Ultrasonographic findings of facial muscles in patients with severe facial palsy who showed no improvement for more than 3 months on acute stage.

INTRODUCTION/AIMS: The study aimed to visualize the changes in the facial muscles of patients with severe facial palsy who showed no improvement for more than 3 months on acute stage. METHODS: The 102 patients with severe facial palsy over House-Brackmann grade IV or an 80% degenerative ratio on ENoG at the initial examination, who showed no improvement for more than 3 months on acute stage were indicated to undergo ultrasonography of the face to evaluate the facial muscles. RESULTS: Muscular degeneration was observed in 537/918 muscles (58.5%). Muscle volume shrinkage was observed in 209/918 muscles (22.8%). Fascial adhesions were observed in 209/918 muscles (22.7%). Among all the muscles assessed for degenerative changes, zygomaticus major/minor was the most affected by degenerative changes (91.2%). Degenerative changes were observed in the levator labii superioris muscle in 84.3% patients. The shrinkage was most frequently observed in the zygomaticus major muscle (61/102 patients [59.8%]), followed by the zygomaticus minor muscle (43.1%). Shrinkage of the levator labii suprioris was observed in 24.5% patients. The zygomaticus major/minor muscle had the highest proportion of fascial adhesions in 61.8% and 66.7% patients respectively. The levator labii suprioris muscle showed the lowest proportion of fascial adhesions, with only 7.8% patients being affected. DISCUSSION: This study confirmed that the zygomaticus major, zygomaticus minor, and levator labii suprioris muscles, which raise the corner of the mouth, are the first to degenerate in patients with severe facial paralysis. This study demonstrated that ultrasonography is a simple and non-invasive examination for facial paralysis.

Exploring the Role of Gut Microbiota in Patients with Alopecia Areata.

Imbalances in gut microbiota reportedly contribute to the development of autoimmune diseases, but the association between the etiopathogenesis of alopecia areata (AA) and gut microbial dysbiosis remains unclear. This cross-sectional study was conducted to identify and compare the composition of the gut microbiome in patients affected by AA and those in a healthy control (HC) group, and to investigate possible bacterial biomarkers for the disease. Fecal samples were collected from 19 AA patients and 20 HCs to analyze the relationship with fecal bacteria. The three major genera constituting the gut microbiome of AA patients were Bacteroides, Blautia, and Faecalibacterium. The alpha diversity of the AA group was not statistically significant different from that of the HC group. However, bacterial community composition in the AA group was significantly different from that of HC group according to Jensen-Shannon dissimilarities. In patients with AA, we found an enriched presence of the genera Blautia and Eubacterium_g5 compared to the HC group (p < 0.05), whereas Bacteroides were less prevalent (p < 0.05). The gut microbiota of AA patients was distinct from those of the HC group. Our findings suggest a possible involvement of gut microbiota in in the as-yet-undefined pathogenesis of AA.

Microbial Community Changes in Silkworms Suspected of Septicemia and Identification of Serratia sp.

Diseases that occur in silkworms include soft rot, hardening disease, digestive diseases, and sepsis. However, research on the causes of bacterial diseases occurring in silkworms and the resulting changes in the microbial community is lacking. Therefore, we examined the morphological characteristics of sepsis and changes in the microbial community between silkworms that exhibit a unique odor and healthy silkworms; thus, we established a relationship between disease-causing microorganisms and sepsis. After producing a 16S rRNA amplicon library for samples showing sepsis, we obtained information on the microbial community present in silkworms using next-generation sequencing. Compared to that in healthy silkworms, in silkworms with sepsis, the abundance of the Firmicutes phylum was significantly reduced, while that of Proteobacteria was increased. Serratia sp. was dominant in silkworms with sepsis. After bacterial isolation, identification, and reinfection through the oral cavity, we confirmed this organism as the disease-causing agent; its mortality rate was 1.8 times higher than that caused by Serratia marcescens. In summary, we identified a new causative bacterium of silkworm sepsis through microbial community analysis and confirmed that the microbial community balance was disrupted by the aberrant proliferation of certain bacteria.

Risk of autoimmune skin and connective tissue disorders after mRNA-based COVID-19 vaccination.

BACKGROUND: Data on the association between the development of autoimmune diseases and COVID-19 vaccination are limited. OBJECTIVE: To investigate the incidence and risk of autoimmune connective tissue disorders following mRNA-based COVID-19 vaccination. METHODS: This nationwide population-based study was conducted in South Korea. Individuals who received vaccination between September 8, 2020-December 31, 2021, were identified. Historical prepandemic controls were matched for age and sex in 1:1 ratio. The incidence rate and risk of disease outcomes were compared. RESULTS: A total of 3,838,120 vaccinated individuals and 3,834,804 controls without evidence of COVID-19 were included. The risk of alopecia areata, alopecia totalis, primary cicatricial alopecia, psoriasis, vitiligo, anti-neutrophil cytoplasmic antibody-associated vasculitis, sarcoidosis, Behcet disease, Crohn disease, ulcerative colitis, rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren syndrome, ankylosing spondylitis, dermato/polymyositis, and bullous pemphigoid was not significantly higher in vaccinated individuals than in controls. The risk was comparable according to age, sex, type of mRNA-based vaccine, and cross-vaccination status. LIMITATIONS: Possible selection bias and residual confounders. CONCLUSION: These findings suggest that most autoimmune connective tissue disorders are not associated with a significant increase in risk. However, caution is necessary when interpreting results for rare outcomes due to limited statistical power.

4-Hexylresorcinol Treatment before Degumming Increases the ß-Sheet Structure of Silk Sericin and BMP-2 Expression in RAW264.7 Cells.

Silk sericin is a degumming product used by the silk industry. The degumming process can affect the protein structure and molecular weight of silk sericin. The present study examined how pretreatment with 4-hexylresorcinol (4HR) affects the biomedical properties of silk sericin. Before the degumming process, silkworm cocoons were treated with 4HR solution. The protein structure of the final degumming product was evaluated by Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy. Untreated silk sericin (S) and silk sericin pretreated with 4HR (S+4HR) were added to RAW264.7 cells, and the expression of BMP-2 was determined. The bone-regenerating capacity of S+4HR was evaluated using the critical-sized rat calvarial defect model. Compared with S, S+4HR showed an increase in ß-sheet structures. Administration of S+4HR to RAW264.7 cells increased expression of BMP-2, mainly via the TLR-mediated signaling pathway. Bone volume, as measured by micro-computerized tomography, was significantly greater in the S+4HR group than in the S, gelatin alone, and unfilled control groups (p < 0.05 each). Expression of BMP-2 and runx2 in tissue specimens was significantly higher following treatment with S+4HR than with S (p < 0.05). Taken together, these findings show that 4HR pretreatment before the degumming process increased the ß-sheet structure of silk sericin, as well as inducing BMP-2 expression and bone regeneration ability.

Hidradenitis suppurativa in South-East Asia and East Asia.

Hidradenitis suppurativa (HS) in South-East Asia and East Asia shows distinct clinical, environmental, physiological and likely genetic differences compared with the West. A male predominance is present, which may be due to differences in smoking habits. Involvement of the buttocks is common in East Asian patients, while the axillae are most commonly affected in South-East Asian patients. Metabolic comorbidities are prevalent in South-East Asian and East Asian HS patients. A family history of HS is less common than noted in Western populations. Asian ethnic subgroups deserve further study.

Excimer laser/light treatment of alopecia areata: A systematic review and meta-analyses.

BACKGROUND: The excimer laser/light (EL) has been reported to be effective for alopecia areata (AA), but its treatment response has not been systematically reviewed. OBJECTIVE: To determine the treatment response and safety of EL treatment of AA. METHODS: A comprehensive search of the Medline, EMBASE, Cochrane library, and Web of Science (from inception to December 31, 2018) was conducted to identify prospective clinical studies assessing the treatment response of EL for AA. The primary outcome was cosmetically acceptable hair regrowth (hair regrowth ≥75%); random-effects meta-analyses using generic inverse variance weighting were performed to estimate treatment responses. The study was registered with PROSPERO (CRD42019121092). RESULTS: Of 52 records initially identified, 13 full-text articles were finally assessed in terms of eligibility. A total of 9 prospective clinical studies (129 AA patients) including 5 controlled clinical trials were identified. Cosmetically acceptable hair regrowth was achieved in 50.2% (95% confidence interval 31.5%-68.9%; 8 studies). EL treatment significantly improved hair regrowth compared with untreated controls (relative risk 7.83; 95% confidence interval 2.11-29.11; 5 controlled clinical trials). No serious adverse effect was noted. CONCLUSIONS: EL treatment appeared to produce a favorable therapeutic response in AA patients. The use of EL should be encouraged for AA patients with the advantages of the non-invasiveness and no systemic effect.

A TRPV1 antagonist, PAC-14028 does not increase the risk of tumorigenesis in chemically induced mouse skin carcinogenesis.

PAC-14028 (Asivatrep: C21H22F5N3O3S) cream is a novel, topical nonsteroidal, anti-inflammatory, and TRPV1 (transient receptor potential vanilloid subfamily, member 1) antagonist for the treatment of mild to moderate atopic dermatitis. Concerns about the risk of tumor development by TRPV1 blockade in the skin have been prompted, but these findings were proved to be indirect or are still controversial. This study was tested to determine whether TRPV1 selective antagonist, PAC-14028 cream is safe from the promotion of skin tumorigenesis in the two-stage carcinogenesis model. PAC-14028 cream, 0.25%, 0.5%, or 1.0% was applied once daily topically to mouse skin for up to 24 weeks in two-stage chemical carcinogenesis testing using 7, 12-dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA). Morbidity/death, clinical signs, tumor formation, activity of EGFR/Akt/mTOR signaling, and systemic exposure to PAC-14028 were investigated. Daily dermal administration of PAC-14028, was not skin carcinogenic. There was also no evidence on the activation of EGFR/Akt/mTOR signaling pathway by the topical treatment of PAC-14028. On Day 169, 1.0% (20 mg/kg/day) of PAC-14028 in female mice resulted in a Cmax and AUC0-τ of 12916.0 ng/mL and 78962.9 ng‧hr/mL, respectively. PAC-14028 cream was well tolerated and did not increase the risk of skin tumorigenesis in two-stage carcinogenesis study.

Orally administered collagen peptide protects against UVB-induced skin aging through the absorption of dipeptide forms, Gly-Pro and Pro-Hyp.

Collagen hydrolysate is a well-known nutritional supplement for the improvement of healthy skin. Here, collagen peptide NS (CPNS) from fish scale was prepared, and its physicochemical properties were investigated. Gly-Pro was revealed as a representative low molecular weight peptide of CPNS, by performing prep-HPLC and LC-MS/MS. CPNS treatment attenuated matrix metalloproteinase-1 production and increased the synthesis of type 1 procollagen in HDF cells. After orally administering CPNS to rats, the plasma concentrations of Gly-Pro and Pro-Hyp increased dramatically. To examine the protective effects of CPNS against ultraviolet B (UVB)-induced photoaging in vivo, the dorsal skins of hairless mice were exposed to UVB and supplemented with CPNS for 12 weeks. The CPNS consumption significantly attenuated UVB-induced wrinkle formation, transepidermal water loss, and epidermis thickness, and increased skin hydration. Collectively, these results suggest that bioactive peptides of CPNS, Gly-Pro and Pro-Hyp, exert beneficial effects on skin health.

Comparison of 311-nm Titanium:Sapphire laser and 308-nm excimer laser treatment for vitiligo: A randomized controlled non-inferiority trial.

OBJECTIVES: The 308-nm excimer laser (EL) has been widely used for localized vitiligo. The recently developed Titanium:Sapphire laser, emits a wavelength of 311 nm, would be expected to be as effective as excimer laser in treatment of vitiligo but few controlled trials have been reported. We sought to compare the efficacy and safety of the TSL and EL as vitiligo treatments. METHODS: A randomized controlled non-inferiority trial based on split-body was conducted. Patients with stable vitiligo between June 2016 and May 2017 were enrolled. Paired symmetrical vitiligo lesions were randomized to either the EL or TSL treatment group, and treated with a 308-nm EL or a 311-nm TSL twice weekly for 12 weeks. The extent of repigmentation was assessed every 4 weeks, and the non-inferiority margin was set to 10%. We also recorded any adverse events. RESULTS: Seventy-four paired lesions in 21 patients were assigned to both the EL group or TSL group. The mean difference between two groups (EL minus TSL) was -2.862%, and the 95% confidence interval (-6.531% to 0.807%) was lower than the non-inferiority margin. No serious adverse events were noted in either group. CONCLUSIONS: The Titanium:Sapphire laser showed similar therapeutic effect to excimer laser in localized vitiligo with good safety profiles in this non-inferiority randomized controlled trial. The Titanium: Sapphire laser can serve as an alternative treatment option for localized vitiligo. Lasers Surg. Med. 51:239-244, 2019. © 2019 Wiley Periodicals, Inc.

Effects of Human Mesenchymal Stem Cells Coculture on Calcium-Induced Differentiation of Normal Human Keratinocytes.

The influence of mesenchymal stem cells (MSCs) on keratinocytes in altered microenvironments is poorly understood. Here, we cocultured umbilical cord blood-derived MSCs with normal human epidermal keratinocytes to evaluate their paracrine effect in the presence of high extracellular calcium (Ca2+ ) concentration. High Ca2+ environment to keratinocytes can disrupt normal skin barrier function due to abnormal/premature differentiation of keratinocytes. Surprisingly, we found that MSCs suppress both proliferation and differentiation of keratinocytes under a high Ca2+ environment in transforming growth factors ß1 (TGFß1)-dependent manner. Furthermore, we determined that MSCs can regulate the mitogen-activated protein kinases, phosphatidylinositol 3-kinase/protein kinase B, and protein kinase C pathways in Ca2+ -induced differentiated keratinocytes. Knockdown of TGFß1 from MSCs results in decreased suppression of differentiation with significantly increased proliferation of keratinocytes compared with control MSCs. MSCs-derived TGFß1 further induced growth inhibition of keratinocyte in high extracellular Ca2+ environment as analyzed by a decrease in DNA synthesis, accumulation of phosphorylated retinoblastoma protein, cdc2, and increased mRNA level of p21, and independent of TGFß1/SMAD pathway. Taken together, we found that MSCs-derived TGFß1 is a critical regulator of keratinocyte function, and involves multiple proximal signaling cascades. Stem Cells 2017;35:1592-1602.

Motorized 0.8-mm micropunch grafting for refractory vitiligo: A retrospective study of 230 cases.

BACKGROUND: Punch grafting for vitiligo is time-consuming and can result in cobblestone-like appearances. We devised a motorized 0.8-mm micropunch grafting procedure to overcome these limitations. OBJECTIVE: To assess the therapeutic effectiveness and adverse events associated with micropunch grafting in refractory vitiligo. METHODS: We retrospectively reviewed 230 cases in 208 patients with stable vitiligo who underwent motorized 0.8-mm micropunch grafting during January 2015-August 2017. Treatment success was defined as ≥75% repigmentation, and factors associated with the outcome were assessed. RESULTS: Overall, 181 of 230 lesions (78.7%) achieved treatment success after a median of 6 months with postoperative excimer therapy. Lesions on the face and neck, and disease stability of ≥12 months were good prognostic factors for treatment success. Common adverse events were color mismatch (24.8%) and cobblestone appearance (18.3%). Overall, the treatment was tolerable. LIMITATIONS: This was a retrospective study. CONCLUSION: Micropunch grafting using a motorized 0.8-mm punch can successfully treat refractory vitiligo with short procedure times and excellent outcomes. This technique could be a rapid and convenient surgical option with acceptable adverse events and is promising for treating refractory vitiligo on an outpatient basis, particularly in patients who are unlikely to tolerate prolonged surgery.

Fermented green tea extract exhibits hypolipidaemic effects through the inhibition of pancreatic lipase and promotion of energy expenditure.

Hyperlipidaemia is a major cause of atherosclerosis and related CVD and can be prevented with natural substances. Previously, we reported that a novel Bacillus-fermented green tea (FGT) exerts anti-obesity and hypolipidaemic effects. This study further investigated the hypotriglyceridaemic and anti-obesogenic effects of FGT and its underlying mechanisms. FGT effectively inhibited pancreatic lipase activity in vitro (IC50, 0·48 mg/ml) and ameliorated postprandial lipaemia in rats (26 % reduction with 500 mg/kg FGT). In hypertriglyceridaemic hamsters, FGT administration significantly reduced plasma TAG levels. In mice, FGT administration (500 mg/kg) for 2 weeks augmented energy expenditure by 22 % through the induction of plasma serotonin, a neurotransmitter that modulates energy expenditure and mRNA expressions of lipid metabolism genes in peripheral tissues. Analysis of the gut microbiota showed that FGT reduced the proportion of the phylum Firmicutes in hamsters, which could further contribute to its anti-obesity effects. Collectively, these data demonstrate that FGT decreases plasma TAG levels via multiple mechanisms including inhibition of pancreatic lipase, augmentation of energy expenditure, induction of serotonin secretion and alteration of gut microbiota. These results suggest that FGT may be a useful natural agent for preventing hypertriglyceridaemia and obesity.

The efficacy of 308-nm excimer laser/light (EL) and topical agent combination therapy versus EL monotherapy for vitiligo: A systematic review and meta-analysis of randomized controlled trials (RCTs).

BACKGROUND: Combination therapies of excimer laser/light (EL) and various topical agents are widely used in the treatment of vitiligo. OBJECTIVE: We sought to compare the efficacy of EL and topical agent combination therapy versus EL monotherapy for vitiligo. METHODS: Manual searches of reference lists and computerized searches of the MEDLINE, EMBASE, and Cochrane library (from inception through December 15, 2014) were conducted to identify randomized controlled trials that assessed the efficacy of EL alone or in combination with topical agents for vitiligo. The primary outcome was treatment success (≥75% repigmentation), and the secondary outcome was treatment failure (<25% repigmentation); meta-analyses were performed when possible. RESULTS: We analyzed 8 randomized controlled trials comprising a total of 425 patches/patients. The combination of EL and topical calcineurin inhibitors (4 studies: relative risk 1.93, 95% confidence interval 1.28-2.91; number needed to treat 4.5, 95% confidence interval 2.9-10) was superior to EL monotherapy for vitiligo. There was insufficient evidence to support beneficial effects of topical vitamin-D3 analogs (3 studies) and corticosteroids (1 study). LIMITATIONS: These findings are based on small numbers of randomized controlled trials and heterogeneities among included studies are another limitation. CONCLUSION: Topical calcineurin inhibitors in conjunction with EL are more effective compared with EL monotherapy.

An implementation intention strategy can improve prospective memory in older adults with very mild Alzheimer's disease.

OBJECTIVES: This study tested whether (1) very mild Alzheimer's disease (AD) is associated with impaired prospective memory (PM) for tasks that are supported by either spontaneous retrieval (focal PM) or strategic monitoring (non-focal PM) and (2) implementation intention (II) encoding could improve PM performance in very mild AD. DESIGN: Thirty-eight healthy older adults and 34 with very mild AD were randomly assigned to perform two PM tasks in either the standard or the II encoding condition. METHOD: All participants performed blocks of category decision in which they were asked to respond to a focal PM target (e.g., the word 'orange') and a non-focal PM target (e.g., words that begin with the letter 'o'). Half of the participants encoded PM instructions in the standard manner, while the other half had a stronger encoding by forming IIs. PM accuracy and category decision accuracy and reaction times were measured. RESULTS: Participants with very mild AD showed deficits in both focal and non-focal PM performance compared to the healthy controls, reflecting deficits in both spontaneous retrieval and strategic monitoring. Participants with very mild AD in the II encoding condition showed better focal PM performance relative to those in the standard encoding condition. CONCLUSIONS: Deficits in both focal and non-focal PM are associated with very mild AD and IIs may be a helpful behavioural intervention for the focal PM deficits. PRACTITIONER POINTS: Multiple deficits in PM are observable in very mild AD. Implementation intentions may enhance focal PM in very mild AD. Future research using larger samples is needed to better understand the effect of II on non-focal PM tasks in healthy older adults and those with very mild AD. The use of simple laboratory PM tasks may limit the generality of our findings. Future research is needed to investigate whether IIs improve PM over a range of more realistic tasks.