Form follows function: the importance of endoplasmic reticulum shape.

The endoplasmic reticulum (ER) has a remarkably complex structure, composed of a single bilayer that forms the nuclear envelope, along with a network of sheets and dynamic tubules. Our understanding of the biological significance of the complex architecture of the ER has improved dramatically in the last few years. The identification of proteins and forces required for maintaining ER shape, as well as more advanced imaging techniques, has allowed the relationship between ER shape and function to come into focus. These studies have also revealed unexpected new functions of the ER and novel ER domains regulating alterations in ER dynamics. The importance of ER structure has become evident as recent research has identified diseases linked to mutations in ER-shaping proteins. In this review, we discuss what is known about the maintenance of ER architecture, the relationship between ER structure and function, and diseases associated with defects in ER structure.

Influence of complications following total mastectomy and immediate reconstruction on breast cancer recurrence.

BACKGROUND: Immediate breast reconstruction is safe from an oncological perspective, but the relatively high rate of postoperative complications raises oncological concerns. The present study aimed to evaluate the potential influence of postoperative complications after immediate breast reconstruction on breast cancer recurrence and survival. METHODS: Patients with breast cancer who had total mastectomy and immediate reconstruction between 2008 and 2013 were followed for at least 5 years. The impact of postoperative complications on oncological outcomes was assessed using multivariable Cox regression analyses. RESULTS: In total, 438 patients with a median follow-up of 82 months were analysed. Five-year local recurrence-free, disease-free and overall survival rates were 95·4, 93·1 and 98·4 per cent respectively. Postoperative complications developed in the operated breast in 120 patients (27·4 per cent) and at other sites (flap donor) in 30 patients (6·8 per cent). Development of breast complications was associated with significantly increased rate of recurrence compared with no complications (16·7 versus 5·9 per cent; P = 0·002). In multivariable analysis, patients with breast complications had significantly worse disease-free survival than those with no complications (hazard ratio (HR) 2·25; P = 0·015). This remained significant in patients who received adjuvant therapy without delay (8 weeks or less after surgery) (HR 2·45; P = 0·034). CONCLUSION: Development of postoperative complications in the breast can have a negative impact on survival and recurrence after immediate reconstruction.

ANTECEDENTES: La reconstrucción mamaria inmediata es una técnica segura desde el punto de vista oncológico, pero con una tasa relativamente alta de complicaciones postoperatorias, lo que preocupa por si puede afectar a los resultados. Este estudio tuvo como objetivo evaluar la influencia potencial de las complicaciones postoperatorias tras la reconstrucción mamaria inmediata en la recidiva y la supervivencia del cáncer de mama. MÉTODOS: Se hizo un seguimiento de al menos 5 años de las pacientes a las que se realizó una mastectomía total por cáncer de mama y una reconstrucción mamaria inmediata entre 2008 y 2013. Se evaluó el impacto de las complicaciones postoperatorias en los resultados oncológicos mediante un análisis multivariables de regresión de Cox. RESULTADOS: Se analizaron 438 pacientes con una mediana de seguimiento de 82 meses. La supervivencia libre de recidiva local a 5 años, la supervivencia libre de enfermedad y la supervivencia global fueron del 95,4%, 93,1% y 98,4%, respectivamente. Hubo complicaciones postoperatorias en la mama en 120 (31,8%) pacientes y en otros lugares (zona donante de colgajo) en 30 (6,8%). La presentación de complicaciones mamarias se asoció con una tasa de recidiva significativamente mayor en comparación con el grupo de pacientes sin complicaciones (16,7% versus 5,9%, P < 0,01). En el análisis multivariable, las pacientes con complicaciones mamarias mostraron una supervivencia libre de enfermedad significativamente menor que aquellas que no padecieron complicaciones (cociente de riesgos instantáneos, hazard ratio, HR 2,25; P = 0,02). También fue significativo el porcentaje de pacientes que recibieron tratamiento adyuvantes sin demora (≤ 8 semanas después de la operación) (HR 2,45; P = 0,03). CONCLUSIÓN: El desarrollo de complicaciones postoperatorias en la mama puede impactar negativamente en la supervivencia y en la recidiva después de la reconstrucción inmediata.

Genetic variants in the folate metabolic pathway genes predict cutaneous melanoma-specific survival.

BACKGROUND: Folate metabolism plays an important role in DNA methylation and nucleic acid synthesis and thus may function as a regulatory factor in cancer development. Genome-wide association studies (GWASs) have identified some single-nucleotide polymorphisms (SNPs) associated with cutaneous melanoma-specific survival (CMSS), but no SNPs were found in genes involved in the folate metabolic pathway. OBJECTIVES: To examine associations between SNPs in folate metabolic pathway genes and CMSS. METHODS: We comprehensively evaluated 2645 (422 genotyped and 2223 imputed) common SNPs in folate metabolic pathway genes from a published GWAS of 858 patients from The University of Texas MD Anderson Cancer Center and performed the validation in another GWAS of 409 patients from the Nurses' Health Study and Health Professionals Follow-up Study, in which 95/858 (11·1%) and 48/409 (11·7%) patients died of cutaneous melanoma, respectively. RESULTS: We identified two independent SNPs (MTHFD1 rs1950902 G>A and ALPL rs10917006 C>T) to be associated with CMSS in both datasets, and their meta-analysis yielded an allelic hazards ratio of 1·75 (95% confidence interval 1·32-2·32, P = 9·96 × 10-5 ) and 2·05 (1·39-3·01, P = 2·84 × 10-4 ), respectively. The genotype-phenotype correlation analyses provided additional support for the biological plausibility of these two variants' roles in tumour progression, suggesting that variation in SNP-related mRNA expression levels is likely to be the mechanism underlying the observed associations with CMSS. CONCLUSIONS: Two possibly functional genetic variants, MTHFD1 rs1950902 and ALPL rs10917006, were likely to be independently or jointly associated with CMSS, which may add to personalized treatment in the future, once further validated. What is already known about this topic? Existing data show that survival rates vary among patients with melanoma with similar clinical characteristics; therefore, it is necessary to identify additional complementary biomarkers for melanoma-specific prognosis. A hypothesis-driven approach, by pooling the effects of single-nucleotide polymorphisms (SNPs) in a specific biological pathway as genetic risk scores, may provide a prognostic utility, and genetic variants of genes in folate metabolism have been reported to be associated with cancer risk. What does this study add? Two genetic variants in the folate metabolic pathway genes, MTHFD1 rs1950902 and ALPL rs10917006, are significantly associated with cutaneous melanoma-specific survival (CMSS). What is the translational message? The identification of genetic variants will make a risk-prediction model possible for CMSS. The SNPs in the folate metabolic pathway genes, once validated in larger studies, may be useful in the personalized management and treatment of patients with cutaneous melanoma.

Depression in North Korean refugees: a mixed methods study.

OBJECTIVE: The objective of this study is to investigate beliefs and experiences about depression in North Korean refugees (NKRs) using both quantitative and qualitative methods. STUDY DESIGN: We used an exploratory sequential mixed methods study design with a quantitative survey followed by an in-depth individual interview. METHODS: We surveyed 329 NKRs who had been in South Korea for at least a year. Eleven participants were selected from the survey sample to complete an additional individual in-depth interview to obtain further understanding about depression among NKRs in their own words and context. RESULTS: About 44% of the sample had mild to severe depression; only 16% indicated that they were being treated for mood disorder. Individual in-depth interviews yielded key themes related to NKRs' depression beliefs and experiences: recognizing depression, factors contributing to depression, overcoming depression, and barriers to seeking help and treatment. Integration of quantitative and qualitative data revealed that although loneliness was one of the prominent subthemes contributing to depression, strong self-determination was noted as being critical to overcoming depression among those who had moderate to moderately severe depression but had no social support. CONCLUSIONS: Future efforts should be directed toward an enhanced support network and targeted education about the South Korean healthcare system, particularly in relation to mental health treatment.

JUNO, the receptor of sperm IZUMO1, is expressed by the human oocyte and is essential for human fertilisation.

STUDY QUESTION: Is JUNO protein present at the surface membrane of human oocytes and involved in the fertilisation process? SUMMARY ANSWER: JUNO protein is expressed on the plasma membrane of human oocytes and its inhibition by a monoclonal antibody completely blocks gamete fusion. WHAT IS KNOWN ALREADY: Fusion of gamete membranes is the culminating event of the fertilisation process, but its molecular mechanisms are poorly understood. Until now, three molecules have been shown to be essential: CD9 tetraspanin in the oocyte, Izumo1 protein on the sperm and Juno, its corresponding receptor on the oocyte. Oocyte CD9 and sperm IZUMO1 have been identified in human gametes and their interaction is also well-conserved among several mammalian species. The presence of JUNO on human oocytes, however, has not yet been reported, nor has its role in fertilisation been investigated. STUDY DESIGN, SIZE, DURATION: We selected an anti-human JUNO antibody in order to investigate the presence of JUNO on the oocyte membrane surface and studied its potential involvement in gamete membrane interaction during fertilisation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Monoclonal antibodies against human JUNO (anti-hJUNO mAb) were produced by immunisation of mice with HEK cells transfected with the putative human JUNO sequence (HEK-hJUNO). These antibodies were used for immunostaining experiments and in vitro fertilisation assays with human gametes (GERMETHEQUE Biobank). MAIN RESULTS AND THE ROLE OF CHANCE: Three hybridoma supernatants, verified by immunostaining, revealed specifically HEK-hJUNO cells. The three purified monoclonal antibodies, FJ2E4 (IgG1), FJ8E8 (IgG1) and FJ4F5 (IgG2a), recognised the soluble recombinant human JUNO protein and, in a western blot of HEK-hJUNO extracts, a protein with an expected MW of 25 kDa. In addition, soluble recombinant human IZUMO protein inhibited the binding of anti-hJUNO mAbs to cells expressing hJUNO. Using these anti-hJUNO mAbs in immunostaining, we identified the presence of JUNO protein at the plasma membrane of human oocytes. Furthermore, we revealed a progressive expression of JUNO according to oocyte maturity. Finally, we showed that human zona-free oocytes, inseminated in the presence of anti-hJUNO mAb, were not fertilised by human sperm. These results suggest that, as seen in the mouse, JUNO is indeed involved in human gamete membrane fusion during fertilisation. LARGE-SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: In accordance with French bioethics laws, functional tests were performed using zona-free oocytes, which of course does not fully encompass all normal in vivo physiological conditions. However, these in vitro tests do provide direct information regarding sperm-oocyte membrane interactions. WIDER IMPLICATIONS OF THE FINDINGS: Mechanisms of gamete fusion appear to be homologous between mice and humans. However, some differences do exist and analysing the human mechanisms is essential. In fact, this is the first report describing the presence of JUNO on human oocytes and its involvement in human fertilisation. This discovery allows further examination of the understanding of molecular mechanisms that drive gamete fusion: a crucial challenge at a time when infertility affects 16% of reproductively active couples. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the Agence Nationale pour la Recherche, Grant no. ANR-13-BVS5-0004, and by Association Institut du Cancer et d'Immunogénétique (ICIG). There are no competing interests.

Magnetic resonance imaging assessment of the substrate for hyposmia in patients with Parkinson's disease.

AIM: To assess whether multimodal magnetic resonance imaging (MRI) could detect neuroanatomical substrates that are distinctive to hyposmic Parkinson's disease (PD). MATERIALS AND METHODS: Among 102 PD patients, 62 were hyposmic and 40 were normosmic. For each patient, a sagittal structural three-dimensional (3D) T1-weighted image was obtained with the magnetisation-prepared rapid acquisition of the gradient-echo sequence to generate subcortical grey matter masking templates and to perform a voxel-based morphometry analysis of the subcortical grey matter volumes. A 3D multi-echo gradient sequence was run to obtain axial magnitude and phase images to produce a quantitative susceptibility map (QSM), and a diffusion-weighted image was acquired to generate an apparent diffusion coefficient (ADC) map. The volumes and average QSM and ADC values of the 15 subcortical grey matter structures were calculated, and the group differences were evaluated using a one-way analysis of covariance with age and gender as covariates. RESULTS: The QSM of the left thalamus significantly increased, while that of the right thalamus significantly decreased in hyposmia. No effects on the cortical volume changes were found other than aging. CONCLUSION: The present results suggest that accumulation of disease-related substances in the left and right thalamus and the increasing asymmetry between the two sides are associated with hyposmia in PD.

Prognostic impact of perihepatic lymph node metastases in patients with resectable colorectal liver metastases.

BACKGROUND: Although perihepatic lymph node metastases (PLNMs) are known to be a poor prognosticator for patients with colorectal liver metastases (CRLMs), optimal management remains unclear. This study aimed to determine the risk factors for PLNMs, and the survival impact of their number and location in patients with resectable CRLMs. METHODS: Data on patients with CRLM who underwent hepatectomy during 2003-2014 were analysed retrospectively. Recurrence-free (RFS) and overall (OS) survival were calculated according to presence, number and location of PLNMs. Risk factors for PLNM were evaluated by logistic regression analysis. RESULTS: Of 1485 patients, 174 underwent lymphadenectomy, and 54 (31·0 per cent) had PLNM. Ten patients (5·7 per cent) who had lymphadenectomy and 176 (13·4 per cent) who did not underwent repeat hepatectomy. Survival of patients with PLNM was significantly poorer than that of patients without (RFS: 5·3 versus 13·8 months, P < 0·001; OS: 20·5 versus 71·3 months; P < 0·001). Median OS was significantly better in patients with para-aortic versus hepatoduodenal ligament PLNMs (58·2 versus 15·5 months; P = 0·011). Patients with three or more PLNMs had significantly worse median OS than those with one or two (16·3 versus 25·4 months; P = 0·039). The presence of primary tumour lymph node metastases (odds ratio 2·35; P = 0·037) and intrahepatic recurrence requiring repeat hepatectomy (odds ratio 5·61; P = 0·012) were significant risk factors for PLNM on multivariable analysis. CONCLUSION: Patients undergoing repeat hepatectomy and those with primary tumour lymph node metastases are at significant risk of PLNM. Although PLNM is a poor prognostic factor independent of perihepatic lymph node station, patients with one or two PLNMs have a more favourable outcome than those with more PLNMs.

Binge eating disorder and depressive symptoms among females of child-bearing age: the Korea Nurses' Health Study.

BACKGROUND: Most studies regarding the relationship between binge eating disorder (BED) and depression have targeted obese populations. However, nurses, particularly female nurses, are one of the vocations that face these issues due to various reasons including high stress and shift work. This study investigated the prevalence of BED and the correlation between BED and severity of self-reported depressive symptoms among female nurses in South Korea. METHODS: Participants were 7,267 female nurses, of which 502 had symptoms of BED. Using the propensity score matching (PSM) technique, 502 nurses with BED and 502 without BED were included in the analyses. Data were analyzed using descriptive statistics, Spearman's correlation, and multivariable ordinal logistic regression analysis. RESULTS: The proportion of binge eating disorder was 6.90% among the nurses, and 81.3% of nurses displayed some levels of depressive symptoms. Multivariable ordinal logistic regression analysis revealed that age (40 years old and older), alcohol consumption (frequent drinkers), self-rated health, sleep problems, and stress were associated with self-reported depression symptoms. Overall, after adjusting for confounders, nurses with BED had 1.80 times the risk (95% CI = [1.41-2.30]; p-value < 0.001) of experiencing a greater severity of self-reported depression symptoms. CONCLUSIONS: Korean female nurse showed a higher prevalence of both binge eating disorder and depressive symptoms, and the association between the two factors was proven in the study. Therefore, hospital management and health policy makers should be alarmed and agreed on both examining nurses on such problems and providing organized and systematic assistance.

A novel missense mutation in NR0B1 causes delayed-onset primary adrenal insufficiency in adults.

A novel missense mutation (c.775T>C; p.ser259Pro) in the NROBI gene cause a late-onset adrenal insufficiency without hypogonadism.

Prognostic value of carbohydrate antigen 19-9 in patients undergoing resection of biliary tract cancer.

BACKGROUND: The clinical significance of abnormally high levels of carbohydrate antigen (CA) 19-9 after resection of biliary tract cancer (BTC) is not well established. The aim of this study was to determine the prognostic value of CA19-9 normalization in patients undergoing resection of BTC with curative intent. METHODS: Patients with BTC undergoing resection with curative intent (1996-2015) were divided into those with normal preoperative CA19-9 level (normal CA19-9 group), those with an abnormally high preoperative CA19-9 level (over 37 units/ml) and normal postoperative CA19-9 level (normalization group), and those with an abnormally high preoperative CA19-9 level and abnormally high postoperative CA19-9 level (non-normalization group). Overall survival (OS) was analysed and predictors of OS were determined. RESULTS: The normal CA19-9 group (180 patients) and normalization group (74) had better OS than the non-normalization group (58) (3-year OS rate 70·4, 73 and 31 per cent respectively; both P < 0·001). The normal CA19-9 and normalization groups had equivalent OS (P = 0·880). On multivariable analysis, factors associated with worse OS were lymph node metastases (hazard ratio (HR) 1·78; P = 0·014) and abnormally high postoperative CA19-9 level (HR 3·16; P < 0·001). In the normalization group, OS did not differ after R0 versus R1 resection (3-year OS rate 69 versus 62 per cent respectively; P = 0·372); in the non-normalization group, patients with R1 resection had worse OS (3-year OS rate 36 and 20 per cent for R0 and R1 respectively; P = 0·032). CONCLUSION: Non-normalization of CA19-9 level after resection of BTC with curative intent was associated with worse OS. R1 resection was associated with a particularly poor prognosis when CA19-9 levels did not normalize.

Sex-dependent effects of uric acid on cerebral microbleed: a cross-sectional study in the general population.

BACKGROUND AND PURPOSE: Elevated serum uric acid (UA) is known to be associated with stroke. However, there is little information on the association between serum UA levels and cerebral microbleed (CMB), a precursor of stroke. Therefore, we investigated the association between UA and CMB in a general population taking into consideration sex-related differences. METHODS: The subjects in this cross-sectional study consisted of 2686 individuals of 40-79 years of age (1403 men and 1283 women) who underwent regular health screenings, including brain magnetic resonance imaging, at Seoul National University Hospital Health Promotion Center. Subjects were categorized into three groups according to tertiles of UA levels by sex. The presence and location of CMB were assessed by gradient-recalled echo magnetic resonance imaging. RESULTS: The prevalence of CMB was 3.8%. In multivariate logistic regression analysis by sex, the highest tertile of UA in male subjects was independently associated with the presence of CMB compared with the lowest tertile of UA (adjusted odds ratio, 2.46; P = 0.013). Meanwhile, the highest tertile of UA in female subjects was inversely associated with CMB compared with the lowest tertile of UA (adjusted odds ratio, 0.39; P = 0.040). CONCLUSIONS: High serum UA value was associated with higher prevalence of CMB in male, but lower prevalence of CMB in female subjects.

Cathelicidin suppresses lipid accumulation and hepatic steatosis by inhibition of the CD36 receptor.

BACKGROUND AND OBJECTIVES: Obesity is a global epidemic which increases the risk of the metabolic syndrome. Cathelicidin (LL-37 and mCRAMP) is an antimicrobial peptide with an unknown role in obesity. We hypothesize that cathelicidin expression correlates with obesity and modulates fat mass and hepatic steatosis. MATERIALS AND METHODS: Male C57BL/6 J mice were fed a high-fat diet. Streptozotocin was injected into mice to induce diabetes. Experimental groups were injected with cathelicidin and CD36 overexpressing lentiviruses. Human mesenteric fat adipocytes, mouse 3T3-L1 differentiated adipocytes and human HepG2 hepatocytes were used in the in vitro experiments. Cathelicidin levels in non-diabetic, prediabetic and type II diabetic patients were measured by enzyme-linked immunosorbent assay. RESULTS: Lentiviral cathelicidin overexpression reduced hepatic steatosis and decreased the fat mass of high-fat diet-treated diabetic mice. Cathelicidin overexpression reduced mesenteric fat and hepatic fatty acid translocase (CD36) expression that was reversed by lentiviral CD36 overexpression. Exposure of adipocytes and hepatocytes to cathelicidin significantly inhibited CD36 expression and reduced lipid accumulation. Serum cathelicidin protein levels were significantly increased in non-diabetic and prediabetic patients with obesity, compared with non-diabetic patients with normal body mass index (BMI) values. Prediabetic patients had lower serum cathelicidin protein levels than non-diabetic subjects. CONCLUSIONS: Cathelicidin inhibits the CD36 fat receptor and lipid accumulation in adipocytes and hepatocytes, leading to a reduction of fat mass and hepatic steatosis in vivo. Circulating cathelicidin levels are associated with increased BMI. Our results demonstrate that cathelicidin modulates the development of obesity.

Association of lipid parameters and insulin resistance with bone health in South Korean adolescents.

UNLABELLED: This study investigated the association between lipid profiles and insulin resistance and bone mineral content (BMC) in Korean adolescents and found that BMC was inversely associated with triglyceride (TG) and homeostasis model assessment of insulin resistance (HOMA-IR). This association did not differ according to obesity status in either boys or girls. INTRODUCTION: To prevent future osteoporosis, it is important to identify factors that affect bone health in adolescents as well as adults. This study aimed to examine the association between lipid profiles and insulin resistance and BMC in Korean adolescents. METHODS: Data from 706 boys and 621 girls, who participated in the Korea National Health and Nutrition Examination Survey from 2008 to 2011, were analyzed. Lipid profiles were measured, and HOMA-IR was calculated to assess insulin resistance. BMC was measured for the total femur, femur neck, and lumbar spine by using whole-body dual-energy X-ray absorptiometry (DXA). RESULTS: TG level and HOMA-IR were negatively correlated with BMC at all three sites in boys. In girls, TG level showed a negative correlation with BMC at the femur neck and lumbar spine, and HOMA-IR was negatively associated with BMC at the femur neck only. These inverse associations did not differ according to obesity status in either sex. Adjusted means of BMC at the three sites in boys tended to decrease in the higher tertile groups of TG and HOMA-IR, and the adjusted means of BMC for the total femur in girls tended to decrease in the higher tertile groups of TG and HOMA-IR. CONCLUSIONS: BMC was inversely associated with TG and HOMA-IR in Korean adolescents, and this association was more pronounced in boys. This association did not differ according to obesity status in either sex.

Induction of fibronectin by HER2 overexpression triggers adhesion and invasion of breast cancer cells.

Fibronectin (FN), an extracellular matrix ligand, plays a pivotal role in cell adhesion, migration, and oncogenic transformation. Aberrant FN expression is associated with poor prognoses in various types of cancer, including breast cancer. In the current study, we investigated the relationship between FN induction and HER2 expression in breast cancer cells. Our results showed that the level of FN expression increased in response to HER family ligands, EGF and TGF-α in a time- and dose-dependent manner. On the other hand, EGF-induced FN expression decreased in response to trastuzumab, which is a HER2-targeted monoclonal antibody. However, EGF-induced FN expression was not affected by trastuzumab in JIMT-1 breast cancer cells, which are trastuzumab insensitive cells. Next, we introduced the HER2 gene into MDA-MB231 cells to verify the relationship between FN and HER2. The level of FN expression significantly increased in HER2-overexpressed MDA-MB231 cells. In contrast, the induction of FN by HER2 was significantly decreased in response to trastuzumab treatment. In addition, the induction of FN by HER2 was down-regulated by the MEK 1/2 specific inhibitor, U0126. Using conditioned culture media of vec- and HER2-overexpressed MDA-MB231 cells, we observed the cell morphology, adhesion, and invasion of MDA-MB231 cells. Interestingly, in conditioned culture media of HER2-overexpressed MDA-MB231 cells, the cell morphology was altered, and adhesion and invasion of MDA-MB231 cells significantly increased. In addition, our results showed that recombinant human FN augmented cell adhesion and invasion of MDA-MB231 cells while these inductions decreased in response to an FN inhibitor. Therefore, we demonstrated that the induction of FN by HER2 triggers cell adhesion and invasion capacities.

Characteristic MRI findings in hyperglycaemia-induced seizures: diagnostic value of contrast-enhanced fluid-attenuated inversion recovery imaging.

AIM: To describe characteristic magnetic resonance imaging (MRI) abnormalities in hyperglycaemia-induced seizures, and evaluate the diagnostic value of contrast-enhanced fluid-attenuated inversion recovery (FLAIR) imaging. Possible underlying mechanisms of this condition are also discussed. MATERIALS AND METHODS: Eleven patients with hyperglycaemia-induced seizures and MRI abnormalities were retrospectively studied. Clinical manifestations, laboratory findings, MRI findings, and clinical outcomes were analysed. RESULTS: All patients, except one, presented with focal seizures, simple or complex partial seizures, or negative motor seizures. All patients had long-standing uncontrolled diabetes mellitus. The MRI abnormalities observed acutely were focal subcortical hypointensities on T2-weighted imaging and FLAIR imaging in all patients with overlying cortical gyral T2 hyperintensities in five. Focal overlying cortical or leptomeningeal enhancement on contrast-enhanced T1-weighted imaging or contrast-enhanced FLAIR imaging was observed in all patients. Contrast-enhanced FLAIR imaging was superior to contrast-enhanced T1-weighted imaging for detecting characteristic cortical or leptomeningeal enhancement. Diffusion-weighted imaging showed mildly restricted diffusion in four of five patients with cortical gyral T2 hyperintensity. In nine patients, the lesions were localised in the parietal or parieto-occipital lobes. The other two patients showed localised precentral gyral lesions. After treatment, the neurological symptoms, including the seizures, improved in all patients. On clinical recovery, the subcortical T2 hypointensity, gyral or leptomeningeal enhancement, and overlying cortical T2 hyperintensities resolved. CONCLUSION: Recognition of these radiological abnormalities in patients with hyperglycaemia-induced seizures is important in restricting unwarranted investigations and initiating early therapy. These patients generally have a good prognosis.

Night-eating syndrome and the severity of self-reported depressive symptoms from the Korea Nurses' Health Study: analysis of propensity score matching and ordinal regression.

OBJECTIVES: The prevalence of night-eating syndrome (NES) and depression is increasing worldwide. Although nurses, in particular, are exposed to work in an environment of irregular eating, shift work, and stressful settings, limited research exist. In fact, the prevalence of NES among Korean nurses has never been reported. The aim of this study was to determine the prevalence of NES as well as the association between NES and severity of self-reported depressive symptoms among South Korean female nurses. STUDY DESIGN: The Korea Nurses' Health Study, following the protocols of the Nurses' Health Study led by the Harvard University, collected data on Korean female nurses. Survey responses from 3617 participants were included, and 404 responses were analyzed in this cross-sectional study using propensity score matching. METHODS: Descriptive, Spearman's and Cramer's correlations, propensity score matching, and multivariable ordinal logistic regression were conducted as statistical analysis. RESULTS: The prevalence of both NES and self-reported depressive symptoms among Korean female nurses were higher compared with nurses in prior studies. Nurses with NES were 1.65 times more likely to have greater severity of depressive symptoms than those without NES (95% confidence interval [1.19-2.10], odds ratio = 1.65) after adjusting for covariates including sociodemographic characteristics, health behavioural factors, and shift work. CONCLUSION: This study suggests significant association between NES and the severity of self-reported depressive symptoms among Korean female nurses after adjusting for covariates. Policy makers and hospital managers need to develop strategies to reduce depression and NES among nurses for enhancement of nurses' mental and physical health as well as for improvement of care quality.

Isolation and characterization of human mesenchymal stem cells from gingival connective tissue.

BACKGROUND AND OBJECTIVE: The main purpose of this study was to isolate and characterize gingival connective tissue-derived mesenchymal stem cells (GMSCs). The secondary purpose was to present a modified isolation method for the GMSCs. MATERIAL AND METHODS: Collected healthy gingival tissue samples were de-epithelialized and minced into small fragments. The tissues were digested by dispase and collagenase IV for 30 min. The first digested cell suspension was discarded, and then additional digestion was performed to the remaining cells in the same solution for 90 min. The isolated cells from gingiva was incubated in 37°C humidified condition and observed by inverted microscope. Cytoskeletal morphology was evaluated by phalloidin immunofluorescence. Potency of the cells was tested by colony-forming unit fibroblast assay. GMSCs were characterized by osteogenic, adipogenic and chondrogenic differentiation, and flow cytometric, immunofluorescence analysis. RESULTS: GMSCs showed spindle-shaped, fibroblast-like morphology, colony-forming abilities, adherence to plastic and multilineage differentiation (osteogenic, adipogenic, chondrogenic) potency. GMSCs expressed CD44, CD73, CD90 and CD105, but did not express CD14, CD45, CD34 and CD19 in flow cytometry. Expression of stem cell markers (SSEA-4, STRO-1, CD146, CD166 and CD271) and a mesenchymal marker (vimentin) were observed by immunofluorescence. CONCLUSIONS: In conclusion, we isolated and characterized stem cells from human gingival connective tissue with modified protocol. GMSCs showed multipotency with high proliferation and characteristics of mesenchymal stem cells. GMSCs are promising sources for tissue engineering and may be obtained during routine procedures under local anesthesia. Further research is needed to evaluate the potential of GSMCs' proliferation and cryopreservation.

Is surviving enough? Coping and impact on activities of daily living among melanoma patients with lymphoedema.

We assessed the impact of lymphoedema (defined as ≥ 10% limb volume change) on quality of life (QOL), ability to perform activities of daily living (ADLs) and coping in 277 melanoma patients. Limb volume was measured prospectively, pre-operatively and every 3-6 months for 18 months post-operatively using a perometer. Three questionnaires were administered to measure QOL, coping and impact on ADLs. Statistical analyses were conducted using longitudinal logistic regression models. At 18 months, the cumulative incidence of lymphoedema was 31% in patients with upper extremity nodal basin treatment and 40% in lower extremity nodal basin treatment patients. Patients with lower extremity lymphoedema reported lower QOL scores than those with upper extremity lymphoedema. Over 18 months, both groups with mild and moderate lymphoedema showed improvement in coping [odds ratio (OR): 6.67, 95% confidence interval (CI): 3.30-13.47] and performance of ADLs (OR: 7.46, CI: 3.38-16.47). Over the course of 18 months, men were found to have poorer coping scores than women (OR: 2.91, CI: 1.35-6.27). Lymphoedema was associated with improvement in coping over time (P = 0.08) and a higher reported interference with ADLs (OR: 2.53, CI: 1.29-4.97). Patient education about lymphoedema at the time of surgical consent may improve self-efficacy and coping ability. Effective management of lymphoedema may improve patient QOL and reduce interference with ADLs.

Development and validation of Chemotherapy-induced Alopecia Distress Scale (CADS) for breast cancer patients.

BACKGROUND: A psychometric scale for assessing the distress that breast cancer patients experience due to the chemotherapy-induced alopecia was developed and validated. PATIENTS AND METHODS: Twenty-five items for chemotherapy-induced alopecia distress were developed based on a qualitative study, and a cross-sectional survey was conducted with 305 Korean women with breast cancer. To extract factor structure and evaluate construct validity, exploratory and confirmatory factor analysis (CFA) was carried out. Concurrent and discriminant validity were tested by correlations with the psychosocial factors. In addition, external validity analysis was conducted using data from another prospective study of 428 breast cancer patients. RESULTS: Exploratory factor analysis and CFA yielded 17 items in four domains and the model fit was good (CFI=0.925). Coefficient alphas ranged from 0.77 to 0.95 for subdomains and 0.95 for total, and it was similar with the validation dataset confirming its external validity. The total Chemotherapy-Induced Alopecia Distress Scale (CADS) was moderately correlated with the body image (r=-0.47, P<0.001), more weakly correlated with the patients' overall quality of life (QOL, r=-0.28, P<0.001), but did not correlate with self-esteem (r=-0.07, P=0.23). CONCLUSIONS: Our study confirmed that the CADS is a reliable and valid tool for measuring distress of chemotherapy-induced alopecia.