Cell type-specific roles of APOE4 in Alzheimer disease.

The ɛ4 allele of the apolipoprotein E gene (APOE), which translates to the APOE4 isoform, is the strongest genetic risk factor for late-onset Alzheimer disease (AD). Within the CNS, APOE is produced by a variety of cell types under different conditions, posing a challenge for studying its roles in AD pathogenesis. However, through powerful advances in research tools and the use of novel cell culture and animal models, researchers have recently begun to study the roles of APOE4 in AD in a cell type-specific manner and at a deeper and more mechanistic level than ever before. In particular, cutting-edge omics studies have enabled APOE4 to be studied at the single-cell level and have allowed the identification of critical APOE4 effects in AD-vulnerable cellular subtypes. Through these studies, it has become evident that APOE4 produced in various types of CNS cell - including astrocytes, neurons, microglia, oligodendrocytes and vascular cells - has diverse roles in AD pathogenesis. Here, we review these scientific advances and propose a cell type-specific APOE4 cascade model of AD. In this model, neuronal APOE4 emerges as a crucial pathological initiator and driver of AD pathogenesis, instigating glial responses and, ultimately, neurodegeneration. In addition, we provide perspectives on future directions for APOE4 research and related therapeutic developments in the context of AD.

PINK1 Phosphorylates MIC60/Mitofilin to Control Structural Plasticity of Mitochondrial Crista Junctions.

Mitochondrial crista structure partitions vital cellular reactions and is precisely regulated by diverse cellular signals. Here, we show that, in Drosophila, mitochondrial cristae undergo dynamic remodeling among distinct subcellular regions and the Parkinson's disease (PD)-linked Ser/Thr kinase PINK1 participates in their regulation. Mitochondria increase crista junctions and numbers in selective subcellular areas, and this remodeling requires PINK1 to phosphorylate the inner mitochondrial membrane protein MIC60/mitofilin, which stabilizes MIC60 oligomerization. Expression of MIC60 restores crista structure and ATP levels of PINK1-null flies and remarkably rescues their behavioral defects and dopaminergic neurodegeneration. In an extension to human relevance, we discover that the PINK1-MIC60 pathway is conserved in human neurons, and expression of several MIC60 coding variants in the mitochondrial targeting sequence found in PD patients in Drosophila impairs crista junction formation and causes locomotion deficits. These findings highlight the importance of maintenance and plasticity of crista junctions to cellular homeostasis in vivo.

Distribution of urinary trace element exposure and dietary sources in women over 50 in an agricultural region- A community-based KoGES cohort study.

BACKGROUND: There is a noticeable lack of information on the levels of both non-essential and essential trace elements in women aged over 50. The main objective of this study is to investigate trace element concentrations and explore the influence of sociodemographic factors and dietary sources of exposure in this demographic. METHODS: We analyzed 19 trace elements, including manganese, cobalt, copper, zinc, molybdenum, chromium, nickel, arsenic, strontium, cadmium, tin, antimony, cesium, barium, tungsten, mercury, thallium, lead, and uranium, using ICP-MS and mercury analyzer. Urine samples were obtained from a cohort of 851 women aged over 50 who participated in the 8th KoGES-Ansung study (2017-2018). Multiple linear models were employed to explore associations between urinary trace element concentrations and sociodemographic factors and dietary sources of exposure. We used K-means clustering to discern patterns of exposure to trace elements and identify contributing factors and sources. RESULTS: Our findings indicate higher concentrations of molybdenum (Mo), arsenic (As), cadmium (Cd), and lead (Pb) in our study population compared to women in previous studies. The study population were clustered into two distinct groups, characterized by lower or higher urinary concentrations. Significant correlations between age and urinary concentrations were observed in Ni. Smoking exhibited positive associations with urinary Cd and As. Associations with dietary sources of trace elements were more distinct in women in the high-exposure group. Urinary antimony (Sb) was positively linked to mushroom and egg intake, As to mushroom and fish, and Hg to egg, dairy products, fish, seaweed, and shellfish. CONCLUSIONS: Our study underscores the significant gap in understanding urinary concentrations of trace elements in women aged over 50. With higher concentrations of certain elements compared to previous studies and significant correlations between age, smoking, and specific food sources, it is imperative to address this gap through targeted dietary source-specific risk management.

ERα inhibits mesenchymal and amoeboidal movement of liver cancer cell via Gα12.

Hepatocellular carcinoma (HCC) is the second most common cancer worldwide, demonstrating aggressiveness and mortality more frequently in men than in women. Despite reports regarding the inhibitory ability of estrogen receptor alpha (ERα, ESR1) in certain cancer progression, targets and the basis of underlying gender disparity in HCC worsening remain elusive. Here, we report the ability of ERα to transcriptionally inhibit G protein subunit alpha 12 (Gα12) responsible for HCC worsening. First, using human samples and public database, the expression of ERα and Gα12 in HCC was examined. Then, quantitative real-time PCR, chromatin immunoprecipitation-assay, luciferase assay and immunoblottings of liver cancer cell lines confirmed the inhibitory ability of ERα on Gα12 and HCC progression. Gα12 promoted mesenchymal characteristics and amoeboidal movement, which was antagonized by ERα overexpression. Additionally, we found microRNA-141 and microRNA-200a as downstream targets of the Gα12 signaling axis for cancer malignancy regulation under the control of ERα. As for in-depth mechanism, PTP4A1 was found to be directly inhibited by microRNA-141 and microRNA-200a. Moreover, we found the inhibitory effect of ERα on amoeboidal movement by analyzing the morphology and blebbing of liver cancer cells and the active form of MLC levels. The identified targets and ESR1 levels are inversely correlated with human specimens, as well as with sex-biased survival rates of HCC patients. Collectively, ERα-dependent repression of Gα12 and consequent changes in the Gα12 signaling may explain the gender disparity in HCC, providing pharmacological clues for the control of metastatic HCC.

Sex, menopause, and age differences in the associations of persistent organic pollutants with thyroid hormones, thyroxine-binding globulin, and peripheral deiodinase activity: A cross-sectional study of the general Korean adult population.

Persistent organic pollutants (POPs) can disrupt the thyroid hormone system in humans. We assessed the associations of several POPs with serum thyroid hormones (T3 and T4) and thyroid-stimulating hormone, and investigated the modulating effects of sex, menopausal status, and age on these associations, in a subgroup of the adult population (n = 1250) from the Korean National Environmental Health Survey. PCB105 and PCB118 were negatively associated with total T4 in premenopausal females and males aged <50, whereas the associations were insignificant in other groups. PCB180, p,p'-DDE, and p,p'-DDT showed positive associations with total T3 in postmenopausal females; however, among males aged ≥50, PCB118, PCB138, and p,p'-DDE showed negative associations with total T3. The effects of exposure to multiple POPs were examined in multi-factor analyses. Factor 2 comprised PCB52, hexachlorobenzene, and BDE-47 was associated with an increase in free T4 in premenopausal females (ß = 0.015, p = 0.024), while Factor 1, which contained most POPs, was associated with a change in total T3 in postmenopausal females (ß = 0.032, p = 0.040) and males aged ≥50 (ß = -0.039, p = 0.023). Changes in total T4 or total T3 could be explained by differences in thyroxine-binding globulin (TBG) and peripheral deiodinase activity (GD). Negative associations of TBG with PCB105 in premenopausal females and PCB153 in males aged <50 may mediate the effect of decreasing total T4. PCB180, p,p'-DDE, p,p'-DDT, and Factor 1 were positively associated with GD, which is consistent with an increased total T3 in postmenopausal females. PCB118 was negatively associated with GD and total T3 in males aged ≥50. BDE-47 and ß-hexachlorocyclohexane were associated with thyroid autoantibodies in premenopausal females and males aged <50. Our observations suggest that the thyroid-disrupting effects of POPs may differ by sex, sex hormonal status, and age, and may be mediated by TBG and GD.

Lead, mercury, and cadmium exposures are associated with obesity but not with diabetes mellitus: Korean National Environmental Health Survey (KoNEHS) 2015-2017.

BACKGROUND: Associations of heavy metal exposures with obesity and obesity-related traits have been suggested, while those with nonalcoholic fatty liver disease (NAFLD) and diabetes mellitus (DM) are often inconsistent. METHODS: This study included 3787 adults aged ≥19 years who participated in the Korean National Environmental Health Survey 2015-2017, and investigated the association of toxic heavy metals with metabolic diseases. Lead (Pb), mercury (Hg), and cadmium (Cd) were measured either in urine (uHg, uCd) or total blood (bPb, bHg). Body mass index (BMI) was calculated, and DM cases were identified through a self-answered medication history. Hepatic Steatosis Index (HSI) as a surrogating index of NAFLD, was calculated using hepatic enzyme measurements, including aspartate aminotransferase (AST) and alanine aminotransferase (ALT). RESULTS: Adults in the highest quartile of bPb, bHg, and uHg showed significantly elevated odds of obesity (BMI ≥25 kg/m2), compared to the lowest quartile (OR 1.58 for bPb, 1.92 for bHg, and 1.81 for uHg). HSI was positively correlated with bHg, uHg, and uCd concentrations. The odds of NAFLD (HSI ≥36) were also increased with increasing quartile of bHg, uHg, and uCd concentrations. For DM, bPb showed a significant negative association, while bHg and uCd exhibited non-monotonic and inconclusive associations. CONCLUSIONS: Among the general adult population of Korea, both Pb and Hg exposures were associated with an increased risk of obesity. In addition, both Hg and Cd exposures were associated with increased odds of NAFLD. These metals, however, were not associated with an increased risk of DM.

Anti-Obesity and Anti-Adipogenic Effects of Administration of Arginyl-Fructose-Enriched Jeju Barley (Hordeum vulgare L.) Extract in C57BL/6 Mice and in 3T3-L1 Preadipocytes Models.

In our previous study, we reported that arginyl-fructose (AF), one of the Amadori rearrangement compounds (ARCs) produced by the heat processing of Korean ginseng can reduce carbohydrate absorption by inhibiting intestinal carbohydrate hydrolyzing enzymes in both in vitro and in vivo animal models. This reduced absorption of carbohydrate might be helpful to control body weight gain due to excessive carbohydrate consumption and support induced calorie restriction. However, the weight management effect, except for the effect due to anti-hyperglycemic action, along with the potential mechanism of action have not yet been determined. Therefore, the efforts of this study are to investigate and understand the possible weight management effect and mechanism action of AF-enriched barley extracts (BEE). More specifically, the effect of BEE on lipid accumulation and adipogenic gene expression, body weight gain, body weight, plasma lipids, body fat mass, and lipid deposition were evaluated using C57BL/6 mice and 3T3-L1 preadipocytes models. The formation of lipid droplets in the 3T3-L1 treated with BEE (500 and 750 µg/mL) was significantly blocked (p < 0.05 and p < 0.01, respectively). Male C57BL/6 mice were fed a high-fat diet (30% fat) for 8 weeks with BEE (0.3 g/kg-body weight). Compared to the high fat diet control (HFD) group, the cells treated with BEE significantly decreased in intracellular lipid accumulation with concomitant decreases in the expression of key transcription factors, peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (CEBP/α), the mRNA expression of downstream lipogenic target genes such as fatty acid binding protein 4 (FABP4), fatty acid synthase (FAS), and sterol regulatory element-binding protein 1c (SREBP-1c). Supplementation of BEE effectively lowered the body weight gain, visceral fat accumulation, and plasma lipid concentrations. Compared to the HFD group, BEE significantly suppressed body weight gain (16.06 ± 2.44 g vs. 9.40 ± 1.39 g, p < 0.01) and increased serum adiponectin levels, significantly, 1.6-folder higher than the control group. These results indicate that AF-enriched barley extracts may prevent diet-induced weight gain and the anti-obesity effect is mediated in part by inhibiting adipogenesis and increasing adiponectin level.

Nonfunctioning Adrenal Incidentalomas are not Clinically Silent: A Longitudinal Cohort Study.

OBJECTIVE: The association between nonfunctioning adrenal incidentalomas (NFAIs) and cardiometabolic diseases remains controversial. This retrospective cohort study investigated whether NFAIs are related with prevalent and incident cardiometabolic diseases. METHODS: This study included 154 patients with biochemically confirmed NFAIs and 1:3 age and sex-matched controls without adrenal incidentalomas (n = 462) among subjects who underwent abdominal computed tomography at a single healthcare center in 2003-2012. Electronic medical records were reviewed for comorbidities at baseline and during a mean follow-up of 7.5 years. The logistic regression analysis for prevalent cardiometabolic diseases and the survival analysis for incident cardiometabolic diseases were performed. RESULTS: The subjects were 55.7±8.8 years of age and predominantly male (73.1%). The NFAI group had a higher body mass index compared to the age and sex-matched control group (25.1±2.8 vs. 24.0±2.8 kg/m2; P<.001). In a cross-sectional design, covariate-adjusted logistic regression showed significantly higher odds ratios (ORs) for diabetes mellitus and hypertension in the NFAI group (adjusted OR [95% confidence interval [CI]], 1.89 [1.17 to 3.06] and 2.26 [1.47 to 3.50], respectively). The NFAI group had a 2-fold higher risk of insulin resistance (adjusted ORs [95% CI], 2.03 [1.06 to 3.90]). Moreover, NFAI subjects with diabetes mellitus had a greater increase in size of adrenal lesions than those without diabetes mellitus (3.4±5.5 vs. 1.4±5.5 mm; P =.048). However, in the survival analysis, the incidence of any cardiometabolic diseases did not differ between the NFAI and control groups. CONCLUSION: NFAIs are related to prevalent diabetes mellitus or hypertension in our cross-sectional study. However, the presence of NFAIs did not affect the development of cardiometabolic diseases. ABBREVIATIONS: ACTH = adrenocorticotropic hormone; AI = adrenal incidentaloma; BMI = body mass index; CI = confidence interval; CT = computed tomography; HbA1c = hemoglobin A1c; HOMA-IR = homeostasis model assessment of insulin resistance; HU = Hounsfield units; MACE = mild autonomous cortisol excess; NFAI = nonfunctioning adrenal incidentaloma; OR = odds ratio.

TomoMQA: Automated analysis program for MVCT quality assurance of helical tomotherapy.

PURPOSE: In this study, we developed a simple but useful computer program, called TomoMQA, to offer an automated quality assurance for mega-voltage computed tomography (MVCT) images generated via helical tomotherapy. METHODS: TomoMQA is written in MATLAB and contains three steps for analysis: (a) open the DICOM dataset folder generated via helical tomotherapy (i.e., TomoTherapy® and Radixact™), (b) call the baseline data for the consistency test and click the "Analysis" button (or click the "Analysis" button without the baseline data and export the results as the baseline data), and (c) print an analyzed report. The overall procedure for the QA analysis included in TomoMQA is referred from the TG-148 recommendation. Here, the tolerances for MVCT QA were implemented from TG-148 recommended values as default; however, it can be modified by a user manually. RESULTS: To test the performance of the TomoMQA program, 15 MVCTs were prepared from five helical tomotherapy machines (1 of TomoTherapy® HD, 2 of TomoTherapy® HDA, and 2 of Radixact™) in 3 months and the QA procedures were performed using TomoMQA. From our results, the evaluation revealed that the developed program can successfully perform the MVCT QA analysis irrespective of the type of helical tomotherapy equipment. CONCLUSION: We successfully developed a new automated analysis program for MVCT QA of a helical tomotherapy platform, called TomoMQA. The developed program will be made freely downloadable from the TomoMQA-dedicated website.

Tumor doubling time predicts response to sorafenib in radioactive iodine-refractory differentiated thyroid cancer.

Sorafenib has emerged as an effective therapeutic option for radioactive iodine (RAI)-refractory, locally advanced or metastatic differentiated thyroid cancer (DTC). We investigated the efficacy and safety of sorafenib treatment in a real-world setting and unveil predictive markers of responsiveness to sorafenib. The treatment response, progression-free survival (PFS), overall survival, and adverse events (AEs) of sorafenib-treated RAI-refractory, locally advanced or metastatic DTC patients at three institutes were retrospectively reviewed, and their tumor doubling time was calculated by three investigators. Total eighty-five patients were treated with sorafenib, and seven patients discontinued sorafenib due to AEs before the first tumor assessment. The median PFS was 14.4 months, and the objective response rate was 10.3% in 78 patients who were able to evaluate the tumor response. Age, sex, histologic type, tumor location, RAI avidity, or the presence of FDG-PET uptake did not affect PFS. However, smaller tumor size (≤1.5 cm) of the target lesions in lung showed better PFS (hazard ratio [HR] 0.39, p = 0.01), and tumors with the shortest doubling time (≤6 months) had worse outcome (HR 2.70, p < 0.01). Because of AEs, dose reductions or drug interruptions were required in 64% of patients, and eventually, 23% of patients discontinued sorafenib permanently. The most common AE was hand-foot skin reaction (HFSR). Patients with severe HFSR showed better PFS, but there were no statistical significance (HR 0.65, p = 0.05). In conclusion, small tumor size and long doubling time of each target lesion can be a prognostic marker to predict the responsiveness to sorafenib in RAI-refractory DTC patients.

Alpha-synuclein delays mitophagy and targeting Miro rescues neuron loss in Parkinson's models.

Alpha-synuclein is a component of Lewy bodies, the pathological hallmark of Parkinson's disease (PD), and is also mutated in familial PD. Here, by extensively analyzing PD patient brains and neurons, and fly models, we show that alpha-synuclein accumulation results in upregulation of Miro protein levels. Miro is a motor/adaptor on the outer mitochondrial membrane that mediates mitochondrial motility, and is removed from damaged mitochondria to facilitate mitochondrial clearance via mitophagy. PD patient neurons abnormally accumulate Miro on the mitochondrial surface leading to delayed mitophagy. Partial reduction of Miro rescues mitophagy phenotypes and neurodegeneration in human neurons and flies. Upregulation of Miro by alpha-synuclein requires an interaction via the N-terminus of alpha-synuclein. Our results highlight the importance of mitochondria-associated alpha-synuclein in human disease, and present Miro as a novel therapeutic target.

Extent of surgery did not affect recurrence during 7-years follow-up in papillary thyroid cancer sized 1-4 cm: Preliminary results.

OBJECTIVE: There is debate whether hemithyroidectomy is sufficient for patients with papillary thyroid cancer (PTC) sized 1-4 cm. Therefore, we investigated whether hemithyroidectomy affects recurrence rate compared with thyroidectomy in patients with PTC sized 1-4 cm. DESIGN: Retrospective observational study. PATIENTS: We included 147 patients with 1-4 cm PTC who underwent hemithyroidectomy between 2004 and 2008. They were matched with 298 patients who underwent thyroidectomy, comparing age, sex, tumour size, multiplicity, extrathyroidal extension status and lymph node (LN) metastasis status. MEASUREMENTS: Recurrence-free survival (RFS) was compared between hemithyroidectomy and thyroidectomy groups. RESULTS: Median follow-up length was 7 years, during which there were nine (6.1%) and 17 (5.7%) recurrences in hemithyroidectomy and thyroidectomy groups, respectively. Recurrence-free survival in the hemithyroidectomy group was not different from that in the thyroidectomy group regardless of variant, multifocality, LN metastasis and radioactive iodine treatment. However, in subgroup analysis, hemithyroidectomy significantly increased the risk of recurrence in patients with contralateral nodules on the preoperative imaging. CONCLUSIONS: Recurrence after hemithyroidectomy was not different from that after thyroidectomy during a median follow-up of 7 years. However, because thyroidectomy might be favoured in patients with contralateral nodules at preoperative evaluation, a thorough evaluation of the contralateral thyroid lobe is necessary.

Expression of activated Notch1 and Hey1 in papillary thyroid carcinoma.

AIMS: The Notch signalling pathway is involved in normal development as well as tumorigenesis. However, it is unclear whether Notch activation is related to diverse clinicopathological factors in papillary thyroid carcinoma (PTC). METHODS AND RESULTS: We examined the relationship between clinicopathological factors and the expression of activated Notch1 and Hey1, which are indicators of Notch signalling pathway activation, in 109 PTC cases. Activated Notch1 showed strong, moderate and weak expression in 23, 48 and 36 cases, respectively. Its expression was related significantly to histopathological variants (P = 0.007), lymph node metastasis (P = 0.016), BRAF mutation (P = 0.036) and extent of surgery (P = 0.014). Hey1 immunostaining could be divided into two groups: positive and negative, with 26 and 83 cases, respectively. Its expression was related significantly to histopathological variants (P = 0.026), extrathyroidal extension (P = 0.005), BRAF mutation (P = 0.048) and recurrence or soft tissue metastasis (P = 0.000). Multivariate analysis revealed that tumour size (>1 cm), Hey1 immunoreactivity and the presence of lymph node metastasis were associated significantly with recurrence or soft tissue metastasis (odds ratio = 7.38, 4.28 and 12.00, respectively). CONCLUSIONS: Thus, we found that activation of Notch signalling was correlated significantly with clinicopathological parameters. Therefore, Notch signalling could be a useful prognostic marker in patients with PTC.

Mutation of the murC and murB Genes Impairs Heterocyst Differentiation in Anabaena sp. Strain PCC 7120.

UNLABELLED: To stabilize cellular integrity in the face of environmental perturbations, most bacteria, including cyanobacteria, synthesize and maintain a strong, flexible, three-dimensional peptidoglycan lattice. Anabaena sp. strain PCC 7120 is a filamentous cyanobacterium capable of differentiating morphologically distinct nitrogen-fixing heterocyst cells in a periodic pattern. While heterocyst development has been shown to require proper peptidoglycan remodeling, the role of peptidoglycan synthesis has remained unclear. Here we report the identification of two peptidoglycan synthesis genes, murC (alr5065) and murB (alr5066), as required for heterocyst development. The murC and murB genes are predicted to encode a UDP-N-acetylmuramate:L-alanine ligase and a UDP-N-acetylenolpyruvoylglucosamine reductase, respectively, and we confirm enzymatic function through complementation of Escherichia coli strains deficient for these enzymes. Cells depleted of either murC or murB expression failed to differentiate heterocysts under normally inducing conditions and displayed decreased filament integrity. To identify the stage(s) of development affected by murC or murB depletion, the spatial distribution of expression of the patterning marker gene, patS, was examined. Whereas murB depletion did not affect the pattern of patS expression, murC depletion led to aberrant expression of patS in all cells of the filament. Finally, expression of gfp controlled by the region of DNA immediately upstream of murC was enriched in differentiating cells and was repressed by the transcription factor NtcA. Collectively, the data in this work provide evidence for a direct link between peptidoglycan synthesis and the maintenance of a biological pattern in a multicellular organism. IMPORTANCE: Multicellular organisms that differentiate specialized cells must regulate morphological changes such that both cellular integrity and the dissemination of developmental signals are preserved. Here we show that the multicellular bacterium Anabaena, which differentiates a periodic pattern of specialized heterocyst cells, requires peptidoglycan synthesis by the murine ligase genes murC (alr5065) and murB (alr5066) for maintenance of patterned gene expression, filament integrity, and overall development. This work highlights the significant influence that intracellular structure and intercellular connections can have on the execution of a developmental program.

Feasibility of a Self-Determination Theory-Based Exercise Program in Community-Dwelling South Korean Older Adults: Experiences from a 13-Month Trial.

Little is known about the effectiveness of self-determination theory (SDT), a representative motivational theory, on exercise domain in older adults. This feasibility study used quantitative and qualitative approaches to evaluate the effectiveness of a 13-month group exercise program applying SDT-based motivational strategies on exercise adherence, physical fitness, and quality of life, and to explore factors affecting exercise adherence in South Korean older adults (N = 18). Exercise attendance rate was high (82.52%). There were significant differences in aerobic endurance (p < .001), lower body strength (p < .05), dynamic balance (p < .001), and perceived social functioning (p < .05) at 13 months compared with baseline. Factors affecting exercise adherence were related to the SDT-based motivational strategies. These results support the importance of health professionals applying SDT-based motivational strategies to exercise programs to help facilitate motivation for participation and to promote physical fitness and quality of life in older adults.

Loss of ERß expression in papillary thyroid carcinoma is associated with recurrence in young female.

OBJECTIVES: We investigated the expression of oestrogen receptors (ERs) in papillary thyroid cancers (PTCs) and evaluated their prognostic role. METHODS: We enrolled 81 female patients who underwent thyroid surgery and had a confirmed diagnosis of PTC between 01 January 1995 and 31 December 1996. Data on clinicopathologic parameters were obtained from patients' medical records. Tissue paraffin blocks of these 81 patients were collected for immunohistochemistry for ERα and ERß. RESULTS: ERα expression was observed in only eight patients (9·9%). In contrast, ERß expression was positive in 36 (44·4%) patients. Total thyroidectomy (84·4% vs 61·1%, P = 0·017) and cervical lymph node metastasis (62·2% vs 22·2%, P = 0·000) were more frequent in the ERß-negative group than in the ERß-positive group. Among younger female patients (<45 years), the ERß-negative group showed a tendency towards more frequent recurrent or persistent disease than the ERß-positive group (42·3% vs 13·6%, P = 0·029). In contrast, the ERα-positive group showed more recurrent or persistent disease than the ERα-negative group in older female patients (100% vs 24·1%, P = 0·024). In multivariate analysis, ERß negativity, extrathyroidal invasion and radioactive iodine treatment were risk factors for recurrence in young female patients. CONCLUSION: Loss of ERß expression was associated with recurrence in young female PTC patients. This finding suggests that oestrogen might play a protective role in the progression of PTC via ERß, especially in young female patients.

Vitamin D level is not a predictor of hypocalcemia after total thyroidectomy.

PURPOSE: As the incidence of thyroid cancer has increased, hypocalcemia, a common complication of thyroid surgery, has become a serious problem. However, no definite predictor of postoperative hypocalcemia is known. In this study, our purpose was to investigate the potential role of vitamin D as a predictor of postoperative hypocalcemia. METHODS: A prospective observational study was performed on patients who underwent total thyroidectomy for thyroid cancer performed by a single experienced surgeon between October 2013 and September 2014. MEASUREMENTS: Their serum 25-OH vitamin D levels were measured preoperatively. On the day after surgery, serum calcium and intact parathyroid hormone levels were measured, and symptoms of hypocalcemia were recorded. RESULTS: Of the 134 patients, laboratory and symptomatic hypocalcemia developed in 52 patients (39 %) and 25 patients (19 %), on the day after surgery. The preoperative vitamin D level was 16.5 ± 9.2 ng/mL, and this value did not differ according to laboratory or symptomatic hypocalcemia (p = 0.94). The incidence of laboratory or symptomatic hypocalcemia did not differ according to vitamin D deficiency. Only incidental parathyroidectomy was associated with symptomatic hypocalcemia (p = 0.03). CONCLUSIONS: Vitamin D level is not a predictor of hypocalcemia after total thyroidectomy for thyroid cancer. Thus, routine preoperative screening for vitamin D is not recommended.

Gamma analysis dependence on specified low-dose thresholds for VMAT QA.

The American Association of Physicists in Medicine Task Group 119 instructed institutions to use a low-dose threshold of 10% or a region of interest determined by the jaw setting when they collected gamma analysis quality assurance (QA) data for the planar dose distribution. However, there are no clinical data to quantitatively demonstrate the impact of the low-dose threshold on the gamma index. Therefore, we performed a gamma analysis with various low-dose thresholds in the range of 0% to 15% according to both global and local normalization and different acceptance criteria (3%/3 mm, 2%/2 mm, and 1%/1 mm). A total of 30 treatment plans--10 head and neck, 10 brain, and 10 prostate cancer cases--were randomly selected from the Varian Eclipse treatment planning system (TPS). For the gamma analysis, a calculated portal image was acquired through a portal dose calculation algorithm in the Eclipse TPS, and a measured portal image was obtained using an electronic portal-imaging device. Then, the gamma analysis was performed using the Portal Dosimetry software (Varian Medical Systems, Palo Alto, CA). The gamma passing rate (%GP) for the global normalization decreased as the low-dose threshold increased, and all low-dose thresholds led to %GP values above 95% for both the 3%/3 mm and 2%/2 mm criteria. However, for the local normalization, %GP for a low-dose threshold of 10% was 7.47%, 10.23%, and 6.71% greater than the low-dose threshold of 0% for head and neck, brain, and prostate for the 3%/3 mm criteria, respectively. The results indicate that applying the low-dose threshold to global normalization does not have a critical impact on patient-specific QA results. However, in the local normalization, the low-dose threshold level should be carefully selected because the excluded low-dose points could cause the average %GP to increase rapidly.

The relationship between body fat and bone mineral density in Korean men and women.

Previous studies of the effects of body fat on bone mineral density (BMD) have shown conflicting results depending on the age, sex, and menopausal status of the subjects. The purpose of the present study was to investigate the effects of body fat on BMD using data from the Fifth Korea National Health and Nutrition Examination Survey, which was conducted in 2010. Our data were drawn from a relevant population within the survey's range of participants, yielding a total of 4,138 subjects aged 20-93 years (1,133 men <50 years, 946 men ≥ 50 years, 1,332 premenopausal women, and 727 postmenopausal women). Percent body fat, fat mass (FM), lean mass (LM), and BMD of the total hip, lumbar spine, and arm were measured in the original survey using dual-energy X-ray absorptiometry. Relationships between FM and BMD were evaluated using multiple linear regression analyses. LM was the strongest determinant of BMD. Although FM also showed a significant positive correlation, even after adjusting for LM, with total hip and lumbar spine BMD in men ≥ 50 years and pre- and postmenopausal women, this positive correlation was not observed in the arm. In an analysis of obese and non-obese subgroups, the positive correlation between FM and BMD disappeared in obese subjects. Furthermore, FM and BMD exhibited a negative correlation in premenopausal obese women. These results suggest that FM contributes to BMD primarily through mechanical loading. FM, then, is not beneficial and may be detrimental to bone health in obese people.

Comparison of surgical and endovascular salvage procedures for juxta-anastomotic stenosis in autogenous wrist radiocephalic arteriovenous fistula.

BACKGROUND: Although dysfunctional radiocephalic arteriovenous fistulas (RCAVFs) are typically treated surgically, the endovascular approach is also considered suitable. The aim of this retrospective study was to compare the cumulative patency rates following surgical and endovascular salvaging of dysfunctional RCAVFs, and to evaluate whether the maturity of vascular access sites at the time of treatment influenced the outcomes. METHODS: A total of 60 patients underwent surgical or endovascular salvage treatment for juxta-anastomotic stenosis of autogenous wrist RCAVFs: 35 patients underwent proximal neo-anastomosis and 25 underwent percutaneous transluminal angioplasty (PTA). RESULTS: Clinical and anatomical success rates were, respectively, 100% and 97.1% in the surgery group, and 100% and 96.0% in the angioplasty group (P = 0.81). The post-treatment restenosis rate was higher in the angioplasty group (n = 11, 46.0%) than in the surgery group (n = 8, 22.8%), without reaching statistical significance (P = 0.15). In a Kaplan-Meier analysis, the primary and assisted primary patency rates were significantly higher in the surgery group (P = 0.036 and P = 0.026, respectively), but there was no significant difference in secondary patency rates between the groups (P = 0.52). When stratified by RCAVF maturity at the time of treatment, no significant difference was noted in primary patency rates between the treatment groups. After adjusting for other variables, the relative risk of restenosis was significantly higher in the angioplasty group (hazard ratio 2.56; 95% confidence interval 1.02-6.46; P = 0.046). CONCLUSIONS: Post-treatment primary and assisted primary patency rates after proximal neo-anastomosis were significantly higher than after PTA, and RCAVF maturity did not influence the outcomes.