Anatomical Considerations for the Injection of Botulinum Neurotoxin in Shoulder and Arm Contouring.

The utilization of botulinum neurotoxin in the field of body contouring is on the rise. Body contouring procedures typically focus on specific muscle groups such as the superior trapezius, deltoid, and lateral head of the triceps brachii. The authors propose identifying optimal injection sites for botulinum neurotoxin to achieve desired aesthetic contouring of the shoulders and arms. The authors conducted a modified Sihler's staining method on specimens of the superior trapezius, deltoid, and lateral head of the triceps brachii muscles, totaling 16, 14, and 16 specimens, respectively. The neural distribution exhibited the most extensive branching patterns within the horizontal section (between 1/5 and 2/5) and the vertical section (between 2/4 and 4/4) of the superior trapezius muscle. In the deltoid muscle, the areas between the anterior and posterior deltoid bellies, specifically within the range of the horizontal 1/3 to 2/3 lines, showed significant intramuscular arborization. Furthermore, the middle deltoid muscle displayed arborization patterns between 2/3 and the axillary line. Regarding the triceps brachii muscle, the lateral heads demonstrated arborization between 4/10 and 7/10. The authors recommend targeting these regions, where maximum arborization occurs, as the optimal and safest points for injecting botulinum toxin.

Chaperone-mediated autophagy dysregulation during aging impairs hepatic fatty acid oxidation via accumulation of NCoR1.

OBJECTIVE: Alterations in lipid metabolism are associated with aging and age-related diseases. Chaperone-mediated autophagy (CMA) is a lysosome-dependent process involved in specific protein degradation. Heat shock cognate 71 kDa protein (Hsc70) recognizes cytosolic proteins with KFERQ motif and allows them to enter the lysosome via lysosome-associated membrane glycoprotein 2 isoform A (LAMP2A). CMA deficiency is associated with dysregulated lipid metabolism in the liver. In this study, we examined the effect of CMA on lipid metabolism in the aged liver. METHODS: 12-week-old and 88-week-old mice were employed to assess the effect of aging on hepatic CMA activity. We generated CMA-deficient mouse primary hepatocytes using siRNA for Lamp2a and liver-specific LAMP2A knockdown mice via adeno-associated viruses expressing short hairpin RNAs to investigate the influence of CMA on lipid metabolism. RESULTS: We noted aging-induced progression toward fatty liver and a decrease in LAMP2A levels in total protein and lysosomes. The expression of genes associated with fatty acid oxidation was markedly downregulated in the aged liver, as verified in CMA-deficient mouse primary hepatocytes. In addition, the aged liver accumulated nuclear receptor corepressor 1 (NCoR1), a negative regulator of peroxisome proliferator-activated receptor α (PPARα). We found that Hsc70 binds to NCoR1 via the KFERQ motif. Lamp2a siRNA treatment accumulated NCoR1 and decreased the fatty acid oxidation rate. Pharmacological activation of CMA by AR7 treatment increased LAMP2A expression, leading to NCoR1 degradation. A liver-specific LAMP2A knockdown via adeno-associated viruses expressing short hairpin RNAs caused NCoR1 accumulation, inactivated PPARα, downregulated the expression of fatty acid oxidation-related genes and significantly increased liver triglyceride levels. CONCLUSIONS: Our results elucidated a novel PPARα regulatory mechanism involving CMA-mediated NCoR1 degradation during aging. These findings demonstrate that CMA dysregulation is crucial for the progression of aging-related fatty liver diseases.

Associations of Polyp Characteristics in Children and Adolescents Presenting with Less Than Five Colorectal Polyps: A Full Colonoscopy Is Still Required.

Background/Aims: A full colonoscopy is currently required in children and adolescents with colorectal polyps, because of their potential of neoplastic transformation and complications such as intussusception. We aimed to analyze the associations of polyp characteristics in children and adolescents with colorectal polyps. Based on these findings, we also aimed to reevaluate the necessity of conducting a full colonoscopy. Methods: Pediatric patients <18 years of age who had undergone a colonoscopic polypectomy and those with <5 colorectal polyps were included in this multicenter, retrospective study. Baseline clinicodemographics, colonoscopic and histologic findings were investigated. Results: A total of 91 patients were included. Multivariate logistic regression analysis showed that polyp size was the only factor associated with the presence of any polyps located proximal to the splenic flexure (odds ratio [OR], 2.25; 95% confidence interval [CI], 1.28 to 4.28; p=0.007). Furthermore, polyp location proximal to the splenic flexure and sessile morphology were associated with the presence of any adenomatous polyp (OR, 8.51; 95% CI, 1.43 to 68.65; p=0.023; OR, 18.41; 95% CI, 3.45 to 173.81; p=0.002, respectively). Conclusions: In children and adolescents presenting with <5 colorectal polyps, polyp size and the presence of any adenomatous polyp were positively associated with polyp location proximal to the splenic flexure. This finding supports the necessity of a full colonoscopic exam in pediatric patients with colorectal polyps for the detection of polyps before the occurrence of complications such as intussusception or neoplastic transformation.

New anatomical insights of the superficial branch of the zygomaticotemporal nerve for treating temporal migraines: An anatomical study.

The zygomaticotemporal nerve is known to contribute to temporal migraines; however, its precise anatomy remains unknown. The potential accessory branches of the zygomaticotemporal nerve may be considered a cause of continued temporal migraines after surgical procedures. In this study, we defined the novel superficial branch of the zygomaticotemporal nerve (sZTN) and investigated its anatomical course, distribution, and clinical implications. Twenty-two hemifaces from 11 fixed Korean cadavers (six males, five females; mean age, 78.3 years) were used in this study. The piercing points of the sZTN through the deep and superficial layers of the deep temporal fascia, and the superficial temporal fascia were defined as P1, P2, and P3, respectively. The distance of each point from the zygomatic tubercle was measured using an image analysis software. The sZTN ascended between the bone and the temporalis after emerging from the zygomaticotemporal foramen. It then pierced the deep temporal fascia without penetrating the temporalis. After then, it pierced the superficial layer of the deep temporal fascia and turned superiorly toward the upper posterior temple. When the sZTN passed through the superficial temporal fascia, it intersected with the superficial temporal artery in every case. The novel findings of the sZTN may help in the treatment of intractable temporal migraines refractory to injection or surgical procedure. Based on our findings, targeting the sZTN may be applied as an alternative treatment strategy for patients who do not show significant improvement with treatment targeted to trigger sites.

Mitochondrial H2O2 Is a Central Mediator of Diclofenac-Induced Hepatocellular Injury.

Nonsteroidal anti-inflammatory drug (NSAID) use is associated with adverse consequences, including hepatic injury. The detrimental hepatotoxicity of diclofenac, a widely used NSAID, is primarily connected to oxidative damage in mitochondria, which are the primary source of reactive oxygen species (ROS). The primary ROS responsible for inducing diclofenac-related hepatocellular toxicity and the principal antioxidant that mitigates these ROS remain unknown. Peroxiredoxin III (PrxIII) is the most abundant and potent H2O2-eliminating enzyme in the mitochondria of mammalian cells. Here, we investigated the role of mitochondrial H2O2 and the protective function of PrxIII in diclofenac-induced mitochondrial dysfunction and apoptosis in hepatocytes. Mitochondrial H2O2 levels were differentiated from other types of ROS using a fluorescent H2O2 indicator. Upon diclofenac treatment, PrxIII-knockdown HepG2 human hepatoma cells showed higher levels of mitochondrial H2O2 than PrxIII-expressing controls. PrxIII-depleted cells exhibited higher mitochondrial dysfunction as measured by a lower oxygen consumption rate, loss of mitochondrial membrane potential, cardiolipin oxidation, and caspase activation, and were more sensitive to apoptosis. Ectopic expression of mitochondrially targeted catalase in PrxIII-knockdown HepG2 cells or in primary hepatocytes derived from PrxIII-knockout mice suppressed the diclofenac-induced accumulation of mitochondrial H2O2 and decreased apoptosis. Thus, we demonstrated that mitochondrial H2O2 is a key mediator of diclofenac-induced hepatocellular damage driven by mitochondrial dysfunction and apoptosis. We showed that PrxIII loss results in the critical accumulation of mitochondrial H2O2 and increases the harmful effects of diclofenac. PrxIII or other antioxidants targeting mitochondrial H2O2 could be explored as potential therapeutic agents to protect against the hepatotoxicity associated with NSAID use.

The Changes in Trends of Lower Gastrointestinal Endoscopy Conducted in Children and Adolescents after the COVID-19 Outbreak in Korea.

Background and Objectives: The coronavirus disease 2019 (COVID-19) pandemic has affected medical practice in diverse ways. We aimed to investigate the change in trends of lower gastrointestinal (LGI) endoscopy conducted in children and adolescents after the COVID-19 outbreak in Korea. Material and Methods: This was a multicenter, retrospective study conducted in Korea. We included children and adolescents aged <19 years who had undergone their first LGI endoscopy between 2016 and 2020. We compared clinicodemographic and endoscopic factors between groups divided according to the pre- and postCOVID-19 era in Korea. Results: We included 1307 patients in this study. Colonoscopies, instead of sigmoidoscopies, were conducted in most patients in the postCOVID-19 era compared to those in the preCOVID-19 era (86.9% vs. 78.5%, p = 0.007). The diagnosis of inflammatory bowel disease (IBD) was also significantly higher in the postCOVID-19 era compared to the preCOVID-19 era (47.2% vs. 28.5%, p < 0.001). According to multivariate logistic regression analysis, age at LGI endoscopy, LGI bleeding indication, and IBD diagnosis were independently associated with the use of a colonoscopy over a sigmoidoscopy (odds ratio (OR) 1.19, 95% confidence interval (CI) 1.12−1.27, p < 0.001; OR 0.56, 95% CI 0.37−0.83, p = 0.005; OR 1.80, 95% CI 1.20−2.77, p = 0.006, respectively). Conclusions: The COVID-19 pandemic has changed LGI endoscopy practice trends of pediatric gastroenterologists in Korea, who tended to perform lesser LGI endoscopies compared to previous years while conducting significantly more colonoscopies than sigmoidoscopies in the postCOVID-19 era. Furthermore, these colonoscopies were significantly associated with the diagnosis of IBD, as well as a significant increase in IBD diagnosis in the postCOVID-19 era.

Epidemiological Trends of Pediatric Inflammatory Bowel Disease in Korea: A Multicenter Study of the Last 3 Years Including the COVID-19 Era.

BACKGROUND: Studies on how the coronavirus pandemic has affected pediatric inflammatory bowel disease (PIBD) are lacking. We aimed to investigate the trends in epidemiology, characteristics, initial management, and short-term outcomes of PIBD in South Korea over the recent three years including the era of coronavirus disease 2019 (COVID-19). METHODS: This multicenter study retrospectively investigated temporal trends in the epidemiology of PIBD in Korea. Annual occurrences, disease phenotypes, and initial management at diagnosis were analyzed from January 2018 to June 2021. RESULTS: A total of 486 patients from 17 institutions were included in this epidemiological evaluation. Analysis of the occurrence trend confirmed a significant increase in PIBD, regardless of the COVID-19 pandemic. In Crohn's disease, patients with post-coronavirus outbreaks had significantly higher fecal calprotectin levels than those with previous onset (1,339.4 ± 717.04 vs. 1,595.5 ± 703.94, P = 0.001). Patients with post-coronavirus-onset ulcerative colitis had significantly higher Pediatric Ulcerative Colitis Activity Index scores than those with previous outbreaks (48 ± 17 vs. 36 ± 15, P = 0.004). In the initial treatment of Crohn's disease, the use of 5-aminosalicylic acid (5-ASA) and steroids significantly decreased (P = 0.006 and 0.001, respectively), and enteral nutrition and the use of infliximab increased significantly (P = 0.045 and 0.009, respectively). There was a significant increase in azathioprine use during the initial treatment of ulcerative colitis (P = 0.020). CONCLUSION: Regardless of the COVID-19 pandemic, the number of patients with PIBD is increasing significantly annually in Korea. The initial management trends for PIBD have also changed. More research is needed to establish appropriate treatment guidelines considering the epidemiological and clinical characteristics of Korean PIBD.

Effects of anxiety on sedation among pediatric patients undergoing esophagogastroduodenoscopy.

We investigated whether the severity of anxiety among children undergoing endoscopy could affect sedation. We prospectively recruited patients under 18 years of age who were scheduled to undergo esophagogastroduodenoscopy (EGD). Baseline anxiety was evaluated using the Spence Children's Anxiety Scale (SCAS). Our analysis considered the type and dose of sedative drugs, degree of sedation, and complications associated with sedation according to the scale score. The mean total SCAS T-scores and each subscale score were significantly higher in the 6-12-year age group. The mean T-score among patients who exhibited irritability during EGD was higher than that among other patients, with significant differences in the Total, Obsessive Disorder, Panic Agoraphobia and General Anxiety subscales. The midazolam doses of children exhibiting irritability were more likely to need higher (p = 0.006). Other sedation-related complications were not associated with the T-scores in each subscale. Total sleep time was not associated with any T-score subscales. Anxiety levels were significantly higher among 6-12-year-olds and children exhibiting irritability. Anxiety was often associated with irritability, difficulties achieving adequate sedation during EGD, and additional sedative drug administration. We recommend higher doses or more potent drugs to facilitate endoscopy for children with high anxiety levels.

Potential Utility of Fecal Calprotectin in Discriminating Colorectal Polyps From Other Major Etiologies in Children Presenting With Isolated Hematochezia.

BACKGROUND: Colorectal polyps are the most common cause of isolated hematochezia in children, which requires a colonoscopy for diagnosis. We aimed to investigate the potential utility of fecal calprotectin (FC) in assessing colorectal polyps detected by colonoscopy among children presenting with isolated hematochezia. METHODS: Pediatric patients of the age of < 18 years who had undergone both colonoscopy and FC tests for isolated hematochezia from June 2016 to May 2020 were included in the present multicenter, retrospective, cross-sectional study. Comparative analysis was conducted between major causes of isolated hematochezia and FC cut-offs for discriminating colorectal polyps were explored. RESULTS: A total 127 patients were included. Thirty-five patients (27.6%) had colorectal polyps, followed by anal fissure (14.2%), ulcerative colitis (UC; 12.6%), and others. A significant difference in FC levels was observed between patients with colorectal polyps (median, 278.7 mg/kg), anal fissures (median, 42.2 mg/kg), and UC (median, 981 mg/kg) (P < 0.001). According to receiver operating characteristic curve analysis, among patients diagnosed with colorectal polyp or anal fissure, the most accurate FC cut-off for discriminating colorectal polyps from anal fissures on colonoscopy was 225 mg/kg (sensitivity, 59.4%; specificity, 94.4%; positive predictive value [PPV], 95.0%; negative predictive value [NPV], 56.7%; area under the curve [AUC], 0.8; 95% confidence interval [CI], 0.678-0.923; P < 0.001), while among patients diagnosed with colorectal polyp or UC, the most accurate FC cut-off for discriminating colorectal polyps from UC on colonoscopy was 879 mg/kg (sensitivity, 81.2%; specificity, 56.2%; PPV, 78.8%; NPV, 60.0%; AUC, 0.687; 95% CI, 0.521-0.852; P < 0.001). CONCLUSION: FC may assist in assessing the cause of lower gastrointestinal tract bleeding in children who present with isolated hematochezia.

A Multicenter Study of Real-world Practice for Management of Abnormal Liver Function Tests in Children with Acute Infectious Diseases.

BACKGROUND: Abnormal liver function tests (LFTs) are commonly seen in pediatric patients with acute infectious diseases. Few studies and no definite clinical guidelines for these conditions are available. The present study aimed to elucidate the causes and factors associated with prolongation of liver enzyme elevation. We also investigated actual real-world practices in Korea. METHODS: A retrospective study was performed on all patients younger than 18 years, who visited six tertiary teaching hospitals around Korea in 2018 for acute infectious diseases and showed alanine aminotransferase (ALT) levels above 60 IU/L without other specific conditions that could cause ALT elevation. We categorized the infections that cause LFT elevation into six groups: respiratory infection, gastrointestinal infection, urinary tract infection, other febrile disease, Epstein-Barr virus infection, and cytomegalovirus infection. We collected data on the medical specialty of the attending physician who followed up the subject, follow-up duration, percentage of follow-up loss, and their investigation. RESULTS: A total of 613 patients were enrolled in this study, half of whom (50.7%) were younger than 12 months. The mean initial aspartate aminotransferase and ALT values were 171.2 ± 274.1 and 194.9 ± 316.1 IU/L (range 23-2,881, 60-2,949 IU/L), respectively; however, other LFTs were within the normal range. Respiratory infection was the most common diagnosis (45.0%), and rhinovirus was the most commonly identified pathogen (9.8%). The follow-up rate was higher with pediatric gastroenterologists (90.5%) and non-gastroenterology pediatricians (76.4%) than with pediatric residents and emergency doctors. Older age was related to better ALT recovery (odds ratio [OR] of age for month = 1.003; 95% confidence interval [CI], 1.001-1.004; P = 0.004), while the number of infection episodes (OR = 0.626; 95% CI, 0.505-0.777; P < 0.001) was associated with poor ALT recovery. Abdominal sonography was the most commonly used diagnostic tool (36.9%), followed by the hepatotropic virus workup. The modalities of hepatitis workup were significantly differently applied by physicians based on their specialties and institutions. CONCLUSION: Abnormal liver function test after a systemic infection was common in respiratory infection and under the age of 1 year. Age, number of infections, and initial results of LFTs were related to ALT recovery time. Inter-physician, inter-institution, and inter-specialty variances were observed in real-world practice.

Procedural Sedation for Pediatric Upper Gastrointestinal Endoscopy in Korea.

BACKGROUND: Sedative upper endoscopy is similar in pediatrics and adults, but it is characteristically more likely to lead to respiratory failure. Although recommended guidelines for pediatric procedural sedation are available within South Korea and internationally, Korean pediatric endoscopists use different drugs, either alone or in combination, in practice. Efforts are being made to minimize the risk of sedation while avoiding procedural challenges. The purpose of this study was to collect and analyze data on the sedation methods used by Korean pediatric endoscopists to help physicians perform pediatric sedative upper endoscopy (PSUE). METHODS: The PSUE procedures performed in 15 Korean pediatric gastrointestinal endoscopic units within a year were analyzed. Drugs used for sedation were grouped according to the method of use, and the depth of sedation was evaluated based on the Ramsay scores. The procedures and their complications were also assessed. RESULTS: In total, 734 patients who underwent PSUE were included. Sedation and monitoring were performed by an anesthesiologist at one of the institutions. The sedative procedures were performed by a pediatric endoscopist at the other 14 institutions. Regarding the number of assistants present during the procedures, 36.6% of procedures had one assistant, 38.8% had 2 assistants, and 24.5% had 3 assistants. The average age of the patients was 11.6 years old. Of the patients, 19.8% had underlying diseases, 10.0% were taking medications such as epilepsy drugs, and 1.0% had snoring or sleep apnea history. The average duration of the procedures was 5.2 minutes. The subjects were divided into 5 groups as follows: 1) midazolam + propofol + ketamine (M + P + K): n = 18, average dose of 0.03 + 2.4 + 0.5 mg/kg; 2) M + P: n = 206, average dose of 0.06 + 2.1 mg/kg; 3) M + K: n = 267, average dose of 0.09 + 0.69 mg/kg; 4) continuous P infusion for 20 minutes: n = 15, average dose of 6.6 mg/kg; 5) M: n = 228, average dose of 0.11 mg/kg. The average Ramsay score for the five groups was 3.7, with significant differences between the groups (P < 0.001). Regarding the adverse effects, desaturation and increased oxygen supply were most prevalent in the M + K group. Decreases and increases in blood pressure were most prevalent in the M + P + K group, and bag-mask ventilation was most used in the M + K group. There were no reported incidents of intubation or cardiopulmonary resuscitation. A decrease in oxygen saturation was observed in 37 of 734 patients, and it significantly increased in young patients (P = 0.001) and when ketamine was used (P = 0.014). Oxygen saturation was also correlated with dosage (P = 0.037). The use of ketamine (P < 0.001) and propofol (P < 0.001) were identified as factors affecting the Ramsay score in the logistic regression analysis. CONCLUSION: Although the drug use by Korean pediatric endoscopists followed the recommended guidelines to an extent, it was apparent that they combined the drugs or reduced the doses depending on the patient characteristics to reduce the likelihood of respiratory failure. Inducing deep sedation facilitates comfort during the procedure, but it also leads to a higher risk of complications.

Three-Dimensional Evaluation of the Depressor Anguli Oris and Depressor Labii Inferioris for Botulinum Toxin Injections.

BACKGROUND: Botulinum toxin type A (BoNT-A) injection administered at an inappropriate site or depth can produce an unwanted change in facial animation because the depressor anguli oris (DAO) and depressor labii inferioris (DLI) muscles are partially overlapped. Therefore, simple BoNT-A injection guidelines, based on 3-dimensional (3D) facial anatomic references and landmarks, would be very useful. OBJECTIVES: The aim of this study was to establish novel BoNT-A injection guidelines that include the soft tissue thickness at the lower perioral region. Data were acquired with a 3D scanning system combined with dissections in order to obtain accurate injection sites and depths for the DAO and DLI. METHODS: 3D scans of the facial skin, superficial fat, and facial muscle surface were performed in 45 embalmed cadavers. The thicknesses of the skin and subcutaneous layer were calculated automatically from superimposed images at each of 5 reference points (P) in the perioral region. RESULTS: In every case (100%), P3 and P5 were located in the DLI and DAO areas, respectively (45/45). Therefore, we defined P3 as the "DLI point" and P5 as the "DAO point." The soft tissue thicknesses at the DLI and DAO points were 6.4 [1.7] mm and 6.7 [1.8] mm, respectively. CONCLUSIONS: The P3 and P5 described in this study are effective guidelines that only target the DLI and DAO. Clinicians, specifically, can easily use facial landmarks, such as the cheilion and pupil, to assign the DLI and DAO points without any measurement or palpation of the modiolus.

Ultrasonography Analysis of Vessels Around the Forehead Midline.

BACKGROUND: Filler injection into the glabella is well known to be a highly dangerous procedure due to the high risk of embolism and intravascular injection. Although it is conventional practice to insert the cannula into the middle of the forehead to perform injections into the glabella or radix, vascular structures can be observed in this region during anatomic dissection procedures. OBJECTIVES: The aim of this study was to characterize the blood vessels around the forehead midline in order to provide crucial anatomic information for ensuring the safety of noninvasive procedures involving the forehead and glabella. METHODS: Ultrasonography image scanning was performed at the following 4 points on the forehead midline: trichion (P1), metopion (P2), halfway point between metopion and glabella (P3), and glabella (P4). The courses and locations of vessels were identified and classified according to their proximity to the forehead midline. RESULTS: Vessels coursing within 0.75 cm either side of the forehead midline were found in 34% to 50% of individuals. Arteries running near the forehead midline tended to be dominant on the right side of the forehead except in the P4 area. About half of the individuals had vessels in the P4 area, of which 96.7% were veins. CONCLUSIONS: The present results indicate that there are superficial vessels running close to the midline of the forehead. This anatomic information can explain the higher incidence of vascular complications during conventional aesthetic procedures. To ensure safety, the cannula entry point or needle puncture point for glabella augmentation should be reconsidered.

Inhibition of Estrogen Sulfotransferase (SULT1E1/EST) Ameliorates Ischemic Acute Kidney Injury in Mice.

BACKGROUND: Studies have suggested that estrogens may protect mice from AKI. Estrogen sulfotransferase (SULT1E1, or EST) plays an important role in estrogen homeostasis by sulfonating and deactivating estrogens, but studies on the role of SULT1E1 in AKI are lacking. METHODS: We used the renal ischemia-reperfusion model to investigate the role of SULT1E1 in AKI. We subjected wild-type mice, Sult1e1 knockout mice, and Sult1e1 knockout mice with liver-specific reconstitution of SULT1E1 expression to bilateral renal ischemia-reperfusion or sham surgery, either in the absence or presence of gonadectomy. We assessed relevant biochemical, histologic, and gene expression markers of kidney injury. We also used wild-type mice treated with the SULT1E1 inhibitor triclosan to determine the effect of pharmacologic inhibition of SULT1E1 on AKI. RESULTS: AKI induced the expression of Sult1e1 in a tissue-specific and sex-specific manner. It induced expression of Sult1e1 in the liver in both male and female mice, but Sult1e1 induction in the kidney occurred only in male mice. Genetic knockout or pharmacologic inhibition of Sult1e1 protected mice of both sexes from AKI, independent of the presence of sex hormones. Instead, a gene profiling analysis indicated that the renoprotective effect was associated with increased vitamin D receptor signaling. Liver-specific transgenic reconstitution of SULT1E1 in Sult1e1 knockout mice abolished the protection in male mice but not in female mice, indicating that Sult1e1's effect on AKI was also tissue-specific and sex-specific. CONCLUSIONS: SULT1E1 appears to have a novel function in the pathogenesis of AKI. Our findings suggest that inhibitors of SULT1E1 might have therapeutic utility in the clinical management of AKI.

The Nasolabial Fold: A Micro-Computed Tomography Study.

BACKGROUND: The nasolabial fold is known to be a challenging midface feature for aesthetic physicians. However, the steric conformation of the structures related to the nasolabial fold has remained undefined because the composition and topography of this region are highly intricate. Therefore, this study aimed to clarify the three-dimensional structures of the nasolabial fold using micro-computed tomography and verify their detailed composition by means of histologic observation. METHODS: Twenty-four specimens were collected from the area beside the alae nasi to the area above the oral angle of 12 cadavers (mean age, 80.3 years) bilaterally. Twelve specimens were evaluated by means of phosphotungstic acid contrast staining, and the rest were evaluated by means of histologic staining. All specimens were divided into three regions and analyzed comprehensively. RESULTS: The medial region of the nasolabial fold had dense irregular connective tissue intermingled with muscle fibers; the lateral region of the nasolabial fold had numerous fibrous septa with abundant adipose tissue. The levator labii alaeque nasi and the zygomaticus minor were attached to the medial part of the nasolabial fold, and the fascial septa were intermittently tethered to the dermis, lateral to the nasolabial fold. The extension of the adipose tissue within the fascial septa was limited by the lateral border of the muscle attachment. CONCLUSIONS: Dimensional and distributional alterations of the adipose tissues with senescence could render the nasolabial fold deeper by increasing the depth of the subcutaneous layer, lateral to the fold. Thus, to ameliorate the fold, the adipose tissue, lateral to the fold, or the muscle traction, medial to the fold, should be altered.

Z-ligustilide and n-Butylidenephthalide Isolated from the Aerial Parts of Angelica tenuissima Inhibit Lipid Accumulation In Vitro and In Vivo.

Abnormal lipid metabolism, such as increased fatty acid uptake and esterification, is associated with nonalcoholic fatty liver disease (NAFLD). The aqueous extract of the aerial part of Angelica tenuissima Nakai (ATX) inhibited high-fat diet-induced hepatic steatosis in mice as well as oleic acid-induced neutral lipid accumulation in HepG2 cells. ATX decreased the mRNA and protein levels of CD36 and diglyceride acyltransferase 2 (DGAT2), the maturation of sterol regulatory element-binding proteins (SREBP), and the expression of the lipogenic target genes fasn and scd1. The ATX components, Z-ligustilide and n-butylidenephthalide, inhibited the expression of FATP5 and DGAT2 and thus oleic acid-induced lipid accumulation in HepG2 cells. These results suggest that ATX and its active components Z-ligustilide and n-butylidenephthalide inhibit fatty acid uptake and esterification in mice and have potential as therapeutics for NAFLD.

Hepatic upregulation of fetuin-A mediates acetaminophen-induced liver injury through activation of TLR4 in mice.

Acetaminophen (APAP)-induced liver injury (AILI) is initiated by the generation of a reactive metabolite and ultimately leads to hepatocyte necrosis. Necrotic cells secrete damage-associated molecular patterns that activate hepatic nonparenchymal cells and induce an inflammatory response. Fetuin-A is a hepatokine with reported involvement in low-grade inflammation in many diseases, due to acting as an endogenous ligand for TLR4. However, little is known about the role of fetuin-A in AILI. In this study, we showed that fetuin-A is involved in the aggravation of hepatotoxicity during the initial phase of AILI progression. Treatment with APAP increased the expression and serum levels of fetuin-A in mice. Fetuin-A upregulated transcription of pro-inflammatory cytokines and chemokines through activation of TLR4 and also increased monocyte infiltration into the liver, leading to necroinflammatory reactions in AILI. However, these reactions were attenuated with the silencing of fetuin-A using adenoviral shRNA. As a result, mice with silenced fetuin-A exhibited less centrilobular necrosis and liver injury compared to controls in response to APAP. In conclusion, our results suggest that fetuin-A is an important hepatokine that mediates the hepatotoxicity of APAP through production of chemokines and thus regulates the infiltration of monocytes into the liver, a critical event in the inflammatory response during the initial phase of AILI. Our results indicate that a strategy based on the antagonism of fetuin-A may be a novel therapeutic approach to the treatment of acetaminophen-induced acute liver failure.

Activation of SIRT1 by L-serine increases fatty acid oxidation and reverses insulin resistance in C2C12 myotubes.

Silent information regulator 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, and the function is linked to cellular metabolism including mitochondrial biogenesis. Hepatic L-serine concentration is decreased significantly in fatty liver disease. We reported that the supplementation of the amino acid ameliorated the alcoholic fatty liver by enhancing L-serine-dependent homocysteine metabolism. In this study, we hypothesized that the metabolic production of NAD+ from L-serine and thus activation of SIRT1 contribute to the action of L-serine. To this end, we evaluated the effects of L-serine on SIRT1 activity and mitochondria biogenesis in C2C12 myotubes. L-Serine increased intracellular NAD+ content and led to the activation of SIRT1 as determined by p53 luciferase assay and western blot analysis of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) acetylation. L-Serine treatment increased the expression of the genes associated with mitochondrial biogenesis and enhanced mitochondrial mass and function. In addition, L-serine reversed cellular insulin resistance determined by insulin-induced phosphorylation of Akt and GLUT4 expression and membrane translocation. L-Serine-induced mitochondrial gene expression, fatty acid oxidation, and insulin sensitization were mediated by enhanced SIRT1 activity, which was verified by selective SIRT1 inhibitor (Ex-527) and siRNA directed to SIRT1. L-Serine effect on cellular NAD+ level is dependent on the L-serine metabolism to pyruvate that is subsequently converted to lactate by lactate dehydrogenase. In summary, these data suggest that L-serine increases cellular NAD+ level and thus SIRT1 activity in C2C12 myotubes.

Locational Relationship between the Lateral Border of the Frontalis Muscle and the Superior Temporal Line.

BACKGROUND: The frontalis is a representative target muscle for botulinum neurotoxin type A injections aimed at treating horizontal wrinkles in the forehead region. However, a lack of information regarding the shape and thickness of the frontalis may lead to unexpected side effects. METHODS: This study dissected hemifaces of 44 embalmed Korean and Thai cadavers and performed ultrasound examinations on 20 Korean volunteers. Two anatomical types were identified: (1) the lateral portion of the frontalis covered the superior temporal line in type I, and (2) the lateral border of the frontalis and the superior temporal line almost coincided in type II. A horizontal line was drawn laterally from the midpoint between the metopion and the glabella, and landmarks F1, F2, and F3 were defined as points where this horizontal reference line intersected with vertical lines from the midpoint of the pupil, the lateral canthus, and the lateral orbital rim, respectively. RESULTS: Type I was more common than type II [84 percent (37 of 44) versus 16 percent (seven of 44)]. When the lateral border of the frontalis ran along the border, there were no cases in which the superior temporal line was not visible. The mean minimum distance in type I was 10.53 mm. The muscle thicknesses at F1, F2, and F3 were 1.80 ± 0.44 mm (mean ± SD), 1.61 ± 0.37 mm, and 0.11 ± 0.04 mm, respectively. CONCLUSIONS: This study yielded data on the location and thickness of the lateral border of the frontalis. An anatomical study-based, ultrasound-guided injection technique can achieve reliable results when noninvasive treatment is applied to the forehead area.

Three-Dimensional Topography of the Emerging Point of the Ophthalmic Artery.

BACKGROUND: During periorbital noninvasive and surgical procedures, there is the risk of iatrogenic injury to the emerging point of the ophthalmic artery. This study aimed to determine the three-dimensional location of the emerging point of the ophthalmic artery and to provide clinicians with anatomical information that would help them to avoid associated complications. METHODS: Seventeen hemifaces of the emerging point of the ophthalmic artery from 10 Korean and seven Thai cadavers were dissected and scanned by a three-dimensional scanner. The emerging points of the ophthalmic artery of 30 healthy Korean volunteers were also detected using an ultrasound imaging system. RESULTS: The transverse distance from the medial canthus to the emerging of the ophthalmic artery was 3.8 ± 1.0 mm medially, and the vertical distance was 14.0 ± 2.9 mm superiorly. The transverse distance from the midline was 16.5 ± 1.7 mm to the emerging point of the ophthalmic artery and 20.0 ± 2.0 mm to the medial canthus. The measured depth from the skin surface to the emerging point of the ophthalmic artery was 4.8 ± 1.7 mm by means of three-dimensional scanning and 4.5 ± 1.1 mm using ultrasound detection. The vertical distance from the inferior margin of the superior orbital rim to the emerging point of the ophthalmic artery was 5.3 ± 1.4 mm. CONCLUSION: These data inform clinicians about the anatomical three-dimensional location of the emerging point of the ophthalmic artery, which will help them to avoid iatrogenic injury when they are performing periorbital clinical procedures.