mice.

BACKGROUND: Atopic dermatitis (AD) is the most common allergic inflammatory skin disease. The activation of innate immunity by house dust mite (Dermatophagoides farinae extract, DFE) allergen plays an important role in the pathogenesis of AD. We previously showed the inhibitory effect of an extract of Amomum xanthioides on allergic diseases, and isolated 1,2,4,5-tetramethoxybenzene (TMB) as a major active component. In this study, we investigated whether TMB relieves DFE-induced allergic inflammation symptoms. METHODS: We established a DFE-induced allergic inflammation model in BALB/c mice by repeated skin exposure to DFE. To define the underlying mechanisms of action, we used a tumor necrosis factor-α and interferon-x03B3;-activated human keratinocytes (HaCaT cell line) and mouse keratinocytes (3PC cell line) cell line model. RESULTS: Oral administration of TMB suppressed allergic inflammation symptoms, such as histopathological analysis and ear thickness, in addition to serum IgE, DFE-specific IgE and IgG2a levels. TMB decreased the serum histamine levels and tissue infiltration of inflammatory cells, including mast cells and eosinophils. TMB also inhibited CD4+IFN-x03B3;+, CD4+IL-4+, and CD4+IL-17A+ lymphocyte expansion in the draining lymph nodes and expression of the Th2 cytokines in the ear tissue. TMB significantly inhibited the expression of cytokines and chemokines by the downregulation of the mitogen-activated protein kinases and nuclear factor of activated cytoplasmic T cells in HaCaT cells. CONCLUSIONS: TMB improved DFE-induced allergic inflammation by suppressing the production of proinflammatory cytokines and chemokines. Our results suggest that TMB might be a potential therapeutic agent for AD.

Alopecia Areata Progression Index, a Scoring System for Evaluating Overall Hair Loss Activity in Alopecia Areata Patients with Pigmented Hair: A Development and Reliability Assessment.

BACKGROUND: No scoring systems to evaluate overall hair loss activity in alopecia areata (AA) have been established. OBJECTIVE: We sought to develop a measurement tool (Alopecia Areata Progression Index, AAPI) for the evaluation of overall hair loss activity in AA patients with pigmented hair. METHODS: The scalp surface area was divided into 4 quadrants. In each quadrant, hair loss activity was scored on the basis of the percentage of alopecic area, clinical findings associated with hair loss. The AAPI was measured in 17 patients with different severities of AA. RESULTS: Interobserver and intraobserver reliabilities were assessed by 4 investigators. A significant correlation of the total AAPI was found among the 4 investigators. In addition, intraobserver reliability was excellent, and interobserver reliability was statistically reliable. CONCLUSION: The AAPI seems to represent a system capable of truly quantifying overall hair loss activity in AA patients with different severity, demonstrating trustworthy interobserver and intraobserver reliability.

Skin Infection due to Trichophyton tonsurans Still Occurs in People in Korea but not as Outbreaks.

Since 1995, Trichophyton tonsurans has been one of the causative agents of dermatophytosis in Korea. Herein we evaluate 77 patients infected with T. tonsurans who visited an outpatient clinic between 2004 and 2014. Infections due to T. tonsurans were diagnosed by mycological examination, which included direct microscopic examination using 15% KOH and culture in potato dextrose agar complemented with 0.5% chloramphenicol. The annual prevalence of infection due to T. tonsurans was the highest in 2014 (15 cases) but remained constant in non-gladiators between 2004 and 2014. The ratio of male to female patients was 1:0.3. The spring season presented the highest incidence compared with other seasons, with 27 cases. The incidence of infections due to T. tonsurans among gladiators was highest in spring compared with the other seasons whereas the incidence in non-gladiators was the highest in the winter. The body site most commonly affected was the face. Tinea corporis was the most common subtype of dermatophytosis caused by T. tonsurans. Herein, we demonstrate that the prevalence of infection with T. tonsurans remain constant throughout the study period in Korea.

Increasing Prevalence of Trichophyton rubrum Identified through an Analysis of 115,846 Cases over the Last 37 Years.

Trichophyton rubrum is the most common dermatophyte in the world with the highest prevalence in Korea. There are few reports about epidemiological and mycological characteristics of T. rubrum based on long-term, large-scale studies. The purpose of this study was to investigate the clinical and epidemiological characteristics of T. rubrum infections in Korea. We retrospectively investigated with patients' records about the epidemiological and mycological status of 115,846 cases with T. rubrum infection that was mycologically diagnosed at Catholic Skin Disease Clinic from 1979 to 2013. Direct microscopy in 15% KOH solution and culture was done in each case. The annual incidence of patients with T. rubrum infection had been increasing during the period; and of 131,122 patients with dermatophytosis, 115,846 patients (88.35%) had T. rubrum infection. Disease was most prevalent among patients in their twenties in the 1970s and 1980s; in their thirties in the 1990s; in their forties in the 2000s; and in their fifties in the 2010s. The sex ratio was 1.5:1. T. rubrum infection was most commonly seen in summer and was found predominantly in patients living in urban areas. Toe webs were most frequently involved, followed by toenails and groin. This epidemiologic findings provide useful information for prevention of T. rubrum infection and future dermatophytosis prospects.

Source activation of P300 correlates with negative symptom severity in patients with schizophrenia.

It is well known that the P300 amplitude is reduced in schizophrenia patients, which may reflect the pathophysiology and symptom severity of schizophrenia, particularly related to negative symptoms. However, the relationship between the underlying neural generator of the P300 and symptomatic outcomes are not yet fully understood. This study aimed to verify the abnormal P300 of schizophrenia in terms of its source activation to and further examine the relationship between reduced source activation and symptom severity of patients. For this purpose, the P300 was recorded from 34 patients with schizophrenia and matched healthy controls using an auditory oddball paradigm. We found that the P300 amplitude of schizophrenia patients was significantly decreased along the midline electrodes and both bilateral temporal areas compared with healthy controls. In comparing the source activation between the two groups, schizophrenia patients showed decreased source activation predominantly over the left hemisphere, including the cingulate, inferior occipital gyrus, middle occipital gyrus, middle temporal gyrus, posterior cingulate, precuneus, and superior occipital gyrus. Furthermore, we found that the decreased activation of the contrasted areas showed significant negative correlation with PANSS negative symptom scores in the middle temporal gyrus, posterior cingulate, precuneus, and superior occipital gyrus. Our findings suggest that the reduced P300 source activation in schizophrenia might reflect deficits in fronto-temporal-parietal circuit.

Decreasing incidence of Trichophyton mentagrophytes in Korea: analysis of 6,250 cases during the last 21-year-period (1992-2012).

Trichophyton mentagrophytes is the second common dermatophyte in Korea. However, few reports have been issued on the epidemiological and mycological characteristics of T. mentagrophytes in Korea based on long-term, large-scale study. The purpose of this study was to elucidate the epidemiological and mycological characteristics of T. mentagrophytes in Korea. During the 21-yr-period from 1992 to 2012, 6,250 patients with T. mentagrophytes were surveyed to determine annual incidence and the distribution of subjects by age, sex, season, involved sites, and place of residence. T. mentagrophytes infections were confirmed by fungal culture. In addition, the colony appearance of T. mentagrophytes was classified as granular, persicolor, powdery, or downy. Epidemiological analysis showed that annual incidence reached a peak in 2005, and then gradually decreased. T. mentagrophytes infection was most common in July, and was found predominantly in middle-aged adults, especially in those in their forties. Mycological analysis showed a powdery colony appearance was the most common, followed by persicolor and granular colonies. Toewebs were most frequently involved. This investigation on T. mentagrophytes provides insights into its incidence and characteristics.

White matter microstructural integrity as a key to effective propagation of gamma entrainment in humans.

Gamma entrainment through sensory stimulation has the potential to reduce the pathology of Alzheimer's disease in mouse models. However, clinical trials in Alzheimer's disease (AD) patients have yielded inconsistent results, necessitating further investigation. This single-center pre-post intervention study aims to explore the influence of white matter microstructural integrity on gamma rhythm propagation from the visual cortex to AD-affected regions in 31 cognitively normal volunteers aged ≥ 65. Gamma rhythm propagation induced by optimal FLS was measured. Diffusion tensor imaging was employed to assess the integrity of white matter tracts of interest. After excluding 5 participants with a deficit in steady-state visually evoked potentials, 26 participants were included in the final analysis. In the linear regression analyses, gamma entrainment was identified as a significant predictor of gamma propagation (p < 0.001). Furthermore, the study identified white matter microstructural integrity as a significant predictor of gamma propagation by flickering light stimulation (p < 0.05), which was specific to tracts that connect occipital and temporal or frontal regions. These findings indicate that, despite robust entrainment of gamma rhythms in the visual cortex, their propagation to other regions may be impaired if the microstructural integrity of the white matter tracts connecting the visual cortex to other areas is compromised. Consequently, our findings have expanded our understanding of the prerequisites for effective gamma entrainment and suggest that future clinical trials utilizing visual stimulation for gamma entrainment should consider white matter tract microstructural integrity for candidate selection and outcome analysis.

Effect of Dynamic Binaural Beats on Sleep Quality: A Proof-of-Concept Study with Questionnaire and Biosignals.

Binaural beat (BB) has been investigated as a potential modality to enhance sleep quality. In this study, we introduce a new form of BB, referred to as dynamic BB (DBB), which incorporates dynamically changing carrier frequency differences between the left and right ears. Specifically, the carrier frequency of the right ear varied between 100 and 103 Hz over a period, while the left ear remained fixed at 100 Hz, yielding a frequency difference range of 0 to 3 Hz. The objective of this study was to examine the effect of DBB on sleep quality. Ten healthy participants were included in a cross-over design, where they experienced both DBB and a SHAM (absence of sound) condition across two consecutive nights, with polysomnography evaluation. DBB was administrated during pre-sleep initiation, sleep onset, and transition from rapid-eye-movement (REM) to non-REM stage. DBB significantly reduced sleep latency compared to the SHAM condition. Electrocardiogram analysis revealed that exposure to DBB led to diminished heart rate variability during the pre-sleep initiation and sleep onset periods, accompanied by a decrease in low frequency power of heart rate during the sleep onset period. DBB might be effective in improving the sleep quality, suggesting its possible application in insomnia treatments.

Open clinical trial for evaluation of efficacy and safety of a portable "dry-type" iontophoretic device in treatment of palmar hyperhidrosis.

BACKGROUND: Palmar hyperhidrosis is characterized by excessive sweating on the palm. Although botulinum toxin is effective and safe treatment for palmar hyperhidrosis, some patients require inexpensive, easy-to-use therapeutic modalities. OBJECTIVE: To evaluate the efficacy and safety of a portable "dry-type" iontophoretic device for treatment of palmar hyperhidrosis. PARTICIPANTS: Twenty-three volunteers with idiopathic palmar hyperhidrosis were enrolled; 20 completed the study. METHODS: Participants were instructed to grasp the device with the left palm for 20 minutes once a day for 4 weeks. Follow-up evaluation was conducted during 4 weeks after termination of the treatment session. Sweat intensity, Investigator Global Assessment (IGA), patient satisfaction assessment (PSA), and hydration capacitance were measured for evaluation of efficacy. Adverse effects were investigated for evaluation of safety. RESULTS: Statistically significantly greater improvement in IGA and hydration capacitance was achieved in the treated palm than in the untreated palm. Improvement in sweat intensity and PSA was not statistically significantly different in the treated and untreated palms. Two cases of mild local adverse effects were noted. CONCLUSION: The device is an effective therapeutic modality for palmar hyperhidrosis in addition to local injection of botulinum toxin, endoscopic sympathectomy, and conventional iontophoretic treatments.

In vitro evaluation of novel inhibitors against the NS2B-NS3 protease of dengue fever virus type 4.

The discovery of potent therapeutic compounds against dengue virus is urgently needed. The NS2B-NS3 protease (NS2B-NS3pro) of dengue fever virus carries out all enzymatic activities needed for polyprotein processing and is considered to be amenable to antiviral inhibition by analogy. Virtual screening of 300,000 compounds using Autodock 3 on the GVSS platform was conducted to identify novel inhibitors against the NS2B-NS3pro. Thirty-six compounds were selected for in vitro assay against NS2B-NS3pro expressed in Pichia pastoris. Seven novel compounds were identified as inhibitors with IC50 values of 3.9 ± 0.6-86.7 ± 3.6 µM. Three strong NS2B-NS3pro inhibitors were further confirmed as competitive inhibitors with Ki values of 4.0 ± 0.4, 4.9 ± 0.3, and 3.4 ± 0.1 µM, respectively. Hydrophobic and hydrogen bond interactions between amino acid residues in the NS3pro active site with inhibition compounds were also identified.