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Necrotizing fasciitis is an uncommon but life-threatening infectious disease. In this report, we describe the cases of two patients who presented with an extremely rare necrotizing fasciitis of the scalp, originating from an odontogenic infection, and who were treated successfully with negative pressure wound therapy (NPWT). Both patients had diabetes mellitus and were admitted to the emergency department. Facial computed tomography revealed multifocal fluid collection, soft tissue swelling, and thickening from the perioral region to the scalp. Extensive incision, drainage, and debridement were performed. Taking into account the pain the patients were suffering and their general condition, NPWT was then applied instead of a povidone iodine-soaked dressing. With appropriate antibiotics, serial surgical debridement, and NPWT, the infection was controlled within a month from the first session of NPWT. For wound closure, one patient underwent primary closure and split thickness skin grafting with bone decortication, and the other patient underwent only primary closure. Although necrotizing fasciitis is associated with high morbidity and mortality, both patients’ general conditions improved, and their surgical wounds healed successfully. NPWT can be a safe, effective treatment for necrotizing fasciitis of the head and neck, and it can reduce both patients’ pain and physicians’ effort.

Purpose: Fillet flap is a “spare part” concept. This technique allows the defect to be covered without donor site morbidity. Over the past 5 years, there were 107 diabetic foot cases of one-toe fillet flap in our hospital. After the operation, in some patients, there was necrosis of the adjacent toe that required additional amputation. The aim of our study was to determine the cause of necrosis of the adjacent toe after fillet flap. Methods: The patients were divided into two groups. One group had no necrosis of the adjacent toe (group A) after the operation, and the other group had necrosis of the adjacent toe that required additional amputation after the operation (group B). Then, to confirm the cause of the additional necrosis of the adjacent toe, χ 2 tests, Fisher’s tests, and logistic regression tests were performed. Results: A total of 107 patients were included, and 48 patients needed additional amputation. The logistic regression test revealed that a fillet flap at the metatarsophalangeal joint (MTPJ), horizontal sutures, and a fillet flap at the second toe were significant risk factors for developing necrosis. Conclusions: If a fillet flap with a second toe, fillet flap on MTPJ level and horizontal closure after fillet flap is needed, the chance of developing necrosis of the adjacent toe and additional revisional surgery must be communicated preoperatively.

Vectoring issues occur due to the dynamics of unidirectional procedure that is selected. To circumvent such difficulties, we have devised subsegmental osteotomy with distraction. In our technique, frontal bone flap was divided into 4 segments that were linked to each other by suturing wires in an 8-year-old patient with trigonocephaly. Subsegmental osteotomy and wiring of bone flap enabled us to slide bone in a more curvilinear manner and achieve natural contour. Distraction was initiated on postoperative day 7 at the rate of 1 mm/d for 20-mm gain. At the 9-year follow-up, the patient showed improved head shape and intellectual status.

사업장에서 산재가 은폐되는 순간 그 사고는 똑같이 재현되거나 유사한 형태로 다시 발생할 수밖에 없다. 산재발생 원인개선이 안되기 때문이다. 그래서 동종재해 및 유사재해 발생을 예방하기 위해서는 원인을 찾아 대책마련을 위한 개선노력이 필요한 것이다. 다만, 산재은폐는 적발도 어려울 뿐 아니라 은폐행위에 영향을 미치는 원인이 다양하고 서로 긴밀하게 결합돼 있어 산재은폐 근절을 위한 근본적인 해결법을 찾는 것은 불가능하지만, 실무상 산재은폐가 지속되는 원인으로 일관되게 지적되고 있는 산재보험료와 관련한 경제적 요인과 근로감독대상에 대한 불안감과 관련한 행정적 요인 그리고 산재미처리에 대한 실정법상 규제할 수 있는 법적 근거마련을 위한 고민 등을 중심으로 산재은폐 감소 및 근절을 위한 입법정책적 개선방안을 살펴본다.

Functional analyses of genes are crucial for unveiling biological responses, genetic engineering, and developing new medicines. However, functional analyses have largely been restricted to model organisms, representing a major hurdle for functional studies and industrial applications. To resolve this, comparative genome analyses can be used to provide clues to gene functions as well as their evolutionary history. To this end, we present Prometheus, a web-based omics portal that contains more than 17,215 sequences from prokaryotic and eukaryotic genomes. This portal supports interkingdom comparative analyses via a domain architecture-based gene identification system and Gene Search, and users can easily and rapidly identify single or entire gene sets in specific pathways. Bioinformatics tools for further analyses are provided in Prometheus or through Bio-Express, a cloud-based bioinformatics analysis platform. Prometheus is a new paradigm for comparative analyses of large amounts of genomic information.

The inframammary fold (IMF) is an essential aesthetic element that influences the outcome of breast surgery. In this study, we introduced a new method for finding the IMF based on retrospective analysis of chest computed tomography (CT) scans of women's breasts. Sagittal sections of 80 female chest CTs were analyzed. Sagittal sections of 80 female chest CTs were analyzed by a single plastic surgeon. The distances between the fifth, sixth, and seventh ribs and the IMF were measured using Photoshop, and the location of the IMF was statistically analyzed according to age and height using paired t tests and Pearson's correlation test. As determined by our new method, the average distance between the IMF and the sixth rib was 5.33 mm, which was less than that between the IMF and any other rib. The IMF was closest to the sixth rib in all age groups (P < 0.001), and all IMFs were located between 39.5 mm superior and 24 mm inferior to the sixth rib. The sixth rib, one of the most visible reference structures in women's surface anatomy, is the "sentinel rib" for the IMF and the most predictive indicator of the location of the IMF. Knowing the original anatomic location of the IMF will enable better outcomes during breast surgery. Clin. Anat. 33:165-172, 2020. © 2019 Wiley Periodicals, Inc.

We introduce a method to extract the maximum amount of cancellous bone from the calvarium and analyze the outcomes using plain radiography and computed tomography.We retrospectively analyzed the medical records of patients who underwent secondary alveolar bone grafts using a maximal harvesting technique for calvarial cancellous bone. Bone survival was determined based on Enemark's grading system using plain radiographs. Alveolar thickness and height were analyzed by computed tomography and compared with radiographic measurements.Our study enrolled 27 patients, 22 unilateral and 5 bilateral, for a total of 32 alveolar clefts. The mean age at surgery was 9.04 ± 0.41 years (range: 6-12 years). Donor sites were successfully recovered without complications, such as hematomas, seromas, infections, or tears in the dura mater. The mean follow-up duration for obtaining plain radiographs was 6.90 ± 0.61 years (range: 2.0-18.50 years). The mean follow-up duration for computed tomography was 6.51 ± 0.99 years (range: 2.0-14.83 years). A canine tooth erupted in 30 cases. Success (Enemark's grades I or II) was achieved in 26 cases. Alveolar height was strongly correlated with the Enemark scale results (γ = 0.878, p 0.001), but alveolar thickness was not correlated (γ = 0.4575, p = 0.08).Our cancellous bone harvesting technique resulted in successful graft survival without serious complications, including dural or brain injuries. Although the ilium is widely accepted as the optimal donor site for secondary alveolar bone grafting, the calvarium could be an alternative donor site that results in equivalent outcomes.

Background The aim of this study was to analyze the clinical results of minimal single palmar-incision carpal tunnel release without a tourniquet. Methods We reviewed the medical records of 75 patients (90 cases of carpal tunnel syndrome) who underwent minimal single-palmar incision carpal tunnel release without a tourniquet from June 2010 to January 2018. Ten patients had a bleeding tendency. We compared the preoperative and postoperative Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) scores. We also analyzed outcomes and complications according to the presence of a bleeding tendency. Results In all cases, there was a complete disappearance or marked improvement in symptoms within 6 months, with no recurrence. The postoperative BCTQ score showed a significant improvement compared to the preoperative score, and no statistically significant difference in BCTQ scores was detected according to the presence of a bleeding tendency. Conclusions Carpal tunnel release without a tourniquet using a minimal single palmar incision is effective and reliable. This technique prevents unnecessary pain associated with the tourniquet and is especially helpful in patients with a bleeding tendency or those treated with hemodialysis.

Caffeoylquinic acids, flavonoids, and coumarins isolated from Artemisia capillaris have recently emerged as therapeutic candidates for diabetes and diabetic complications; however, there have been very few studies of the anti-diabetic potential of polyacetylenes. In the present study, we investigated the anti-diabetic potential of two polyacetylenes isolated from A. capillaris, namely capillin and capillinol by investigating their ability to inhibit α-glucosidase, protein tyrosine phosphatase 1B (PTP1B), and rat lens aldose reductase (RLAR). Capillin displayed potent inhibitory activity against α-glucosidase, PTP1B, and RLAR, while capillinol showed moderate inhibitory activity against α-glucosidase and PTP1B at the concentrations tested. In addition, a kinetic study revealed that capillin inhibited α-glucosidase and RLAR in a noncompetitive manner, while inhibited PTP1B in a mixed-type manner. Capillinol inhibited α-glucosidase and PTP1B in a mixed-type manner. Docking simulations of these compounds demonstrated negative binding energies and close proximity to residues in the binding pocket of PTP1B, indicating that these polyacetylenes have a high affinity and tight binding capacity for the active site of the enzyme. Furthermore, capillin dose-dependently inhibited peroxynitrite (ONOO(-))-mediated tyrosine nitration. The results clearly demonstrate the promising potential of capillin and capillinol as therapeutic interventions for the management of diabetes as well as diabetes-associated complications.

Acetylcholinesterase (AChE) inhibitors increase the availability of acetylcholine in central cholinergic synapses and are the most promising drugs currently available for the treatment of Alzheimer's disease (AD). Our screening study indicated that the water fraction of the methanolic extract of Lycopodiella cernua (L.) Pic. Serm. significantly inhibited AChE in vitro. Bioassay-guided fractionation led to the isolation of a new lignan glycoside, lycocernuaside A (12), and fourteen known compounds (1-11 and 13-15). Compound 7 exhibited the most potent AChE inhibitory activity with an IC50 value of 0.23 μM. Compound 15 had the most potent inhibitory activity against BChE and BACE1 with IC50 values of 0.62 and 2.16 μM, respectively. Compounds 4 and 7 showed mixed- and competitive-type AChE inhibition. Compound 7 noncompetitively inhibited BChE whereas 15 showed competitive and 8, 13, and 14 showed mixed-type inhibition. The docking results for complexes with AChE or BChE revealed that inhibitors 4, 7, and 15 stably positioned themselves in several pocket/catalytic domains of the AChE and BChE residues.

Three new serratene-type triterpenoids (1–3) and a new hydroxy unsaturated fatty acid (13) together with nine known compounds (4–12) were isolated from Lycopodiella cernua. The chemical structures were established using NMR, MS, and Mosher’s method. Compound 13 showed the most potent inhibitory activity against acetylcholinesterase (AChE) with an IC50 value of 0.22 μM. For butyrylcholinesterase (BChE) inhibitory activity, 5 showed the most potent activity with an IC50 value of 0.42 μM. Compound 2 showed the most potent activity with an IC50 of 0.23 μM for BACE-1 inhibitory activity. The kinetic activities were investigated to determine the type of enzyme inhibition involved. The types of AChE inhibition shown by compounds 4, 5, and 13 were mixed; BChE inhibition by 5 was competitive, while 2 and 6 showed mixed-types. In addition, molecular docking studies were performed to investigate the interaction of these compounds with the pocket sites of AChE. The docking results revealed that the tested inhibitors 3, 4, and 13 were stably present in several pocket domains of the AChE residue.

SummaryOrganisms must be able to respond to low oxygen in a number of homeostatic and pathological contexts. Regulation of hypoxic responses via the hypoxia-inducible factor (HIF) is well established, but evidence indicates that other, HIF-independent mechanisms are also involved. Here, we report a hypoxic response that depends on the accumulation of lactate, a metabolite whose production increases in hypoxic conditions. We find that the NDRG3 protein is degraded in a PHD2/VHL-dependent manner in normoxia but is protected from destruction by binding to lactate that accumulates under hypoxia. The stabilized NDRG3 protein binds c-Raf to mediate hypoxia-induced activation of Raf-ERK pathway, promoting angiogenesis and cell growth. Inhibiting cellular lactate production abolishes the NDRG3-mediated hypoxia responses. Our study, therefore, elucidates the molecular basis for lactate-induced hypoxia signaling, which can be exploited for the development of therapies targeting hypoxia-induced diseases.

Background Alar transfixion sutures are commonly used for vestibular web correction. The purpose of this study was to evaluate the long-term results of the use of alar transfixion sutures in patients with a unilateral cleft lip nasal deformity using photogrammetric analysis. Methods The study included 42 patients who were divided into child and adult groups. A total of 4 measurement items were evaluated from a basal view by photogrammetry using standardized clinical photographic techniques preoperatively, immediately postoperatively, 3 months postoperatively, and 6 months postoperatively. Results When the preoperative and last postoperative values were compared, no significant changes in any measurement items were noted in the adult group. In the child group, the proportional index (the ratio of the cleft side to the noncleft side) of the alar slope line inclination was significantly increased, but other measurement items showed no significant change. When the measurement items were compared between time points, no significant changes in any measurement items were noted in the adult group. In the child group, the proportional indexes of the alar length, the width between the subnasale and the alare, and the webbing degree were significantly decreased immediately postoperatively compared with the preoperative values. However, these significant changes were diminished at 3 months postoperatively. The proportional index of the alar slope line inclination was significantly increased at 3 months postoperatively compared with the preoperative value, but the significant change was diminished at 6 months postoperatively. Conclusions The alar transfixion suture procedure is not effective for correcting a vestibular web and alar-facial groove.

Functional analyses of genes are crucial for unveiling biological responses, for genetic engineering, and for developing new medicines. However, functional analyses have largely been restricted to model organisms, representing a major hurdle for functional studies and industrial applications. To resolve this, comparative genome analyses can be used to provide clues to gene functions as well as their evolutionary history. To this end, we present Prometheus (http://prometheus.kobic.re.kr),web-based omics portal that contains more than 17,215 sequences from prokaryotic and eukaryotic genomes. This portal supports interkingdom comparative analyses via a domain architecture-based gene identification system, Gene Search, and users can easily and rapidly identify single or entire gene sets in specific pathways. Bioinformatics tools for further analyses are provided in Prometheus or through BioExpress, a cloud-based bioinformatics analysis platform. Prometheus suggests a new paradigm for comparative analyses with large amounts of genomic information.

Ulceration is a serious consequence of diabetes that can lead to disability in patients with diabetes. One of the risk factors for ulceration is high foot pressure. The thickness of the pedal soft tissue is important because it has a cushioning effect. Soft tissue atrophy causes elevation in the plantar pressure, which, in turn, causes ischemia. Therefore, we investigated the severity of pedal soft tissue atrophy caused by diabetes and aging. From February 2009 to February 2016, we examined the feet of 261 patients treated in our hospital using magnetic resonance imaging. We divided the patients enrolled in the study into 2 groups. The first group included 52 patients with diabetes but without peripheral arterial disease and the second group included 47 patients without diabetes. We measured the vertical distances under all patients' metatarsal heads using T1-weighted magnetic resonance imaging and measured the pedal soft tissue thickness using the PACS workstation (m-view). We compared the soft tissue thicknesses of the 2 groups and performed statistical analyses of the relationships between these data and other parameters using 2-way analysis of variance. The soft tissue under the first to fourth metatarsal heads was thinner in the diabetic patients than in the nondiabetic patients (first metatarsal, 6.4 versus 8.69; second metatarsal, 8.85 versus 10.64; third metatarsal, 8.15 versus 9.21; fourth metatarsal, 7.38 versus 8.54; p .05). Aging had no effect on pedal soft tissue atrophy in either group. In conclusion, our study confirmed that diabetic patients experience more severe plantar soft tissue atrophy than nondiabetic patients. We have developed a standard procedure to enable the prediction of pedal soft tissue atrophy severity in diabetic patients.

Since insulin sensitivity to cells is attributed to phosphorylation of the insulin receptor (IR), protein tyrosine phosphatase 1B (PTP1B), which dephosphorylates the tyrosine residues of IR proteins, is primarily responsible for insulin resistance in type 2 diabetes. Therefore, PTP1B inhibitors ameliorating the insulin-dependent signaling pathway are potential therapeutic candidates for the treatment and prevention of diabetes. As part of our continuous search for diterpenes derived from Aralia continentalis as potent PTP1B inhibitors, five active diterpenoids, including ent-pimara-8(14),15-diene-19-oic acid (1); 7-oxo-ent-pimara-8(14),15-diene-19-oic acid (2); 7β-hydroxy-ent-pimara-8(14),15-diene-19-oic acid (3); ent-pimara-8(14),15-diene-19-ol (4); 8α-hydroxy-ent-pimara-15-en-19-ol (5); and ent-kaur-16-en-19-oic-acid (6) were investigated using the enzyme kinetic assay. With the exception of 1 showing mixed inhibition, compounds 2 and 4-6 exhibited noncompetitive inhibition against PTP1B with K i values ranging 3.29-12.86 μM. In particular, 2 with an oxo group in the C-7 position showed increased PTP1B inhibition compared to nonsubstituted 1. Based on the structure and activity relationship, the 3D docking simulations of 1, 2, and 3 were also performed. Compounds 1-3 showed negative binding energies of -5.3 to -6.1 kcal/mol and a high affinity to PTP1B residues (Phe182 and Asp181 in the WPD loop; Cys215 in the active sites; Tyr46, Arg47, Asp48, Val49, Ser216, Ala217, Gly218, Ile219, Gly220, Arg221, Gln262, and Gln266 in the pocket site), indicating that they may stabilize the open form and generate tighter binding to the catalytic sites of PTP1B. The enzymatic kinetics and docking results clearly indicate the promising potential of pimarane-type diterpenes as PTP1B inhibitors.

Acetylsalicylic acid (ASA), generally well known as aspirin, has various biomedical functions. In this study, we revealed that ASA reversibly inhibits tyrosinase (EC 1.14.18.1) in a mixed-type manner with a Ki = 11.778 ± 2.01 mM. Time-interval kinetics showed that the inhibition followed first-order reaction kinetics. Measurements of ANS-binding fluorescence showed that ASA did not induce significant detectable changes in the hydrophobic surface of tyrosinase. For further insight, we performed molecular dynamics simulations to predict the key interactions between tyrosinase and ASA and found that the acetate and carboxylic acid groups of ASA play a critical role in binding to several residues (HIS61, HIS85, HIS94, HIS259, HIS263, and ALA286) on tyrosinase that are thought to be pivotal for docking. Our study suggested that ASA could be a useful depigmentation agent due to the structural functions of the acetic and carboxyl groups on tyrosinase.

Alpha-glucosidase (EC 3.2.1.20) is an enzyme, which is related with diabetes mellitus type 2 clinically, and is also generally used to convert starch to fermentable sugars in the industry. Therefore, study on this enzyme structures and functions is important. In this study, we investigated structural changes in the alpha-glucosidase during trifluoroethanol (TFE)-induced unfolding. The activity of alpha-glucosidase was significantly inactivated by TFE in a dose-dependent manner. The inactivation was composed of two-phases. TFE inhibited alpha-glucosidase in a parabolic mixed-type reaction (Ki = 0.72 ± 0.08 M). TFE directly induced the unfolding and hydrophobic exposure of alpha-glucosidase. We also simulated the docking between alpha-glucosidase and TFE, as well as molecular dynamics. The computational simulations suggested that several residues, such as ASP68, TYR71, VAL108, HIS111, PHE177, ASP214, THR215, GLU276, HIS348, ASP349, and ARG439, interact with TFE. The molecular dynamics simulation confirmed the binding mechanisms, between the alpha-glucosidase and TFE, and suggested that TFE inhibits the glucose binding site. Our study provides insights into the alpha-glucosidase folding behaviors, and cosolvent binding under a 3D structural simulation.

Fucoidan is a complex sulfated polysaccharide extracted from brown seaweed and has a wide variety of biological activities. In this study, we investigated the inhibitory effect of fucoidan on tyrosinase via a combination of inhibition kinetics and computational simulations. Fucoidan reversibly inhibited tyrosinase in a mixed-type manner. Time-interval kinetics showed that the inhibition was processed as first order with biphasic processes. For further insight, we simulated dockings with various sizes of molecular models (monomer to decamer) of fucoidan and showed that the best binding energy change results were obtained from the pentamer (-1.89 kcal/mol) and the hexamer (-1.97 kcal/mol) models of AutoDock Vina. The molecular dynamics simulation confirmed the binding mechanisms between tyrosinase and fucoidan and suggested that fucoidan mostly interacts with several residues including copper ions located in the active site. Our study suggests that fucoidan might be a potential natural antipigment agent.