Research Note: Interactions among the MDA5, MAVS, and STING signaling pathways in chicken cells.

Innate immunity, as an organism's first line of defense, plays a crucial role in rapidly responding to and protecting the body against invading pathogens. As a cytosolic RNA sensor for viral infections, including infections caused by influenza virus, the innate immune system in chickens has 2 major pathogen-recognition receptors (PRRs): Toll-like receptor 3 (TLR3) and melanoma differentiation-associated protein 5 (MDA5). The signaling pathways activated by PRRs are complex, systemic processes that underlie the response to foreign molecules. In this study, we investigated the interactions among MDA5, mitochondrial antiviral signaling protein (MAVS), and stimulator of interferon genes (STING) signaling in chicken cells. To exclude the effects of TLR3, we transfected the clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 (CRISPR-Cas9) expression vector and TLR3-targeted gRNA plasmid into chicken DF-1 cells. We selected TLR3-knockout (KO) cell line and sequentially, we established 2 double-KO cell lines: TLR3-MAVS KO and TLR3-STING KO. After treatment with polyinosinic:polycytidylic acid (poly(I:C)), type I interferon (IFN), IFN-stimulated gene, and antiviral gene (IFN regulatory factor 7, IFNß, Mx1, and protein kinase R1) expression was not completely activated in TLR3-MAVS KO cells, whereas it was consistently upregulated in wild-type and TLR3-STING KO DF-1 cells. These results suggest that STING is not an intermediator between MDA5 and MAVS; moreover, it does not directly interact with MDA5 during innate immune activation in chicken DF-1 cells.

Production of chickens with green fluorescent protein-knockin in the Z chromosome and detection of green fluorescent protein-positive chicks in the embryonic stage.

OBJECTIVE: The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) system, which is the most efficient and reliable tool for precisely targeted modification of the genome of living cells, has generated considerable excitement for industrial applications as well as scientific research. In this study, we developed a gene-editing and detection system for chick embryo sexing during the embryonic stage. METHODS: By combining the CRISPR/Cas9 technical platform and germ cell-mediated germline transmission, we not only generated Z chromosome-targeted knockin chickens but also developed a detection system for fluorescence-positive male chicks in the embryonic stage. RESULTS: We targeted a green fluorescent protein (GFP) transgene into a specific locus on the Z chromosome of chicken primordial germ cells (PGCs), resulting in the production of ZGFP-knockin chickens. By mating ZGFP-knockin females (ZGFP/W) with wild males (Z/Z) and using a GFP detection system, we could identify chick sex, as the GFP transgene was expressed on the Z chromosome only in male offspring (ZGFP/Z) even before hatching. CONCLUSION: Our results demonstrate that the CRISPR/Cas9 technical platform with chicken PGCs facilitates the production of specific genome-edited chickens for basic research as well as practical applications.

Earlobe Reconstruction Using Two Opposed Periauricular Dermal Pedicled Flap.

There are several flap techniques of earlobe reconstruction. The ideal method should be a 1-stage procedure that is simple, has fewer complications, and has excellent esthetic outcomes with a proper earlobe texture and volume. We report a case of a 45-year-old man presented with skin and soft tissue defect of right ear lobule. He underwent composite graft using 2×1 cm sized stump. Two weeks later, total necrosis of graft site was observed. After that, he underwent 2 opposed periauricular dermal pedicled flap. Each flap caudally based periauricular flaps were elevated and consisted of redundant fat tissue. These flaps were sutured like sandwich and the donor sites were closured by primary repair. There was no complication as flap congestion or hematoma. After 6 months, the patient was satisfied esthetically and there was no need of additional surgical procedure. We introduce new technique of earlobe reconstruction named 2 opposed periauricular flap. This method affords reconstruction of large sized and full-thickness earlobe defect in a simple, easy manner. It provides proper texture and volume as normal earlobe. Also, it is 1-stage method not requiring skin graft or debulking procedure. Therefore, if plastic surgeon reconstructs a large defect of earlobe, our technique can be thought of as one good option.

Scalp metastasis of advanced gastric cancer.

Head and neck cutaneous metastasis of advanced gastric cancer is uncommon, and scalp metastasis is particularly rare. We present the case of a 60-year-old man who was diagnosed with cutaneous metastasis on the scalp originating from advanced gastric cancer. The patient was referred to the plastic surgery department for a scalp mass near the hairline. He had been diagnosed with advanced gastric cancer and undergone total gastrectomy and Roux esophagojejunostomy 3 years previously. The differential diagnosis for a single flesh-colored nodule on the scalp included benign tumors such as epidermal cyst or lipoma; therefore, the patient underwent excision and biopsy. In the operative field, the mass was found to be located in the frontalis muscle. The biopsy result showed that the mass was a metastatic lesion of advanced gastric cancer. Whole-body computed tomography revealed a gastric tumor with blood vessel infiltration, peritoneal carcinomatosis, liver metastasis, and multiple disseminated subcutaneous metastases. Although scalp metastasis originating from an internal organ is extremely rare, plastic surgeons should always consider a metastatic lesion in the differential diagnosis if a patient with a scalp lesion has a history of malignant cancer.

Isolated temporalis muscle metastasis of renal cell carcinoma.

Isolated head and neck metastasis of renal cell carcinoma (RCC) is relatively rare and metastasis to the temple area is very rare. Here, we present the case of a 51-year-old man who was diagnosed with RCC 2 years earlier and had a contralateral metastatic temple area lesion. The patient who was diagnosed with renal cell cancer and underwent a nephrectomy 2 years ago was referred to the plastic surgery department for a temple mass on the contralateral side. In the operative field, the mass was located in the temporalis muscle with a red-to-purple protruding shape. Biopsy of the mass revealed a metastatic RCC lesion. Computed tomography imaging showed a lobulated, contoured enhancing lesion. Positron emission tomography/computed tomography imaging showed high-fluorodeoxyglucose uptake in the right temporalis muscle. The patient underwent wide excision of the metastatic RCC including the temporalis muscle at the plastic surgery department. Skeletal muscle metastasis of head and neck lesions is extremely rare in RCC. Isolated contralateral temporalis muscle metastasis in RCC has not been previously reported in the literature. If a patient has a history of malignant cancer, plastic surgeons should always consider metastatic lesions of head and neck tumors. Because of its high metastatic ability and poor prognosis, it is very important to keep this case in mind.

One-stage reconstruction of full-thickness alar defects with a folded nasolabial island flap.

BACKGROUND: The reconstruction of large full-thickness alar defects requires complex surgical procedures that are usually performed in two stages, with concomitant disadvantages in terms of patient trauma, surgical risk, and cost. This study presents a functional folded nasolabial island flap (FNIF) that can be used to repair large-sized full-thickness alar defects in a straightforward manner. METHODS: This retrospective study included seven patients who received a FNIF for a full-thickness alar defect between January 2007 and December 2020. The FNIF is different from the conventional nasolabial flap in that it is folded and twisted to achieve nostril reconstruction with a satisfactory three-dimensional mucosal lining in a single stage. The cosmetic and functional results of FNIF were evaluated by both patients and physicians. RESULTS: The age ranged from 51 to 82 years (mean, 65.6 years). The causes of the defects were squamous cell carcinoma, basal cell carcinoma, and trigeminal trophic syndrome. The nostril lining did not collapse, there was no hypertrophic scarring, and air movement through the nostrils on the flap side was normal. Overall, FNIF produced excellent aesthetic and functional outcomes, with minimal patient discomfort. There were no postoperative complications. CONCLUSION: Compared with existing reconstruction methods for large full-thickness alar defects, FNIF can easily achieve aesthetic and functional success in a single-stage procedure. It provides satisfactory results for both the patient and the surgeon.

Structural Characteristic of the Arcuate Fasciculus in Patients with Fluent Aphasia Following Intracranial Hemorrhage: A Diffusion Tensor Tractography Study.

This study investigated the relationship between the structural characteristics of the left arcuate fasciculus (AF) reconstructed using diffusion tensor image (DTI) and the type of fluent aphasia according to hemorrhage lesions in patients with fluent aphasia following intracranial hemorrhage (ICH). Five patients with fluent aphasia following ICH (three males, two females; mean age 55.0 years; range 47 to 60 years) and with sixteen age-matched heathy control subjects were involved in this study. The ICHs of patients 1 and 2 were located in the left parietal lobe and the left basal ganglia. ICHs were located in the left anterior temporal of patient 3, the left temporal lobe of patient 4, and the left frontal lobe of patient 5. We assessed patients' language function using K-WAB (the Korean version of the Western Aphasia Battery) and reconstructed the AF using DTI. We measured DTI parameters including the fractional anisotropy (FA), tract volume (TV), fiber number (FN), and mean diffusivity (MD). All patients showed neural tract injury (the decrement of FA, TV, and FN and increment of MD). The left AFs in patients 1 and 2 were shifted from Broca's and Wernicke's territories. The destruction of Wernicke's territory resulted in conduction or transcortical sensory aphasia in patients 3 and 4. The structural difference of the AF in patients following ICH in the left hemisphere was associated with various types of fluent aphasia.

Injury of Corticospinal Tract in a Patient with Subarachnoid Hemorrhage as Determined by Diffusion Tensor Tractography: A Case Report.

We report diffusion tensor tractography (DTT) of the corticospinal tract (CST) in a patient with paresis of all four limbs following subarachnoid hemorrhage (SAH) with intraventricular hemorrhage (IVH) after the rupture of an anterior communicating artery (ACoA) aneurysm rupture. The 73-year-old female was admitted to our emergency room in a semi-comatose mental state. After coil embolization-an acute SAH treatment-she was transferred to our rehabilitation department with motor weakness development, two weeks after SAH. Upon admission, she was alert but she complained of motor weakness (upper limbs: MRC 3/5, and lower limbs: MRC 1/5). Four weeks after onset, DTT showed that the bilateral CSTs failed to reach the cerebral cortex. The left CST demonstrated a wide spread of fibers within the corona radiata as well as significantly lower tract volume (TV) and higher fractional anisotropy (FA) as well as mean diffusivity (MD) compared to the controls. On the other hand, the right CST shifted to the posterior region at the corona radiata, and MD values of the right CST were significantly higher when compared to the controls. Changes in both CSTs were attributed to vasogenic edema and compression caused by untreated hydrocephalus. We demonstrate in this case, two different pathophysiological entitles, contributing to this patient's motor weakness after SAH.

Cone-beam computed tomography analysis of transverse dental compensation in patients with skeletal Class III malocclusion and facial asymmetry.

OBJECTIVE: The purpose of this study was to analyze the transverse dental compensation in reference to the maxillary and mandibular basal bones using cone-beam computed tomography (CBCT) and evaluate the correlations between transverse dental compensation and skeletal asymmetry variables in patients with skeletal Class III malocclusion and facial asymmetry. METHODS: Thirty patients with skeletal Class I (control group; 15 men, 15 women) and 30 patients with skeletal Class III with menton deviation (asymmetry group; 16 men, 14 women) were included. Skeletal and dental measurements were acquired from reconstructed CBCT images using OnDemand3D 1.0 software. All measurements were compared between groups and between the deviated and nondeviated sides of the asymmetry group. Correlation coefficients for the association between skeletal and dental measurements were calculated. RESULTS: Differences in the ramus inclination (p < 0.001), maxillary canine and first molar inclinations (p < 0.001), and distances from the canine and first molar cusp tips to the midmaxillary or midmandibular planes (p < 0.01) between the right and left sides were significantly greater in the asymmetry group than in the control group. In the asymmetry group, the ramus inclination difference (p < 0.05) and mandibular canting (p < 0.05) were correlated with the amount of menton deviation. In addition, dental measurements were positively correlated with the amount of menton deviation (p < 0.05). CONCLUSIONS: Transverse dental compensation was correlated with the maxillary and mandibular asymmetry patterns. These results would be helpful in understanding the pattern of transverse dental compensation and planning surgical procedure for patients with skeletal Class III malocclusion and facial asymmetry.

Cone-beam computed tomography based evaluation of rotational patterns of dentofacial structures in skeletal Class III deformity with mandibular asymmetry.

OBJECTIVE: The purpose of this study was to assess rotational patterns of dentofacial structures according to different vertical skeletal patterns by cone-beam computed tomography (CBCT) and analyze their influence on menton deviation in skeletal Class III deformity with mandibular asymmetry. METHODS: The control group consisted of 30 young adults (15 men, 15 women) without any severe skeletal deformity. The asymmetry group included 55 adults (28 men, 27 women) with skeletal Class III deformity and at least 3-mm menton deviation from the midsagittal plane; it was divided into the hyperdivergent and hypodivergent subgroups using a mandibular plane angle cutoff of 35°. Fourteen rotational variables of the dental arches and mandible were measured and compared among the groups. Correlations between menton deviation and the other variables were evaluated. RESULTS: The asymmetry group showed significantly larger measurements of roll and yaw in the mandible than the control group. The hypodivergent subgroup showed significant differences in maxillary posterior measurements of yaw (p < 0.01) and maxillary anterior shift (p < 0.05) compared with the hyperdivergent subgroup. All the mandibular measurements had significant correlations with menton deviation (p < 0.01). Most measurements of roll were positively correlated with one another (p < 0.01). Measurements of yaw and roll in the posterior regions were also positively correlated (p < 0.05). CONCLUSIONS: Menton deviation in skeletal Class III deformity with mandibular asymmetry is influenced by rotation of mandibular posterior dentofacial structures. The rotational patterns vary slightly according to the vertical skeletal pattern.

Clinical use of conditioned media of adipose tissue-derived stem cells in female pattern hair loss: a retrospective case series study.

BACKGROUND: Female pattern hair loss (FPHL) is a common disorder but presents severe psychosocial problems in many female patients. Adipose tissue-derived stem cells (ADSCs) and conditioned media of ADSCs (ADSC-CM) are reported to promote hair growth in vitro. However, there are no clinical reports on the treatment of alopecia using ADSC-CM. OBJECTIVES: This study evaluates our clinical experience in the use of ADSC-CM for the treatment of FPHL. METHODS: A retrospective, observational study of outcomes in 27 patients with FPHL treated with ADSC-CM was performed. To evaluate the efficacy of the treatment, patients' medical records and phototrichographic images were analyzed. RESULTS: The application of ADSC-CM showed efficacy in treating FPHL after 12 weeks of therapy. Hair density increased from 105.4 to 122.7 hairs/cm(2) (P < 0.001). Hair thickness increased from 57.5 µm to 64.0 µm (P < 0.001). None of the patients reported severe adverse reactions. CONCLUSIONS: The application of ADSC-CM is a potential treatment option for FPHL.

Association of premature hair graying with family history, smoking, and obesity: a cross-sectional study.

BACKGROUND: Many researchers have been concerned about the association of hair graying with systemic diseases. However, the common factors associated with hair graying and systemic diseases have not been elucidated. OBJECTIVE: This study aimed to identify risk factors for premature hair graying (PHG) in young men. METHODS: We conducted a cross-sectional study using questionnaires in young men. After a pilot study that included 1069 men, we surveyed 6390 men younger than 30 years about their gray hair status and various socioclinical characteristics. RESULTS: The age of participants in the main survey was 20.2 ± 1.3 years (mean ± SD). Of the 6390 participants, 1618 (25.3%) presented with PHG. Family history of PHG (odds ratio [OR], 12.82), obesity (OR, 2.61), and >5 pack-years history of smoking (OR, 1.61) were significantly associated with PHG. In the multivariate analysis, family history of PHG (OR, 2.63) and obesity (OR, 2.22) correlated with the severity of PHG. LIMITATIONS: Owing to the use of questionnaires, the possibility of recall bias exists. Women were not evaluated in this study. CONCLUSION: Smoking, family history of PHG, and obesity are important factors associated with PHG.

Differences in the known cellular composition of benign pigmented skin lesions reflected in computer-aided image analysis.

BACKGROUND: Computer-aided image analysis (CAIA) has been suggested as an effective diagnostic tool for pigmented skin lesions (PSLs), especially melanoma. However, few studies on benign PSLs have been reported. OBJECTIVE: The purpose of this study was to evaluate benign PSLs with our CAIA software and analyze the differences between the parameters of those lesions. METHODS: By using homegrown CAIA software, we analyzed 3 kinds of PSLs-nevus, lentigo, and seborrheic keratosis. The group of seborrheic keratosis was divided into pigmented seborrheic keratosis, sebolentigine, and hyperkeratotic seborrheic keratosis. The CAIA was used to extract the color, as well as the morphological, textural, and topological features from each image. RESULTS: In line with clinical observations, the objective parameters indicated that nevus was dark and round, lentigo was small and bright, and seborrheic keratosis was large and spiky. The surface of nevus showed the highest contrast and correlation. In topological analysis, the concentricity clearly separated melanocytic lesions from seborrheic keratosis. The parameters of pigmented seborrheic keratosis were between those of typical nevus and seborrheic keratosis. CONCLUSION: We confirmed that definite correlations exist between the subjective differentiation by experts' examination and the objective evaluation by using CAIA. We also found that the morphological differences observed in CAIA were greatly influenced by the composition ratios of keratinocytes and melanocytes, which are already known histopathological characteristics of each PSL.

Remission period in psoriasis after multiple cycles of narrowband ultraviolet B phototherapy.

The aim of this study was to investigate the duration of remission periods in psoriasis after narrowband ultraviolet B (NB-UVB) phototherapy, especially during multiple cycles of treatment. We analyzed 63 patients (101 cases) demonstrating marked improvement after NB-UVB phototherapy. The remission period was defined as the duration of time from the end of phototherapy until treatment using either phototherapy or systemic treatments was required again. It was found that an age of 60 years or older, history of systemic therapy within 6 months and three or more phototherapy cycles were significantly associated with shorter remission periods. Furthermore, multivariate analysis confirmed that three or more phototherapy cycles (odds ratio [OR], 4.0; 95% confidence interval [CI], 1.73-9.33; P = 0.001) and a history of systemic therapy (OR, 2.2; 95% CI, 1.27-3.95; P = 0.005) were independently associated with the shorter remission period. In conclusion, when planning NB-UVB phototherapy for psoriatic patients who have undergone multiple phototherapy cycles, clinicians should consider the possibility of shorter remission periods.

Teledermatology consultation using a smartphone multimedia messaging service for common skin diseases in the Korean army: a clinical evaluation of its diagnostic accuracy.

We evaluated the diagnostic accuracy of teleconsultations for skin diseases common in the army using a smartphone multimedia messaging service (MMS). Images of skin lesions were obtained from 100 army patients using digital cameras built into smartphones. Three remotely located dermatologists received the dermatology images and associated clinical information via the MMS. The teledermatologists' diagnoses were compared with those obtained from face-to-face examinations. The three most common diagnoses made at the dermatology clinics were eczema, viral warts and fungal infections. The mean diagnostic agreement between face-to-face and teledermatology consultations was 71% (SD 2). The mean kappa coefficient was 0.73 (SD 0.06) for the three most common diagnostic categories. The mean values for sensitivity were 78% (SD 0), 88% (SD 21) and 61% (SD 11) for eczema, viral warts and fungal infections, respectively, and the specificity values were above 90% for these skin diseases. Teledermatology consultation using smartphones is simple. Although diagnoses using telemedicine do not perfectly match diagnoses from face-to-face consultations the diagnostic accuracy using smartphones is superior to that of clinicians who are not specialized in dermatology.

Pretreatment of epidermal growth factor promotes primary hair recovery via the dystrophic anagen pathway after chemotherapy-induced alopecia.

Epidermal growth factor (EGF) is not only a cell growth stimulant but also has a catagen-inducing effect. Because chemotherapeutic agents primarily damage anagen hair follicles, it would be important to investigate whether catagen inducers have beneficial effects in chemotherapy-induced alopecia (CIA). We pretreated hair follicles with topical EGF-liposomal solution in the C57BL/6 mouse model of cyclophosphamide-induced alopecia and observed the catagen-inducing property and damage response pathway after CIA. We confirmed that topical EGF application induced a catagen-like stage and found that these catagen-like hairs were protected from chemotherapy-mediated damage. Moreover, our results showed that EGF treatment favoured primary hair recovery via the dystrophic anagen pathway after CIA. Given that hair follicles subjected to less severe chemotherapeutic insult enter the dystrophic anagen pathway followed by primary recovery, the results of this study suggest that catagen inducers could be useful as a new alopecia-protection strategy, especially in the context of CIA.

Exomic sequencing of immune-related genes reveals novel candidate variants associated with alopecia universalis.

Alopecia areata (AA) is a common autoimmune disorder mostly presented as round patches of hair loss and subclassified into alopecia totalis/alopecia universalis (AT/AU) based on the area of alopecia. Although AA is relatively common, only 5% of AA patients progress to AT/AU, which affect the whole scalp and whole body respectively. To determine genetic determinants of this orphan disease, we undertook whole-exome sequencing of 6 samples from AU patients, and 26 variants in immune-related genes were selected as candidates. When an additional 14 AU samples were genotyped for these candidates, 6 of them remained at the level of significance in comparison with 155 Asian controls (p<1.92×10(-3)). Linkage disequilibrium was observed between some of the most significant SNPs, including rs41559420 of HLA-DRB5 (p<0.001, OR 44.57) and rs28362679 of BTNL2 (p<0.001, OR 30.21). While BTNL2 was reported as a general susceptibility gene of AA previously, HLA-DRB5 has not been implicated in AA. In addition, we found several genetic variants in novel genes (HLA-DMB, TLR1, and PMS2) and discovered an additional locus on HLA-A, a known susceptibility gene of AA. This study provides further evidence for the association of previously reported genes with AA and novel findings such as HLA-DRB5, which might represent a hidden culprit gene for AU.