Gut microbiome predicts cognitive function and depressive symptoms in late life.

Depression in older adults with cognitive impairment increases progression to dementia. Microbiota is associated with current mood and cognition, but the extent to which it predicts future symptoms is unknown. In this work, we identified microbial features that reflect current and predict future cognitive and depressive symptoms. Clinical assessments and stool samples were collected from 268 participants with varying cognitive and depressive symptoms. Seventy participants underwent 2-year follow-up. Microbial community diversity, structure, and composition were assessed using high-resolution 16 S rRNA marker gene sequencing. We implemented linear regression to characterize the relationship between microbiome composition, current cognitive impairment, and depressive symptoms. We leveraged elastic net regression to discover features that reflect current or future cognitive function and depressive symptoms. Greater microbial community diversity associated with lower current cognition in the whole sample, and greater depression in participants not on antidepressants. Poor current cognitive function associated with lower relative abundance of Bifidobacterium, while greater GABA degradation associated with greater current depression severity. Future cognitive decline associated with lower cognitive function, lower relative abundance of Intestinibacter, lower glutamate degradation, and higher baseline histamine synthesis. Future increase in depressive symptoms associated with higher baseline depression and anxiety, lower cognitive function, diabetes, lower relative abundance of Bacteroidota, and lower glutamate degradation. Our results suggest cognitive dysfunction and depression are unique states with an overall biological effect detectable through gut microbiota. The microbiome may present a noninvasive readout and prognostic tool for cognitive and psychiatric states.

Foot care knowledge and self-care practices among diabetic patients in Penang: A primary care study.

INTRODUCTION: In Malaysia, the prevalence of diabetes mellitus has been increasing annually, currently affecting 18.3% of the population. Diabetic foot ulcer, a common complication of diabetes, is associated with high morbidity and mortality, consequently increasing health care expenditure. A previous study showed that foot care knowledge and foot self-care practices help to reduce the development of ulcers.1,2 This study aims to identify the level of foot care knowledge and self-care practices among diabetic patients in the primary care setting. OBJECTIVE: This study was to determine the level of foot care knowledge and foot self-care practices among diabetic patients in the primary care setting in Penang Island and its determinants and the correlation between level of foot care knowledge and self-care practices among diabetic patients. MATERIAL AND METHODS: A cross sectional study was performed on 311 diabetic patients who were registered to two government health clinics in Penang. Information regarding respondents' demographic status, foot care knowledge, and foot self-care practices were gathered using a self-administered questionnaire. Data were analysed using the Statistical Package for the Social Sciences (SPSS) 22. The Mann-Whitney U test and Kruskal-Wallis test were applied to the analysis. Multiple linear regression was performed to identify the determinants. Correlation between knowledge and self-care practice was determined using the linear regression model. RESULTS: One hundred and sixty-five (53.1%) respondents achieved good knowledge scores and 196 respondents (63%) achieved good self-care practice scores. The median age of respondents was 61 years, who were mostly females (56.6%), Malays (41.2%), and unemployed (48.6%). Median HbA1c level was 7.5%, and 42.8% of respondents had diabetes for 5 to 10 years. Lowest scores for knowledge and self-care practices were observed in foot skin care questions. Formal foot care education was found to be a significant predictor of foot care knowledge (p<0.05, 95% CI -1.102, -0.098). Foot care knowledge was significantly and positively correlated with foot self-care practices (p<0.001, 95% CI 0.548, 0.727). CONCLUSION: Foot care knowledge has significant positive correlation with foot self-care practices. Empowering diabetic patients with foot care knowledge may lead to significantly better foot self-care practices.

[Value of shear wave elastrography image classification in the diagnosis of breast masses].

Objective: To analyze the image features of shear wave elastrography (SWE) in breast masses, and to evaluate their values in the differentiation of benign and malignant breast lesions. Methods: A total of 361 patients with 403 breast lesions who simultaneously underwent conventional ultrasound and SWE examination from February 2015 to January 2018 were selected. Diagnosis in all patients was confirmed by aspiration biopsy or operative pathology. The SWE images were collected and the elastic images were divided into 5 types. The SWE image features of different breast pathological types were summarized, and their values in benign and malignant breast lesion diagnoses were evaluated. Results: The main features of benign breast lesion were type Ⅰ and Ⅱ, the main features of the malignant lesion were type Ⅳ and Ⅴ, and the proportion of which were 43.6% (71/163), 37.4% (61/163), 22.1% (53/240) and 57.9% (139/240), respectively. Type Ⅲ accounted for a certain proportion in both benign and malignant lesions. The SWE image features of benign and malignant lesions were compared and a significant difference was observed (P<0.001). The type Ⅴ features were mainly observed in invasive ductal carcinoma, invasive lobular carcinoma and other types of invasive carcinoma, while the type Ⅳ features were mostly presented in ductal carcinoma in situ and mucinous carcinoma. Fibroadenoma, fibroadenosis accompanied with fibroadenoma, and fibroadenosis were featured with type Ⅰ. Both intraductal papilloma and benign phyllodes tumor were mostly type Ⅱ, while type Ⅲ and Ⅴ were more common in chronic granulomatous mastitis. When type Ⅰ and typeⅡof breast lesions were classified as benign features while type Ⅳ and Ⅴ were malignant features, the sensitivity and specificity of breast malignant lesion diagnosis were 91.2% and 84.7% by application of SWE combined with breast imaging reporting and data system (BI-RADS). The sensitivity of combined diagnosis was slightly lower than that of conventional ultrasound (P>0.05), but the specificity was significantly higher than conventional ultrasound (P<0.01). Conclusion: The SWE is a simple and effective method. Combination of SWE with conventional ultrasound may improve the diagnostic differentiation of benign and malignant breast lesions.

Study on the heat flux reconstruction with the infrared thermography for the divertor target plates in the KSTAR tokamak.

An infrared (IR) thermography is the preferred diagnostic that can quantify heat flux by measuring the surface temperature distributions of the divertor plates. The IR thermography is successfully instrumented on Korea Superconducting Tokamak Advanced Research (KSTAR). In this study, finite volume method is considered to solve the heat conduction equations. 1D-, 2D-, and 3D models are developed and compared with various calculation algorithms, such as Duhamel's theorem and THEODOR. These comparisons show good agreement. In order to acquire more efficient and reliable calculation results, we consider two numerical analysis schemes, influence of temperature on thermal properties and image stabilization. Recently, this reconstruction code is successfully applied to the KSTAR IR thermography.

Optics design of the divertor infrared television of KSTAR.

The divertor Infrared television (IR TV) system for monitoring the temperature of a divertor and localized hot spots will be installed on the upper port of the N-port in the Korea Superconducting Tokamak Advanced Research (KSTAR). The cassette of KSTAR makes a periscope inevitable for the divertor IR TV. In this article, 4 design concepts for the periscope were examined, and the design based on Keplerian was shown to have better stabilities in alignment and the vibration. The final optics design based on an f-theta lens, Keplerian, and telecentric lens was derived.

The anti-glioma effect of suicide gene therapy using BMSC expressing HSV/TK combined with overexpression of Cx43 in glioma cells.

The disseminated neoplastic foci of malignant gliomas are essentially responsible for the limited efficacy of current available therapeutic modalities. Bone marrow-derived stem cells (BMSCs) have the ability to migrate into these tumors and even track infiltrating tumor cells, making them to be promising cellular vehicles for delivering therapeutic agents to glioma cells. The herpes simplex virus thymidine kinase (HSV-TK)/ganciclovir (GCV) suicide gene therapy with a potent bystander effect has been considered as one of the most promising therapeutic strategies for malignant gliomas. In this study, we evaluate the anti-glioma effect of suicide gene therapy using BMSCs expressing HSV-TK combined with overexpression of connexin 43 (Cx43), which can restore the gap junction of intercellular communication and may enhance the bystander effect of suicide gene therapy. To assess the potential of BMSCs to track glioma cells, a spheroid co-culture system in matrigel was used to show that some BMSCs migrated to C6 glioma cell microspheres. Transwell assay showed the tumor tropic property of BMSCs. In addition, BrdU-labeled BMSCs injected directly into the cerebral hemisphere opposite to the established C6 rat gliomas were capable of migrating into the xenograft gliomas. C6 cell growth was more intensively inhibited by HSV-TK/GCV treatment mediated by BMSCs, and could be further enhanced by combination with Cx43 transfection into glioma cells. The same result was observed in vivo by the growth of C6 gliomas and the survival analysis of rats bearing C6 glioma. In conclusion, Cx43 combined with HSV-TK/GCV gene therapy using BMSCs as vehicles was highly effective in a rat glioma model and therefore hold great potential as a novel approach for the gene therapy of human malignant gliomas.

Fresh-frozen, optimal cutting temperature (OCT) compound-embedded bone marrow aspirates: a reliable resource for morphological, immunohistochemical and molecular examinations.

The usefulness of fresh-frozen, optimal cutting temperature (OCT) compound-embedded (FFOE) bone marrow (BM) aspirates was evaluated as a reliable resource for morphological, immunohistochemical and molecular examinations. One hundred BM aspirates were collected in polypropylene tubes and immediately frozen for 2 h in a deep freezer. Frozen BM was transferred to a cryomold filled with OCT compound and the prepared samples were stored in a deep freezer. Histological examination and immunohistochemical staining, polymerase chain reaction (PCR), sequencing and reverse transcription (RT)-PCR were performed to evaluate the quality of the FFOE BM sections in 10% of randomly selected samples. FFOE BM sections revealed better morphologies than paraffin-embedded clot sections in haematoxylin and eosin staining because mature erythrocytes were removed during the staining process in frozen BM sections. Immunohistochemical staining for CD34 revealed excellent staining quality and oil red O staining showed that fat vacuoles in cells were well preserved. The quality of genomic DNA in FFOE BM sections was suitable for obtaining about 2000 bp PCR product for the human leucocyte antigen-A locus followed by direct sequencing of the sample, and the quality of total RNA was suitable for detection of BCR-ABL fusion transcript. FFOE BM aspirates are a reliable resource for various laboratory tests of diagnostic and research arenas.

Thyroid dose estimation with potassium iodide (KI) administration in a nuclear emergency.

In a breach-of-containment nuclear reactor accident, the near-field exposure is primarily through inhalation of radioiodine. Thyroid blockade by oral potassium iodide (KI) is a practical and effective protective measure for the general public in such an emergency. The retention functions incorporating the thyroid blocking effects by KI have been derived using a standard three-compartment model of iodine metabolism. This allows more accurate estimation of the thyroid dose by calculating the blocking factor.

Age-dependent potassium iodide effect on the thyroid irradiation by 131I and 133I in the nuclear emergency.

The initial near-field exposure is primarily through inhalation in a nuclear emergency and the dominant contribution to the effective inhalation dose comes from radioiodine. Thyroid blockade by oral potassium iodide (KI) is efficient and practical for public in the nuclear emergency. Age-dependent radioprotective effect of KI on the thyroid irradiation by (131)I and (133)I has been derived using the simplified compartment model of iodine metabolism and WinSAAM program. Administration of KI within 2 h after (131)I and (133)I intake can block thyroid uptake significantly, yielding protective effect of 78.9% and 74.3%, respectively, for (131)I and (133)I for adults. The mean absorbed doses decrease with age, while protective effects of KI are similar for all age groups.

Evaluation of pre- and posttransplantation serum interferon-gamma and soluble CD30 for predicting liver allograft rejection.

The aim of the present study was to identify whether the serum interferon-gamma (IFNgamma), a Th1 cytokine, or soluble CD30 (sCD30), a marker for activation of Th2 cytokine-producing T cells, predict acute cellular rejection episodes among liver graft patients. Pretransplant and posttransplant sera from 32 living donor liver transplant recipients obtained on days 1, 3, and 7 after surgery were tested for serum IFNgamma and sCD30 concentrations using commercial enzyme-linked immunosorbent assay kits. Recipients with an acute rejection episode (ARE) (n=14) displayed significantly higher IFNgamma concentrations pretransplant than did the patients with no ARE (n=18) (P<.05). The pretransplant serum levels of sCD30 were not different between the non-ARE and ARE groups. However, in comparison with the non-ARE group, who showed steadily decreasing serum sCD30 levels after transplantation, 12 among the 14 patients in the ARE group showed increasing sCD30 levels from day 1 to day 3 after transplantation (P<.05). These results suggest that the sCD30 increment during the early period after liver transplantation affects the immune response of rejection. This observation emphasizes the clinical relevance of serum sCD30, in addition to serum IFNgamma, as predictive markers for acute liver graft rejection.

Suppression of EGFR expression by antisense or small interference RNA inhibits U251 glioma cell growth in vitro and in vivo.

Epidermal growth factor receptor (EGFR) had been reported as one of the major responsible genes for malignant progression and phenotype reversion of gliomas, and has been used as one of the most important therapeutic targets. In the present study, small interference RNA (siRNA) and antisense EGFR expression constructs, which target sequences of human EGFR catalytic domain (2400-2420) and the 3'-coding region, respectively, were used to examine the growth inhibition effects on U251 glioma cells. Cell growth was significantly inhibited and G2/M arrest was observed in antisense- and siRNA-treated groups. Matrigel matrix demonstrated spotted cell clustering pattern in antisense- and siRNA-transfected U251 cells, indicating poor cell growth activities. In addition, the tumor volumes in U251 subcutaneous mice model treated with antisense and siRNA were significantly smaller than those treated with control siRNA and phosphate-buffered saline. Also, glial fibrillary acidic protein expression was upregulated in antisense- and siRNA-treated groups than the control groups. Our results demonstrated that antisense- or siRNA-targeting intracellular region of EGFR can inhibit EGFR expression, exerted growth inhibition effect on U251 glioma cells in vitro and in vivo. Consequently, siRNA expression plasmid-mediated gene therapy would be a new strategy in treatment of gliomas.

Diagnostic approach using the expression profiling of the P53 tumor suppressor gene and its related proteins in ovarian epithelial tumors.

The initial aim of this study was to examine the expression profiles of P53 and its upstream genes, downstream genes, and cell cycle regulators to determine whether these markers are useful for making a differential diagnosis among the benign, borderline, and malignant ovarian epithelial tumors. Between borderline and malignant tumors, the increased expression levels of P53, Bax, Cyclin E, and cyclin-dependent kinase-2 as well as the decreased expression levels of growth arrest and DNA damage (GADD45) and murine double minute-2 (MDM2) were significantly associated with malignancy (P < 0.01, each). Using the receiver operating curve (ROC), the most reliable cutoff value of the added-up staining scores of those markers was 4.5 with 79% sensitivity and 89% specificity for malignancy. Between benign and borderline tumors, the P21 and Bax expression levels were significantly higher in borderline tumors, whereas the Bcl-2 expression level was much higher in benign tumors (P < 0.01, each). Using the ROC, the cutoff value of the added-up staining scores used to discriminate between the two groups was 2.5 with 70% sensitivity and 74% specificity for borderline tumors. Thus, for the differential diagnosis between borderline and malignant tumors, the cutoff value 4.5 of the cumulative staining scores can be used. However, the cutoff value 2.5 for discrimination between benign and borderline tumors may not be useful because of its relatively low sensitivity and specificity. In addition, the P53, GADD45, Cyclin E, and MDM2 expression levels in malignant ovarian tumors might be useful for determining the histologic grade and type.

The application of non-parametric statistical techniques to an ALARA programme.

For the cost-effective reduction of occupational radiation dose (ORD) at nuclear power plants, it is necessary to identify what are the processes of repetitive high ORD during maintenance and repair operations. To identify the processes, the point values such as mean and median are generally used, but they sometimes lead to misjudgment since they cannot show other important characteristics such as dose distributions and frequencies of radiation jobs. As an alternative, the non-parametric analysis method is proposed, which effectively identifies the processes of repetitive high ORD. As a case study, the method is applied to ORD data of maintenance and repair processes at Kori Units 3 and 4 that are pressurised water reactors with 950 MWe capacity and have been operating since 1986 and 1987 respectively, in Korea and the method is demonstrated to be an efficient way of analysing the data.

Subcapital fractures associated with extensive osteonecrosis of the femoral head.

The authors reviewed 10 patients with subcapital fractures associated with extensive osteonecrosis of the femoral head and distinguished these fractures from traumatic femoral neck fractures The mean age of the patients was 52 years (range, 36-68 years). Nine patients were younger than 60 years. Eight patients had risk factors for osteonecrosis. Necrosis was extensive and involved nearly the whole femoral head. Fracture occurred at the junction between a necrotic bone and reparative bone and extended downward through the reparative interface to the healthy inferior cortex of the femoral neck. Patients experienced hip pain that was aggravated gradually during a period of 1 to 24 weeks before diagnosis of the fracture. In all patients, the opposite femoral head was involved with osteonecrosis. In two femoral heads, slight collapse or subchondral fracture (crescent sign) also was observed. No patient had a history of precipitating trauma. In patients younger than 60 years with a subcapital fracture, fracture associated with extensive osteonecrosis of the femoral head should be suspected when a history of trauma is not obvious, when the opposite hip shows findings of osteonecrosis, and when the patient has a risk factor of osteonecrosis. In these fractures, osteosynthesis rarely should be considered because of the high failure rate caused by additional progression of extensive osteonecrosis and the probability of nonunion.

Oncogenic osteomalacia associated with soft tissue chondromyxoid fibroma.

Oncogenic osteomalacia is a rarely described clinical entity characterized by hypophosphatemia, phosphaturia, and a low concentration of 1,25-dihydroxyvitamin D(3). It is most often associated with benign mesenchymal tumor and can be cured with surgical removal of the tumor. In this paper, we present a case of oncogenic osteomalacia caused by chondromyxoid fibroma in the soft tissue of the sole of the foot in a 56-year-old woman.

Epstein-Barr virus infection, drug resistance and prognosis in Korean T- and NK-cell lymphomas.

T-cell lymphomas are a biologically heterogeneous group of diseases with varying clinical presentations and outcomes. We tried to understand the effect of Epstein-Barr virus (EBV) on lymphogenesis, prognostic factors and drug resistance of T-cell lymphomas, and to establish their relationship with international prognostic factors. Formalin-fixed paraffin-embedded tissue sections from 35 patients (12 women and 23 men) with T-cell lymphomas were examined to detect the presence of EBV using RNA in situ hybridization for EBV-encoded small nuclear RNA (EBER) 1/2 and immunohistochemical stain for latent membrane protein (LMP)-1. We also tried to establish the expression of p53 and P-glycoprotein (P-gp) using immunohistochemistry. The distribution according to the subgroup was: two T-lymphoblastic lymphomas, 13 NK/T-cell lymphomas, one angioimmunoblastic T-cell lymphoma, 17 peripheral T-cell lymphomas, unspecified, and two anaplastic large cell lymphomas. The EBER was detected in 15 of 35 T-cell lymphomas (42.9%) and among these it was detected in five of 17 nodal lymphomas (29.4%) and 10 of 18 extranodal lymphomas (55.6%). There was close correlation between EBER positivity and NK/T-cell lymphoma (P = 0.032). Expression of LMP was found in a proportion of tumor cells in seven of the 15 EBER-positive cases (46.7%). There was no correlation between EBER expression and complete response (CR rate), but coexpression of EBER and p53 was associated with treatment failure (P = 0.047). The 18 patients (51.4%) with p53 expression had significantly poorer outcomes compared with the 17 patients without p53 expression (CR rate, P < 0.0005; overall survival, P = 0.0102). Twenty of 35 patients (57.1%) were positive for P-gp expression. P-gp expression was significantly associated with treatment failure (P = 0.001) and overall survival (P = 0.0089). Seventeen of 35 patients (48.6%) treated with systemic chemotherapy or radiation therapy achieved a CR after initial treatment. When the prognostic factors were grouped using the international prognostic index, the CR rate was 58.8% for the low risk group, 50.0% for the low-intermediate risk group, 14.3% for the high-intermediate risk group, and 0% for the high risk group. In conclusion, high incidence of EBV was detected among Korean patients with T-cell lymphomas. Our study supports the prediction that patients who express p53 and P-gp have a poorer prognosis than those who do not and this should be considered when treatment strategies for individual patients are selected.

Somatic mutations of TRAIL-receptor 1 and TRAIL-receptor 2 genes in non-Hodgkin's lymphoma.

Tumor necrosis factor-related apoptosis-inducing ligand-receptor 1 (TRAIL-R1) and tumor necrosis factor-related apoptosis-inducing ligand-receptor 2 (TRAIL-R2) are cell-surface receptors involved in tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell-death signaling. TRAIL-R1 and TRAIL-R2 genes have recently been mapped to chromosome 8p21-22, which is a frequent site of allelic deletions in many types of human tumors, including non-Hodgkin's lymphoma (NHL). Because TRAIL/TRAIL receptor system plays an important role in lymphocyte homeostasis, we hypothesized that the mutations of TRAIL-R1 and TRAIL-R2 may be involved in the development of NHL and that such mutations may be responsible for the allelic losses of 8p21-22 in NHL. In this study, we analysed the entire coding region of TRAIL-R2 gene and the death domain region of TRAIL-R1 gene for the detection of the somatic mutations in a series of 117 human NHLs using polymerase chain reaction (PCR)-based single strand conformation polymorphism (SSCP) analysis. Overall, eight tumors (6.8%) were found to have two TRAIL-R1 gene mutations or six TRAIL-R2 gene mutations. Interestingly, of the eight mutations, six missense mutations (two TRAIL-R1 and four TRAIL-R2) were detected in the death domains and one nonsense mutation of TRAIL-R2 was detected just before the death domain. Our data suggest that somatic mutations of TRAIL-R1 and TRAIL-R2 genes may play a role in the pathogenesis of some NHLs and that TRAIL-R1 and TRAIL-R2 genes might be the relevant genes to the frequent loss of chromosome 8p21-22 in human NHL.