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Genetic testing is recommended for all patients with pheochromocytomas and paragangliomas (PPGL) to establish genotype–phenotype associations. We investigated germline mutations in 59 patients with PPGL at six Korean university hospitals using next-generation sequencing (NGS) targeting 38 PPGL-associated genes, including those recommended by the Korean PPGL Task Force. Germline mutations were identified in 13 patients (22%), and affected four genes: RET, NF1, VHL, and SDHD. Germline mutations were significantly associated with a family history of PPGL, smaller tumor size, and the presence of other types of tumors. Using 95 Korean PPGL cases with germline mutations identified through a literature review and 13 cases from our cohort, we characterized genotype–phenotype correlations. Mutation hotspots were identified in specific codons of RET (codons 631 and 634), VHL (157 and 167), and SDHB (131 and 253). NF1 mutations varied, indicating the absence of common hotspots. These findings highlight the efficacy of the recommended NGS panel for Korean patients with PPGL and the importance of genetic testing in establishing clinical management and personalized therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination. Methods: In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (=1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998). Results: Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, -0.65% and -0.55%; 95% confidence interval [CI], -0.79 to -0.51 and -0.71 to -0.39; P<0.0001). The proportion of patients achieving HbA1c <7% was higher in the triple combination group at week 52 (32.14% vs. 8.51% in placebo; odds ratio, 5.62; P<0.0001). Evogliptin significantly reduced the fasting glucose levels and mean daily glucose levels with improvement in homeostatic model assessment of ß-cell function (LS mean difference, 9.04; 95% CI, 1.86 to 16.21; P=0.0138). Adverse events were similar between the groups, and no serious adverse drug reactions were reported in the evogliptin group. Conclusion: Long-term triple combination with evogliptin added to DAPA/MET showed superior HbA1c reduction and glycemic control compared to placebo at 52 weeks and was well tolerated. [ABSTRACT FROM AUTHOR]

Invasion and metastasis are important hallmarks of breast cancer and are the leading cause of patient mortality. Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer characterized by a poor prognosis and a lack of effective targeted therapies. The present study investigated the inhibitory effect of a novel FTY720 derivative on the invasive phenotype of TNBC cells. Here, we showed that a novel compound with an isoxazole ring, 4-(3-Decylisoxazol-5-yl)-1-hydroxy-2-(hydroxymethyl)butan-2-aminium chloride (CM2-II-173), significantly inhibited invasiveness of MDA-MB-231 TNBC cells. Expression of matrix metalloproteinase (MMP)-9 and invasiveness of MCF10A normal breast cells induced by sphingosine-1-phosphate (S1P) were reduced by CM2-II-173 treatment. Activations of pMEK1, pAkt, pERK, and p38 MAPK by S1P were inhibited by treatment with CM2-II-173. Proliferation and anchorage-independent growth of MDA-MB-231 TNBC cells were significantly decreased by CM2-II-173. CM2-II-173 efficiently induced apoptosis in MDA-MB-231 TNBC cells. CM2-II-173 significantly inhibited invasive phenotypes of breast, liver, prostate, and ovarian cancer cells. CM2-II-173 exhibited a more potent effect on the invasiveness of MDA-MB-231 TNBC cells compared to FTY720. Taken together, this study demonstrated that CM2-II-173 has the potential to be a lead compound that can inhibit cancer progression of not only TNBC cells, but also of liver, prostate, and ovarian cancer cells. [ABSTRACT FROM AUTHOR]

Background: Hürthle cell carcinoma (HCC), a type of thyroid carcinoma, is rare in South Korea, and few studies have investigated its prognosis. Methods: This long-term multicenter retrospective cohort study evaluated the clinicopathological features and clinical outcomes in patients with HCC who underwent thyroid surgery between 1996 and 2009. Results: The mean age of the 97 patients included in the study was 50.3 years, and 26.8% were male. The mean size of the primary tumor was 3.2±1.8 cm, and three (3.1%) patients had distant metastasis at initial diagnosis. Ultrasonographic findings were available for 73 patients; the number of nodules with low-, intermediate-, and high suspicion was 28 (38.4%), 27 (37.0%), and 18 (24.7%), respectively, based on the Korean-Thyroid Imaging Reporting and Data System. Preoperatively, follicular neoplasm (FN) or suspicion for FN accounted for 65.2% of the cases according to the Bethesda category, and 13% had malignancy or suspicious for malignancy. During a median follow-up of 8.5 years, eight (8.2%) patients had persistent/recurrent disease, and none died of HCC. Older age, gross extrathyroidal extension (ETE), and widely invasive types of tumors were significantly associated with distant metastasis (all P<0.01). Gross ETE (hazard ratio [HR], 27.7; 95% confidence interval [CI], 2.2 to 346.4; P=0.01) and widely invasive classification (HR, 6.5; 95% CI, 1.1 to 39.4; P=0.04) were independent risk factors for poor disease-free survival (DFS). Conclusion: The long-term prognosis of HCC is relatively favorable in South Korea from this study, although this is not a nationwide data, and gross ETE and widely invasive cancer are significant prognostic factors for DFS. The diagnosis of HCC by ultrasonography and cytopathology remains challenging. [ABSTRACT FROM AUTHOR]

This report presents the status of diabetic neuropathy (DN) in Korea as determined using a National Health Insurance Service-National Sample Cohort (NHIS-NSC). Annual prevalences of DN were estimated by age and gender using descriptive statistics. Pharmacological treatments for DN were also analyzed. The annual prevalence of DN increased from 24.9% in 2006 to 26.6% in 2007, and thereafter, gradually subsided to 20.8% in 2015. In most cases, pharmacological treatments involved a single drug, which accounted for 91.6% of total prescriptions in 2015. The most commonly used drugs (in decreasing order) were thioctic acid, an anti-convulsive agent, or a tricyclic antidepressant. In conclusion, the prevalence of DN decreased over the 10-year study period. Thioctic acid monotherapy was usually prescribed for DN. To reduce the socio-economic burden of DN, more attention should be paid to the diagnosis of this condition and to the appropriate management of patients. [ABSTRACT FROM AUTHOR]

Background: The study aimed to compare the prognostic value of the 4th edition of World Health Organization classification (WHO-2017) with the previous WHO classification (WHO-2004) for follicular thyroid carcinoma (FTC). Methods: This multicenter retrospective cohort study included 318 patients with FTC from five tertiary centers who underwent thyroid surgery between 1996 and 2009. We evaluated the prognosis of patients with minimally invasive (MI), encapsulated angioinvasive (EA), and widely invasive (WI) FTC according to WHO-2017. Further, we evaluated the proportion of variation explained (PVE) and Harrell's C-index to compare the predictability of disease-free survival (DFS) and disease-specific survival (DSS). Results: In total, 227, 58, and 33 patients had MI-, EA-, and WI-FTC, respectively. During a median follow-up of 10.6 years, 46 (14.5%) patients had disease recurrence and 20 (6.3%) patients died from FTC. The 10-year DFS rates of patients with MI-, EA-, and WI-FTC were 91.1%, 78.2%, and 54.9%, respectively (P<0.001, PVE=7.1%, C-index=0.649). The corresponding 10-year DSS rates were 95.9%, 93.5%, and 73.5%, respectively (P<0.001, PVE=2.6%, C-index=0.624). The PVE and C-index values were higher using WHO-2017 than using WHO-2004 for the prediction of DFS, but not for DSS. In multivariate analysis, older age (P=0.02), gross extrathyroidal extension (ETE) (P=0.003), and distant metastasis (P<0.001) were independent risk factors for DSS. Conclusion: WHO-2017 improves the predictability of DFS, but not DSS, in patients with FTC. Distant metastasis, gross ETE and older age (≥55 years) were independent risk factors for DSS. [ABSTRACT FROM AUTHOR]

Background: Concerns have arisen about the classification of extra-thyroidal extension (ETE) and lateral cervical lymph node metastasis (N1b) in the 8th edition of the tumor-node-metastasis staging system (TNM-8). This study evaluated the prognostic validity of a modified-TNM staging system, focusing on ETE and N1b, in differentiated thyroid carcinoma (DTC) patients. Methods: This multicenter retrospective cohort study included 4,878 DTC patients from five tertiary hospitals. In the modified- TNM, T3b in TNM-8 was down-staged to T2, and stage II was subdivided into stages IIA and IIB. Older patients with N1b were reclassified as stage IIB. Results: The modified-TNM resulted in staging migration in 540 patients (11%) classified as stage II according to the TNM-8, with 75 (14%), 381 (71%), and 84 patients (16%) classified as stages I, IIA, and IIB, respectively. The 10-year disease-specific survival (DSS) rates in patients classified as stages I, II, III, and IV by TNM-8 were 99.8%, 95.9%, 81.0%, and 41.6%, respectively. The DSS rates of patients classified as stages I, IIA, IIB, III, and IV according to the modified-TNM were 99.8%, 96.4%, 93.3%, 81.0%, and 41.6%, respectively. DSS curves between stages on TNM-8 (P<0.001) and modified-TNM (P<0.001) differed significantly, but the modified-TNM discriminated better than TNM-8. The proportions of variation explained values of TNM-8 and modified-TNM were 6.3% and 6.5%, respectively. Conclusion: Modification of the TNM staging system focusing on ETE and N1b could improve the prediction of DSS in patients with DTC. Further researches are needed to validate the prognostic accuracy of this modified-TNM staging system. [ABSTRACT FROM AUTHOR]

Objective: This study examined the association between baseline BMI, percentage weight change, and the risk of dementia in patients newly diagnosed with type 2 diabetes.Research Design and Methods: Using the South Korean National Health Insurance Service-National Health Screening Cohort database, we identified 167,876 subjects aged ≥40 years diagnosed with new-onset type 2 diabetes between 2007 and 2012. Their weight changes were monitored for ∼2 years after diagnosis, with follow-up assessments occurring for an average of 3.5 years. The hazard ratios (HRs) and Bonferroni-adjusted 95% CIs of all-cause dementia, Alzheimer disease (AD), and vascular dementia were estimated using multivariable Cox proportional hazards regression models.Results: We identified 2,563 incident dementia cases during follow-up. Baseline BMI among patients with new-onset type 2 diabetes was inversely associated with the risk of all-cause dementia and AD, independent of confounding variables (P for trend <0.001). The percentage weight change during the 2 years after a diagnosis of type 2 diabetes showed significant U-shaped associations with the risk of all-cause dementia development (P < 0.001); the HRs of the disease increased significantly when weight loss or gain was >10% (1.34 [95% CI 1.11-1.63] and 1.38 [1.08-1.76], respectively). Additionally, weight loss >10% was associated with an increased risk of AD (HR 1.26 [95% CI 1.01-1.59]).Conclusions: A lower baseline BMI was associated with increased risks of all-cause dementia and AD in patients with new-onset type 2 diabetes. Weight loss or weight gain after the diagnosis of diabetes was associated with an increased risk of all-cause dementia. Weight loss was associated with an increased risk of AD. [ABSTRACT FROM AUTHOR]

In multilevel multiple-indicator multiple-cause (MIMIC) models, covariates can interact at the within level, at the between level, or across levels. This study examines the performance of multilevel MIMIC models in estimating and detecting the interaction effect of two covariates through a simulation and provides an empirical demonstration of modeling the interaction in multilevel MIMIC models. The design factors include the location of the interaction effect (i.e., between, within, or across levels), cluster number, cluster size, intraclass correlation (ICC) level, magnitude of the interaction effect, and cross-level measurement invariance status. Type I error, power, relative bias, and root mean square of error of the interaction effects are examined. The results showed that multilevel MIMIC models performed well in detecting the interaction effect at the within or across levels. However, when the interaction effect was at the between level, the performance of multilevel MIMIC models depended on the magnitude of the interaction effect, ICC, and sample size, especially cluster number. Overall, cross-level measurement noninvariance did not make a notable impact on the estimation of interaction in the structural part of multilevel MIMIC models when factor loadings were allowed to be different across levels. [ABSTRACT FROM AUTHOR]

Background: We previously reported a patient with congenital adrenal hyperplasia (CAH) with compound heterozygous mutations in the cytochrome P450 17A1 (CYP17A1) gene. One allele had a p.His373Leu and the other a new p.Glu383fsX36 mutation. The aim of this study was to investigate the functional properties of a new allele present in a compound heterozygote of CYP17A1. Methods: To understand how p.His373Leu and p.Glu383fsX36 affect P450c17 enzymatic activity, wild type and mutant CYP17A1 cDNAs were cloned into flag-tagged pcDNA3 vector and introduced into human embryonic kidney cells 293T (HEK293T) cells. Protein expression levels of CYP17A1 were then analyzed. And the activities of 17α-hydroxylase and 17,20-lyase of CYP17A1 were evaluated by measuring the conversion of progesterone to 17α-hydroxyprogesterone and of 17α-hydroxypregnenolone to dehydroepiandrosterone, respectively. In addition a computer model was used to create the three-dimensional structure of the mutant CYP17A1 enzymes. Results: Production of the p.His373Leu mutant protein was significantly lower than that of the wild type protein, and the p.Glu383fsX36 protein was hardly produced. Similarly the enzymatic activity derived from the p.His373Leu mutant vector was significantly lower than that obtained from the wild type vector, and little activity was obtained from the p.Glu383fsX36 vector. Three-dimensional modeling of the enzyme showed that p.His373 was located in region important for heme-binding and proper folding. Neither the p.His373Leu nor the p.Glu383fsX36 mutant protein formed a heme-binding structure. Conclusion: Enzyme activity measured in both mutants disappeared completely in both 17α-hydroxylase and 17,20-lyase. This result accounts for the clinical manifestations of the patient with the compound heterozygous CYP17A1 mutations. [ABSTRACT FROM AUTHOR]

Purpose: Urinary incontinence (UI) is associated with nursing home admission, functional decline, and risk of death among community-dwelling older adults. Little information, however, is available on sex differences in lower urinary tract symptoms (LUTS) in older Korean adults exclusively living in rural areas. This study examined sex-related differences in LUTS, factors associated with UI in older adults living in rural areas, and health-related quality of life (HRQoL) in incontinent older adults. Methods: This was a cross-sectional study in which face-to-face interviews were conducted at 15 rural community-health centres. A total of 323 older adults aged ⩾65 years from rural areas of Korea participated. LUTS prevalence was evaluated and HRQoL was measured using the King's Health Questionnaire. The chi-square test and t -test were used to examine sex differences in characteristics, LUTS, and HRQoL. Multivariable logistic regression was used to identify risk factors associated with UI. Results: Nocturia was the most prevalent symptom, affecting 87% of men and 86% of women. Women (53%) had significantly more UI of any kind than did men (35%) (P=0.007). Urgency UI was the most frequent type of UI in men, whereas stress UI was the most frequent in women. Regarding HRQoL, men had significantly higher scores in the domains of sleep/energy disturbances (P=0.032) than did women, and women reported greater effects from the severity of incontinence (P=0.001) than did men. Arthritis was the only factor associated with UI in men (odds ratio [OR], 6.88; 95% confidence interval [CI], 1.46- 32.36). However, women with diabetes mellitus were less likely to have UI than those without (OR, 0.43; 95% CI, 0.23-0.82). Conclusions: LUTS were found to be highly prevalent in community-dwelling older Korean adults in rural areas. Interventions to improve sleep and to reduce UI severity are needed for incontinent men and women, respectively. [ABSTRACT FROM AUTHOR]

Background: Anaplastic thyroid cancer (ATC) is one of the most lethal human malignancies. Docetaxel, a microtubule stabilizer, is a common chemotherapeutic agent used to treat various metastatic cancers. However, prolonged use results in various side effects and drug resistance. Flavonoids, such as baicalein, are accepted chemotherapeutic and dietary chemopreventive agents with many advantages, such as greater accessibility, affordability, and lower toxicity, compared with traditional chemotherapy agents. In this study, we evaluated whether baicalein enhances the effects of docetaxel on apoptosis and metastasis in 8505c ATC cells. Methods: The 8505c cells were treated with baicalein or docetaxel individually and in combination. Cell viability was measured by MTT (thiazolyl blue tetrazolium bromide) assay, and apoptosis was detected by fluorescence microscopy of Hoechst-stained cells. The expression of apoptotic (Bax and caspase-3), anti-apoptotic (Bcl-2), angiogenic (vascular endothelial growth factor [VEGF], transforming growth factor ß [TGF-ß], E-cadherin, and N-cadherin), and signaling (extracellular signal-regulated kinase [ERK] mitogen activated protein kinase [MAPK], Akt, and mammalian target of rapamycin [mTOR]) proteins was determined by Western blot analysis. Results: The combination of baicalein (50 or 100 µM) and docetaxel (10 nM) significantly inhibited proliferation and induced apoptosis compared with monotherapies. The combination treatment significantly inhibited the expression of Bax, caspase-3, VEGF, TGF-ß1, E-cadherin, N-cadherin, and mTOR, but decreased the expression of Bcl-2 and significantly decreased the phosphorylation of ERK and Akt. Conclusion: The combination of baicalein and docetaxel effectively induced apoptosis and inhibited metastasis in 8505c cells through downregulation of apoptotic and angiogenic protein expression and blocking of the ERK and Akt/mTOR pathways in 8505c cells. These results suggest that baicalein enhances the anticancer effects of docetaxel in ATC. [ABSTRACT FROM AUTHOR]

Background: Little is known regarding disease-specific mortality of differentiated thyroid cancer (DTC) patients and its risk factors in Korea. Methods: We retrospectively reviewed a large multi-center cohort of thyroid cancer from six Korean hospitals and included 8,058 DTC patients who underwent initial surgery between 1996 and 2005. Results: Mean age of patients at diagnosis was 46.2±12.3 years; 87% were females. Most patients had papillary thyroid cancer (PTC; 97%) and underwent total thyroidectomy (85%). Mean size of the primary tumor was 1.6±1.0 cm. Approximately 40% of patients had cervical lymph node (LN) metastases and 1.3% had synchronous distant metastases. During 11.3 years of follow-up, 150 disease-specific mortalities (1.9%) occurred; the 10-year disease-specific survival (DSS) rate was 98%. According to the year of diagnosis, the number of disease-specific mortality was not different. However, the rate of disease-specific mortality decreased during the study period (from 7.7% to 0.7%). Older age (≥45 years) at diagnosis, male, follicular thyroid cancer (FTC) versus PTC, larger tumor size (>2 cm), presence of extrathyroidal extension (ETE), lateral cervical LN metastasis, distant metastasis and tumor node metastasis (TNM) stage were independent risk factors of disease-specific mortality of DTC patients. Conclusion: The rate of disease-specific mortality of Korean DTC patients was 1.9%; the 10-year DSS rate was 98% during 1996 to 2005. Older age at diagnosis, male, FTC, larger tumor size, presence of ETE, lateral cervical LN metastasis, distant metastasis, and TNM stages were significant risk factors of disease-specific mortality of Korean DTC patients. [ABSTRACT FROM AUTHOR]

Appropriate model specification is fundamental to unbiased parameter estimates and accurate model interpretations in structural equation modeling. Thus detecting potential model misspecification has drawn the attention of many researchers. This simulation study evaluates the efficacy of the Bayesian approach (the posterior predictive checking, or PPC procedure) under multilevel bifactor model misspecification (i.e., ignoring a specific factor at the within level). The impact of model misspecification on structural coefficients was also examined in terms of bias and power. Results showed that the PPC procedure performed better in detecting multilevel bifactor model misspecification, when the misspecification became more severe and sample size was larger. Structural coefficients were increasingly negatively biased at the within level, as model misspecification became more severe. Model misspecification at the within level affected the between-level structural coefficient estimates more when data dependency was lower and the number of clusters was smaller. Implications for researchers are discussed. [ABSTRACT FROM AUTHOR]

This study reports a case of nodular fasciitis incidentally detected in a patient with papillary thyroid cancer. A 47-year-old woman underwent a total thyroidectomy and radioactive iodine therapy for papillary thyroid cancer. On a follow‑up fluorodeoxyglucose (18F‑FDG) PET/computed tomography (CT) scan after 12 months, a focal 18F‑FDG‑avid lesion was incidentally detected in the paraspinal muscle. It was well‑enhanced on CT and magnetic resonance imaging, indicating metastasis. However, the lesion was not iodine avid on the 123I whole body scan, which favored benign etiology over metastasis from thyroid cancer. For pathological confirmation, surgical excision was performed and the paraspinal lesion was finally confirmed as nodular fasciitis. Therefore, it was suggested that nodular fasciitis may be included in the differential diagnosis of a 18F‑FDG avid/iodine non‑avid soft tissue lesion in patients with thyroid cancer. In such circumstances, 123I whole body scans may serve a role in non‑invasive work‑up, and prevent unnecessary surgical procedures. [ABSTRACT FROM AUTHOR]

Purpose: This study was intended to standardize the Kangaroo care protocol for fathers, and to determine the effect of fathers' Kangaroo care experience on paternal attachment. Methods: The data was collected from February to April, 2013. The study subjects were 34 fathers (17 experimental group subjects, 17 control group subjects) of premature babies, bornatatertiaryhospitalinSeoul, who agreed to participate . The standardized Kangaroo care protocol, which consisted of at least three 60-minutes sessions during the hospitalization period in a neonatal intensive care unit, was carried out with the experimental group. The data was analyzed by a X2-test and Mann-Whitney U test. Results: The results were as follows: 1) There were no between-group differences in the general characteristics of babies and their fathers. 2) The Kangaroo care fathers showed higher scores of paternal attachment than the control group (Z=-3.657, p=0.008). Conclusion: Fathers who attended the Kangaroo care sessions showed stronger paternal attachment than those who did not. Therefore, use of a Kangaroo care program for fathers of premature babies at neonatal intensive care units is recommended. [ABSTRACT FROM AUTHOR]

Background: Hyperthyroidism is associated with increased thrombotic risk. As contact system activation through formation of neutrophil extracellular traps (NET) has emerged as an important trigger of thrombosis, we hypothesized that the contact system is activated along with active NET formation in hyperthyroidism and that their markers correlate with disease severity. Subjects and methods: In 61 patients with hyperthyroidism and 40 normal controls, the levels of coagulation factors (fibrinogen, and factor VII, VIII, IX, XI and XII), D-dimer, thrombin generation assay (TGA) markers, NET formation markers (histone–DNA complex, double-stranded DNA and neutrophil elastase) and contact system markers (activated factor XII (XIIa), high-molecular-weight kininogen (HMWK), prekallikrein and bradykinin) were measured. Results: Patients with hyperthyroidism showed higher levels of fibrinogen (median (interquartile range), 315 (280–344) vs 262 (223–300), P = 0.001), D-dimer (103.8 (64.8–151.5) vs 50.7 (37.4–76.0), P < 0.001), peak thrombin (131.9 (102.2– 159.4) vs 31.6 (14.8–83.7), P < 0.001) and endogenous thrombin potential (649 (538–736) vs 367 (197–1147), P = 0.021) in TGA with 1 pM tissue factor, neutrophil elastase (1.10 (0.39–2.18) vs 0.23 (0.20–0.35), P < 0.001), factor XIIa (66.9 (52.8–87.0) vs 73.0 (57.1–86.6), P < 0.001), HMWK (6.11 (4.95–7.98) vs 3.83 (2.60–5.68), P < 0.001), prekallikrein (2.15 (1.00–6.36) vs 1.41 (0.63–2.22), P = 0.026) and bradykinin (152.4 (137.6–180.4) vs 118.3 (97.1–137.9), P < 0.001) than did normal controls. In age- and sex-adjusted logistic regression analysis, fibrinogen, factor VIII, IX and XIIa, D-dimer, peak thrombin, neutrophil elastase, HMWK and bradykinin showed significant odds ratios representing hyperthyroidism’s contribution to coagulation and contact system activation. Free T4 was significantly correlated with factors VIII and IX, D-dimer, double-stranded DNA and bradykinin. Conclusion: This study demonstrated that contact system activation and abundant NET formation occurred in the high thrombin generation state in hyperthyroidism and were correlated with free T4 level. [ABSTRACT FROM AUTHOR]

Background: This study investigated the association between serum gamma-glutamyltransferase (GGT) level and subclinical atherosclerosis in patients with type 2 diabetes. Methods: This cross-sectional study involved 1024 patients with type 2 diabetes mellitus. Measurement of brachialankle pulse wave velocity (baPWV; as a marker of arterial stiffness) and an ultrasound assessment of carotid atherosclerosis were performed. Subclinical atherosclerosis was defined by the presence of a high baPWV (≥1720 cm/s), carotid atherosclerosis (intima-media thickness >0.8 mm or the presence of plaques), and carotid stenosis (≥50 % of luminal narrowing). The subjects were stratified into quartiles according to GGT level, and the relationship between GGT level and subclinical atherosclerosis was analysed. Results: Serum GGT levels were closely associated with obesity, atherogenic dyslipidemia, and metabolic syndrome. However, serum GGT levels did not show a linear association with baPWV, carotid intima-media thickness, or plaque grade. The prevalence of high baPWV, carotid atherosclerosis, and carotid stenosis did not differ between the quartiles in men and women. Multivariate logistic regression analyses revealed no association between GGT level and high baPWV, carotid atherosclerosis, and carotid stenosis, either as continuous variables or quartiles. Conclusions: Serum GGT levels were significantly associated with obesity, atherogenic dyslipidaemia, and metabolic syndrome, but not with the early and late stages of atherosclerotic vascular changes, in patients with type 2 diabetes. Serum GGT level may not be a reliable marker of subclinical atherosclerosis in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Rising concern about America's ability to maintain its competitive position in the global economy has renewed interest in STEM education. The power and the promise of STEM education is based on the need for technological literacy. Technology education is a discipline devoted to the delivery of technological literacy for all. Nevertheless, a decision to pursue a STEM major is a longitudinal process that builds during secondary education and carries into postsecondary studies. When analyzed appropriately, course-taking patterns may offer valuable insight into a student's academic history and momentum through college as well as illuminate patterns that effectively and wisely engage academic resources that may shape students' entrance in STEM related careers. This study utilized High School Transcipt Study data to examine and compare the patterns of STEM courses taken by technology students and those of high school students as a whole, the patterns of courses taken by technology students and those of high school students as a whole, and the GPAs of technology students with the GPAs of other high school student GPAs. Findings revealed that there was a significant difference in overall GPA between technology students, as defined in this study, and the general student population of the data set. There was also a significant difference in GPAs between technology students and the general student population in STEM courses. [ABSTRACT FROM AUTHOR]

Metastasis is a major cause of cancer-related mortality in patients with gastric cancer. Ursolic acid, a pentacyclic triterpenoid compound derived from medicinal herbs, has been demonstrated to exert anticancer effects in various cancer cell systems. However, to the best of our knowledge, the inhibitory effect of ursolic acid on the invasive phenotype of gastric cancer cells has yet to be reported. Therefore, the aim of the present study was to investigate the effect of ursolic acid on the invasiveness of SNU-484 human gastric cancer cells. Ursolic acid efficiently induced apoptosis, possibly via the downregulation of B-cell lymphoma 2 (Bcl-2), the upregulation of Bcl-2-associated X protein and the proteolytic activation of caspase-3. Furthermore, the activation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase was increased by the administration of ursolic acid. In addition, ursolic acid significantly suppressed the invasive phenotype of the SNU-484 cells and significantly decreased the expression of matrix metalloproteinase (MMP)-2, indicating that MMP-2 may be responsible for the anti-invasive activity of ursolic acid. Taken together, the results of the present study demonstrate that ursolic acid induces apoptosis and inhibits the invasive phenotype of gastric cancer cells; therefore, ursolic acid may have a potential application as a chemopreventive agent to prevent the metastasis of gastric cancer or to alleviate the process of metastasis. [ABSTRACT FROM AUTHOR]

Loss of ovarian function causes oxidative stress as well as bone loss. We hypothesized that reactive oxygen species (ROS) induced by the failure of ovarian function are responsible for the bone loss by increasing the number of osteoclasts (OC). We found that ROS enhanced OC survival via Src homology 2 domain-containing phosphatase-1 (SHP-1), c-Src, Akt, and ERK. ROS induced the association of SHP-1 with c-Src as well as the oxidation of c-Src and SHP-1. This resulted in inactivation of SHP-1 and activation of c-Src via phosphorylation of Tyr416. Knockdown of c-Src or SHP-1 abolished the effect of ROS on OC survival. Moreover, downregulation of SHP-1 upregulated activation of c-Src, Akt, and ERK in the absence of any stimulus, suggesting that inactivation of SHP-1 is required for OC survival. We demonstrated that the association and oxidation of c-Src and SHP-1 by ROS are key steps in enhancing OC survival, which are responsible for increased bone loss when ovarian function ceases. [ABSTRACT FROM AUTHOR]

Background: Anaplastic thyroid cancer (ATC) is one of the most aggressive malignancies in humans, and its progression is poorly controlled by existing therapeutic methods. Curcumin has been shown to suppress inflammation and angiogenesis. In this study, we evaluated whether curcumin could augment docetaxel-induced apoptosis of ATC cells. We also analyzed changes in nuclear factor κB (NF-κB) and cyclooxygenase-2 (COX-2) expression levels to delineate possible mechanisms of their combined action. Methods: ATC cells were cultured and treated with curcumin and docetaxel alone or in combination. The effects on cell viability were determined by MTS assay. Apoptosis was assessed by annexin V staining and confirmed by flow cytometric analysis. Caspase, COX-2, NF-κB levels were assayed by Western blotting. Results: Curcumin combined with docetaxel led to lower cell viability than treatment with docetaxel or curcumin alone. Annexin V staining followed by flow cytometric analysis demonstrated that curcumin treatment enhanced the docetaxel-induced apoptosis of ATC cells. Additionally, curcumin inhibited docetaxel-induced p65 activation and COX-2 expression. Conclusion: We conclude that curcumin may enhance docetaxel's antitumor activity in ATC cells by interfering with NF-κB and COX-2. Our results suggest that curcumin may emerge as an attractive therapeutic candidate to enhance the antitumor activity of taxanes in ATC treatment. [ABSTRACT FROM AUTHOR]

We investigated whether thyroid function could identify obesity phenotype in euthyroid subjects. A cross-sectional analysis was performed among nondiabetic, euthyroid subjects. We stratified subjects into four groups by BMI and insulin resistance (IR). Of 6241 subjects, 33.8% were overweight or obese (OW/OB) and 66.2% were normal weight (NW). Free thyroxine (FT4) levels were negatively associated with bodymass index, waist circumference, triglyceride, c-reactive protein, and HOMA-IR and positivelywith high-density lipoprotein cholesterol in both genders. Inmultivariate regression analysis, FT4 level, a continuous measurement, was negatively correlated with HOMA-IR (β = -0.155, P < 0.001 in men; β = -0.175, P < 0.001 in women). After adjustment for age, sex, metabolic, and life style factors, subjects in the lowest FT4 quartile had an odds ratio (OR) for IR of 1.99 (95% confidence interval 1.61-2.46), as compared to those in the highest quartile. The association between low FT4 and IR remained significant in both NW and OW/OB subgroups. In conclusion, low normal FT4 levels were independently related to IR in NW and OW/OB euthyroid subjects. Further studies are needed to investigate the mechanisms by which low FT4 levels are linked to high IR in euthyroid ranges. [ABSTRACT FROM AUTHOR]

To elucidate the role of tumor necrosis factor receptor superfamily member 14 (TNFRSF14) in metabolic disturbance due to loss of ovarian function, ovariectomy (OVX) was performed in TNFRSF 14-knockout mice. OVX increased fat mass and infiltration of highly inflammatory CD11c cells in the adipose tissue (AT), which was analyzed by flow cytometry, and resulted in disturbance of glucose metabolism, whereas TNFRSF14 deficiency attenuated these effects. TNFRSF14 deficiency decreased recruitment of CD11c-expressing cells in AT and reduced the polarization of bone marrow-derived macrophages to M1. Upon engagement of LIGHT, a TNFRSF14 ligand, TNFRSF14 enhanced the expression of CD11c via generation of reactive oxygen species, suggesting a role of TNFRSF14 as a redox modulator. TNFRSF14 participated in OVX-induced AT inflammation via upregulation of CD11c, resulting in metabolic perturbation. TNFRSF14 could be used as a therapeutic target for the treatment of postmenopausal syndrome by reducing AT inflammation. [ABSTRACT FROM AUTHOR]

This study investigated two major approaches in testing measurement invariance for ordinal measures: multiple-group categorical confirmatory factor analysis (MCCFA) and item response theory (IRT). Unlike the ordinary linear factor analysis, MCCFA can appropriately model the ordered-categorical measures with a threshold structure. A simulation study under various conditions was conducted for the comparison of MCCFA and IRT with respect to the power to detect the lack of invariance across groups. Both MCCFA and IRT showed reasonable power to identify the noninvariant item when differential item functioning (DIF) was large. The false positive rates were relatively high in both methods, however. The adjustment of critical values improved the performance of MCCFA by reducing false positive rates substantially and yet yielding adequate power. Alternative model fit indexes of MCCFA were also examined and they were found to be reliable to detect DIF, in general. [ABSTRACT FROM AUTHOR]

OBJECTIVE--α-Melanocyte-stimulating hormone (α-MSH) and agouti-related peptide (AgRP) control energy homeostasis by their opposing actions on melanocortin receptors (MC3/4R) in the hypothalamus. We previously reported that thyroid transcription factor-1 (TTF-1) controls feeding behavior in the hypothalamus. This study aims to identify the function of TTF-1 in the transcriptional regulation of AgRP and α-MSH synthesis for the control of feeding behavior. RESEARCH DESIGN AND METHODS--TTF-1 activity in AgRP and pro-opiomelanocortin (POMC) transcription was examined using gel-shift and promoter assays and an in vivo model of TTF-1 synthesis inhibition by intracerebroventricular injection of an antisense (AS) oligodeoxynucleotide (ODN). Double immunohistochemistry was performed to colocalize TTF-1 and AgRP or α-MSH in the hypothalamic arcuate nucleus (ARC). To determine whether TTF-1 action on food intake is mediated through MC3/4R, we measured changes in food intake upon intracerebroventricular injection of MC3/4R antagonists (SHU9119 and AgRP) into rat brain preinjected with the AS ODN. RESULTS--TTF-1 stimulated AgRP but inhibited POMC transcription by binding to the promoters of these genes. TTF-1 was widely distributed in the hypothalamus, but we identified some cells coexpressing TTF-1 and AgRP or α-MSH in the ARC. In addition, intracerebroventricular administration of leptin decreased TTF-1 expression in the hypothalamus, and AS ODN-induced inhibition of TTF-1 expression decreased food intake and AgRP expression but increased (α-MSH expression. Anorexia induced by the AS ODN was attenuated by the administration of MC3/4R antagonists. CONCLUSIONS--TTF-1 transcriptionally regulates synthesis of AgRP and α-MSH in the ARC and affects feeding behavior via the melanocortin pathway. [ABSTRACT FROM AUTHOR]

Although a common reaction in anaerobic environments, the conversion of formate and water to bicarbonate and H2 (with a change in Gibbs free energy of ΔG° = +1.3 kJ mol−1) has not been considered energetic enough to support growth of microorganisms. Recently, experimental evidence for growth on formate was reported for syntrophic communities of Moorella sp. strain AMP and a hydrogen-consuming Methanothermobacter species and of Desulfovibrio sp. strain G11 and Methanobrevibacter arboriphilus strain AZ. The basis of the sustainable growth of the formate-users is explained by H2 consumption by the methanogens, which lowers the H2 partial pressure, thus making the pathway exergonic. However, it has not been shown that a single strain can grow on formate by catalysing its conversion to bicarbonate and H2. Here we report that several hyperthermophilic archaea belonging to the Thermococcus genus are capable of formate-oxidizing, H2-producing growth. The actual ΔG values for the formate metabolism are calculated to range between −8 and −20 kJ mol−1 under the physiological conditions where Thermococcus onnurineus strain NA1 are grown. Furthermore, we detected ATP synthesis in the presence of formate as a sole energy source. Gene expression profiling and disruption identified the gene cluster encoding formate hydrogen lyase, cation/proton antiporter and formate transporter, which were responsible for the growth of T. onnurineus NA1 on formate. This work shows formate-driven growth by a single microorganism with protons as the electron acceptor, and reports the biochemical basis of this ability. [ABSTRACT FROM AUTHOR]

Background:The association between autoimmune thyroiditis (AIT) and thyroid cancer is still not clear despite many previous reports. This study investigated whether serologic thyroid antibodies are predictive of thyroid cancer in patients with thyroid nodules.Method:We retrospectively reviewed records of patients with thyroid nodules evaluated by ultrasonography-guided fine-needle aspiration cytology at our institution between January 2006 and December 2008. Thyroid autoimmunity was assessed by measuring thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb). The final outcome deciding a benign or malignant status involved a combination of cytology and histology.Results:Of the 1638 patients, malignant nodules had a higher rate of positive TgAb (30.8% vs. 19.6%; p< 0.001) and elevated thyrotropin (TSH) levels (2.5 ± 2.8 mIU/L vs. 2.1 ± 2.0 mIU/L; p= 0.021) than benign nodules. The rate of positive TPOAb was not higher in malignant nodules, although both TPOAb and TgAb were well correlated with TSH levels and histological AIT. In the multivariate analysis, a positive TgAb was significantly associated with thyroid cancer (odds ratio [OR] = 1.61, 95% confidence interval [CI] 1.12–2.33) with upper tertile of normal range of TSH levels (OR = 1.72, 95% CI 1.12–2.63) and above normal range of TSH levels (OR = 1.98, 95% CI 1.06–3.70).Conclusion:We report for the first time that a positive serum TgAb test was an independent predictor for thyroid malignancy in thyroid nodules along with serum TSH levels regardless of the presence of AIT. Our results suggest that TgAb measurement could give additional information for predicting malignancy in cytologically indeterminate thyroid nodules in conjunction with clinical risk factors and TSH levels. [ABSTRACT FROM AUTHOR]

This article examines glottalization and lenition in Nuu-chah-nulth. These processes involve features introduced via affixation, features that are sometimes compatible with the final segment of the stem and sometimes incompatible. An understanding of the intricacies of these patterns requires a focus on featural representations, with lexical representations involving floating features and variable specifications for features. Both of these properties follow from the postulation of a rich base, with features freely combining in inputs. The analysis argues for covert features, for constraints holding more strongly in small domains than large domains, and for the importance of a markedness scale on glottalizability. [ABSTRACT FROM AUTHOR]

Condensation of 2-pyridinecarboxaldehyde with a stoichiometric amount of triethylenetetramine in isopropyl alcohol yields a mixture of at least two products, a Schiff dibase L1and a cyclization product with two imidazolidine rings L2, and possibly a Schiff monobase with one imidazolidine ring L3. The 3d metal(ii) salts, Mn(SCN)2, MnCl2, CuBr2, MnI2and ZnBr2, react selectively with L1or L2in this mixture solution to produce Mn(L2)(NCS)21, Mn(L2)Cl22, [Cu(L2)Br]Br·H2O 3, [Mn(L1)]I24, and [Zn(L1)][ZnBr4] 5, respectively. The presence of the two imidazolidine rings in the coordinated ligand L2of 1–3generates two chiral carbon centers. The Mn(ii) ion coordinates stereo-selectively to the [R,R] or [S,S] form of the L2in hexa-coordinate Mn(ii) compounds 1and 2, whereas the Cu(ii) ion coordinates with the meso[R,S] form of L2in 3. [ABSTRACT FROM AUTHOR]

Phosphatidylinositol 3-kinase has been reported to be important for normal plant growth. To characterize the role of the enzyme further, we attempted to isolate Arabidopsis (Arabidopsis thaliana) plants that do not express the gene, but we could not recover homozygous mutant plants. The progeny of VPS34/vps34 heterozygous plants, harboring a T-DNA insertion, showed a segregation ratio of 1:1:0 for wild-type, heterozygous, and homozygous mutant plants, indicating a gametophytic defect. Genetic transmission analysis showed that the abnormal segregation ratio was due to failure to transmit the mutant allele through the male gametophyte. Microscopic observation revealed that 2-fold higher proportions of pollen grains in heterozygous plants than wild-type plants were dead or showed reduced numbers of nuclei. Many mature pollen grains from the heterozygous plants contained large vacuoles even until the mature pollen stage, whereas pollen from wild-type plants contained many small vacuoles beginning from the vacuolated pollen stage, which indicated that vacuoles in many of the heterozygous mutant pollen did not undergo normal fission after the first mitotic division. Taken together, our results suggest that phosphatidylinositol 3-kinase is essential for vacuole reorganization and nuclear division during pollen development. [ABSTRACT FROM AUTHOR]

In this article we examine the phonetic properties of labialization in Nuuchahnulth, a Southern Wakashan language spoken on Vancouver Island. Given the moribund status of this language, we make use of available archival materials from the early twentieth century along with more recent recordings in order to ascertain the exact nature of the process. Early work on this language was conducted by Edward Sapir, who transcribed data in a more or less phonetic form. A second goal of our paper is to test the accuracy of Sapir's transcriptions. Finally, we examine the characteristics of Nuuchahnulth labialization which mark it as an important typological phenomenon. [ABSTRACT FROM AUTHOR]

Xyloglucan endotransglucosylase/hydrolases (XTHs) are a group of the enzymes that are responsible for reorganization of the cellulose–xyloglucan framework by catalyzing cleavage and religation of the xyloglucan chains in the plant cell wall. In this study, we report the isolation and characterization of a XTH gene from a pistil cDNA library of Brassica campestris. Sequence analysis of the gene, designated BcXTH1, revealed that it is homologous to the XTH9 gene of Arabidopsis. The highly conserved domain (DEIDFEFLG) found among all XTHs was also present in BcXTH1 but with the two amino acid substitutions ( NE FDFEFLG) also found in Arabidopsis XTH9. These results suggest that BcXTH1 is the B. campestris homologue of XTH9. Expression analysis of BcXTH1 revealed that it was expressed in most of the plant organs. In situ hybridization showed that the gene is highly expressed in the floral primodia, especially in the epidermal cell layer. Southern blot analysis indicated that the BcXTH1 gene exists as a multi-copy gene in the B. campestris genome. The function of the BcXTH1 gene was deduced from using an overexpression strategy in Arabidopsis. Interestingly, the transgenic plants showed a pronounced cell expansion phenotype. Immunoelectron microscopy shows that BcXTH1 is localized almost exclusively to the cell wall, supporting our conclusion that it participates in the regulation of cell expansion in B. campestris. [ABSTRACT FROM AUTHOR]

Abstract In this paper, we report a novel pentatricopeptide repeat (PPR) protein gene in rice. PPR, a characteristic repeat motif consisted of tandem 35 amino acids, has been found in various biological systems including plant. Sequence analysis revealed that the gene designated OsPPR1 consisted of an open reading frame of 2433 nucleotides encoding 810 amino acids that include 11 PPR motifs. Blast search result indicated that the gene did not align with any of the characterized PPR genes in plant. The OsPPR1 gene was found to contain a putative chloroplast transit peptide in the N-terminal region, suggesting that the gene product targets to the chloroplast. Southern blot hybridization indicated that the OsPPR1 is the member of a gene family within the rice genome. Expression analysis and immunoblot analysis suggested that the OsPPR1 was accumulated mainly in rice leaf. Antisense transgenic strategy was used to suppress the expression of OsPPR1 and the resulted transgenic rice showed the typical phenotypes of chlorophyll-deficient mutants; albinism and lethality. Cytological observation using microscopy revealed that the antisense transgenic plant contained a significant defect in the chloroplast development. Taken together, the results suggest that the OsPPR1 is a nuclear gene of rice, encoding the PPR protein that might play a role in the chloroplast biogenesis. This is the first report on the PPR protein required for the chloroplast biogenesis in rice. [ABSTRACT FROM AUTHOR]

In some instances, thyroid cancer may be diagnosed with histological examination after resection of putative or suspected benign nodule. In these cases, completion thyroidectomy followed by radioiodine ablation is usually recommended to prevent recurrence. If small intrathyroidal cancer is found, completion thyroidectomy may not be performed. Many patients have separate cancers in the contralateral lobe and in these cases completion thyroidectomy is essential even though primary tumour is small and limited within thyroid. We analysed the frequency of malignant lesions in the contralateral lobe after completion thyroidectomy and assessed the predictive factors that may anticipate the presence of malignant lesion that may necessitate completion thyroidectomy. Between 1995 and 2001, 243 patients were operated under the cytological diagnosis of follicular neoplasm. A total of 214 of them underwent lobectomy and isthmectomy and 81 turned out to have malignant disease in the resected lobe and they underwent completion thyroidectomy within a week to 6 months after the permanent section diagnosis of cancer. Their mean age was 40·7 ± 12·1 years (range 14–71 years). After initial surgery, 53 patients had follicular carcinoma, 24 papillary carcinoma, one Hürthle cell carcinoma, one medullary, one insular and one anaplastic carcinoma. Mean tumour size was 4·1 ± 2·6 cm (range 0·9–11 cm). After completion thyroidectomy, factors predicting the presence of cancer in the contralateral lobe were assessed according to clinical parameters and pathologic findings in ipsilateral lobe. First surgery revealed cancer multifocality in 34 cases, perithyroidal tumour extension in six and regional lymph node metastases in three. After completion thyroidectomy, 29 of the 81 patients revealed additional cancer in the contralateral lobe. Age, sex, size or pathologic type of the primary tumour was not associated with the presence of additional tumour in the contralateral lobe. Cancer multifocality in the ipsilateral lobe was the only significant variable to predict the presence of additional cancer in the contralateral lobe (relative risk = 6·03, confidence interval 2·23–16·35). Coexistence of benign nodule in ipsilateral lobe was not associated with increased cancer risk in the contralateral lobe. When diagnosed as thyroid cancer after unilateral surgery, the only predictive factor for the presence of additional contralateral cancer was multifocality of cancer in the ipsilateral lobe. We suggest that completion thyroidectomy is mandatory if multifocal cancers are found in the resected lobe, even though the cancers are very small and limited within the thyroid. [ABSTRACT FROM AUTHOR]

OBJECTIVE--This study was conducted to investigate the association of diabetic peripheral neuropathy (DPN) with both arterial stiffness and intima-media thickness (IMT). RESEARCH DESIGN AND METHODS--We conducted a cross-sectional analysis of 731 subjects with type 2 diabetes. DPN was diagnosed on the basis of neuropathic symptoms, insensitivity to a 10-g monofilament, abnormal pin-prick sensation, and abnormal current perception threshold. Arterial stiffness was assessed by cardio-ankle vascular index (CAVI), and IMT was assessed by B-mode ultrasonography. RESULTS--Patients with DPN had higher CAVI than those without DPN in multivariateadjusted models, whereas no differences in IMT were observed between patients with and without DPN after adjustment for age and sex. In the multivariate analysis, CAVI was a significant determinant of DPN (odds ratio 1.36 [95% CI 1.13-1.65], P = 0.001). CONCLUSIONS--DPN is significantly associated with arterial stiffness without carotid intimal changes in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background/Aims The Aim of this study is to evaluate the predictive factors prior to the initiation of biofeedback therapy in patients with dyssynergic defecation or fecal incontinence. Methods We retrospectively reviewed patients who underwent biofeedback therapy at tertiary referral hospital between October 2004 and April 2015 for symptoms of defecatory dysfunction and fecal incontinence. Clinical response was recorded after a course of biofeedback therapy and response rates based on patient opinion (3 points or more satisfaction and two or more times a week increased the number of defecation). Results A total of 238 patients who underwent biofeedback therapy. One hundred sixty- nine (71%) were responder and 69 (29%) were not. Of those who underwent at least four biofeedback sessions, subjective short-term response rates were 113 of 167 (67%) in the constipation group and 27 of 39 (69%) in the FI group, 26 of 29 (89%) in the combination group and 3 of 3 (100%) in the anal pain group. Multivariate analysis was performed for those variables significant in the univariate analysis. The global bowel satisfaction score before biofeedback therapy (odds ratio [OR], 0.718; 95% confidence interval [CI], 0.583 to 0.886; p=0.002), the bowel movement frequency before biofeedback therapy (OR, 0.860; 95% CI, 0.764 to 0.968; p=0.012), rectal volume for constant sensation (OR, 0.989; 95% CI, 0.979 to 1.000; p=0.047), and pelvic floor descent (OR, 0.655; 95% CI, 0.456 to 0.942; p=0.022) were found to be the factors independently associated with good respond to biofeedback therapy. Conclusions Our data show that the higher global bowel satisfaction score, higher bowel movement frequency before biofeedback therapy, higher rectal volume for constant sensation, and higher pelvic floor descent are associated with poor response to biofeedback therapy for patients with dyssynergic defecation or fecal incontinence. [ABSTRACT FROM AUTHOR]