Giant cell aortitis leading to Stanford type B and type A aortic dissection.

This report provides a rare histological example and the appropriate management of spontaneous aortic dissection secondary to giant cell arteritis.

Gross and relative energy cost of domestic household activities in Asian men.

BACKGROUND/OBJECTIVES: Obesity is on the rise and participation in exercise has declined. Domestic household activities may help meet the recommended daily physical activity levels. This study aimed to measure the energy costs of household activities among Asian males. SUBJECTS/METHODS: This was a randomised cross-over study conducted in a whole-body calorimeter. The energy costs of 14 domestic household activities, divided into two studies, were measured in 10 healthy Asian males. Participants' weight, height, body composition and basal metabolic rate were measured on the first test visit. A standard breakfast was served and participants rested for an hour before the measurement of energy costs of domestic household activities. During the measurements, each activity was performed for 20 min, and participants rested for 30 min between activities. RESULTS: The mean energy costs of domestic household activities ranged from 5.92 to 11.97 kJ/min, which were significantly different between activities (repeated measures analysis of variance, P<0.001). When expressed as metabolic equivalents (METS), all domestic household activities were classified as low-intensity physical activities. Actual METS (METSactual) were significantly different to standard METS of eight activities, which may be partly explained by the universal assumption of 3.5 ml O2/kg/min made during the calculation of METS in the Asian population. CONCLUSIONS: The energy costs of a range of domestic household activities reported in this study may assist in the planning of physical activities among Asians to meet national physical activity guidelines.

JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma.

Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available.

Prevalence of falls among community-dwelling elderly and its associated factors: A cross-sectional study in Perak, Malaysia

Abstract Introduction: Fall is a major cause of injuries and can increase the risk of early mortality among elderly. The objective of this study was to determine the prevalence of falls among community-dwelling elderly in rural Malaysia and its associated factors. Methods: Data were obtained from a cross-sectional survey in five randomly selected districts in the state of Perak, Malaysia. A total of 250 households were randomly selected. A total of 811 individuals aged 60 years or more were recruited and interviewed using a structured questionnaire. Information about socio-demographic, history of falls in the past 1 year, medical history, drug history and physical activity level were enquired. Results: The prevalence of falls in the past 1 year among community-dwelling elderly was reported to be 4.07%. Indigenous elderly (Adjusted odd ratio, AOR = 6.06, 95% CI = 1.10–33.55, p = 0.039) and living alone (AOR = 2.60, 95% CI = 1.04–6.50, p = 0.042) were shown to be factors associated with falls. Physical activity level, number of co-morbidities and number of medications used were not associated with falls. Conclusion: Elderly of indigenous ethnicity and living alone are the main factors associated with falls in this population. Indigenous people may be at higher risk, which warrant further investigation with a larger sample to improve the precision of estimates.

Bioinformatics analysis of gene expression profiles in hepatocellular carcinoma.

OBJECTIVE: The aim of this study is to identify the gene expression profile specific to Hepatocellular Carcinoma (HCC) by comparing the different expression profiles in cirrhosis, dysplastic nodule (DN) and HCC tissues. MATERIALS AND METHODS: The microarray data were downloaded from Gene Expression Omnibus (GEO) repository, involving 39 samples of normal liver tissues, 33 samples of cirrhosis, 17 samples of DNs and 286 samples of HCCs of different stages. Differential Expressed Genes (DEGs) of cirrhosis, DN and HCC liver tissues were analyzed by BRB-ArrayTool software; besides, the Gene Ontology (GO) analysis, Kyoto encyclopedia of Genes and Genomes (KEGG) and Biocarta pathway enrichment analysis were also performed. A protein-protein interaction (PPI) network was then constructed by STRING software using the genes in significantly different pathways. The resulting network was analyzed by Cytoscape software with CentiScaPe plugin to calculate the topological characteristics of the network and its individual node. Key genes were screened according to betweenness and degree of nodes. RESULTS: few overlaps occurred in the GO categories of DEGs and in the gene sets from pathway analysis between HCCs, cirrhosis and DNs. DEGs in abnormal tissues were shown to be enriched in 29 KEGG pathways and 18 Biocarta pathways; and 43 key genes were identified to be involved in the maintenance of PPI network. In addition, the gene expression profiles were significantly different among cirrhosis, DN and HCC tissues. CONCLUSIONS: The bioinformatic analysis of GEO datasets of HCC identified the functional gene sets associated with the genesis and development of HCC, and the key genes that were playing important roles in the maintenance of the molecular network for biological function specific to HCC. It provides the insights for more precise understandings of pathogenic mechanism, which will further expand the study on biomarker and targeted therapy of HCC.

Virtual reality system based on Kinect for the elderly in fall prevention.

BACKGROUND: Daily life movements require balance ability. Good balance control is closely related to body stability and its development. Therefore, balance training is necessary for any age group. OBJECTIVE: This study proposes the combination of Kinect and virtual reality to build an information platform of interactive scenarios, for practice and evaluation of balance ability. Real-time monitoring of SpO_2, pulse rate, velocity and reaction time during the training process is presented for the training activities of elderly physical function. METHODS: Based on the indicators of balance ability, this information platform sets out various training activities to improve balance ability, making the supposedly tedious process fun and vivid and leading to much better training results. RESULTS: The data (SpO_2, pulse rate, velocity, reaction time) collected from this platform can be sorted and analysed, and the results used to evaluate the performance of balance training, and referenced for follow-up planning in the future. The real-time pulse rate and SpO_2 measurement information indicating the training activities for the elderly to maintain physical function has a positive significance. A noninvasive and unconstrained real-time method to detect the pulse rate and SpO_2 during exercises is presented. The results of balance assessment scale testing of BBS and TUG for the experimental group show that effective balance really improved. The difference between the experimental group and the control group was achieved by using paired t-test. The data were analysed by the descriptive statistics on significant level of P < 0.01. CONCLUSIONS: From the training results of the participants, we know that the information platform developed for enhancing balance ability is in line with practical needs. Furthermore, the fun and interesting game-like exercises it introduces are very helpful in improving balance ability, and certainly in preventing falls.

Type II EATL (epitheliotropic intestinal T-cell lymphoma): a neoplasm of intra-epithelial T-cells with predominant CD8αα phenotype.

In this multicentre study, we examined 60 cases of Type II enteropathy-associated T-cell lymphoma (EATL) from the Asia-Pacific region by histological review, immunohistochemistry and molecular techniques. Patients were mostly adult males (median age: 58 years, male:female 2.6:1), presenting with abdominal pain (60%), intestinal perforation (40%) and weight loss (28%). None had a history of coeliac disease and the median survival was only 7 months. Histologically, these tumours could be divided into (i) central tumour zone comprising a monotonous population of neoplastic lymphocytes, (ii) peripheral zone featuring stunted villi and morphologically atypical lymphocytes showing epitheliotropism, and (iii) distant mucosa with normal villous architecture and cytologically normal intra-epithelial lymphocytes (IELs). Characterized by extensive nuclear expression of Megakaryocyte-associated tyrosine kinase (MATK) (87%) and usually a CD8(+)CD56(+) (88%) cytotoxic phenotype, there was frequent aberrant expression of CD20 (24%). T-cell receptor (TCR) expression was silent or not evaluable in 40% but of the remainder, there was predominant expression of TCRαß over TCRγδ (1.6:1). In keeping with the normal ratio of IEL subsets, CD8(+) cases showed predominant CD8αα homodimer expression (77%), regardless of TCR lineage. These tumours constitute a distinct entity from classical EATL, and the pathology may reflect tumour progression from IEL precursors, remnants of which are often seen in the distant mucosa.

Effects of fruit and vegetable, consumed in solid vs beverage forms, on acute and chronic appetitive responses in lean and obese adults.

BACKGROUND: The effects of fruits and vegetables in solid vs beverage forms on human appetite and food intake, acutely and chronically, are unclear. METHODS: This 21-week, randomized, crossover study assessed appetitive ratings following the inclusion of fruits and vegetables, in solid and beverage form, into the habitual diet of healthy lean (n=15) and overweight/obese (n=19) adults with low customary consumption. The primary acute outcomes were satiation (amount of challenge meal consumed), satiety (latency of subsequent eating event) and dietary compensation after a 400 kcal fruit preload. Ratings of appetite were also obtained before and after 8 weeks of required increased fruit and vegetable consumption (20% estimated energy requirement). RESULTS: Acutely, overweight/obese participants reported smaller reductions of hunger after consuming the fruit preload in beverage compared with solid form (preload × form × body mass index effects, P=0.03). Participants also consumed significantly less of a challenge meal (in both gram and energy) after the ingestion of the solid fruit preload (P<0.005). However, the subsequent meal latency was not significantly different between the solid and the beverage fruit preloads. Total daily energy intake was significantly higher when the obese participants consumed the beverage fruit preload compared with the solid (P<0.001). Daily energy intake was markedly, but not significantly, higher among the lean with the beverage vs solid food form. Hunger and fullness ratings remained stable when participants consumed fruits and vegetables in solid or beverage form for 8 weeks each. CONCLUSION: Acute post-ingestive appetitive responses were weaker following consumption of fruits in beverage vs solid food forms. Consumption of beverage or solid fruit and vegetable food loads for 8 weeks did not chronically alter appetitive responses.

Expression of the CD2AP adaptor molecule in normal, reactive and neoplastic human tissue.

AIMS: To study the expression of CD2-associated protein (CD2AP), an adaptor protein involved in T-cell signalling and renal function, in normal, reactive and neoplastic human lymphoid tissues. METHODS AND RESULTS: We used immunohistochemical techniques to evaluate monoclonal antibodies against CD2AP on over 400 formalin fixed paraffin embedded tissue blocks retrieved from the host institutions of three authors. The samples tested included normal, reactive and neoplastic lymphoid tissue. In lymphoid tissues, strong CD2AP staining was observed in plasmacytoid dendritic cells (pDCs), weak and variable in mantle zone B cells and moderate in rare germinal center cells. CD2AP labeled cortical and rare medullary thymocytes and isolated mononuclear cells in bone marrow trephines. Furthermore, epithelial and endothelial cells expressed CD2AP. Among neoplasms, the greatest number of CD2AP-positive cases were found in diffuse large B cell (21/94), NK T-cell lymphomas (7/67), "blastic plasmacytoid dendritic cell neoplasms" (9/10) and some types of solid tumor. CONCLUSIONS: Our finding that mature peripheral T cells are CD2AP-negative but immature cortical thymocytes are positive may prove useful for diagnostic purposes. Moreover, our results demonstrate that CD2AP represents a useful marker of normal and neoplastic pDC and may be used in a diagnostic panel in reactive or neoplastic lymphoid proliferations.

Short term effects of energy restriction and dietary fat sub-type on weight loss and disease risk factors.

BACKGROUND AND AIMS: Decreasing energy intake relative to energy expenditure is the indisputable tenet of weight loss. In addition to caloric restriction modification of the type of dietary fat may provide further benefits. The aim of the present study was to examine the effect of energy restriction alone and with dietary fat modification on weight loss and adiposity, as well as on risk factors for obesity related disease. METHODS AND RESULTS: One-hundred and fifty overweight men and women were randomized into a 3month controlled trial with four low fat (30% energy) dietary arms: (1) isocaloric (LF); (2) isocaloric with 10% polyunsaturated fatty acids (LF-PUFA); (3) low calorie (LF-LC) (-2MJ); (4) low calorie with 10% PUFA (LF-PUFA-LC). Primary outcomes were changes in body weight and body fat and secondary outcomes were changes in fasting levels of leptin, insulin, glucose, lipids and erythrocyte fatty acids. Changes in dietary intake were assessed using 3day food records. One-hundred and twenty-two participants entered the study and 95 completed the study. All groups lost weight and body fat (P<0.0001 time effect for both), but the LC groups lost more weight (P=0.026 for diet effect). All groups reduced total cholesterol levels (P<0.0001 time effect and P=0.017 intervention effect), but the LC and PUFA groups were better at reducing triacylglycerol levels (P=0.056 diet effect). HDL increased with LF-LC and LF-PUFA but not with LF-PUFA-LC (0.042 diet effect). The LF and LF-LC groups reported greater dietary fat reductions than the two PUFA groups (P=0.043). CONCLUSION: Energy restriction has the most potent effect on weight loss and lipids, but fat modification is also beneficial when energy restriction is more modest.

Long-term effects of increased dietary polyunsaturated fat from walnuts on metabolic parameters in type II diabetes.

BACKGROUND/OBJECTIVES: Most dietary interventions have metabolic effects in the short term, but long-term effects may require dietary fat changes to influence body composition and insulin action. This study assessed the effect of sustained high polyunsaturated fatty acids (PUFA) intake through walnut consumption on metabolic outcomes in type II diabetes. SUBJECTS/METHODS: Fifty overweight adults with non-insulin-treated diabetes (mean age 54+/-8.7 years) were randomized to receive low-fat dietary advice +/-30 g per day walnuts targeting weight maintenance (around 2000 kcal, 30% fat) for 1 year. Differences between groups were assessed by changes in anthropometric values (body weight, body fat, visceral adipose tissue) and clinical indicators of diabetes over treatment time using the general linear model. RESULTS: The walnut group consumed significantly more PUFA than the control (P=0.035), an outcome attributed to walnut consumption (contributing 67% dietary PUFA at 12 months). Most of the effects were seen in the first 3 months. Despite being on weight maintenance diets, both groups sustained a 1-2 kg weight loss, with no difference between groups (P=0.680). Both groups showed improvements in all clinical parameters with significant time effects (P<0.004), bar triacylglycerol levels, but these were just above normal to begin with. The walnut group produced significantly greater reductions in fasting insulin levels (P=0.046), an effect seen largely in the first 3 months. CONCLUSIONS: Dietary fat can be manipulated with whole foods such as walnuts, producing reductions in fasting insulin levels. Long-term effects are also apparent but subject to fluctuations in dietary intake if not of the disease process.

High dose intravenous immunoglobin for systemic lupus erythematosus with lupus nephritis and associated studies - case report

Systemic lupus erythematosus (SLE) is one of the commonest systemic autoimmune diseases that can present with variable clinical manifestations. Intravenous Immunoglobulin (IVIG) has been used as a salvage therapy for severe lupus with encouraging results though there is yet randomised trial to support the usage. This report highlights the efficacy and safety of high dose IVIG in SLE patients with multi-organ involvement particularly lupus nephritis. We also reviewed the literature on the usage of IVIG for lupus nephritis. However, more studies are needed to further clarify the optimal therapeutic dosage and regime for IVIG and to identify the group of patients who might benefit the most from this expensive therapy.

Jaw1/LRMP, a germinal centre-associated marker for the immunohistological study of B-cell lymphomas.

Jaw1, also known as lymphoid-restricted membrane protein (LRMP), is an endoplasmic reticulum-associated protein. High levels of Jaw1/LRMP mRNA have been found in germinal centre B-cells and in diffuse large B-cell lymphomas of 'germinal centre' subtype. This paper documents Jaw1/LRMP expression at the protein level in human tissues by immunohistochemical and western blotting analysis using an antibody reactive with paraffin-embedded tissues. Jaw1/LRMP was highly expressed in germinal centre B-cells (in keeping with gene expression data), in 'monocytoid B-cells', and in splenic marginal zone B-cells. It was absent, or present at only low levels, in mature T-cells, although cortical thymocytes were weakly positive. Among lymphoid neoplasms, Jaw1/LRMP was found in germinal centre-derived lymphomas (follicle centre lymphoma, Burkitt's lymphoma, lymphocyte-predominant Hodgkin's disease) but not in T-cell neoplasms (with the exception of a single T lymphoblastic lymphoma). Classical Hodgkin's disease and myeloma lacked Jaw1/LRMP but many cases of chronic lymphocytic leukaemia (but not mantle zone lymphoma) were Jaw1/LRMP-positive. Approximately half of the marginal zone lymphomas were Jaw1/LRMP-positive. In diffuse large B-cell lymphomas, Jaw1/LRMP was found in three-quarters (24/32) of the cases classified phenotypically as being of 'germinal centre' type, but it was also expressed in almost half (13/28) of the 'non-germinal centre' cases. A similar proportion of 'non-germinal centre' cases were positive for the protein products of two other genes expressed highly in germinal centre cells (HGAL/GCET2 and PAG). The fact that all three of these proteins are expressed in a significant proportion of diffuse large B-cell lymphomas assigned to the 'non-germinal centre' category indicates that the immunophenotypic categorization of diffuse large B-cell lymphoma according to cellular origin may be more complicated than currently understood. Finally, the expression of Jaw1/LRMP in other types of lymphoma and in non-lymphoid tissues/tumours may be of interest in differential diagnosis and research.

Primary retroperitoneal mucinous cystadenocarcinoma in a male patient.

Primary retroperitoneal mucinous cystadenocarcinomas (PRMCs) are rare. This is the first reported case in the literature in English of PRMC in a man. The 64-year-old man presented with a large retroperitoneal cystic tumour measuring 24 x 20 x 16 cm3, which was removed intact. Areas ranging from a benign mucinous cyst to borderline mucinous tumour to mucinous cystadenocarcinoma were observed on microscopy. Strong patchy staining for cytokeratins 7 and 20 and strong diffuse staining for MUC2 and MUC5AC core peptides, similar to staining patterns in ovarian mucinous tumours, were shown in the benign and atypical epithelium. Staining for CA19.9 and carcinoembryonic antigen was also shown by both components. The theory of its origin from the mucinous metaplasia of peritoneal (mesothelial) inclusion cysts, rather than from ectopic ovarian tissue or ovarian teratomas, is supported by the occurrence of such a tumour in a male patient.

The influence of CYP3A gene polymorphisms on cyclosporine dose requirement in renal allograft recipients.

Cyclosporine is a substrate of cytochrome P-450 3A (CYP3A) subfamily of enzymes and characterized by a narrow therapeutic range with wide interindividual variation in pharmacokinetics. A few single-nucleotide polymorphisms detected in CYP3A genes have been shown to correlate significantly with the CYP3A protein expression and activity. We therefore postulated that these polymorphisms could be responsible for some of the interindividual variation in cyclosporine pharmacokinetics. The objective of our study is to determine correlation if any between single-nucleotide polymorphisms of CYP3A5 and CYP3AP1 on cyclosporine dose requirement and concentration-to-dose ratio in renal allograft recipients. Cyclosporine-dependent renal allograft recipients were genotyped for CYP3A5 A6986G and CYP3AP1 G-44A. The cyclosporine dosages prescribed and the corresponding cyclosporine trough levels for each patient were recorded so that cyclosporine dose per weight (mg/kg/day) and concentration-to-dose ratio (C(0)/D, whereby C(0) is trough level and D is daily dose per weight) could be calculated. A total of 67 patients were recruited for our study. The dose requirement for 1, 3, and 6 months post-transplantation ranged 2.3-11.4, 1.0-9.0, and 1.4-7.2 mg/kg/day, respectively. Patients with *1*1*1*1 (n=5) CYP3A5- and CYP3AP1-linked genotypes needed higher dose of cyclosporine compared to patients with *1*3*1*3 (n = 27) and *3*3*3*3 (n = 33) linked genotypes in months 3 and 6 post-transplantation (P < 0.016). The identification of patients with *1*1*1*1 by CYP3A5 and CYP3AP1 genotyping may have a clinically significant and positive impact on patient outcome with reduced rejection rate by providing pretransplant pharmacogenetic information for optimization of cyclosporine A dosing.

Peritoneal implantation of ureter in a cadaveric kidney transplant recipient

We report here a case of a kidney transplant recipient in whom the ureter was initially implanted into the peritoneum. Excessive ultrafiltration volume and reversal of serum vs dialysate creatinine ratio when the patient was recommenced on continuous ambulatory peritoneal dialysis first suggested the diagnosis which was subsequently confirmed by a plain abdominal x-ray demonstrating placement of ureteric stent in the peritoneum. This rare complication was successfully corrected with surgical re-implantation of ureter into the bladder and 5 years later, the patient remains well with good graft function.