The MODY-associated KCNK16 L114P mutation increases islet glucagon secretion and limits insulin secretion resulting in transient neonatal diabetes and glucose dyshomeostasis in adults.

The gain-of-function mutation in the TALK-1 K+ channel (p.L114P) is associated with maturity-onset diabetes of the young (MODY). TALK-1 is a key regulator of ß-cell electrical activity and glucose-stimulated insulin secretion. The KCNK16 gene encoding TALK-1 is the most abundant and ß-cell-restricted K+ channel transcript. To investigate the impact of KCNK16 L114P on glucose homeostasis and confirm its association with MODY, a mouse model containing the Kcnk16 L114P mutation was generated. Heterozygous and homozygous Kcnk16 L114P mice exhibit increased neonatal lethality in the C57BL/6J and the CD-1 (ICR) genetic background, respectively. Lethality is likely a result of severe hyperglycemia observed in the homozygous Kcnk16 L114P neonates due to lack of glucose-stimulated insulin secretion and can be reduced with insulin treatment. Kcnk16 L114P increased whole-cell ß-cell K+ currents resulting in blunted glucose-stimulated Ca2+ entry and loss of glucose-induced Ca2+ oscillations. Thus, adult Kcnk16 L114P mice have reduced glucose-stimulated insulin secretion and plasma insulin levels, which significantly impairs glucose homeostasis. Taken together, this study shows that the MODY-associated Kcnk16 L114P mutation disrupts glucose homeostasis in adult mice resembling a MODY phenotype and causes neonatal lethality by inhibiting islet insulin secretion during development. These data suggest that TALK-1 is an islet-restricted target for the treatment for diabetes.

The MODY-associated KCNK16 L114P mutation increases islet glucagon secretion and limits insulin secretion resulting in transient neonatal diabetes and glucose dyshomeostasis in adults.

The gain-of-function mutation in the TALK-1 K + channel (p.L114P) is associated with maturity-onset diabetes of the young (MODY). TALK-1 is a key regulator of ß-cell electrical activity and glucose-stimulated insulin secretion (GSIS). The KCNK16 gene encoding TALK-1, is the most abundant and ß-cell-restricted K + channel transcript. To investigate the impact of KCNK16 L114P on glucose homeostasis and confirm its association with MODY, a mouse model containing the Kcnk16 L114P mutation was generated. Heterozygous and homozygous Kcnk16 L114P mice exhibit increased neonatal lethality in the C57BL/6J and the mixed C57BL/6J:CD-1(ICR) genetic background, respectively. Lethality is likely a result of severe hyperglycemia observed in the homozygous Kcnk16 L114P neonates due to lack of glucose-stimulated insulin secretion and can be reduced with insulin treatment. Kcnk16 L114P increased whole-cell ß-cell K + currents resulting in blunted glucose-stimulated Ca 2+ entry and loss of glucose-induced Ca 2+ oscillations. Thus, adult Kcnk16 L114P mice have reduced glucose-stimulated insulin secretion and plasma insulin levels, which significantly impaired glucose homeostasis. Taken together, this study shows that the MODY-associated Kcnk16 L114P mutation disrupts glucose homeostasis in adult mice resembling a MODY phenotype and causes neonatal lethality by inhibiting islet hormone secretion during development. These data strongly suggest that TALK-1 is an islet-restricted target for the treatment of diabetes.

Effect of dexamethasone and ramosetron on the prevention of postoperative nausea and vomiting in low-risk patients: a randomized, double-blind, placebo-controlled, multicenter trial.

BACKGROUND: Several studies have investigated the effect of antiemetics on postoperative nausea and vomiting (PONV) in high-risk groups. However, few studies have investigated the effect of antiemetics in patients at low risk of developing PONV. METHODS: In this prospective, randomized, double-blinded trial, 177 patients undergoing surgery under general anesthesia were randomly allocated to three groups. Patients allocated to group C (control group) received 2 mL of intravenous 0.9% saline, those allocated to group R (ramosetron group) received 0.3 mg of intravenous ramosetron, and those allocated to group DR (ramosetron plus dexamethasone group) received 5 mg of intravenous dexamethasone and 0.3 mg of intravenous ramosetron. RESULTS: Finally, 174 patients completed the study, and the types of surgeries were orthopedic (n = 80), rhinologic (n = 47), urologic (n = 29), and others (n = 18). The incidence of PONV up to 48 h postoperatively was significantly lower in group DR than in group C. The incidence of PONV up to 0-1 h postoperatively was significantly lower in groups R and DR than in group C. The usage pattern of rescue antiemetics was consistent with the incidence of PONV. The percentage of patients requiring rescue analgesics 0-1 h postoperatively was significantly lower in groups R and DR than in group C. CONCLUSIONS: The combination of dexamethasone and ramosetron demonstrated a superior effect in preventing PONV for 48 h after surgery under general anesthesia than saline in patients at low risk of developing PONV. Compared with saline injections, ramosetron injections yielded better outcomes for the incidence of PONV and the use of rescue antiemetics and rescue analgesics 0-1 h postoperatively. TRIAL REGISTRATION: Clinical trial registration number: criskorea@korea.kr, KCT0006749.

Contralateral oblique view can prevent dural puncture in fluoroscopy-guided cervical epidural access: a prospective observational study.

INTRODUCTION: Although the contralateral oblique (CLO) view at 50°±5° is clinically useful for cervical epidural access, no previous studies have confirmed its safety. This prospective observational study was conducted to assess the safety profile, including the risk of dural puncture, in fluoroscopically guided cervical epidural access using the CLO view. METHODS: In cervical epidural access using the CLO view, the incidence of dural puncture was investigated as the primary outcome. Other intraprocedural complications, including intravascular entry, subdural entry, spinal cord injury and vasovagal injury, and postprocedural complications were investigated as secondary outcomes. Procedural variables including first-pass success, final success, needling time, total number of needle passes and false loss of resistance (LOR) were evaluated. RESULTS: Of the 393 patients who underwent cervical interlaminar epidural access were included for analysis, no instances of dural puncture or spinal cord injury were observed. The incidence of intravascular entry, vasovagal reaction and subdural entry were 3.1%, 0.5% and 0.3%, respectively. All procedures were successfully performed, with 85.0% of first-pass success rate. The mean needling time was 133.8 (74.9) s. The false-positive and false-negative LOR rates were 8.2% and 2.0%, respectively. All needle tips were visualized clearly during the procedure. CONCLUSIONS: The fluoroscopy-guided CLO view at 50°±5° avoided dural puncture or spinal cord injury and decreased the incidence of false LOR during cervical epidural access with a paramedian approach. TRIAL REGISTRATION NUMBER: NCT04774458.

Cohort Profile: Korean Tuberculosis and Post-Tuberculosis Cohort Constructed by Linking the Korean National Tuberculosis Surveillance System and National Health Information Database.

We aimed to review the current data composition of the Korean Tuberculosis and Post-Tuberculosis Cohort, which was constructed by linking the Korean Tuberculosis Surveillance System (KNTSS; established and operated by the Korean Disease Control and Prevention Agency since 2000) and the National Health Information Database (NHID; established by the National Health Insurance Service in 2012). The following data were linked: KNTSS data pertaining to patients diagnosed with tuberculosis between 2011 and 2018, NHID data of patients with a history of tuberculosis and related diseases between 2006 and 2018, and data (obtained from the Statistics Korea database) on causes of death. Data from 300 117 tuberculosis patients (177 206 men and 122 911 women) were linked. The rate of treatment success for new cases was highest in 2015 (86.7%), with a gradual decrease thereafter. The treatment success rate for previously treated cases showed an increasing trend until 2014 (79.0%) and decreased thereafter. In total, 53 906 deaths were confirmed among tuberculosis patients included in the cohort. The Korean Tuberculosis and Post-Tuberculosis Cohort can be used to analyze different measurement variables in an integrated manner depending on the data source. Therefore, these cohort data can be used in future epidemiological studies and research on policy-effect analysis, treatment outcome analysis, and health-related behaviors such as treatment discontinuation.

The Roles and Associated Mechanisms of Adipokines in Development of Metabolic Syndrome.

Metabolic syndrome is a cluster of metabolic indicators that increase the risk of diabetes and cardiovascular diseases. Visceral obesity and factors derived from altered adipose tissue, adipokines, play critical roles in the development of metabolic syndrome. Although the adipokines leptin and adiponectin improve insulin sensitivity, others contribute to the development of glucose intolerance, including visfatin, fetuin-A, resistin, and plasminogen activator inhibitor-1 (PAI-1). Leptin and adiponectin increase fatty acid oxidation, prevent foam cell formation, and improve lipid metabolism, while visfatin, fetuin-A, PAI-1, and resistin have pro-atherogenic properties. In this review, we briefly summarize the role of various adipokines in the development of metabolic syndrome, focusing on glucose homeostasis and lipid metabolism.

Immediate intravenous iron administration improves anaemia recovery following total knee arthroplasty: A propensity-matched analysis.

BACKGROUND AND OBJECTIVES: Patients who undergo total knee arthroplasty (TKA) have a risk of postoperative anaemia. This observational study evaluated whether single-dose intravenous ferric carboxymaltose (FCM) administered immediately after TKA facilitates the correction of anaemia. MATERIALS AND METHODS: We retrospectively analysed 722 patients who underwent primary TKA. The FCM group receiving 1000 mg intravenous FCM within one postoperative hour was compared with the non-FCM group that did not receive the medication. A propensity score matching with multiple logistic regression analysis was used to minimize intergroup differences in the baseline characteristics and postoperative blood loss. The rate and severity of postoperative anaemia were compared between the groups, along with haemoglobin (Hb) value, transfusion rate and complications. RESULTS: After propensity score matching, 231 patients were included in each group. In the FCM group, the rate of anaemia at postoperative day (POD) 7 (p = 0.021) and postoperative week (POW) 5 (p < 0.001) and the transfusion rate were significantly lower (p = 0.008). The rate of moderate to severe anaemia at POW-5 was also significantly lower in the FCM group (p < 0.001). In patients without preoperative anaemia (n = 322), the transfusion rate and rate and severity of anaemia at POD-7 and POW-5 were significantly lower in the FCM group than in the non-FCM group. CONCLUSION: Postoperative intravenous FCM administration facilitated recovery of surgery-related anaemia by improving Hb and may reduce the need for transfusion in TKA patients. Preoperative non-anaemic patients could also benefit from accelerated recovery by intravenous iron treatment.

Occupational Exposure to Pesticides and Lung Cancer Risk: A Propensity Score Analyses.

PURPOSE: Occupational exposure to pesticides is thought to be associated with lung cancer, but studies have yielded conflicting results. We performed a propensity score (PS) based analyses to evaluate the relationship between occupational exposure to pesticides and lung cancer risk in the Korea National Cancer Center community-based cohort study (KNCCCS). MATERIALS AND METHODS: During the follow-up period, 123 incidental lung cancer cases were identified, of the 7,471 subjects in the final statistical analysis. Information about occupational exposure to pesticides and other factors was collected at enrollment (2003-2010). Cox proportional hazards regression analyses were conducted. Four PS-based approaches (i.e., matching, stratification, inverse probability-of-treatment weighting, and the use of the PS as a covariate) were adopted, and the results were compared. PS was obtained from the logistic regression model. Absolute standardized differences according to occupational exposure to pesticides were provided to evaluate the balance in baseline characteristics. RESULTS: In the Cox proportional hazards regression model, the hazard ratio (HR) for lung cancer according to occupational exposure to pesticides was 1.82 (95% confidence interval [CI], 1.11 to 2.98). With all the propensity score matching (PSM) methods, the HRs for lung cancer based on exposure to pesticides ranged from 1.65 (95% CI, 1.04 to 2.64) (continuous term with PSM) to 2.84 (95% CI, 1.81 to 4.46) (stratification by 5 strata of the PS). The results varied slightly based on the method used, but the direction and statistical significance remained the same. CONCLUSION: Our results strengthen the evidence for an association between occupational exposure to pesticides and the risk of lung cancer.

Serum Sorbitol Dehydrogenase as a Novel Prognostic Factor for Hepatocellular Carcinoma after Surgical Resection.

The majority of patients with hepatocellular carcinoma (HCC) undergoing curative resection experience tumor recurrence. To examine the association between preoperative serum sorbitol dehydrogenase (SORD), a liver-derived enzyme that reflects liver damage, and recurrence of HCC after curative resection, 92 patients were randomly selected who underwent curative resection for HCC between 2011 and 2012 from a prospective registry. Recurrence-free survival (RFS) was compared based on serum SORD levels. Cox proportional hazard models were used to investigate prognostic factors for RFS. During a median follow-up duration of 57.1 months, 43 patients experienced HCC recurrence. Patients with serum SORD ≥15 ng/mL (HR, 3.46; 95% CI, 1.76-6.81; p < 0.001) had worse RFS compared with patients with serum SORD <15 ng/mL. Serum AFP and SORD levels were two independent prognostic factors for RFS. When patients were stratified by baseline serum SORD and AFP levels, patients with serum AFP levels ≥400 ng/mL and serum SORD levels ≥15 ng/mL had a distinctly poor prognosis with the lowest RFS rates (HR, 22.08; 95% CI, 6.91-70.50; p < 0.001). Baseline serum SORD is an effective prognostic factor for HCC after resection. It may help guide patient selection for surgery, especially when combined with serum AFP levels.

Comparison of General and Spinal Anaesthesia on Systemic Inflammatory Response in Patients Undergoing Total Knee Arthroplasty: A Propensity Score Matching Analysis.

Background and Objectives: Some of the postoperative complications following orthopaedic surgeries are associated with a systemic inflammatory response (SIR), which varies depending on the anaesthetic technique. We aimed to compare the effects of general and spinal anaesthesia on the SIR after total knee arthroplasty (TKA), based on C-reactive protein (CRP) levels, the platelet-lymphocyte ratio (PLR), and the neutrophil-lymphocyte ratio (NLR). Materials and Methods: Patients who underwent TKA between January 2014 and December 2018 were included. Electronic medical records of the patients were retrospectively reviewed and analysed. To reduce the impact of potential confounding factors, we performed propensity score matching according to the anaesthetic technique. Results: A total of 1311 TKA cases were analysed. After propensity score matching, the maximal CRP value and changes in CRP levels in the general anaesthesia group were higher than those in the spinal anaesthesia group. However, the maximal NLR and PLR and the changes in NLR and PLR were not different between the two groups. There were no differences in postoperative clinical outcomes. Conclusion: Spinal anaesthesia tended to induce a lower inflammatory response than general anaesthesia when considering CRP levels in patients undergoing TKA. However, the effects of anaesthetic techniques on the overall outcomes were not significant.

Urine and Serum Electrolytes and Biochemical Values Associated with Osteoporosis in Premenopausal and Postmenopausal Women: A Longitudinal and Cross-Sectional Study Using Korean Genome and Epidemiology Study (KoGES) Cohort.

Osteoporosis is a major public health concern, especially in women. This study aims to identify early biomarkers from biochemical measurements of serum and urine for recognizing the development of osteoporosis and osteopenia in premenopausal and postmenopausal women. From the Korean Genome and Epidemiology Study (KoGES) cohort, longitudinal study participants with normal bone density were enrolled and assessed for the association of baseline clinical and biochemical factors with osteoporosis development over 4 years. In addition, a cross-sectional study between normal bone density and osteopenia/osteoporosis was conducted to validate the risk factors found in the longitudinal cohort. Of the 5272 female participants in the KoGES cohort, 813 women (501 premenopausal and 312 menopausal) who had normal bone density at baseline were included in the longitudinal study. During the 4 years of follow-up, 64 patients developed osteoporosis and 354 developed osteopenia. In a multivariate logistic regression analysis, serum calcium and urine uric acid levels were significantly associated with elevated osteoporosis risk in premenopausal and postmenopausal women, respectively (risk of osteoporosis by serum calcium levels in premenopausal women: 4.03 (1.09-14.93), p = 0.037; risk of osteoporosis by urine uric acid levels in postmenopausal women: 24.08 (1.79-323.69), p = 0.016). For the cross-sectional study, serum and urine parameters were compared between women with osteopenia or osteoporosis at baseline and those with normal bone density. Urine uric acid levels were found to be significantly higher in both premenopausal and postmenopausal women with bone loss than in women with normal bone density (p < 0.001 and p = 0.004, respectively). Uric acid level in urine may be an early marker for the development of osteoporosis in women, especially after menopause.

The Novel Benzothiazole Derivative PB11 Induces Apoptosis via the PI3K/AKT Signaling Pathway in Human Cancer Cell Lines.

Among several anti-cancer therapies, chemotherapy can be used regardless of the stage of the disease. However, development of anti-cancer agents from potential chemicals must be executed very cautiously because of several problems, such as safety, drug resistance, and continuous administration. Most chemotherapeutics selectively cause cancer cells to undergo apoptosis. In this study, we tested the effects of a novel chemical, the benzothiazole derivative N-[2-[(3,5-dimethyl-1,2-oxazol-4-yl)methylsulfanyl]-1,3-benzothiazol-6-yl]-4-oxocyclohexane-1-carboxamide (PB11) on the human cell lines U87 (glioblastoma), and HeLa (cervix cancer). It was observed that this chemical was highly cytotoxic for these cells (IC50s < 50 nM). In addition, even 40 nM PB11 induced the classical apoptotic symptoms of DNA fragmentation and nuclear condensation. The increase of caspase-3 and -9 activities also indicated an increased rate of apoptosis, which was further confirmed via Western blotting analysis of apoptosis-associated proteins. Accordingly, PB11 treatment up-regulated the cellular levels of caspase-3 and cytochrome-c, whereas it down-regulated PI3K and AKT. These results suggest that PB11 induces cytotoxicity and apoptosis in cancer cells by suppressing the PI3K/AKT signaling pathways and, thus, may serve as an anti-cancer therapeutic.

Argininosuccinate synthase 1 suppresses tumor progression through activation of PERK/eIF2α/ATF4/CHOP axis in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant cancers worldwide, and liver cancer has increased in mortality due to liver cancer because it was detected at an advanced stages in patients with liver dysfunction, making HCC a lethal cancer. Accordingly, we aim to new targets for HCC drug discovery using HCC tumor spheroids. METHODS: Our comparative proteomic analysis of HCC cells grown in culture as monolayers (2D) and spheroids (3D) revealed that argininosuccinate synthase 1 (ASS1) expression was higher in 3D cells than in 2D cells due to upregulated endoplasmic reticulum (ER) stress responses. We investigated the clinical value of ASS1 in Korean patients with HCC. The mechanism underlying ASS1-mediated tumor suppression was investigated in HCC spheroids. ASS1-mediated improvement of chemotherapy efficiency was observed using high content screening in an HCC xenograft mouse model. RESULTS: Studies of tumor tissue from Korean HCC patients showed that, although ASS1 expression was low in most samples, high levels of ASS1 were associated with favorable overall survival of patients. Here, we found that bidirectional interactions between ASS1 ER stress responses in HCC-derived multicellular tumor spheroids can limit HCC progression. ASS1 overexpression effectively inhibited tumor growth and enhanced the efficacy of in vitro and in vivo anti-HCC combination chemotherapy via activation of the PERK/eIF2α/ATF4/CHOP axis, but was not dependent on the status of p53 and arginine metabolism. CONCLUSIONS: These results demonstrate the critical functional roles for the arginine metabolism-independent tumor suppressor activity of ASS1 in HCC and suggest that upregulating ASS1 in these tumors is a potential strategy in HCC cells with low ASS1 expression.

Comparison of the onset time between 0.375% ropivacaine and 0.25% levobupivacaine for ultrasound-guided infraclavicular brachial plexus block: a randomized-controlled trial.

At centers with pressure on rapid operating room turnover, onset time is one of the important considerations for choosing a local anesthetic drug. To hasten the onset of the block, higher concentrations of local anesthetics are sometimes used. However, the use of diluted local anesthetics may be safer. Therefore, we aimed to compare the onset times of equipotential levobupivacaine and ropivacaine at low concentrations for infraclavicular brachial plexus block. Adult patients undergoing upper extremity surgery under ultrasound-guided infraclavicular brachial plexus block at our center were randomly allocated to the levobupivacaine and ropivacaine groups. Infraclavicular brachial plexus block was induced with 0.25% levobupivacaine or 0.375% ropivacaine depending on the assigned group. The degrees of sensory and motor blockade were assessed for 40 min after the administration of local anesthetics. A total of 46 patients were included in the analysis. Infraclavicular brachial plexus block with 0.25% levobupivacaine and 0.375% ropivacaine provided sufficient surgical anesthesia. The sensory onset time of 0.375% ropivacaine was shorter than that of 0.25% levobupivacaine (group R, 15 [15.0-22.5] min; group L, 30 [17.5-35.0] min, p = 0.001). There were no significant differences in other block characteristics and clinical outcomes between the two groups. Thus, when a quicker block onset is required, 0.375% ropivacaine is a better choice than 0.25% levobupivacaine.Trial registration ClinicalTrials.gov (NCT03679897).

Serum concentrations of persistent organic pollutants and colorectal cancer risk: A case-cohort study within Korean National Cancer Center Community (KNCCC) cohort.

BACKGROUND & AIMS: Recent prospective cohort studies have suggested that circulating persistent organic pollutants (POPs) may be associated with the development of cancers. We investigated the association between pre-diagnostic serum concentrations of POPs and colorectal cancer (CRC) risk. METHODS: A case-cohort study within a community-based prospective cohort was performed, including 104 CRC cases and 235 subcohort participants. Serum concentrations of POPs were measured by high resolution gas chromatography/high-resolution mass spectrometry. Multivariable Cox proportional hazards regression models were used. RESULTS: The association between serum concentrations of organochlorine pesticides (OCs) and CRC risk was significant (cis-heptachlor epoxide: 3rd tercile [HR (95% CI): 2.76 (1.25-6.07); trans-nonachlor: 2nd tercile [HR (95% CI): 3.90 (1.56-9.75)], 3rd tercile [HR (95% CI): 4.86 (1.95-12.16)]); p,p'-DDD: 2nd tercile [HR (95% CI): 6.02 (2.05-17.70)], 3rd tercile [HR (95% CI): 7.43 (2.42-22.84)]). Certain polychlorinated biphenyls (PCBs) congeners were significantly associated with CRC risk (PCB-105: 3rd tercile HR [95% CI]: 3.15 [1.38-7.19], PCB-118: 3rd tercile HR [95% CI]: 2.68 [1.22-5.92]; PCB-138: 2nd tercile [HR (95% CI): 2.51 (1.19-5.28)], 3rd tercile [HR (95% CI): 3.27 (1.50-7.12)]; PCB-153: 2nd tercile [HR (95% CI): 3.93 (1.81-8.54)], 3rd tercile [HR (95% CI): 5.02 (2.09-12.07)]; PCB-156: 2nd tercile [HR (95% CI): 2.61 (1.21-5.59)], 3rd tercile [HR (95% CI): 4.07 (1.73-9.61)]; PCB-180: 2nd tercile [HR (95% CI): 2.58 (1.15-5.78)], 3rd tercile [HR (95% CI): 4.01 (1.68-9.59)]).results CONCLUSIONS: This study suggests that serum concentrations of POPs could increase the CRC risk in the general population.

Association between environmental exposure to cadmium and risk of suspected non-alcoholic fatty liver disease.

AIM: We evaluated the associations between blood Cadmium (Cd) concentrations and risk of suspected NAFLD using nationally representative data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2008-2013, 2016 and 2017. METHODS: This cross-sectional study included 12,099 adults for the serum alanine aminotransferase (ALT) and hepatic steatosis index (HSI) analyses and 2,904 adults for the serum gamma-glutamyl transferase (GGT) and fatty liver index (FLI) analyses, without significant alcohol consumption. Blood Cd concentrations were measured by graphite furnace atomic absorption spectrometry. Data were analyzed using survey logistic regression models. RESULTS: Odds ratios (ORs) of suspected NAFLD increased significantly per unit of natural log-transformed blood Cd concentration (OR [95% (CI)], for ALT, overall: 1.50 [1.34, 1.68], men: 1.64 [1.40, 2.10] and women: 1.29 [1.08, 1.47]; for GGT, overall: 1.77 [1.33, 2.35], men: 2.28 [1.53, 3.41] and women: 1.27 [0.82, 1.97]; for FLI, overall: 1.84 [1.32, 2.57], men: 1.91 [1.24, 2.94] and women: 1.58 [0.87, 2.86]; for HSI, overall: 1.19 [1.07, 1.32], men: 1.17 [1.01, 1.37] and women: 1.14 [0.99, 1.32]). The blood Cd concentrations associated with risk of suspected NAFLD were lower than those previously reported (for ALT, > 0.64 µg/L, for GGT, > 1.41 µg/L, for FLI, > 0.96 µg/L, and for HSI, > 1.41 µg/L). CONCLUSIONS: This study suggests that the reference level of blood Cd should probably be lower than the previously recommended value to prevent adverse health effects due to Cd exposure.

Metabolic Syndrome and Colorectal Cancer Risk: Results of Propensity Score-Based Analyses in a Community-Based Cohort Study.

BACKGROUND: This study aimed to determine the effects of metabolic syndrome (MetS) on colorectal cancer (CRC) using propensity score (PS) methods. METHODS: The study subjects were 2417 men and 4568 women from the Korean National Cancer Center (KNCC) Community Cohort enrolled between 2003 and 2010. Odds risks (ORs) and 95% confidence intervals (CIs) using PS matching analysis, regression models adjusted by the PS or stratified into five strata according to PS, and PS weighting methods were calculated. RESULTS: In women, MetS and abnormally high triglyceride (TG) levels were associated with CRC risk using the PS matching analysis (ORs, for MetS, 2.19 (95% CI, 1.10-4.33); for abnormal TG levels, 2.08 (95% CI, 1.07-4.02)). However, there were no significant associations between MetS and TG levels and CRC risk in men. CONCLUSIONS: Our study might provide additional evidence that deteriorated metabolic profiles increase the risk of CRC in women rather than men. Thus, this may have an important role in effective population-level interventions for deteriorated metabolic profiles at an early stage.

IFITM proteins inhibit the late step of feline foamy virus replication.

Interferon-induced transmembrane (IFITM) proteins as host restriction factors are known to inhibit the replication of several viruses. In this study, transient IFITM expression vectors were used to investigate whether IFITMs inhibit feline foamy viral (FFV) replication and which step of viral replication is inhibited. In our studies, viral production was significantly reduced when cells were infected with FFV at almost same times such as -3, 0, or 3 h post-transfection with IFITM vector. However viral production was not reduced even though cells were infected with FFV at 3 or 6 days post-transfection when production of IFITM proteins was maximized. Considering that IFITM expression was maximized at 3 days post-transfection, the stage of viral replication inhibited by IFITM appears to be the late step of viral replication. Moreover, the viral Gag proteins detected in the virus-infected cell lysates were proportionally correlated with viral titer of the culture supernatants. Therefore, it is likely that IFITMs can restrict production of FFV at the late step of viral replication.

A novel three-dimensional magnetic particle imaging system based on the frequency mixing for the point-of-care diagnostics.

The magnetic particle imaging (MPI) is a technology that can image the concentrations of the superparamagnetic iron oxide nanoparticles (SPIONs) which can be used in biomedical diagnostics and therapeutics as non-radioactive tracers. We proposed a point-of-care testing MPI system (PoCT-MPI) that can be used for preclinical use for imaging small rodents (mice) injected with SPIONs not only in laboratories, but also at emergency sites far from laboratories. In particular, we applied a frequency mixing magnetic detection method to the PoCT-MPI, and proposed a hybrid field free line generator to reduce the power consumption, size and weight of the system. The PoCT-MPI is [Formula: see text] in size and weighs less than 100 kg. It can image a three-dimensional distribution of SPIONs injected into a biosample with less than 120 Wh of power consumption. Its detection limit is [Formula: see text], 10 mg/mL, [Formula: see text] (Fe).

Foamy Virus Integrase in Development of Viral Vector for Gene Therapy.

Due to the broad host suitability of viral vectors and their high gene delivery capacity, many researchers are focusing on viral vector-mediated gene therapy. Among the retroviruses, foamy viruses have been considered potential gene therapy vectors because of their non-pathogenicity. To date, the prototype foamy virus is the only retrovirus that has a high-resolution structure of intasomes, nucleoprotein complexes formed by integrase, and viral DNA. The integration of viral DNA into the host chromosome is an essential step for viral vector development. This process is mediated by virally encoded integrase, which catalyzes unique chemical reactions. Additionally, recent studies on foamy virus integrase elucidated the catalytic functions of its three distinct domains and their effect on viral pathogenicity. This review focuses on recent advancements in biochemical, structural, and functional studies of foamy virus integrase for gene therapy vector research.