Ramucirumab is a vascular endothelial growth factor (VEGF) receptor-2 inhibiting monoclonal antibody for the treatment of gastric cancer, non-small cell lung cancer, colorectal cancer, and hepatocellular carcinoma. Some VEGF inhibitors are known to increase the risk of ischemic stroke; however, their association with ramucirumab remains controversial. To the best of our knowledge, only two cases of ischemic stroke following ramucirumab treatment have been reported worldwide. We herein present the first case of acute cerebral infarction secondary to ramucirumab in Korea.

OBJECTIVES: The objective of this study was to investigate the relationship between restricted, repetitive behaviors and interests (RRBI) and autistic symptoms in Korean high functioning autism spectrum disorder (ASD) children and to examine the structure of RRBI. METHODS: Participants included 147 high functioning ASD subjects and 181 unaffected siblings. ASD subjects were divided into two groups based on the presence of RRBI. The domain scores of the Korean version of Autism Diagnostic Interview-Revised (K-ADI-R), Korean version of Asperger Syndrome Diagnostic Scale and total scores of Korean translated version of Social Responsiveness Scale, Korean version of Social Communication Scale were used for comparison of ASD symptoms between the groups. Eleven items from the RRBI domain of the K-ADI-R were used in principal axis factor analysis (PAF). RESULTS: A statistically lower nonverbal IQ score was observed for ASD with RRBI than for ASD without RRBIs, and more social deficit, communication deficit, and behavioral and emotional problems were observed for ASD with RRBI compared to ASD without RRBI. Using PAF, two distinct factors were identified. 'Resistance to trivial changes in environment', 'Difficulty with minor changes in personal routine & environment', and 'Compulsion/ritual' were included as one factor. CONCLUSION: Analysis of the data suggests that the presence of RRBI in high functioning ASD is associated with a more severe presentation of autistic disorder. In addition, there appears to be heterogeneity within RRBI in autism except insistence on sameness.
Asperger Syndrome ; Autistic Disorder ; Axis, Cervical Vertebra ; Autism Spectrum Disorder* ; Child* ; Factor Analysis, Statistical ; Humans ; Population Characteristics ; Siblings

BACKGROUND: The efficacy of bisphosphonates for osteoporotic fracture has been consistently reported in recent randomized controlled trials (RCTs) enrolling hundreds of patients. The objective of this study was to update knowledge on the efficacy of available bisphosphonates in the prevention of vertebral and non-vertebral fractures. METHODS: An approach “using systematic reviews” on PubMed and Cochrane Library was taken. Twenty-four RCTs investigating the effects of bisphosphonates for the prevention of osteoporotic fracture were included in final analysis. A pairwise meta-analysis was conducted with a random effects model. Subgroup analysis was performed according to the type of bisphosphonate. RESULTS: The use of bisphosphonate decrease the risk of overall osteoporotic fracture (odds ratio [OR] 0.62; P<0.001), vertebral fracture (OR 0.55; P<0.001) and non-vertebral fracture (OR 0.73; P<0.001). Subgroup analysis indicated that zoledronic acid showed the lowest risk reduction (OR 0.61; P<0.001) for overall osteoporotic fractures but no significance was observed for etidronate (OR 0.34; P=0.127). CONCLUSIONS: This update meta-analysis re-confirmed that bisphosphonate use can effectively reduce the risk of osteoporotic fracture. However, there is a lack of evidence regarding etidronate for the prevention of osteoporotic fracture.
Diphosphonates* ; Etidronic Acid ; Humans ; Meta-Analysis as Topic ; Osteoporosis ; Osteoporotic Fractures* ; Risk Reduction Behavior

OBJECTIVE: Despite the good prognosis of borderline ovarian tumors (BOTs), a few BOT patients experience the relapse of disease, either borderline or malignant. However, the risk of recurrence of BOTs is somewhat controversial. We intended to find out the specific characteristics and prognosis of the recurrence of BOTs. METHODS: Between 1995 and 2012, 130 women were diagnosed with BOTs at a single institution. Eleven patients diagnosed and treated for the recurrence of BOTs including seven cancerous and four borderline relapses were included for the analysis in this retrospective study. Clinicopathological characteristics and surgical procedures as well as follow-up data with overall survival were assessed. Statistical analyses was performed using the chi2 test, t-test and log-rank test with Cox regression. RESULTS: One hundred and thirty patients with mean follow-up of 65.8 months were evaluated, of whom half were below 40 years old at their first diagnosis of BOTs. Among 11 recurrent cases (8.5%), 7 cancerous transformations (5.4%) and 4 borderline recurrences (3.1%) were detected with median time of 6 and 71 months after the primary surgery, respectively. Nine out of 11 recurrences were happened at their equal or below 40-years-old age at the primary diagnosis (P=0.027). Also, all 7 cancerous relapses arose from premenopausal women of median age of 35 years old. Twenty (15%) patients had laparoscopic surgery and they were all treated conservatively. Among those 20, 5 were suffered from relapse of BOTs and laparoscopic approach was proved to be a significant risk factor for disease relapse in our study (P=0.013). Although laparoscopic surgery was revealed had meaningful influence on disease free survival (P=0.024), it was not significant on overall survival (P=0.226). CONCLUSION: Laparoscopic conservative surgery for BOTs can be accepted under close follow-ups. And younger patients should be followed for long period to evaluate recurrence.
Diagnosis ; Disease-Free Survival ; Epithelial-Mesenchymal Transition ; Female ; Follow-Up Studies ; Humans ; Laparoscopy ; Ovarian Neoplasms ; Prognosis ; Recurrence* ; Retrospective Studies ; Risk Factors

OBJECTIVE: This study aimed to compare perioperative and postoperative morbidity of older and younger women undergoing sacrocolpopexy (SCP). METHODS: A retrospective study included 271 patients who underwent laparotomic SCP for symptomatic pelvic organ prolapse from November 2008 to June 2013 at our institution. By the review of medical records, perioperative and postoperative data including the length of the surgery, estimated blood loss, blood transfusion, the length of hospital stay, wound complications and febrile morbidity were collected. In addition, cardiovascular, pulmonary, gastrointestinal, genitourinary, or neurological adverse events were retrieved. The need for an indwelling urinary catheter or performance of clean intermittent self-catheterization, mesh erosion rate and the number of days required for each were included in the postoperative outcomes. For the outcome variable analyzed in this study, the patients was dichomotized into women aged 65 and older and those younger than 65. RESULTS: One hundred and thirty-five (49.8%) patients were younger than 65 and 136 (50.2%) were aged 65 and older. Older women had higher body mass index, vaginal parity and prior surgery for hysterectomy than younger women (P<0.05). And older women had higher baseline comorbidities, such as hypertension, diabetes, cardiac disease (P<0.05), and their American society of Anesthesiologist class was higher (P<0.001). In the perioperative and postoperative complication, older group showed no differences in most of the operation-related complication rates, but gastrointestinal complication rate. Also, mesh erosion rate was not found to be significantly different between the two groups at the last visit. CONCLUSION: Older women undergoing laparotomic SCP have similar perioperative and postoperative morbidities as younger women, suggesting surgeons can counsel older and younger women similarly in terms of operative risks.
Blood Transfusion ; Body Mass Index ; Comorbidity ; Female ; Heart Diseases ; Humans ; Hypertension ; Hysterectomy ; Length of Stay ; Medical Records ; Parity ; Pelvic Organ Prolapse ; Postoperative Complications ; Retrospective Studies ; Urinary Catheters ; Wounds and Injuries

PURPOSE: Ultraviolet (UV) irradiation decreases epidermal hydration, which is maintained by reduction of natural moisturizing factors (NMFs). Among various NMFs, free amino acids (AA) are major constituents generated by filaggrin degradation. This experiment was conducted to determine whether or not dietary supplementation of green tea extract (GTE) in UV-irradiated mice can improve epidermal levels of hydration, filaggrin, free AAs, and peptidylarginine deiminase-3 (PAD3) expression (an enzyme involved in filaggrin degradation). METHODS: Hairless mice were fed a diet of 1% GTE for 10 weeks in parallel with UV irradiation (group UV+1%GTE). As controls, hairless mice were fed a control diet in parallel with (group UV+) or without (group UV-) UV irradiation. RESULTS: In group UV+, epidermal levels of hydration and filaggrin were lower than those in group UV-; these levels increased in group UV+1% GTE to levels similar to group UV-. Epidermal levels of PAD3 and major AAs of NMF, alanine, glycine and serine were similar in groups UV- and UV+, whereas these levels highly increased in group UV+1% GTE. CONCLUSION: Dietary GTE improves epidermal hydration by filaggrin generation and degradation into AAs.
Alanine ; Amino Acids ; Animals ; Diet ; Dietary Supplements ; Epidermis* ; Glycine ; Metabolism* ; Mice ; Mice, Hairless* ; Serine ; Tea*

Objective: : This study aims to investigate the incidence of vestibular schwannoma (VS) and demographic characteristics in Korea using population-based National Health Insurance Service data. Methods: : This study analyzed Korean National Health Insurance Service data from 2005 to 2020, based on the International Classification of Diseases, 10th version, Clinical Modification codes D333 and D431. Only those patients who had undergone magnetic resonance imaging and audiologic tests were considered definitive cases. Demographic variables included age, sex, treatment modality, hypertension, diabetics, dyslipidemia, smoking history, alcohol history, and income status. Results: : The total number of VS patients was 5751. The average incidence rate was 0.71 per 100000 from 2005 to 2020, and the annual incidence rate increased from 0.33 in 2005 to 1.32 in 2019 but decreased to 0.80 in 2020. Incidence was highest in those aged 60–69 years (1.791) and lowest in those younger than 20 years (0.041). Incidence was higher in females, and the number of patients who received radiosurgery (46.64%) was largest compared to the wait and scan group (37.96%), microsurgery group (12.85%), or the group who received both (2.56%). Diabetes, dyslipidemia, and alcohol consumption increased the risk of VS, while cigarette smoking reduced the risk of VS. Conclusion : The incidence of VS exhibited an increasing trend from 2005 to 2019. Radiosurgery (46.64%) was the most common treatment modality. Diabetes, dyslipidemia, and alcohol consumption increased the risk of VS, while cigarette smoking reduced the risk of VS.

The 26S proteasome irreversibly hydrolyzes polyubiquitylated substrates to maintain protein homeostasis; it also regulates immune responses by generating antigenic peptides. An alternative form of the 26S proteasome is the immunoproteasome, which contains substituted catalytic subunits (β1i/PSMB9, β2i/PSMB10, and β5i/PSMB8) instead of constitutively expressed counterparts (β1/PSMB6, β2/PSMB7, and β5/PSMB5). The immunoproteasome expands the peptide repertoire presented on MHC class I molecules. However, how its activity changes in this context is largely elusive, possibly due to the lack of a standardized methodology to evaluate its specific activity. Here, we describe an assay protocol that measures the immunoproteasome activity of whole-cell lysates using commercially available fluorogenic peptide substrates. Our results showed that the most accurate assessment of immunoproteasome activity could be achieved by combining β5itargeting substrate Ac-ANW-AMC and immunoproteasome inhibitor ONX-0914. This simple and reliable protocol may contribute to future studies of immunoproteasomes and their pathophysiological roles during viral infection, inflammation, and tumorigenesis.

Purpose: Gambling disorder is highly prevalent, and harms individuals, families, interpersonal relationships, and society. However, the efforts to treat and recover from a gambling disorder are insufficient. The purpose of this study was to construct an integrated body of knowledge related to the recovery of gambling disorder, by synthesizing qualitative studies showing the recovery process in gambling. Methods: The qualitative meta-synthesis method was used to search for qualitative studies on recovery from gambling, and the experiences of 213 people of 22 articles were analyzed. Results: The overall theme representing the recovery of a gambling disorder was derived as ‘the journey of becoming the master of my life and growing together’. The process of recovery from a gambling disorder was subdivided into the decision-making phase, life-reconstruction phase, and life-fulfillment phase. The factors that enable as well as hinder recovery are presented in detail. Conclusion It is expected that the results of this study can be used as an empirical basis, for planning gambling-related policies and programs in practice through the experiences of recovering gamblers.

Despite evidence that bacteria-sensing Toll-like receptors (TLRs) are activated in salivary gland tissues of Sjogren syndrome (SS) patients, the role of oral bacteria in SS etiopathogenesis is unclear. We previously reported that two SS-associated oral bacteria, Prevotella melaninogenica (Pm) and Rothia mucilagenosa (Rm), oppositely regulate the expression of major histocompatibility complex class I (MHC I) in human salivary gland (HSG) cells. Here, we elucidated the mechanisms underlying the differential regulation of MHC I expression by these bacteria. The ability of Pm and Rm to activate TLR2, TLR4, and TLR9 was examined using TLR reporter cells. HSG cells were stimulated by the TLR ligands, Pm, and Rm. The levels of MHC I expression, bacterial invasion, and viability of HSG cells were examined by flow cytometry. The hypoxic status of HSG cells was examined using Hypoxia Green. HSG cells upregulated MHC I expression in response to TLR2, TLR4, and TLR9 activation. Both Pm and Rm activated TLR2 and TLR9 but not TLR4. Rm-induced downregulation of MHC I strongly correlated with bacterial invasion and cell death. Rm-induced cell death was not rescued by inhibitors of the diverse cell death pathways but was associated with hypoxia. In conclusion, Pm upregulated MHC I likely through TLR2 and TLR9 activation, while Rm-induced hypoxia-associated cell death and the downregulation of MHC I, despite its ability to activate TLR2 and TLR9. These findings may provide new insight into how oral dysbiosis can contribute to salivary gland tissue damage in SS.