Meta-Analysis of Studies on the Effects of Digital Therapeutics.

Digital therapeutics (DTx), novel treatment methods that have the potential to surpass traditional approaches such as pills, have received considerable research attention. Various efforts have been made to explore effective treatment methods that actively integrate DTx. This review investigates DTx treatment outcomes comprehensively through a meta-analysis. The analysis-a manual search of studies on "digital therapeutics"-includes DTx studies from January 2017 to October 2022. Hedges' g is used to quantify effect size for fifteen studies analyzed, encompassing eight control groups. Further, a quality assessment is performed using the Bias Risk Assessment Tool. The Hedges' g analysis results provide weighted average effect sizes across the eight control groups, revealing a substantial value of 0.91 (95% CI: 0.62 to 1.20); this signifies a moderate to large effect size. Further refinement, which excludes one study, yields an increased weighted average effect size of 1.13 (95% CI: 0.91 to 1.36). The quality assessment results consistently indicate a low risk of bias across studies. The meta-analysis results indicate that DTx can provide significant pivotal therapeutic impacts and offer a means to personalize treatment approaches and streamline the management of patients' treatment processes.

Efficacy and Safety of High Density LED Irradiation Therapy for Patients With Hand Osteoarthritis: A Single-Center Clinical Study.

OBJECTIVE: To assess the safety and effectiveness of high-density light-emitting diode (LED) irradiation therapy in patients with hand osteoarthritis (OA) and compare the pre- and post-intervention symptoms. METHODS: Twenty-three patients with hand OA underwent eight sessions of high-density LED irradiation therapy directed at the five most painful areas in the finger joints. Each session lasted for 18 minutes; and the sessions were conducted twice a week, for 4 weeks. We evaluated the degree of pain using the visual analogue scale, ring size, and passive range of motion (flexion+extension) for two most painful joints from the baseline to post-therapy (weeks 4 and 6). RESULTS: High-density LED irradiation therapy significantly reduced the pain posttreatment compared with that observed at the baseline (p<0.001). Although improvements were observed in ring size and joint range of motion at 4 and 6 weeks, they were not statistically significant (p>0.05). No adverse events were observed. CONCLUSION: We examined the safety and effectiveness of high-density LED irradiation therapy in reducing pain and hand swelling and improving joint mobility in patients with hand OA. These results suggest that high-density LED irradiation therapy has the potential to be an important strategy for managing hand OA.

Preclinical Study of Dual-Wavelength Light-Emitting Diode Therapy in an Osteoarthritis Rat Model.

OBJECTIVE: To evaluate the efficacy of light-emitting diode (LED) and their dual-wavelengths as a treatment strategy for osteoarthritis. METHODS: We induced osteoarthritis in male Sprague-Dawley rats by intra-articular injection of sodium iodoacetate into the right rear knee joint. The animals with lesions were divided into an untreated group and an LED-treated group (n=7 each). In the LED-treated group, the lesioned knee was irradiated with lasers (850 and 940 nm) and dose (3.15 J/cm2) for 20 minutes per session, twice a week for 4 weeks. Knee joint tissues were stained and scanned using an in vivo micro-computed tomography (CT) scanner. Serum interleukin (IL)-6 and IL-18 levels were determined using enzyme-linked immuno-sorbent assay. Several functional tests (lines crossed, rotational movement, rearing, and latency to remain rotating rod) were performed 24 hours before LED treatment and at 7, 14, 21, and 28 days after treatment. RESULTS: LED-treated rats showed improved locomotor function and suppressed matrix-degrading cytokines. Micro-CT images indicated that LED therapy had a preserving effect on cartilage and cortical bone. CONCLUSION: LED treatment using wavelengths of 850 and 940 nm resulted in significant functional, anatomical, and histologic improvements without adverse events in a rat model. Further research is required to determine the optimal wavelength, duration, and combination method, which will maximize treatment effectiveness.

A Double-Blinded, Randomized, Dose-Comparison Pilot Study to Comparatively Evaluate Efficacy and Safety of Two Doses of Botulinum Toxin Type A Injection for Deltoid Muscle Hypertrophy.

BACKGROUND: Botulinum toxin type A (BTX-A) injection is being widely used off-label for muscular hypertrophy, including deltoid muscle hypertrophy. However, very few studies have evaluated the optimal dosage and its clinical response. OBJECTIVE: This study aimed to assess the efficacy and safety of different doses of Prabotulinum toxin A (PBoNT) for treating deltoid muscle hypertrophy. METHODS: Twelve particiapants with bilateral deltoid muscle hypertrophy were enrolled and randomly received either 16 U or 32 U of PBoNT. In each participant, the same dose was administered to both deltoid muscles. Both participants and evaluators were blinded. Deltoid muscle thickness and upper arm circumference were measured on day 0, and weeks 2, 4, and 12 after the PBoNT injection. RESULTS: Upper arm circumference significantly decreased in both groups; however, deltoid muscle thickness was reduced in the 16 U group only. No major complications were reported in both groups. However, a few minor complications were reported in the 16 U injection group. CONCLUSION: Both 16 U and 32 U of PBoNT intramuscular injections are safe and effective in treating deltoid hypertrophy.

Gene nceA encodes a Ni/Co-sensing transcription factor to regulate metal efflux in Corynebacterium glutamicum.

The function of Corynebacterium glutamicum open reading frame (ORF) NCgl2684 (named nceA in this study), which was annotated to encode a metalloregulator, was assessed using physiological, genetic, and biochemical approaches. Cells with deleted-nceA (ΔnceA) showed a resistant phenotype to NiSO4 and CoSO4 and showed faster growth in minimal medium containing 20 µM NiSO4 or 10 µM CoSO4 than both the wild-type and nceA-overexpressing (P180-nceA) cells. In the ΔnceA strain, the transcription of the downstream-located ORF NCgl2685 (nceB), annotated to encode efflux protein, was increased approximately 4-fold, whereas gene transcription decreased down to 30% level in the P180-nceA strain. The transcriptions of the nceA and nceB genes were stimulated, even when as little as 5 nM NiSO4 was added to the growth medium. Protein NceA was able to bind DNA comprising the promoter region (from -14 to + 18) of the nceA--nceB operon. The protein-DNA interaction was abolished in the presence of 20 µM NiSO4, 50 µM CoSO4, or 50 µM CdSO4. Although manganese induced the transcription of the nceA and nceB genes, it failed to interrupt protein-DNA interaction. Simultaneously, the P180-nceA cells showed increased sensitivity to oxidants such as menadione, hydrogen peroxide, and cumene hydroperoxide, but not diamide. Collectively, our data show that NceA is a nickel- and cobalt-sensing transcriptional regulator that controls the transcription of the probable efflux protein-encoding nceB. The genes are able to suppress intracellular levels of nickel to prevent reactions, which can cause oxidative damage to cellular components.

Spermidine-induced recovery of human dermal structure and barrier function by skin microbiome.

An unbalanced microbial ecosystem on the human skin is closely related to skin diseases and has been associated with inflammation and immune responses. However, little is known about the role of the skin microbiome on skin aging. Here, we report that the Streptococcus species improved the skin structure and barrier function, thereby contributing to anti-aging. Metagenomic analyses showed the abundance of Streptococcus in younger individuals or those having more elastic skin. Particularly, we isolated Streptococcus pneumoniae, Streptococcus infantis, and Streptococcus thermophilus from face of young individuals. Treatment with secretions of S. pneumoniae and S. infantis induced the expression of genes associated with the formation of skin structure and the skin barrier function in human skin cells. The application of culture supernatant including Streptococcal secretions on human skin showed marked improvements on skin phenotypes such as elasticity, hydration, and desquamation. Gene Ontology analysis revealed overlaps in spermidine biosynthetic and glycogen biosynthetic processes. Streptococcus-secreted spermidine contributed to the recovery of skin structure and barrier function through the upregulation of collagen and lipid synthesis in aged cells. Overall, our data suggest the role of skin microbiome into anti-aging and clinical applications.

Length-Dependent Evolution of Type II Heterojunctions in Bottom-Up-Synthesized Graphene Nanoribbons.

The ability to tune the band-edge energies of bottom-up graphene nanoribbons (GNRs) via edge dopants creates new opportunities for designing tailor-made GNR heterojunctions and related nanoscale electronic devices. Here we report the local electronic characterization of type II GNR heterojunctions composed of two different nitrogen edge-doping configurations (carbazole and phenanthridine) that separately exhibit electron-donating and electron-withdrawing behavior. Atomically resolved structural characterization of phenanthridine/carbazole GNR heterojunctions was performed using bond-resolved scanning tunneling microscopy and noncontact atomic force microscopy. Scanning tunneling spectroscopy and first-principles calculations reveal that carbazole and phenanthridine dopant configurations induce opposite upward and downward orbital energy shifts owing to their different electron affinities. The magnitude of the energy offsets observed in carbazole/phenanthridine heterojunctions is dependent on the length of the GNR segments comprising each heterojunction with longer segments leading to larger heterojunction energy offsets. Using a new on-site energy analysis based on Wannier functions, we find that the origin of this behavior is a charge transfer process that reshapes the electrostatic potential profile over a long distance within the GNR heterojunction.

Concentration Dependence of Dopant Electronic Structure in Bottom-up Graphene Nanoribbons.

Bottom-up fabrication techniques enable atomically precise integration of dopant atoms into the structure of graphene nanoribbons (GNRs). Such dopants exhibit perfect alignment within GNRs and behave differently from bulk semiconductor dopants. The effect of dopant concentration on the electronic structure of GNRs, however, remains unclear despite its importance in future electronics applications. Here we use scanning tunneling microscopy and first-principles calculations to investigate the electronic structure of bottom-up synthesized N = 7 armchair GNRs featuring varying concentrations of boron dopants. First-principles calculations of freestanding GNRs predict that the inclusion of boron atoms into a GNR backbone should induce two sharp dopant states whose energy splitting varies with dopant concentration. Scanning tunneling spectroscopy experiments, however, reveal two broad dopant states with an energy splitting greater than expected. This anomalous behavior results from an unusual hybridization between the dopant states and the Au(111) surface, with the dopant-surface interaction strength dictated by the dopant orbital symmetry.

The Effects of Chunghyul-Dan, an Agent of Korean Medicine, on a Mouse Model of Traumatic Brain Injury.

Chunghyul-Dan (CHD) is the first choice agent for the prevention and treatment of stroke at the Kyung Hee Medical Hospital. To date, CHD has been reported to have beneficial effects on brain disease in animals and humans, along with antioxidative and anti-inflammatory effects. The aim of this study was to evaluate the pharmacological effects of CHD on a traumatic brain injury (TBI) mouse model to explore the possibility of CHD use in patients with TBI. The TBI mouse model was induced using the controlled cortical impact method. CHD was orally administered twice a day for 5 d after TBI induction; mice were assessed for brain damage, brain edema, blood-brain barrier (BBB) damage, motor deficits, and cognitive impairment. Treatment with CHD reduced brain damage seen on histological examination and improved motor and cognitive functions. However, CHD did not reduce brain edema and BBB damage. In conclusion, CHD could be a candidate agent in the treatment of patients with TBI. Further studies are needed to assess the exact mechanisms of the effects during the acute-subacute phase and pharmacological activity during the chronic-convalescent phase of TBI.

Herbal medicine treatment for drug-induced parkinsonism.

OBJECTIVES: To evaluate the role of herbal medicine in drug-induced parkinsonism (DIP) and identify an optimal treatment approach. DESIGN: Retrospective review of DIP cases treated with herbal medicine. SETTINGS/LOCATION: The Parkinson's clinic at Kyung Hee Traditional Korean Medicine Hospital, Korea. PATIENTS: Twenty-one patients whose clinical outcome and offending drug could be identified. OUTCOME MEASURES: Clinical features, treatments, and outcomes and summarized the clinical course and treatment in each case. RESULTS: Twelve patients had levosulpiride-induced parkinsonism and 9 had parkinsonism induced by another drug. The offending drugs were discontinued in all patients, and all patients received herbal medications during treatment. Nine of 12 patients with parkinsonism from levosulpiride and 4 of 9 patients with parkinsonism from other drugs had complete reversal of symptoms. The most frequently used herbal formula was Ukgansan (Yigansan). DIP in the levosulpiride group tended to improve faster with herbal medicine, and the percentage of improvement was higher. CONCLUSIONS: Optimal herbal medicine treatments chosen after a careful history and evaluation for risk factors may be helpful in reversing DIP.

Decreased ATP synthesis and lower pH may lead to abnormal muscle contraction and skin sensitivity in human skin.

BACKGROUND: Sensitive skin represents hyperactive sensory symptoms showing exaggerated reactions in response to internal stimulants or external irritants. Although sensitive skin is a very common condition affecting an estimated 50% of the population, its pathophysiology remains largely elusive, particularly with regard to its metabolic aspects. OBJECTIVE: The objective of our study was to investigate the pathogenesis of sensitive skin. METHODS: We recruited healthy participants with 'sensitive' or 'non-sensitive' skin based on standardized questionnaires and 10% lactic acid stinging test, and obtained skin samples for microarray analysis and subsequent experiments. RESULTS: Microarray transcriptome profiling revealed that genes involved in muscle contraction, carbohydrate and lipid metabolism, and ion transport and balance were significantly decreased in sensitive skin. These altered genes could account for the abnormal muscle contraction, decreased ATP amount in sensitive skin. In addition, pain-related transcripts such as TRPV1, ASIC3 and CGRP were significantly up-regulated in sensitive skin, compared with non-sensitive skin. CONCLUSIONS: Our findings suggest that sensitive skin is closely associated with the dysfunction of muscle contraction and metabolic homeostasis.

Temporary increase of PPAR-γ and transient expression of UCP-1 in stromal vascular fraction isolated human adipocyte derived stem cells during adipogenesis.

In this study, cells from the stromal vascular fraction of human subcutaneous tissues were induced to differentiate toward adipose cells in vitro for 2 weeks. During adipogenic differentiation, we followed the chronological changes in their morphology with Coherent anti-Stokes Raman scattering (CARS) microscopy and checked the PPAR-γ and UCP-1 expression with RT-PCR. On day 4 after inducing adipogenic differentiation, CARS imaging showed multiple small lipid droplets (LD) distributed peripherally along the cellular membrane. PPAR-γ began to express at this time and increased until day 14 at a steady rate. On day 7, the cells appeared as brown adipocytes with numerous small LD throughout the cytoplasm, and the mRNA level of UCP-1 rose abruptly by 6- to 7-fold. After an additional 7 days, CARS imaging showed the development of a large LD, which is characteristic of white adipocytes, and the mRNA level of UCP-1 slumped significantly. These results demonstrate the possibility that ADSC pass through a brown adipocyte-like stage while differentiating into white adipocytes.

0.5% Liposome-encapsulated 5-aminolevulinic acid (ALA) photodynamic therapy for acne treatment.

BACKGROUND: Photodynamic therapy using topical 5-aminolevulinic acid (ALA) has been successful in treating acne vulgaris, but sun avoidance for at least 48 hours after treatment is necessary due to the risk of post-treatment photosensitivity. Recently, a lower concentration of liposome-encapsulated 5-ALA was introduced to minimize this risk. OBJECTIVES: To evaluate the efficacy and safety of liposome-encapsulated 0.5% 5-ALA in the photodynamic therapy of inflammatory acne and its effects on sebum secretion in Asian skin. METHODS: Thirteen Korean subjects with inflammatory acne were administered 0.5% ALA spray before photoradiation treatment. Photoradiation was performed at 3.5-6.0 J/cm(2) three times during each of two visits, performed 2 weeks apart. Improvement of acne was evaluated subjectively and objectively based on the Korean Acne Grading System. Sebum secretion was measured quantitatively at each visit. RESULTS: The mean reduction in acne grade at the end of the treatment was 43.2%. Of the patients, 69.2% reported improvements in subjective skin oiliness, but fewer showed objective reductions in sebum secretion as determined by the Sebumeter® SM10. No serious adverse events were observed. CONCLUSION: Photodynamic therapy using liposome-encapsulated 0.5% 5-ALA improved inflammatory acne with minimal side effects in Asians.

Acidic pH-activated Cl Current and Intracellular Ca Response in Human Keratinocytes.

The layers of keratinocytes form an acid mantle on the surface of the skin. Herein, we investigated the effects of acidic pH on the membrane current and [Ca(2+)](c) of human primary keratinocytes from foreskins and human keratinocyte cell line (HaCaT). Acidic extracellular pH (pH(e)

Pemphigus in Korea: clinical manifestations and treatment protocol.

Pemphigus, a rare, chronic blistering disease of the skin and mucous membranes with severe morbidity and occasional mortality, is the most common autoimmune bullous disease in Korea. The purpose of this study was to evaluate the clinical features and propose a treatment strategy for patients with pemphigus. A retrospective analysis was conducted of 51 pemphigus patients seen between 1993 and 2001. Pemphigus vulgaris (PV) was the most common type with 32 cases, followed by 19 cases of pemphigus foliaceus (PF). The male to female ratio was 1:1.3, with females predominating, particularly among PV patients (PV, 1:1.5; PF, 1:1.1). The average ages at onset of PV and PF were 44.3 and 51.0 years old, respectively. Mucosal involvement was noted in 27 cases (84.4%) of PV but in only 3 cases (15.8%) of PF. Most patients initially received relatively low to intermediate doses (0.3-1.0 mg/kg/day) of prednisolone, and 23 (71.9%) PV patients and 10 (52.6%) PF patients also received immunosuppressive agents. Oral prednisolone and azathioprine (100 mg/day) formed the mainstay of treatment for our patients (47.1%). At the time of writing, 25.5% (13/51) of patients are in complete remission, and 72.5% (37/51) are undergoing maintenance therapy. One patient died due to sepsis during the treatment. For the treatment of pemphigus, a course of the lowest possible corticosteroid dosage in combination with immunosuppressive agents appears to be effective and less toxic than a high corticosteroid dosage.

LEOPARD syndrome with a new association of congenital corneal tumor, choristoma.

A 5-year-old girl with a family history of LEOPARD syndrome had multiple lentigines on the face and trunk, hypertelorism, and growth retardation. In addition, she had congenital corneal tumors on both eyes. Histologically the tumors were choristoma. The neuroectodermal origin hypothesis of LEOPARD syndrome could explain the presence of a congenital corneal tumor in this patient. We suggest that corneal tumor may represent an unrecognized associated finding in this syndrome.