Cancer risks in patients with ankylosing spondylitis and the effects of biologic agents: a population-based study.

OBJECTIVES: To conduct a population-based analysis of the malignancy risks of patients with ankylosing spondylitis (AS). METHODS: A total of 1,796 patients with AS and 7,184 age- and sex-matched controls (1:4 ratio) were selected from the Korea National Health Insurance Service-National Sample Cohort database. Data of patients diagnosed with AS (code M45) according to the International Classification of Diseases (ICD) 10th edition, between 2002 and 2019, were reviewed. These data were extracted based on the ICD codes assigned to cancer patients. RESULTS: Cancer developed in 168/1,796 patients (9.3%) after the AS diagnosis. After adjusting for confounders, the cancer risk of patients with AS was not significantly increased compared with that of controls (adjusted hazard ratio [HR]: 1.1; 95% confidence interval [CI]: 0.93-1.31). However, the risks for upper gastrointestinal (GI) cancer (adjusted HR: 1.51; 95% CI: 1.07-2.12) and haematologic malignancy (adjusted HR: 2.36; 95% CI: 1.2-4.65) were significantly higher in patients with AS than in controls. There were no significant differences in the risks for other major cancers between patients with AS and controls. Regarding medication for AS, the HR of upper GI cancer was higher in patients with AS compared with controls (adjusted HR: 1.51; 95% CI: 1.00-2.29). CONCLUSION: The overall cancer risks in patients with AS were not significantly different compared with the controls. However, while the effect of non-steroidal anti-inflammatory drugs on upper GI cancer cannot be ruled out, patients with AS exhibited a significant increase in the risk of both upper GI cancer and hematologic malignancy.

Life expectancy and healthy life expectancy of Korean registered disabled by disability type in 2014-2018: Korea National Rehabilitation Center database.

BACKGROUND: Conducting a distinct comparison between the life expectancy (LE) and healthy life expectancy (HALE) of people with disabilities (PWDs) and the general population is necessary due to the various environmental and health conditions they encounter. Therefore, this study aimed to develop the life table for PWDs and calculate those of LE and HALE based on sex, severity, and disability types among the registered Korean PWDs. METHODS: We used aggregated data of registered PWDs from the Korea National Rehabilitation Center database between 2014 and 2018. Overall, 345,595 deaths were included among 12,627,428 registered PWDs. First, we calculated the LE for total PWDs and non-disabled people using a standard life table, extending the old age mortality among nine models. Subsequently, we calculated the LE for each type of disability using the relationship between the mortality of total PWDs and those of each type of disability. Finally, HALE was calculated using the Sullivan method for three types as follows: disability-free and perceived health (PH) using the National Survey, and hospitalized for ≥ 7 days using the Korea National Health Insurance System (NHIS) database. RESULTS: The calculated LE/HALE-NHIS (years) at registration in males and females were 81.32/73.32 and 87.38/75.58, 68.54/58.98 and 71.43/59.24, 73.87/65.43 and 78.25/67.51, and 61.53/50.48 and 62.41/49.72 years among non-disabled, total PWDs, mild disabled, and severe disabled, respectively. LE/HALE-NHIS was lowest and highest in respiratory dysfunction and hearing disabilities, respectively. CONCLUSIONS: Males with disabilities had shorter LE and HALE at registration than females, except for those with severe disabilities, and there were variabilities in the LE based on the disability types.

Exposure to Hazardous Substances and Their Health Effects Among Residents Living Near Three Industrial Waste Incinerators in Korea.

BACKGROUND: This study aimed to evaluate exposure to various hazardous substances emitted by incineration facilities and their likely effect on the health for residents of Bugi-myeon, Cheongju, Korea, which has three incineration facilities. METHODS: Heavy metals, polycyclic aromatic hydrocarbons (PAHs), and dioxin concentrations in the air and soil of exposed and control areas were measured. Moreover, the exposure levels to harmful substances and its effects on health were investigated in 1,124 exposed and 232 control adults. RESULTS: PAHs and dioxin concentrations in the air in the exposed area were significantly higher than in the control area. Urinary cadmium and PAHs metabolite concentrations were significantly higher in the exposed group than in the control group. The exposure group also had a higher prevalence of depression and self-reported allergic symptoms than the control group. CONCLUSION: The possibility of residents in Bugi-myeon being exposed to hazardous substances at incineration facilities cannot be ruled out. To prevent them from further exposure to hazardous substances, it is necessary to prohibit the expansion of additional incineration facilities in this area and to implement continuous monitoring projects for residents.

Discovery of New Anti-Cancer Agents against Patient-Derived Sorafenib-Resistant Papillary Thyroid Cancer.

Thyroid cancer is the most well-known type of endocrine cancer that is easily treatable and can be completely cured in most cases. Nonetheless, anti-cancer drug-resistant metastasis or recurrence may occur and lead to the failure of cancer therapy, which eventually leads to the death of a patient with cancer. This study aimed to detect novel thyroid cancer target candidates based on validating and identifying one of many anti-cancer drug-resistant targets in patient-derived sorafenib-resistant papillary thyroid cancer (PTC). We focused on targeting the sarco/endoplasmic reticulum calcium ATPase (SERCA) in patient-derived sorafenib-resistant PTC cells compared with patient-derived sorafenib-sensitive PTC cells. We discovered novel SERCA inhibitors (candidates 33 and 36) by virtual screening. These candidates are novel SERCA inhibitors that lead to remarkable tumor shrinkage in a xenograft tumor model of sorafenib-resistant patient-derived PTC cells. These results are clinically valuable for the progression of novel combinatorial strategies that facultatively and efficiently target extremely malignant cancer cells, such as anti-cancer drug-resistant PTC cells.

Association of indoor and outdoor short-term PM2.5 exposure with blood pressure among school children.

The association between particulate matter and children's increased blood pressure is inconsistent, and few studies have evaluated indoor exposure, accounting for time-activity. The present study aimed to examine the association between personal short-term exposure to PM2.5 and blood pressure in children. We conducted a panel study with up to three physical examinations during different seasons of 2018 (spring, summer, and fall) among 52 children. The indoor PM2.5 concentration was continuously measured at home and classroom of each child using indoor air quality monitors. The outdoor PM2.5 concentration was measured from the nearest monitoring station. We constructed a mixed effect model to analyze the association of short-term indoor and outdoor PM2.5 exposure accounting for time-activity of each participant with blood pressure. The average PM2.5 concentration was 34.3 ± 9.2 µg/m3 and it was highest in the spring. The concentration measured at homes was generally higher than that measured at outdoor monitoring station. A 10-µg/m3 increment of the up to previous 3-day mean (lag0-3) PM2.5 concentration was associated with 2.7 mmHg (95%CI = 0.8, 4.0) and 2.1 mmHg (95%CI = 0.3, 4.0) increases in systolic and diastolic blood pressure, respectively. In a panel study comprehensively evaluating both indoor and outdoor exposures, which enabled more accurate exposure assessment, we observed a statistically significant association between blood pressure and PM2.5 exposure in children.

Cancer risk in the residents of a town near three industrial waste incinerators in Korea: a retrospective cohort study.

BACKGROUND: Three industrial waste incinerators (IWIs) were built in 1999, 2001, and 2010, within a 3 km radius of a town with a population of around 5000 in Korea. This study evaluated whether residents near these three IWIs had increased cancer incidence than those from other areas in Korea using regional health data. METHODS: Standardized incidence ratios (SIR) were calculated using the frequency of cancer cases in the National Cancer Registry of the exposed area (Buki-myeon), Chungcheongbuk-do (Chungbuk, state including Buki-myeon), and whole Korea from 1999 to 2017. A retrospective cohort was created using National Health Insurance System data from 2002 to 2018. The exposed group was defined as those having a residential history in the exposed area. The control group was defined as those having a residential history in nearby towns or counties in Chungbuk, excluding counties having living and cultural areas in other provinces and cities. Hazard ratio (HR) and 95% confidence intervals (CI) were estimated using the Cox proportional hazard model adjusted for age, level of health insurance fee, and smoking history. RESULTS: In the ecological study using National Cancer Registry data, the risk of all cancers, all cancers excluding thyroid, esophageal, stomach, and lung cancers in the exposed area were 1.13 (95% CI 1.03-1.24), 1.15 (95% CI 1.04-1.26), 1.91 (95% CI 1.13-2.89), 1.39 (95% CI 1.14-1.66), and 1.29 (95% CI 1.03-1.57) times higher than in whole Korea among exposed males, respectively. In the retrospective cohort, 4300 males (26,821 person-years) and 3796 females (24,746 person-years) in exposed group, 150,964 males (1,212,010 person-years) and 134,535 females (1,104,025 person-years) in control group were analyzed. After adjusting for several confounding factors, the risks for gallbladder cancer among males and kidney cancer among females were 2.65 (95% CI 1.38-5.06) and 2.82 (95% CI 1.13-7.03) times higher in the exposed group versus the control group, respectively. CONCLUSIONS: Cancer risk was higher in Koreans having residential history living near IWIs compared to the other areas. Further study warrants nationwide effects and longer follow-up of WIs for cancers in Korea.

Prevention of urethral fibrosis induced by transforming growth factor beta 1 using selective Wnt/ß-catenin signaling inhibitors in a rat model.

OBJECTIVES: To determine the anti-fibrotic effects of Wnt/ß-catenin signaling inhibitors on urethral stricture. METHODS: Human fibroblasts were exposed to transforming growth factor beta 1 combined with various concentrations of Wnt/ß-catenin inhibitors (ICG-001, IWR-1, and PRI-724), and cell proliferation and migration were evaluated. Urethral fibrosis was induced in male Sprague-Dawley rats by urethral injection of transforming growth factor beta 1 and co-treatement with inhibitors. Urethral tissues were harvested 2 weeks after the injection. The messenger ribonucleic acid and protein expression was examined for fibrosis markers Axin-1, collagen type 1, alpha smooth muscle actin, and ß-catenin. Histological analysis of fibrosis and collagen deposition was also performed. RESULTS: Cell migration was ameliorated by ICG-001 and PRI-724. Protein and messenger ribonucleic acid expression of collagen type 1 and alpha smooth muscle actin in transforming growth factor beta 1-treated fibroblasts decreased in a concentration-dependent manner with the ICG-001 and PRI-724 treatments (P < 0.05). However, there were no significant changes with the IWR-1 treatment. Collagen type I and alpha smooth muscle actin messenger ribonucleic acid and protein expression were both significantly increased in the urethral tissues of rats with transforming growth factor beta 1-induced urethral fibrosis. Rats co-treated with ICG-001 or PRI-724 showed relatively mild fibrosis and significantly reduced collagen type I and alpha smooth muscle actin messenger ribonucleic acid and protein expression (P < 0.05). CONCLUSIONS: ICG-001 and PRI-724 significantly ameliorated urethral fibrosis induced by transforming growth factor beta 1 in rats. These results suggest that ICG-001 and PRI-724 can be developed as therapeutics for treating urethral stricture.

Drug Discovery Using Evolutionary Similarities in Chemical Binding to Inhibit Patient-Derived Hepatocellular Carcinoma.

Drug resistance causes therapeutic failure in refractory cancer. Cancer drug resistance stems from various factors, such as patient heterogeneity and genetic alterations in somatic cancer cells, including those from identical tissues. Generally, resistance is intrinsic for cancers; however, cancer resistance becomes common owing to an increased drug treatment. Unfortunately, overcoming this issue is not yet possible. The present study aimed to evaluate a clinical approach using candidate compounds 19 and 23, which are sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA) inhibitors, discovered using the evolutionary chemical binding similarity method. mRNA sequencing indicated SERCA as the dominant marker of patient-derived anti-cancer drug-resistant hepatocellular carcinoma (HCC), but not of patient-derived anti-cancer drug-sensitive HCC. Candidate compounds 19 and 23 led to significant tumor shrinkage in a tumor xenograft model of anti-cancer drug-resistant patient-derived HCC cells. Our results might be clinically significant for the development of novel combinatorial strategies that selectively and efficiently target highly malignant cells such as drug-resistant and cancer stem-like cells.

Potential Therapeutic Agents against Paclitaxel-And Sorafenib-Resistant Papillary Thyroid Carcinoma.

Thyroid carcinoma, a disease in which malignant cells form in the thyroid tissue, is the most common endocrine carcinoma, with papillary thyroid carcinoma (PTC) accounting for nearly 80% of total thyroid carcinoma cases. However, the management of metastatic or recurrent therapy-refractory PTC is challenging and requires complex carcinoma therapy. In this study, we proposed a new clinical approach for the treatment of therapy-refractory PTC. We identified sarco/endoplasmic reticulum calcium ATPase (SERCA) as an essential factor for the survival of PTC cells refractory to the treatment with paclitaxel or sorafenib. We validated its use as a potential target for developing drugs against resistant PTC, by using patient-derived paclitaxel- or sorafenib-resistant PTC cells. We further discovered novel SERCA inhibitors, candidates 7 and 13, using the evolutionary chemical binding similarity method. These novel SERCA inhibitors determined a substantial reduction of tumors in a patient-derived xenograft tumor model developed using paclitaxel- or sorafenib-resistant PTC cells. These results could provide a basis for clinically meaningful progress in the treatment of refractory PTC by identifying a novel therapeutic strategy: using a combination therapy between sorafenib or paclitaxel and specific SERCA inhibitors for effectively and selectively targeting extremely malignant cells such as antineoplastic-resistant and carcinoma stem-like cells.

Team-based primary care program for disabled people and changes in rate of unmet health care needs.

BACKGROUND: Few studies have been conducted on the application of specific and practical methods, such as interventions, for reducing the unmet health care needs (UHCN) of disabled people. OBJECTIVES: The study aims to evaluate the impact of the team-based primary care program (TPCP) for disabled people on UHCN. METHOD: In 2017, we surveyed 696 disabled people who were enrolled in the TPCP at one of the 11 institutions belonging to the Korea Health Welfare Social Cooperative Federation from 2015 to 2017 to assess their unmet needs before and after enrolment. We conducted a logistic regression analysis before and after the program to evaluate the relationship between participation period and unmet needs after adjusting for physician type, gender, age, drinking, monthly income, disability type, personal assistance services and living alone. RESULT: After using the service, the proportion of disabled people with unmet needs decreased from 42.9% to 20.4% for a medical doctor and 43.6% to 18.6% for a Korean medical (KM) doctor. After adjusting for related factors and stratifying with type of physician, the proportion of disabled people with unmet needs decreased significantly in response to the participation period for the medical doctor-involved program (P-trend < 0.001); this was not observed in the KM counterpart (P-trend = 0.6). CONCLUSION: The TPCP for disabled people provides disease prevention, health care and health promotion activities and is crucial for solving the unmet needs.

Mobile Phone Use and Time Trend of Brain Cancer Incidence Rate in Korea.

This study evaluated the time trends in mobile phone subscriber number by mobile network generation (G) and brain cancer incidence by type in Korea. We obtained data from the Information Technology Statistics of Korea (1984-2017) and Korea Central Cancer Registry (1999-2017). The average annual percent change was estimated using Joinpoint regression analysis. We evaluated 29,721 brain cancer cases with an age-standardized incidence rate (ASR) of 2.89/100,000 persons. The glioma and glioblastoma annual ASR significantly increased in 2.6% and 3.9% of males and 3.0% and 3.8% of females, respectively. The ASR for frontal lobe involvement was the highest. The ASR of gliomas of unspecified grade annually increased by 7.8%; those for unspecified topology and histology decreased. The incidence of glioma, glioblastoma, frontal, temporal, and high-grade glioma increased among those aged ≥60 years. No association was observed between the mobile phone subscriber number and brain cancer incidence in Korea. Furthermore, long-term research is warranted because of the latency period of brain cancer. © 2021 Bioelectromagnetics Society.

Who has sustained psychological symptoms nine years after the Hebei Spirit oil spill?: The Health Effect Research on Hebei Spirit oil spill (HEROS) study.

This study evaluated risk factors for sustained psychological symptoms in affected residents, nine years after the Hebei Spirit oil spill in Korea in 2007. The participants included residents of high-exposure areas, living within 2 km from the contaminated coast (n = 2013), among the cohort of the Health Effect Research on Hebei Spirit oil spill study from 2009 to 2016. Symptoms for post-traumatic stress disorder (PTSD), depression, psychosocial distress, and anxiety, as well as sociodemographic information were assessed through questionnaire interviews. Trajectory analysis was conducted to identify the group with sustained symptoms over time and logistic regression analysis was performed to identify risk factors for sustained symptoms adjusted for covariates. A longer duration of clean-up work, lower household income, and presence of a chronic disease in all type of symptoms, and being female, younger age, and higher educational level in all symptoms but PTSD, showed a significant association with increased risk of sustained symptoms. The highest risk was found in the subgroup with a longer clean-up together with offshore and maritime occupations or lower income in PTSD, depression, and anxiety, compared with those with a shorter clean-up and other occupation or higher income. Increased risk of sustained PTSD in relation to a longer clean-up was limited to those with a lower educational level (p-interaction = 0.009). The results suggested that participating longer in clean-up work increased sustained psychological symptoms, synergistically with socioeconomic factors such as offshore and maritime occupations, lower household income, or economic losses related to educational level.

Patient-Derived, Drug-Resistant Colon Cancer Cells Evade Chemotherapeutic Drug Effects via the Induction of Epithelial-Mesenchymal Transition-Mediated Angiogenesis.

Cancer cells can exhibit resistance to different anticancer drugs by acquiring enhanced anti-apoptotic potential, improved DNA injury resistance, diminished enzymatic inactivation, and enhanced permeability, allowing for cell survival. However, the genetic mechanisms for these effects are unknown. Therefore, in this study, we obtained drug-sensitive HT-29 cells (commercially) and drug-resistant cancer cells (derived from biochemically and histologically confirmed colon cancer patients) and performed microarray analysis to identify genetic differences. Cellular proliferation and other properties were determined after treatment with oxaliplatin, lenvatinib, or their combination. In vivo, tumor volume and other properties were examined using a mouse xenograft model. The oxaliplatin and lenvatinib cotreatment group showed more significant cell cycle arrest than the control group and groups treated with either agent alone. Oxaliplatin and lenvatinib cotreatment induced the most significant tumor shrinkage in the xenograft model. Drug-resistant and metastatic colon cancer cells evaded the anticancer drug effects via angiogenesis. These findings present a breakthrough strategy for treating drug-resistant cancer.

Recall of mobile phone usage and laterality in young people: The multinational Mobi-Expo study.

OBJECTIVE: To study recall of mobile phone usage, including laterality and hands-free use, in young people. METHODS: Actual mobile phone use was recorded among volunteers aged between 10 and 24 years from 12 countries by the software application XMobiSense and was compared with self-reported mobile phone use at 6 and 18 months after using the application. The application recorded number and duration of voice calls, number of text messages, amount of data transfer, laterality (% of call time the phone was near the right or left side of the head, or neither), and hands-free usage. After data cleaning, 466 participants were available for the main analyses (recorded vs. self-reported phone use after 6 months). RESULTS: Participants were on average 18.6 years old (IQR 15.2-21.8 years). The Spearman correlation coefficients between recorded and self-reported (after 6 months) number and duration of voice calls were 0.68 and 0.65, respectively. Number of calls was on average underestimated by the participants (adjusted geometric mean ratio (GMR) self-report/recorded = 0.52, 95% CI = 0.47-0.58), while duration of calls was overestimated (GMR=1.32, 95%, CI = 1.15-1.52). The ratios significantly differed by country, age, maternal educational level, and level of reported phone use, but not by time of the interview (6 vs. 18 months). Individuals who reported low mobile phone use underestimated their use, while individuals who reported the highest level of phone use were more likely to overestimate their use. Individuals who reported using the phone mainly on the right side of the head used it more on the right (71.1%) than the left (28.9%) side. Self-reported left side users, however, used the phone only slightly more on the left (53.3%) than the right (46.7%) side. Recorded percentage hands-free use (headset, speaker mode, Bluetooth) increased with increasing self-reported frequency of hands-free device usage. Frequent (≥50% of call time) reported headset or speaker mode use corresponded with 17.1% and 17.2% of total call time, respectively, that was recorded as hands-free use. DISCUSSION: These results indicate that young people can recall phone use moderately well, with recall depending on the amount of phone use and participants' characteristics. The obtained information can be used to calibrate self-reported mobile use to improve estimation of radiofrequency exposure from mobile phones.

Cesium-137 Contaminated Roads and Health Problems in Residents: an Epidemiological Investigation in Seoul, 2011.

BACKGROUND: In 2011, two roads in a residential area in Seoul were found to be contaminated with the radionuclide cesium-137 (137Cs). In response to public concerns, an epidemiological study was conducted. METHODS: The standardized cancer incidence ratios in the affected and neighboring regions were calculated based on the central cancer registry. Households in the region were sampled using the random stratified sampling technique, and questionnaires were administered to family members, via home visit and via students in elementary to high schools. Information on duration of residency and frequency of use of the roads was applied to calculate cumulative radiation exposure dose from the roads, alongside with the reported 137Cs contamination amounts. Information on past medical history, perceived risk, anxiety and psychological stress was also obtained. Of the 31,053 residents, 8,875 were analyzed. To examine possible associations between radiation exposure and health problems, logistic regression adjusted for covariates were performed with consideration of the sampling design, population weight and stratification. RESULTS: No significant association was found between self-informed diseases, including cancers, and estimated radiation exposure dose. According to an increase of radiation level, a significant increase in anxiety in all and a decline in the psychosocial wellbeing of the adults was noted. The risk perception level was higher in the elderly, females, the less educated, and the highest exposed individuals. CONCLUSION: This study provides a basis for risk communication with residents and community environmental health policy.

Secondhand Smoke Exposure and Low Blood Lead Levels in Association With Attention-Deficit Hyperactivity Disorder and Its Symptom Domain in Children: A Community-Based Case-Control Study.

AIM: Secondhand smoke (SHS) is a major indoor pollutant. We examined the possible association between exposure to both SHS and low levels of lead and attention-deficit-hyperactivity disorder (ADHD) and its symptom domain in children. METHODS: This case-control study was based on the results of a community survey using the ADHD rating scale conducted in 49 elementary schools. Both cases and control subjects were confirmed by a child psychiatrist. Each case was matched with one control subject according to gender, school, and grade in school. Using a multivariate conditional logistic regression model, we analyzed 214 case-control pairs of children who ranged in age from 6 to 10 years. Urine and blood levels of cotinine and of lead were determined, and information pertaining to SHS exposure was obtained by means of a questionnaire. RESULTS: Exposure to low levels of lead (geometric mean = 1.65 µg/dL) was related to ADHD, particularly inattention (odds ratio [OR] = 1.67, 95% confidence interval [CI] = 1.07-2.59), whereas SHS exposure was associated mainly with hyperactivity/impulsivity (OR = 3.85, 95% CI = 1.55-9.56). In the pathway from blood lead to hyperactivity/impulsivity, children's SHS exposure mediated and indirectly accounted for about 73% of this relationship. The combined exposure to lead and SHS synergistically increased the risk of ADHD, evident as both inattention and hyperactivity/impulsivity. CONCLUSION: SHS, which is associated with hyperactivity/impulsivity in particular, combined with exposure to low blood levels of lead synergistically increased the risk of ADHD. Therefore, the exposure of children to both SHS and lead needs to be reduced. IMPLICATIONS: Although exposure to low levels of lead has been shown to be associated with ADHD, there is little evidence of symptom domain specificity. In our study, low blood lead levels were related to inattention. In addition, prenatal or postnatal exposure to SHS increased the risk of ADHD, particularly hyperactivity/impulsivity. Combined exposure to lead and SHS synergistically increased the risk for both these ADHD symptom domains. To protect children from environmental risk factors related to ADHD, it is necessary to further reduce children's exposure to SHS and lead, even in those with low blood lead levels.

Neurodevelopment for the first three years following prenatal mobile phone use, radio frequency radiation and lead exposure.

BACKGROUND: Studies examining prenatal exposure to mobile phone use and its effect on child neurodevelopment show different results, according to child's developmental stages. OBJECTIVES: To examine neurodevelopment in children up to 36 months of age, following prenatal mobile phone use and radiofrequency radiation (RFR) exposure, in relation to prenatal lead exposure. METHODS: We analyzed 1198 mother-child pairs from a prospective cohort study (the Mothers and Children's Environmental Health Study). Questionnaires were provided to pregnant women at ≤20 weeks of gestation to assess mobile phone call frequency and duration. A personal exposure meter (PEM) was used to measure RFR exposure for 24h in 210 pregnant women. Maternal blood lead level (BLL) was measured during pregnancy. Child neurodevelopment was assessed using the Korean version of the Bayley Scales of Infant Development-Revised at 6, 12, 24, and 36 months of age. Logistic regression analysis applied to groups classified by trajectory analysis showing neurodevelopmental patterns over time. RESULTS: The psychomotor development index (PDI) and the mental development index (MDI) at 6, 12, 24, and 36 months of age were not significantly associated with maternal mobile phone use during pregnancy. However, among children exposed to high maternal BLL in utero, there was a significantly increased risk of having a low PDI up to 36 months of age, in relation to an increasing average calling time (p-trend=0.008). There was also a risk of having decreasing MDI up to 36 months of age, in relation to an increasing average calling time or frequency during pregnancy (p-trend=0.05 and 0.007 for time and frequency, respectively). There was no significant association between child neurodevelopment and prenatal RFR exposure measured by PEM in all subjects or in groups stratified by maternal BLL during pregnancy. CONCLUSIONS: We found no association between prenatal exposure to RFR and child neurodevelopment during the first three years of life; however, a potential combined effect of prenatal exposure to lead and mobile phone use was suggested.

Mitochondrial Sirt3 supports cell proliferation by regulating glutamine-dependent oxidation in renal cell carcinoma.

Clear cell renal carcinoma (RCC), the most common malignancy arising in the adult kidney, exhibits increased aerobic glycolysis and low mitochondrial respiration due to von Hippel-Lindau gene defects and constitutive hypoxia-inducible factor-α expression. Sirt3 is a major mitochondrial deacetylase that mediates various types of energy metabolism. However, the role of Sirt3 as a tumor suppressor or oncogene in cancer depends on cell types. We show increased Sirt3 expression in the mitochondrial fraction of human RCC tissues. Sirt3 depletion by lentiviral short-hairpin RNA, as well as the stable expression of the inactive mutant of Sirt3, inhibited cell proliferation and tumor growth in xenograft nude mice, respectively. Furthermore, mitochondrial pyruvate, which was used for oxidation in RCC, might be derived from glutamine, but not from glucose and cytosolic pyruvate, due to depletion of mitochondrial pyruvate carrier and the relatively high expression of malic enzyme 2. Depletion of Sirt3 suppressed glutamate dehydrogenase activity, leading to impaired mitochondrial oxygen consumption. Our findings suggest that Sirt3 plays a tumor-progressive role in human RCC by regulating glutamine-derived mitochondrial respiration, particularly in cells where mitochondrial usage of cytosolic pyruvate is severely compromised.

Diagnostic validity of alternative manual stress radiographic technique detecting subtalar instability with concomitant ankle instability.

PURPOSE: To incorporate a diagnostic technique for measuring subtalar motion, namely "talar rotation", into the manual supination-anterior drawer stress radiographs for evaluation of the severity of rotational instability, and to determine its clinical relevance. METHODS: Sixty-six patients with combined injuries of the anterior talofibular (ATFL) and calcaneofibular ligament (CFL) underwent three bilateral manual stress radiographs, and mean increments of anterior talar translation (mm), talar tilt (°), and talar rotation (%) in the injured ankle compared to the normal opposite side were measured with the technique. Intraobserver and interobserver reliability of each measure was assessed, and the difference in the degree of increments was compared according to the presence of additional cervical ligament insufficiency. RESULTS: Ankle stress radiographic intraobserver and interobserver agreement was ICC = 0.91 and 0.82 for talar rotation (%), ICC = 0.64 and 0.51 for anterior talar translation, and ICC = 0.78 and 0.71 for talar tilt angle, respectively. In group 2 including patients with combined injuries of the ATFL and CFL along with additional cervical ligament insufficiency, a significantly higher increment of talar rotation, mean 6.4% (SD 3.4%), was observed compared to that of talar rotation, mean 4.1% (SD 2.7 ), in the other group (group 1) with an intact cervical ligament (p < 0.001). CONCLUSIONS: A new comprehensive stress radiographic technique for diagnosis of chronic lateral ankle instability presented in this study might be a reliable and representable measurement tool to assess additional injury or instability of the subtalar joint. LEVEL OF EVIDENCE: Prospective cohort study, Level II.

Usefulness of the diameter-axial-polar nephrometry score for predicting perioperative parameters in robotic partial nephrectomy.

PURPOSE: The present study aimed to verify the association between diameter-axial-polar (DAP) nephrometry and surgical outcomes, postoperative renal function, and perioperative complications in patients undergoing robotic partial nephrectomy (RPN). METHODS: Diameter-axial-polar nephrometry was assessed using computed tomography or magnetic resonance imaging on 158 patients who received RPN between July 2007 and February 2013. Demographic data, surgical data, and perioperative complications were recorded, and percent change between the preoperative and last estimated glomerular filtration rate (eGFR) was determined. Linear regression analysis was conducted to assess the relationship between the DAP sum score and warm ischemia time (WIT), estimated blood loss (EBL), and percent decrease in eGFR. Multivariable linear regression analysis was conducted to determine the relationship between each DAP scoring parameter and surgical outcomes. RESULTS: The median patient age was 50.5 years and median DAP sum score was 6. On linear regression, the DAP sum score was associated with WIT and EBL. On multivariable regression, all DAP parameters were associated with WIT, but the polar distance was not associated with EBL. Patients with a higher DAP sum score showed greater decrease in eGFR after RPN. Patients with a DAP sum score of 6 or higher had a higher risk of major complications than those with a DAP sum score below 6. CONCLUSIONS: Diameter-axial-polar nephrometry predicted WIT and EBL in patients who underwent RPN. It was also associated with the decrease in eGFR and rate of major perioperative complications, and thus can be useful for surgical planning or patient counseling before RPN.