Association between oil spill clean-up work and thyroid cancer: Nine years of follow-up after the Hebei Spirit oil spill accident.

In 2007, an unprecedented oil spill occurred in Taean, Korea. Although crude oil contains chemicals that could increase thyroid cancer risk, few studies have examined the long-term effects of oil exposure during clean-up and thyroid cancer incidence. We investigated the long-term thyroid cancer incidence among participants involved in clean-up work. 1798 participants engaged in at least two surveys since the baseline was tracked from 2008 to 2018. Participants reported the days they participated in oil clean-up works and cancer diagnoses. Cox proportional hazard models were used to estimate the hazard ratios between clean-up work duration and thyroid cancer. Over the 9-year follow-up, 30 thyroid cancer cases were diagnosed. A positive association was observed between clean-up duration and thyroid cancer risk. This effect was more pronounced among residents living <50 m from traffic roads. Our results indicate that crude oil clean-up work participation may increase the thyroid cancer risk.

Long-term effects of the Hebei Spirit oil spill on the prevalence and incidence of allergic disorders.

The Hebei Spirit oil spill accident occurred in December 2007, approximately 10 km off the coast of Taean, South Korea, a location notably close to residential areas. Crude oil substances have been detected in various environmental mediums since the accident, yet previous studies have primarily focused on the acute effects of oil exposure due to the short latency period of allergic diseases. Therefore, this study evaluated the long-term effects of oil spill exposure on allergic disorders. Our study included adult residents who had participated in the Health Effects Research on Hebei Spirit Oil Spill (HEROS) study up to five years post-incident, which was a prospective cohort to monitor the health status of Taean residents. We used two indicators to assess oil spill exposure, namely the distance from the initial contaminated coastline to each participant's residence and the number of days participants had engaged in oil clean-up work. Current symptoms such as asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and multimorbidity were considered allergic disorders. In the baseline survey, the prevalence of asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and allergic multimorbidity symptoms was associated with both exposure indicators; however, these associations were not observed in the two consecutive surveys. Significant longitudinal associations between oil spill exposure indicators and the four allergic disorders, as well as multimorbidity incidences, were observed during a five-year follow-up period. Our results suggest that oil spill exposure can affect acute and long-term allergic symptoms in residents near the accident site.

Mitochondria-derived peptide SHLP2 regulates energy homeostasis through the activation of hypothalamic neurons.

Small humanin-like peptide 2 (SHLP2) is a mitochondrial-derived peptide implicated in several biological processes such as aging and oxidative stress. However, its functional role in the regulation of energy homeostasis remains unclear, and its corresponding receptor is not identified. Hereby, we demonstrate that both systemic and intracerebroventricular (ICV) administrations of SHLP2 protected the male mice from high-fat diet (HFD)-induced obesity and improved insulin sensitivity. In addition, the activation of pro-opiomelanocortin (POMC) neurons by SHLP2 in the arcuate nucleus of the hypothalamus (ARC) is involved in the suppression of food intake and the promotion of thermogenesis. Through high-throughput structural complementation screening, we discovered that SHLP2 binds to and activates chemokine receptor 7 (CXCR7). Taken together, our study not only reveals the therapeutic potential of SHLP2 in metabolic disorders but also provides important mechanistic insights into how it exerts its effects on energy homeostasis.

Cost-utility analysis of endoscopic lumbar discectomy following a uniform clinical pathway in the Korean national health insurance system.

INTRODUCTION: Full-endoscopic lumbar discectomy (FELD) is a type of minimally invasive spinal surgery for lumbar disc herniation (LDH). Sufficient evidence exists to recommend FELD as an alternative to standard open microdiscectomy, and some patients prefer FELD due to its minimally invasive nature. However, in the Republic of Korea, the National Health Insurance System (NHIS) controls the reimbursement and use of supplies for FELD, but FELD is not currently reimbursed by the NHIS. Nonetheless, FELD has been performed upon patients' request, but providing FELD for patients' sake is inherently an unstable arrangement in the absence of a practical reimbursement system. The purpose of this study was to conduct a cost-utility analysis of FELD to suggest appropriate reimbursements. METHOD: This study was a subgroup analysis of prospectively collected data including 28 patients who underwent FELD. All patients were NHIS beneficiaries and followed a uniform clinical pathway. Quality-adjusted life years (QALYs) were assessed with a utility score using the EuroQol 5-Dimension (EQ-5D) instrument. The costs included direct medical costs incurred at the hospital for 2 years and the price of the electrode ($700), although it was not reimbursed. The costs and QALYs gained were used to calculate the cost per QALY gained. RESULT: Patients' mean age was 43 years and one-third (32%) were women. L4-5 was the most common surgical level (20/28, 71%) and extrusion was the most common type of LDH (14, 50%). Half of the patients (15, 54%) had jobs with an intermediate level of activity. The preoperative EQ-5D utility score was 0.48±0.19. Pain, disability, and the utility score significantly improved starting 1 month postoperatively. The average EQ-5D utility score during 2 years after FELD was estimated as 0.81 (95% CI: 0.78-0.85). For 2 years, the mean direct costs were $3,459 and the cost per QALY gained was $5,241. CONCLUSION: The cost-utility analysis showed a quite reasonable cost per QALY gained for FELD. A comprehensive range of surgical options should be provided to patients, for which a practical reimbursement system is a prerequisite.

Direct medical costs after surgical or nonsurgical treatment for degenerative lumbar spinal disease: A nationwide matched cohort study with a 10-year follow-up.

OBJECTIVE: The demand for treating degenerative lumbar spinal disease has been increasing, leading to increased utilization of medical resources. Thus, we need to understand how the budget of insurance is currently used. The objective of the present study is to overview the utilization of the National Health Insurance Service (NHIS) by providing the direct insured cost between patients receiving surgery and patients receiving nonsurgical treatment for degenerative lumbar disease. METHODS: The NHIS-National Sample Cohort was utilized to select patients with lumbar disc herniation, spinal stenosis, spondylolisthesis or spondylolysis. A matched cohort study design was used to show direct medical costs of surgery (n = 2,698) and nonsurgical (n = 2,698) cohorts. Non-surgical treatment included medication, physiotherapy, injection, and chiropractic. The monthly costs of the surgery cohort and nonsurgical cohort were presented at initial treatment, posttreatment 1, 3, 6, 9, and 12 months and yearly thereafter for 10 years. RESULTS: The characteristics and matching factors were well-balanced between the matched cohorts. Overall, surgery cohort spent $50.84/patient/month, while the nonsurgical cohort spent $29.34/patient/month (p<0.01). Initially, surgery treatment led to more charge to NHIS ($2,762) than nonsurgical treatment ($180.4) (p<0.01). Compared with the non-surgical cohort, the surgery cohort charged $33/month more for the first 3 months, charged less at 12 months, and charged approximately the same over the course of 10 years. CONCLUSION: Surgical treatment initially led to more government reimbursement than nonsurgical treatment, but the charges during follow-up period were not different. The results of the present study should be interpreted in light of the costs of medical services, indirect costs, societal cost, quality of life and societal willingness to pay in each country. The monetary figures are implied to be actual economic costs but those in the reimbursement system instead reflect reimbursement charges from the government.

Change in left inferior frontal connectivity with less unexpected harmonic cadence by musical expertise.

In terms of harmonic expectancy, compared to an expected dominant-to-tonic and an unexpected dominant-to-supertonic, a dominant-to-submediant is a less unexpected cadence, the perception of which may depend on the subject's musical expertise. The present study investigated how aforementioned 3 different cadences are processed in the networks of bilateral inferior frontal gyri (IFGs) and superior temporal gyri (STGs) with magnetoencephalography. We compared the correct rate and brain connectivity in 9 music-majors (mean age, 23.5 ± 3.4 years; musical training period, 18.7 ± 4.0 years) and 10 non-music-majors (mean age, 25.2 ± 2.6 years; musical training period, 4.2 ± 1.5 years). For the brain connectivity, we computed the summation of partial directed coherence (PDC) values for inflows/outflows to/from each area (sPDCi/sPDCo) in bilateral IFGs and STGs. In the behavioral responses, music-majors were better than non-music-majors for all 3 cadences (p < 0.05). However, sPDCi/sPDCo was prominent only for the dominant-to-submediant in the left IFG. The sPDCi was more strongly enhanced in music-majors than in non-music-majors (p = 0.002, Bonferroni corrected), while the sPDCo was vice versa (p = 0.005, Bonferroni corrected). Our data show that music-majors, with higher musical expertise, are better in identifying a less unexpected cadence than non-music-majors, with connectivity changes centered on the left IFG.

P110ß in the ventromedial hypothalamus regulates glucose and energy metabolism.

Phosphoinositide 3-kinase (PI3K) signaling in hypothalamic neurons integrates peripheral metabolic cues, including leptin and insulin, to coordinate systemic glucose and energy homeostasis. PI3K is composed of different subunits, each of which has several unique isoforms. However, the role of the PI3K subunits and isoforms in the ventromedial hypothalamus (VMH), a prominent site for the regulation of glucose and energy homeostasis, is unclear. Here we investigated the role of subunit p110ß in steroidogenic factor-1 (SF-1) neurons of the VMH in the regulation of metabolism. Our data demonstrate that the deletion of p110ß in SF-1 neurons disrupts glucose metabolism, rendering the mice insulin resistant. In addition, the deletion of p110ß in SF-1 neurons leads to the whitening of brown adipose tissues and increased susceptibility to diet-induced obesity due to blunted energy expenditure. These results highlight a critical role for p110ß in the regulation of glucose and energy homeostasis via VMH neurons.

Effect of perioperative oral nutritional supplementation in malnourished patients who undergo gastrectomy: A prospective randomized trial.

BACKGROUND: The aim of this study was to examine the effect of a perioperative oral nutritional supplement in malnourished patients who undergo gastrectomy. METHODS: Patients who were determined as being moderately or severely malnourished according to a patient-generated subjective global assessment or who had a body mass index <18.5, were enrolled. The oral nutritional supplement group received 500 mL/d of standard oral nutritional supplement for 2 weeks before gastrectomy and for 4 weeks postoperatively. The primary endpoint was postoperative complications (Clavien-Dindo classification ≥II). The secondary endpoints included body weight changes, biochemical parameters, and quality of life survey results. RESULTS: A total of 127 patients (65 in the oral nutritional supplement group and 62 in the control group) were enrolled. The complication rates were not significantly different (29.2% versus 37.1%, P = .346). However, the incidences of overall complications, complications persisting until postoperative week 3 or 5, and severe complications (grade ≥IIIa) were significantly lower in the oral nutritional supplement group for patients with patient-generated subjective global assessment grade C. Total lymphocyte counts were significantly higher in the oral nutritional supplement group at postoperative weeks 3 and 5. For most patients, oral nutritional supplement was well tolerated preoperatively. However, only 26.2% and 50.8% of the patients in the oral nutritional supplement group could consume >250 mL/d of oral nutritional supplement postoperatively during the 2nd and 4th weeks, respectively. CONCLUSIONS: The routine application of perioperative oral nutritional supplement is not recommended for malnourished patients receiving gastrectomy. However, perioperative standard oral nutritional supplement administration may reduce the incidence, severity, and duration of complications after gastrectomy in severely malnourished patients (patient-generated subjective global assessment grade C).

4-hydroxy-3-methoxycinnamic acid regulates orexigenic peptides and hepatic glucose homeostasis through phosphorylation of FoxO1.

4-hydroxy-3-methoxycinnamic acid (ferulic acid, FA) is known to have numerous beneficial health effects, including anti-obesity and anti-hyperglycemic properties. However, the molecular networks that modulate the beneficial FA-induced metabolic effects have not been well elucidated. In this study, we explored the molecular mechanisms mediating the beneficial metabolic effects of FA. In mice, FA protected against high-fat diet-induced weight gain, reduced food intake and exhibited an overall improved metabolic phenotype. The food intake suppression by FA was accompanied by a specific reduction in hypothalamic orexigenic neuropeptides, including agouti-related protein and neuropeptide Y, with no significant changes in the anorexigenic peptides pro-opiomelanocortin and cocaine and amphetamine-regulated transcript. FA treatment also inhibited fat accumulation in the liver and white adipose tissue and suppressed the expression of gluconeogenic genes, including phosphoenolpyruvate carboxylase and glucose-6-phosphatase. Furthermore, we show that FA phosphorylated and inactivated the transcription factor FoxO1, which positively regulates the expression of gluconeogenic and orexigenic genes, providing evidence that FA might exert its beneficial metabolic effects through inhibition of FoxO1 function in the periphery and the hypothalamus.

Efficacy and Tolerability of GCSB-5 for Hand Osteoarthritis: A Randomized, Controlled Trial.

PURPOSE: The aim of this study was to investigate the efficacy and tolerability of GCSB-5, a mixture of 6 purified herbal extracts, in treating hand osteoarthritis (OA). METHODS: A randomized, double-blind, placebo-controlled trial enrolled 220 patients with hand OA who had baseline a visual analog scale joint pain score of >30 of 100 mm at 3 hospitals between September 2013 and November 2014. After randomization, patients were allocated to receive oral GCSB-5 600 mg or placebo, bid for 12 weeks. The primary end point was the change in the Australian/Canadian OA Hand Index (AUSCAN)-defined pain score at 4 weeks relative to baseline. Secondary end points included the frequency Outcome Measures in Rheumatology-OA Research Society International (OMERACT-OARSI)-defined response at 4, 8, 12, and 16 weeks after randomization. FINDINGS: The allocated treatment was received by 109 and 106 patients in the GCSB-5 and placebo groups, respectively. At 4 weeks, the median (interquartile range) change in AUSCAN pain score relative to baseline was significantly greater in the GCSB-5 group than in the placebo group (-9.0 [-23.8 to -0.4] vs -2.2 [-16.7 to 6.0]; P = 0.014), with sustained improvement at 8, 12, and 16 weeks (P = 0.039). The GCSB-5 group also had a significantly greater OMERACT-OARSI-defined response rate than did the placebo group at 4 weeks (44.0% vs 30.2%), 8 weeks (51.4% vs 35.9%), 12 weeks (56.9% vs 40.6%), and 16 weeks (50.5% vs 37.7%) (P = 0.0074). The 2 treatments exhibited comparable safety profiles. IMPLICATIONS: GCSB-5 was associated with improved symptoms of hand OA, with good tolerability, in these patients. GCSB-5 may be a well-tolerated alternative of, or addition to, the treatment of hand OA. ClinicalTrials.gov identifier: NCT01910116.

Sex, Age, and the Association of Serum Phosphorus With All-Cause Mortality in Adults With Normal Kidney Function.

BACKGROUND: High serum phosphorus levels are associated with cardiovascular morbidity and mortality in kidney disease. Although serum phosphorus levels possibly influence on mortality in individuals without kidney disease, this is uncertain because of the variable sex- and age-based distribution of serum phosphorus levels. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: Clinical and biochemical data were collected from 138,735 adults undergoing routine health checkups in 3 tertiary hospitals. Individuals with estimated glomerular filtration rates < 60 mL/min/1.73 m2 and urine dipstick albumin ≥ 1+ were excluded. PREDICTOR: Sex-specific quartiles of serum phosphorus and sex. OUTCOMES: All-cause mortality. RESULTS: The study included 92,756 individuals. Generally, women showed higher serum phosphorus levels than men. In women, serum phosphorus levels increased with age until 60 years old, then decreased with age. Men with higher serum phosphorus levels were younger and less likely to have hypertension, whereas women with higher serum phosphorus levels were older and more likely to have diabetes and hypertension. During a median follow-up of 75 months, 1,646 participants died. In the overall population, higher serum phosphorus levels were an independent predictor for all-cause mortality after adjustment (adjusted HR for the highest vs. lowest quartile, 1.34; 95% CI, 1.15-1.56; P<0.001). We observed that this increased risk was present in men but not in women (adjusted HR of 1.43 [95% CI, 1.22-1.68] vs. 1.01 [95% CI, 0.76-1.33]), but interaction by sex was not significant (P=0.8). LIMITATIONS: A single phosphorus measurement and low power to test for interactions by sex and age. CONCLUSIONS: We demonstrated that higher serum phosphorus levels influenced all-cause mortality in individuals with normal kidney function. Our findings suggest that the association may differ by sex, but future studies with adequate power to test for effect modification are needed to confirm our findings.

CYP3A4 and seasonal variation in vitamin D status in addition to CYP2D6 contribute to therapeutic endoxifen level during tamoxifen therapy.

Tamoxifen is a widely utilized adjuvant anti-estrogen agent for hormone receptor-positive breast cancer, known to undergo CYP2D6-mediated bioactivation to endoxifen. However, little is known regarding additional genetic and non-genetic determinants of optimal endoxifen plasma concentration. Therefore, 196 breast cancer patients on tamoxifen were enrolled in this prospective study over a 24-month period. Blood samples were collected for pharmacogenetic and drug-level analysis of tamoxifen and metabolites. Regression analysis indicated that besides CYP2D6, the recently described CYP3A4*22 genotype, seasonal variation, and concomitant use of CYP2D6-inhibiting antidepressants were significant predictors of endoxifen concentration. Of note, genetic variation explained 33 % of the variability while non-genetic variables accounted for 13 %. Given the proposed notion of a sub-therapeutic endoxifen concentration for predicting breast cancer recurrence, we set the therapeutic threshold at 18 nM, the 20th percentile for endoxifen level among enrolled patients in this cohort. Nearly 70 % of CYP2D6 poor metabolizers as well as extensive metabolizers on potent CYP2D6-inhibiting antidepressants exhibited endoxifen levels below 18 nM, while carriers of CYP3A4*22 were twofold less likely to be in sub-therapeutic range. Unexpectedly, endoxifen levels were 20 % lower during winter months than mean levels across seasons, which was also associated with lower vitamin D levels. CYP3A4*22 genotype along with sunshine exposure and vitamin D status may be unappreciated contributors of tamoxifen efficacy. The identified covariates along with demographic variables were integrated to create an endoxifen concentration prediction algorithm to pre-emptively evaluate the likelihood of individual patients falling below the optimal endoxifen concentration.

Water extract of Aralia elata prevents cataractogenesis in vitro and in vivo.

The water extract of Aralia elata (Aralia extract) has been used in Korean traditional medicine to treat diabetes mellitus. Here, we investigated the aldose reductase inhibitory activity, antioxidant activity and anticataract capacity of Aralia extract using various experimental systems. To determine its aldose reductase inhibitory activity and its antioxidant effect, we used rat lens homogenates. Rat lens cultures and a rat model were used to observe anticataract activity. The resulting IC50 value of Aralia extract in vitro as an aldose reductase inhibitor was 11.3 microg/ml and as an antioxidant was 25.1 microg/ml. Rat lenses in media containing 20 mM xylose developed a distinctly opaque ring in 9h, and treatment with Aralia extract at a concentration of 1mg/ml lowered lens opacity by 36.4 and 31.3% after 24 and 48 h, respectively. In vivo experiments were performed with streptozotocin (STZ) induced diabetic rats. The diabetic control animals developed cataracts at 11 weeks after STZ injection, while oral Aralia extract administered at 300 and 600 mg/kg body weight for 11 weeks reduced cataract formation by 15 and 12%, respectively. The present study shows that Aralia extract inhibits aldose reductase and acts in vitro as an antioxidant, and suggests that these activities have a preventive effect on cataractogenesis in xylose containing lens organ cultures and in in vivo in STZ induced diabetic rats.