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Alzheimer's disease (AD), as the most typical type of dementia, is a chronic neurodegenerative disorder characterized by progressive learning and memory impairment. It is known that the main causes of AD are the accumulation of β-amyloid (Aβ) plaques and neurofibrillary tangles (NFT) containing hyperphosphorylated tau protein. Naringin is a flavonoid from citrus fruits, especially in grapefruit, which has anti-inflammatory, antioxidant, anti-apoptotic, and neuroprotective activities. However, the effect of naringin in AD caused by Aβ has not been clearly studied, and there are few studies on the electrophysiological aspect. Thus, we investigated the ex vivo neuroprotective effect of naringin through the long-term potentiation (LTP) on organotypic hippocampal slice cultures. We evaluated the in vivo effects of naringin (100mg/kg/day) orally treated for 20 days on learning, memory, and cognition which was impaired by bilateral CA1 subregion injection of Aβ. Cognitive behaviors were measured 2 weeks after Aβ injection using behavioral tests and the hippocampal expression of apoptotic and neurotrophic regulators were measured by immunoblotting. In hippocampal tissue slices, naringin dose-dependently increased the field excitatory postsynaptic potential (fEPSP) after theta burst stimulation and attenuated Aβ-induced blockade of fEPSP in the hippocampal CA1 area. In Aβ injected rats, naringin improved object recognition memory in the novel object test, avoidance memory in the passive avoidance test and spatial recognition memory in the Morris water maze test. In the hippocampus, naringin attenuated the Aβ-induced cyclooxygenase-2, Bax activation and Bcl-2, CREB, BDNF and TrkB inhibition. These results suggest that naringin has therapeutic potential to reduce neuronal inflammation and apoptosis induced by Aβ related with the BDNF/TrkB/CREB signaling.

With the age of exposure to illegal substances decreasing and abuse of drugs such as methamphetamine increasing, substance abuse is no longer limited to adults. We report a Korean case of a 17-year-old girl with acute methamphetamine poisoning. The girl visited the emergency department for vomiting and loss of consciousness, with needle marks found on both arms. QT prolongation was confirmed on the initial electrocardiogram, so that we suspected drug addiction and proceeded with toxicologic tests. A lethal dose of methamphetamine was confirmed. We discontinued QT prolonging drugs, and closely monitored the girl in the pediatric emergency intensive care unit until the QT prolongation was resolved. This case highlights the recognition of pediatric methamphetamine poisoning in emergency departments.

On September 10, 2021, the Haliburton, Kawartha, Pine Ridge District Health Unit in Ontario, Canada, received a case report of Legionella pneumophila serogroup 1 in a patient (case 1) hospitalized for pneumonia. A second case (case 2) within the same household was also identified. Case 1 was laboratory diagnosed by urine antigen testing, whereas case 2 was diagnosed by PCR and culture from a respiratory specimen collected from case 2, both at Public Health Ontario Laboratory, Ontario, Canada. Cases were linked by household and both cases were exposed via a newly purchased but previously used hot tub. Samples from the hot tub were culture positive when tested at PHO’s Laboratory. Given a respiratory culture isolate was available, together with an environmental isolate from the hot tub, sequence based typing was undertaken. Having both a clinical and an environmental culture isolate is essential for molecular investigations. The sequence type for the clinical isolate was the same as the environmental isolate, providing additional evidence that the hot tub was the source of infection for both cases.

This study aimed to investigate the contamination sources of button mushrooms by assessing the microbial load on the mushrooms and in the agricultural inputs that come into contact with the mushroom. A total of 234 samples including mushrooms, compost, casing soil, and tools from A, B, C, and D farms were tested for sanitary indicators (aerobic bacteria, coliforms, and Escherichia coli) and foodborne pathogens (E. coli O157:H7, Salmonella spp., Staphylococcus aureus, and Listeria monocytogenes). To identify the contamination source, E. coli was isolated and analyzed using MLST (Multi-Locus Sequence Typing). The number of aerobic bacteria remained consistent during composting (⟩7 log CFU/g); however, the occurrence of coliforms and E. coli was reduced to the detection limit (⟨1.0 log). Salmonella spp. and L. monocytogenes were detected in the raw material; however, they were inactivated during composing. More than 6.0 log of aerobic bacteria and 3.0 log of coliforms were observed in the casing soil from A, B, and C farms and in the gloves from the C farm. MLST indicated that the STs of E. coli isolated from casing soil layer and from the harvested mushrooms were identical at ST 189. Therefore, cross contamination occurred through the casing soil layer, and this could contribute to E. coli contamination in mushrooms. It is necessary to practice hygiene guidelines, such as sterilization of casing soil, worker hygiene, and facility sanitation, to minimize the potential of microbial contamination in mushrooms.

Purpose We aimed to investigate manifestations and patterns of care for patients with brain metastasis (BM) from breast cancer (BC) and compared their overall survival (OS) from 2005 through 2014 in Korea.Materials and Methods We retrospectively reviewed 600 BC patients with BM diagnosed between 2005 and 2014. The median follow-up duration was 12.5 months. We categorized the patients into three groups according to the year when BM was initially diagnosed (group I [2005-2008], 98 patients; group II [2009-2011], 200 patients; and group III [2012-2014], 302 patients).Results Over time, the median age at BM diagnosis increased by 2.2 years (group I, 49.0 years; group II, 48.3 years; and group III, 51.2 years; p=0.008). The percentage of patients with extracranial metastasis was 73.5%, 83.5%, and 86.4% for group I, II, and III, respectively (p=0.011). The time interval between BC and BM was prolonged in patients with stage III primary BC (median, 2.4 to 3 years; p=0.029). As an initial brain-directed treatment, whole-brain radiotherapy alone decreased from 80.0% in 2005 to 41.1% in 2014. Meanwhile, stereotactic radiosurgery or fractionated stereotactic radiotherapy alone increased from 13.3% to 34.7% during the same period (p=0.005). The median OS for group I, II, and III was 15.6, 17.9, and 15.0 months, respectively, with no statistical significance.Conclusion The manifestations of BM from BC and the pattern of care have changed from 2005 to 2014 in Korea. However, the OS has remained relatively unchanged over the 10 years.

Background We conducted a comparative study to evaluate the efficacy of poloxamer 407-based ropivacaine hydrogel at the wound site (Gel) and continuous thoracic paravertebral block (On-Q) for postoperative pain following thoracoscopic pulmonary resection. Methods This prospective, randomized, noninferiority study included 89 patients randomized into the two groups; Gel (poloxamer 407-based 0.75% ropivacaine, 22.5 mg) and On-Q (0.2% ropivacaine, 4 mg/hour for 48 hours). The primary outcome measure was total fentanyl consumption and secondary outcome measures were the need for rescue analgesia and pain intensity using the numeric rating scale (NRS). Results There was no significant difference in total fentanyl consumption between the Gel group and the On-Q group (1504.29 ± 315.72 mcg vs 1560.32 ± 274.81 mcg, p = 0.374). Pain intensity using the NRS between the Gel group and the On-Q group demonstrated no statistical differences (6 hours: 3.56 vs 3.55, p = 0.958; 24 hours: 3.21 vs 3.00, p = 0.250; 48 hours: 2.75 vs 2.49, p = 0.233; and 72 hours: 2.39 vs 2.33, p = 0.811), and there was no significant difference in the frequency of analgesic rescue medication use (3.70 vs 3.33, p = 0.417). Conclusions We confirm the noninferiority of Gel compared with On-Q for acute postoperative pain following thoracoscopic pulmonary resection. Considering a technical simplicity and low systemic toxicity of the local injection of Gel, this analgesic modality may be worthy of further research and is thus considered to have potential as a viable alternative to On-Q for regional analgesia.

Purpose: Although systemic treatment is the mainstay for advanced hepatocellular carcinoma (HCC), numerous studies have highlighted the added value of local treatment. This study aimed to investigate the clinical efficacy of liver-directed combined radiotherapy (LD combined RT) compared with that of sorafenib, a recommended treatment until recently for locally advanced HCC presenting portal vein tumor thrombosis (PVTT), using a multinational patient cohort. Materials and Methods: We identified patients with HCC presenting PVTT treated with either sorafenib or LD combined RT in 10 tertiary hospitals in Asia from 2005 to 2014. Propensity score matching (PSM) was performed to minimize the imbalance between the two groups. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and treatment-related toxicity. Results: A total of 1035 patients (675 in the LD combined RT group and 360 in the sorafenib group) were included in this study. After PSM, 305 patients from each group were included in the analysis. At a median follow-up of 22.5 months, the median OS was 10.6 and 4.2 months for the LD combined RT and sorafenib groups, respectively (p < 0.001). The conversion rate to curative surgery was significantly higher (8.5% vs. 1.0%, p < 0.001), while grade ≥ 3 toxicity was fewer (9.2% vs. 16.1%, p < 0.001) in the LD combined RT group. Conclusions: LD combined RT improved survival outcomes with a higher conversion rate to curative surgery in patients with locally advanced HCC presenting PVTT. Although further prospective studies are warranted, active multimodal local treatment involving radiotherapy is suggested for locally advanced HCC presenting PVTT.

This article provides a clinical review of radiofrequency ablation (RFA) for the treatment of uterine leiomyomas.RFA is an effective and durable treatment for fibroids with sustained improvements in fibroid volume, bleeding, and patient reported outcomes with low reintervention rates. Although fertility data is limited, it is overall positive and may represent a uterine conserving and fertility preserving treatment modality.RFA is a safe and effective uterine preserving treatment option for symptomatic leiomyomas.

The diagnosis of type 2 autoimmune pancreatitis (AIP) is dependent on typical radiologic imaging and the presence of the granulocytic epithelial lesion (GEL), which is characterized by ductal neutrophilic infiltration with or without neutrophilic acinar infiltration.We evaluated GEL and related clinicopathologic factors in 165 resected heterotopic pancreata (HPs) [57 gastric (35%), 56 duodenal (34%), 30 omental (18%), and 22 jejunal (13%)] and 29 matched orthotopic pancreata routinely examined during surgery.GEL was noted in 8% (13/165) of HPs, including ductal epithelial (6/13, 46%) and intraluminal (8/13, 62%) neutrophilic infiltrations. However, there was no GEL in orthotopic pancreata. Abdominal pain was observed in 6 (46%) patients with GEL-positive HPs. GEL was more commonly observed in HPs having symptoms (p = 0.029), a larger size (p = 0.028), and an infiltrative growth pattern (p = 0.006). In addition, periductal lymphoplasmacytic infiltration and fibrosis (both p 0.001), interstitial fibrosis (p = 0.017), acinar neutrophilic infiltration (p = 0.032), venulitis (p = 0.050), acinar ductal metaplasia (ADM; p = 0.040), and pancreatic intraepithelial neoplasia/intraductal papillary mucinous neoplasms (PanIN/IPMN; p 0.001) were more commonly seen in HPs with GEL than in those without GEL. Inflammatory bowel disease was present only in one patient with GEL-negative HP.GELs are detected in a subset of HPs without clinical evidence of AIP. Therefore, for the diagnosis of AIP, GEL should be carefully interpreted with the context of other histologic, clinical, and radiologic findings.

EUS-guided transluminal drainage (EUS-TD) is increasingly used for the treatment of postoperative pancreatic fluid collections (POPFCs). A novel lumen-apposing metal stent (LAMS) was recently developed and used for the drainage of POPFCs. This study aimed to evaluate the efficacy and safety of a novel LAMS in patients with POPFCs.Forty-seven patients with symptomatic POPFCs who underwent EUS-TD with a novel LAMS (Niti-S SPAXUS; Taewoong Medical Co, Ltd, Ilsan, South Korea) between April 2019 and July 2020 were included in this study. Clinical outcomes, including technical success, clinical success, and adverse events, were retrospectively evaluated.EUS-TD was technically successful in 41 of 47 patients (87.2%). Clinical success was achieved in 37 of 41 patients (90.2%). The mean procedure time was 13.7 ± 3.5 minutes. The mean POPFC size was 59 ± 18.9 mm. The mean time interval from surgery to EUS-TD was 24.2 ± 37.6 days. Five patients experienced 6 procedural adverse events (12.8%): 4 (8.5%) POPFC infections and 2 (4.3%) distal stent migrations. The 4 patients with POPFC infection underwent additional endoscopic interventions. Of the 2 patients with stent migration, 1 underwent laparoscopic exploration and surgical extraction of the stent and 1 (2.1%) experienced POPFC recurrence, which was managed with percutaneous drainage.EUS-TD for symptomatic POPFCs with a novel LAMS is technically feasible and effective, with an acceptable adverse event rate. Further larger-scale prospective studies are required to confirm the findings of this study.

Supplementary Figures S1-S2; Supplementary Materials and Methods; Supplementary Figure Legend; Supplementary Tables S1-S3

Purpose: CD99 is a cell adhesion molecule associated with human tumors. The aim of the present study was to characterize its role in the development and progression of human gastric adenocarcinoma.Experimental Design: The expression of CD99 was investigated in 283 gastric adenocarcinomas and related lesions and 9 gastric carcinoma cell lines. We also analyzed the methylation status of CD99 gene by using methylation-specific PCR and examined loss of heterozygosity (LOH) of this gene locus by using an intragenic marker. Moreover, we assessed whether SP1, a positive transcription factor for CD99, is expressed in these samples.Results: We found that the decreased expression of CD99 was strongly associated with poor survival and unfavorable clinicopathologic variables. Promoter region methylation (15 of 89, 16.9%) and LOH (21 of 74, 28.4%) were observed and significantly associated with CD99 down-regulation (P < 0.05). In addition, most of the gastric adenocarcinoma cases with CD99 down-regulation had reduced expression of SP1 (47 of 103, 45.6%; P < 0.01). This relationship between CD99 and SP1 was consolidated by using SP1 small interfering RNA transfection experiment and CD99 promoter luciferase assay. Furthermore, we showed that CD99 down-regulation was associated with proliferation and migration in gastric carcinoma cell line.Conclusion: These observations suggest that CD99 down-regulation is a critical event in the progression of gastric adenocarcinoma, and CD99 promoter methylation, CD99 LOH, and SP1 down-regulation were responsible for the down-regulation of CD99.

Supplementary Table 1 from Ectopic Expression of X-Linked Lymphocyte-Regulated Protein pM1 Renders Tumor Cells Resistant to Antitumor Immunity

Supplementary Figure 3 from Ectopic Expression of X-Linked Lymphocyte-Regulated Protein pM1 Renders Tumor Cells Resistant to Antitumor Immunity

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Supplementary Figure 5 from Ectopic Expression of X-Linked Lymphocyte-Regulated Protein pM1 Renders Tumor Cells Resistant to Antitumor Immunity

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PDF file - 1008KB, mRNA and protein expression of Api5 in TC-1/P0 and TC-1/P3 A17 cells (S1). Api5 expression in murine tumors and their immune resistance (S2). In vitro Generation and Characterization of KKM MART1-specific CTL clone (S3). Characterization of antigen presenting capacity of A375/no insert and A375/API5 cells in vitro (S4). API5 activates FGFR1 signaling pathway (S5).

Supplementary Figure 4 from Ectopic Expression of X-Linked Lymphocyte-Regulated Protein pM1 Renders Tumor Cells Resistant to Antitumor Immunity

Supplementary Table 3 from Ectopic Expression of X-Linked Lymphocyte-Regulated Protein pM1 Renders Tumor Cells Resistant to Antitumor Immunity

Supplementary Figure 2 from Ectopic Expression of X-Linked Lymphocyte-Regulated Protein pM1 Renders Tumor Cells Resistant to Antitumor Immunity

Supplementary Table 2 from Ectopic Expression of X-Linked Lymphocyte-Regulated Protein pM1 Renders Tumor Cells Resistant to Antitumor Immunity

Background: We analyzed the treatment outcome of breast cancer patients with brain metastases (BM) in Korea to identify the prognostic factors and the role of whole brain radiation therapy (WBRT). Methods: Seven hundred thirty patients of breast cancer with BM treated at 17 institutions in Korea from 2000 to 2014 were analyzed. The median follow-up duration was 12 months. The analysis consisted of three cohorts: in cohort A, a total of 730 patients were included; in cohort B, 538 patients with available follow-up imaging after initial brain-directed treatment; and in cohort C, 54 patients receiving salvage WBRT due to recurrent BM after initial Stereotactic radiosurgery or WBRT. Overall survival (OS) was calculated from BM diagnosis in cohort A or from the last day of salvage WBRT in cohort C. Results: Median OS of cohort A was 15 months. In multivariate analysis, histologic grade 3, extracranial metastasis, number of BM >4, hormone receptor (HR) or HER2 negativity, and shorter time interval to diagnosis of BM were associated with inferior OS. Among 538 patients in cohort B, 201 showed subsequent development of new BM at a median of 11 months after stereotactic radiosurgery or WBRT for the management of initial BM (at 1 year, HR+/HER2- 51.9%, HER2+ 44.0%, and TNBC 69.6%, respectively; p=0.008). Upfront WBRT reduced subsequent development of new BM, which showed the significant difference among molecular subtypes (HR+/HER2-, 42% reduction at 1 year, p4, and involvement of both tentoria increased subsequent development of new BM. Anti-HER2 therapy for HER2+ patients and upfront WBRT significantly reduced risk of new BM. In cohort C, upfront WBRT prolonged the salvage WBRT-free duration (median 6.9 vs. 8.7 months, p=0.058). Median OS was 6.8 months after salvage WBRT. Longer interval to salvage WBRT, controlled primary tumor, high dose of salvage WBRT (BED10 >37.5 Gy), and systemic treatment after salvage WBRT showed better OS. Uncontrolled extracranial systemic disease and salvage WBRT due to local progression without distant intracranial failure showed worse OS. Conclusions: The rates of new BM showed the significant differences among molecular subtypes. Upfront WBRT decreased subsequent development of new BM and this effect was dependent on the molecular subtype as well. Anti-HER2 therapy for HER2+ patients significantly decreased the subsequent development of new BM. On salvage WBRT setting, the patients having high dose of salvage WBRT, stable extracranial systemic disease and subsequent systemic therapy showed better OS. Citation Format: Jae Sik Kim, Kyubo Kim, Wonguen Jung, Kyung Hwan Shin, Seock-Ah Im, Hee-Jun Kim, Yong Bae Kim, Jee Suk Chang, Jee Hyun Kim, Doo Ho Choi, Yeon Hee Park, Dae Yong Kim, Tae Hyun Kim, Byung Ock Choi, Sea-Won Lee, Suzy Kim, Jeanny Kwon, Ki Mun Kang, Woong-Ki Chung, Kyung Su Kim, Won Sup Yoon, Jin Hee Kim, Jihye Cha, Yoon Kyeong Oh, In Ah Kim. Multicenter study for brain metastasis from breast cancer in Korea: The significance of molecular subtype (KROG 1612) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-21-01.