Recent evidence supports a neuroprotective role of Src homology 2-containing protein tyrosine phosphatase 2 (SHP-2) against ischemic brain injury. However, the molecular mechanisms of SHP-2 activation and those governing how SHP-2 exerts its function under oxidative stress conditions are not well understood. Recently we have reported that reactive oxygen species (ROS)-mediated oxidative stress promotes the phosphorylation of endogenous SHP-2 through lipid rafts, and that this phosphorylation strongly occurs in astrocytes, but not in microglia. To investigate the molecules involved in events leading to phosphorylation of SHP-2, raft proteins were analyzed using astrocytes and microglia. Interestingly, caveolin-1 and -2 were detected only in astrocytes but not in microglia, whereas flotillin-1 was expressed in both cell types. To examine whether the H2O2-dependent phosphorylation of SHP-2 is mediated by caveolin-1, we used specific small interfering RNA (siRNA) to downregulate caveolin-1 expression. In the presence of caveolin-1 siRNA, the level of SHP-2 phosphorylation induced by H2O2 was significantly decreased, compared with in the presence of control siRNA. Overexpression of caveolin-1 effectively increased H2O2-induced SHP-2 phosphorylation in microglia. Lastly, H2O2 induced extracellular signal-regulated kinase (ERK) activation in astrocytes through caveolin-1. Our results suggest that caveolin-1 is involved in astrocyte-specific intracellular responses linked to the SHP-2-mediated signaling cascade following ROS-induced oxidative stress.
Animals ; Astrocytes/*metabolism ; Caveolin 1/*genetics/metabolism ; Caveolin 2/genetics ; Cell Line ; Cells, Cultured ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Gene Expression ; Humans ; Microglia/metabolism ; Phosphoric Monoester Hydrolases/*metabolism ; Phosphorylation ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/*metabolism ; Rats ; Reactive Oxygen Species/*metabolism

Composition of the gut microbiota changes with aging and plays an important role in age-associated disease such as metabolic syndrome, cancer, and neurodegeneration. The gut microbiota composition oscillates through the day, and the disruption of their diurnal rhythm results in gut dysbiosis leading to metabolic and immune dysfunctions. It is well documented that circadian rhythm changes with age in several biological functions such as sleep, body temperature, and hormone secretion. However, it is not defined whether the diurnal pattern of gut microbial composition is affected by aging. To evaluate aging effects on the diurnal pattern of the gut microbiome, we evaluated the taxa profiles of cecal contents obtained from young and aged mice of both sexes at daytime and nighttime points by 16S rRNA gene sequencing. At the phylum level, the ratio of Firmicutes to Bacteroidetes and the relative abundances of Verrucomicrobia and Cyanobacteria were increased in aged male mice at night compared with that of young male mice. Meanwhile, the relative abundances of Sutterellaceae, Alloprevotella, Lachnospiraceae UCG-001, and Parasutterella increased in aged female mice at night compared with that of young female mice. The Lachnospiraceae NK4A136 group relative abundance increased in aged mice of both sexes but at opposite time points. These results showed the changes in diurnal patterns of gut microbial composition with aging, which varied depending on the sex of the host. We suggest that disturbed diurnal patterns of the gut microbiome can be a factor for the underlying mechanism of age-associated gut dysbiosis.

Purpose: Primary tumor at the carotid bifurcation is uncommon, which includes paraganglioma, schwannoma, and lymphoma. Due to their rarity, characteristics of these tumors and problems related to their surgical treatment have not been well known. We tried to elucidate different clinical characteristics and surgical complications of these tumors. Materials and Methods: We retrospectively reviewed 21 patients with carotid bifurcation tumor from the Vascular Surgery division of a Korean tertiary institution from 1995 to 2018. We investigated patients’ demographics and clinical features, image characteristics, treatment details, and surgical outcomes. Results: During the period from January 1995 to January 2018, we experienced surgical resections of 21 carotid bifurcation tumors which included 16 (76.2%) paragangliomas and 5 (23.8%) schwannomas. The most common clinical feature was a non-tender cervical mass. According to Shamblin classification, paragangliomas were classified into class II in 68.8% and class III in 25.0%. On the preoperative computed tomography images, all the paragangliomas showed characteristic splaying of the carotid bifurcation and hypervascularity of the tumors. On the contrary, all the schwannomas showed hypovascularity and splaying sign in 60%.Surgical complications related to cervical nerve injury developed in 50% and 60% of patients with Shamblin class III paraganglioma and schwannoma, respectively.During the mean follow-up period of 25 months (range, 1 to 163 months), distant metastases developed in 2 (12.5%) of paraganglioma patients. Conclusion Neurologic complications were more common after surgical resection of Shamblin class III paraganglioma and schwannoma. For patients with paraganglioma, postoperative periodic follow-up examination is advised to detect distant metastasis.

Exercise has long been recognized as an important component of treatment for various diseases. However, the benefits and risks of exercise interventions must be carefully evaluated to ensure the former outweighs the latter. As cancer patients undergo diverse treatment modalities with distinct objectives, a systematic approach partitioning the cancer journey into distinct phases is necessary to inform tailored exercise prescriptions. This narrative review summarizes exercise benefits and mechanisms for cancer patients and survivors across four distinct survivorship periods—before surgery, after surgery and before adjuvant treatment, during nonsurgical treatment (adjuvant and neoadjuvant), and during extended survival. In summary, exercise reduces the risks of complications and declines in physical functioning while improving fatigue, quality of life, and the ability to manage treatment effects. Although additional research is warranted, existing evidence is sufficient to integrate exercise into clinical oncology practice and cancer survivorship programs.

Compartment syndrome is a clinical condition associated with decreased blood circulation that can lead to swelling of tissue in limited space. Several factors including lithotomy position, prolonged surgery, intermittent pneumatic compressor, and reperfusion after treatment of arterial thrombosis may contribute to compartment syndrome. However, compartment syndrome rarely occurs after gynecologic surgery. In this case, the patient was diagnosed as compartment syndrome due to reperfusion injury after treatment of arterial thrombosis, which occurred after laparoscopic radical hysterectomy and pelvic lymph node dissection for cervical cancer. Despite its rarity, prevention and identifying the risk factors of complication should be performed perioperatively; furthermore, gynecologist should be aware of the possibility of complications.
Blood Circulation ; Compartment Syndromes* ; Female ; Gynecologic Surgical Procedures ; Humans ; Hysterectomy* ; Lower Extremity* ; Lymph Node Excision* ; Lymph Nodes* ; Reperfusion Injury* ; Reperfusion* ; Risk Factors ; Thrombosis* ; Uterine Cervical Neoplasms*

Fixed drug eruption (FDE) is an eruption, which recurs at the same site or sites on each administration of the causative drug, and heals with residual hyperpigmentation. FDE is caused by many drugs, barbiturates, tetracyclines, sulfonamide, and phenolphthalein. Salicylate and nonsteroidal anti-inflammatory drugs (NSAIDs) also cause FDE, but acetaminophen does so only rarely. A 9-year-old girl presented with a 3-year-history of symptomatic pigmented macules on her face, abdomen, and extremities. The eruption was first appeared three years ago, which was when she took medicine after she was discharged following suspicions of Kawasaki disease. Thereafter, she had the same eruption on the same sites when she took medicine for common colds including acetaminophen and ibuprofen. The oral challenge provocation test for ibuprofen was negative, whereas for acetaminophen it was positive. We report a rare case of FDE due to acetaminophen with clinical findings and results of oral challenge test.
Abdomen ; Acetaminophen* ; Barbiturates ; Child* ; Common Cold ; Drug Eruptions* ; Extremities ; Female ; Humans ; Hyperpigmentation ; Ibuprofen ; Mucocutaneous Lymph Node Syndrome ; Phenolphthalein ; Tetracyclines

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease. To date, a large number of clinical studies have been conducted to investigate the association between genetic variations and COPD. However, little is known regarding the genetic susceptibility of Koreans to this disease. MER receptor tyrosine kinase (MERTK) plays important roles in the inhibition of inflammation and in the clearance of apoptotic cells. Here, we investigated the association between genetic variations in MERTK and the development of COPD in Koreans. METHODS: We conducted genetic analysis of MERTK using genomic DNA samples from 87 patients with COPD and 88 healthy controls and compared the frequency of each variation or haplotype between the patient and control groups. Subsequently, the effect of each variation was evaluated using in vitro assays. RESULTS: Ten variations were identified in this study, four of them for the first time. In addition, we found that the frequency of each variation or haplotype was comparable between the patient and control groups. However, we observed that the frequency for the wild-type haplotype was higher in the control group, compared to that in the group of patients with COPD, in the subgroup analysis of current smokers, although the difference was not statistically significant (P = 0.080). In in vitro assays, we observed that none of the variations affected the activity of the promoter or the expression of MERTK. CONCLUSION: Our findings indicate that the susceptibility to COPD is not related to the genetic variations or haplotypes of MERTK in Koreans.
DNA ; Genetic Predisposition to Disease ; Genetic Variation ; Haplotypes ; Humans ; In Vitro Techniques ; Inflammation ; Lung Diseases ; Protein-Tyrosine Kinases ; Pulmonary Disease, Chronic Obstructive ; Smoking

Background: Although the first choice of treatment for abdominal aortic aneurysm (AAA) is endovascular aneurysm repair, especially in elderly patients, some patients require open surgical repair. The purpose of this study was to compare the mortality outcomes of open AAA repair between octogenarians and younger counterparts and to identify the risk factors associated with mortality. Methods: All consecutive patients who underwent elective open AAA repair due to degenerative etiology at a single tertiary medical center between 1996 and June 2020 were included in this retrospective review. Medical records and imaging studies were reviewed to collect the following information: demographics, comorbid medical conditions, clinical presentations, radiologic findings, surgical details, and morbidity and mortality rates. For analysis, patients were divided into two groups: older and younger than 80 years of age. Multivariate analysis was performed to identify factors associated with mortality after elective open AAA repair. Results: Among a total of 650 patients who underwent elective open AAA repair due to degenerative AAA during the study period, 58 (8.9%) were octogenarians and 595 (91.1%) were non-octogenarians. Patients in the octogenarian group were predominantly female and more likely to have lower body weight and body mass index (BMI), hypertension, chronic kidney disease, and lower preoperative serum hemoglobin and albumin compared with patients in the non-octogenarian group. Maximal aneurysm diameter was larger in octogenarians. During the median follow-up duration of 34.4 months for 650 patients, the median length of total hospital and intensive care unit stay was longer in octogenarians. The 30-day (1.7% vs. 0.7%, P= 0.374) and 1-year (6.9% vs. 2.9%, P = 0.108) mortality rates were not statistically significantly different between the two groups. Multivariate analysis showed that low BMI was associated with increased 30-day (odds ratio [OR], 16.339; 95% confidence interval [CI], 1.192–224.052; P= 0.037) and 1-year (OR, 8.236; CI, 2.301–29.477; P= 0.001) mortality in all patients. Conclusion Because the mortality rate of octogenarians after elective open AAA repair was not significantly different compared with their younger counterparts, being elderly is not a contraindication for open AAA repair. Low BMI might be associated with increased postoperative mortality.