Prospective evaluation of dietary and lifestyle pattern indices with risk of colorectal cancer in a cohort of younger women.

BACKGROUND: Although colorectal cancer (CRC) incidence in the USA is declining overall, its incidence is increasing among those younger than 50 years of age. The reasons underlying the increasing trend are largely unknown, although behavioral changes, such as unhealthy diet and lifestyle factors, may be partially responsible. DESIGN: A prospective cohort study included 94 217 women aged 26-45 years at baseline. Validated anthropometric measures and lifestyle information were self-reported biennially. Exposures were four recommendation-based dietary indices-the prime diet quality score and three plant-based dietary indices; and two mechanism-based indices-the empirical dietary and lifestyle index for hyperinsulinemia (EDIH and ELIH). We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for overall CRC and for early-onset (before age 50) and after age 50 CRC separately. RESULTS: We documented 332 cases of CRC during 24 years of follow-up (2 113 655 person-years), with an average age of 52 ± 7 years at diagnosis. Hyperinsulinemic dietary and lifestyle patterns were associated with a higher risk of CRC. Multivariable-adjusted HRs (95% CIs) comparing participants in the highest versus lowest quartile were: 1.67 for EDIH (95% CI: 1.15-2.44, P-trend = 0.01) and 1.51 for ELIH (95% CI: 1.10-2.08, P-trend = 0.01). Moreover, per 75% increment in rank, ELIH appeared to be a stronger risk factor for early-onset CRC (HR = 1.86, 95% CI: 1.12-3.07) than after age 50 CRC (HR = 1.20, 95% CI: 0.83-1.73, P-heterogeneity = 0.16). The four recommendation-based indices were not significantly associated with overall, early-onset, or after age 50 CRC risk (per 75% increment in rank, HRs ranged from 0.75 to 1.28). CONCLUSION: Dietary and lifestyle patterns contributing to hyperinsulinemia were associated with greater CRC risk in younger women. Moreover, the hyperinsulinemic lifestyle showed a suggestively stronger positive association with early-onset CRC risk, compared with after age 50 CRC. Our findings suggest that dietary and lifestyle interventions to reduce insulinemic potential may be effective for CRC prevention among younger women.

Disruption of effective connectivity from the dorsolateral prefrontal cortex to the orbitofrontal cortex by negative emotional distraction in obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) has been associated with abnormal cognitive and emotional functions and these dysfunctions may be dependent on the disruption of dynamic interactions within neuronal circuits associated with emotion regulation. Although several studies have shown the aberrant cognitive-affective processing in OCD patients, little is known about how to characterize effective connectivity of the disrupted neural interactions. In the present study, we applied effective connectivity analysis using dynamic causal modeling to explore the disturbed neural interactions in OCD patients. METHOD: A total of 20 patients and 21 matched healthy controls performed a delayed-response working memory task under emotional or non-emotional distraction while undergoing functional magnetic resonance imaging. RESULTS: During the delay interval under negative emotional distraction, both groups showed similar patterns of activations in the amygdala. However, under negative emotional distraction, the dorsolateral prefrontal cortex (DLPFC) and the orbitofrontal cortex (OFC) exhibited significant differences between groups. Bayesian model averaging indicated that the connection from the DLPFC to the OFC was negatively modulated by negative emotional distraction in patients, when compared with healthy controls (p < 0.05, Bonferroni-corrected). CONCLUSIONS: Exaggerated recruitment of the DLPFC may induce the reduction of top-down prefrontal control input over the OFC, leading to abnormal cortico-cortical interaction. This disrupted cortico-cortical interaction under negative emotional distraction may be responsible for dysfunctions of cognitive and emotional processing in OCD patients and may be a component of the pathophysiology associated with OCD.

Intraperitoneal injection of the pancreatic peptide amylin potently reduces behavioral impairment and brain amyloid pathology in murine models of Alzheimer's disease.

Amylin, a pancreatic peptide, and amyloid-beta peptides (Aß), a major component of Alzheimer's disease (AD) brain, share similar ß-sheet secondary structures, but it is not known whether pancreatic amylin affects amyloid pathogenesis in the AD brain. Using AD mouse models, we investigated the effects of amylin and its clinical analog, pramlintide, on AD pathogenesis. Surprisingly, chronic intraperitoneal (i.p.) injection of AD animals with either amylin or pramlintide reduces the amyloid burden as well as lowers the concentrations of Aß in the brain. These treatments significantly improve their learning and memory assessed by two behavioral tests, Y maze and Morris water maze. Both amylin and pramlintide treatments increase the concentrations of Aß1-42 in cerebral spinal fluid (CSF). A single i.p. injection of either peptide also induces a surge of Aß in the serum, the magnitude of which is proportionate to the amount of Aß in brain tissue. One intracerebroventricular injection of amylin induces a more significant surge in serum Aß than one i.p. injection of the peptide. In 330 human plasma samples, a positive association between amylin and Aß1-42 as well as Aß1-40 is found only in patients with AD or amnestic mild cognitive impairment. As amylin readily crosses the blood-brain barrier, our study demonstrates that peripheral amylin's action on the central nervous system results in translocation of Aß from the brain into the CSF and blood that could be an explanation for a positive relationship between amylin and Aß in blood. As naturally occurring amylin may play a role in regulating Aß in brain, amylin class peptides may provide a new avenue for both treatment and diagnosis of AD.

A chemogenomic approach to understand the antifungal action of Lichen-derived vulpinic acid.

AIM: To determine uncovered antifungal activity of lichen-derived compound, vulpinic acid, by using chemical-genetic analyses. METHODS AND RESULTS: Haploinsufficiency and homozygous-profiling assays were performed, revealing that strains lacking GLC7, MET4, RFC2, YAE1 and PRP18 were sensitive to three concentrations (12·5, 25 and 50% of inhibitory concentration) of vulpinic acid and independently validated. To verify inhibition of those genes, cell cycle analysis using flow cytometry was performed and relative expressions were measured. Under vulpinic acid-treated condition, cell cycle was arrested in S and G2/M phases and sensitive strains' relative expressions were significantly lower than the wild type yeast. CONCLUSIONS: Vulpinic acid mainly affects cell cycle, glycogen metabolism, transcription and translation to fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: Although lichen-derived compounds are commercially valuable, few studies have determined their modes of action. This study used a chemogenomic approach to gain insight into the mechanisms of one of well-known lichen-derived compound, vulpinic acid.

Chest CT findings of toxocariasis: correlation with laboratory results.

AIM: To assess the relationship between chest computed tomography (CT) findings of patients with toxocariasis and levels of serological markers. MATERIALS AND METHODS: A total of 38 cases of patients diagnosed with toxocariasis by enzyme-linked immunosorbent assay (ELISA), CT, and serological markers were retrospectively reviewed. The presence of nodule with or without ground-glass opacity (GGO) halo, consolidation, focal GGO, pleural effusion, and lymphadenopathy at chest CT were evaluated. Statistical analysis was performed with the Fisher's exact test. RESULTS: The most common chest CT findings were nodule (n = 12, 31.6%) and focal GGO (n = 12, 31.6%). In patients with normal eosinophil levels, focal GGO (n = 9, 37.5%) was the most common finding. In contrast, nodule with a GGO halo (n = 7, 50%) was the most common finding in the eosinophilia group. Nodule with a GGO halo was more common in the eosinophilia group, with a statistically significant difference (p = 0.017). Nodule was more common in the eosinophilia group, and focal GGO was more common in the normal eosinophil group. CONCLUSION: The most common chest CT findings in toxocariasis were nodule with or without GGO halo, and focal GGO. In the eosinophilia group, nodule with a GGO halo was significantly more frequent. Other CT findings did not show a statistically significant relationship with serological markers.

Risk factors for in-hospital acquisition of carbapenem-resistant Enterobacterales in patients with severe burns.

BACKGROUND: Although patients with severe burns are prone to severe infections with antibiotic-resistant bacteria and inevitably have some risk factors for carbapenem-resistant Enterobacterales (CRE) acquisition, risk factors for CRE infection or colonization in these patients have not been investigated. AIM: To identify the independent risk factors for CRE acquisition in patients with severe burns. METHODS: Patients admitted to the burn intensive care unit (BICU) for acute burn care were categorized based on culture results during BICU care into the CRE group and non-CRE group, which included the carbapenem-susceptible Enterobacterales (CSE) and control groups. Clinical and microbiological factors were compared between the CRE and non-CRE groups, and between the CRE and CSE groups to identify independent risk factors for in-hospital CRE acquisition. FINDINGS: Among the included 489 patients, 101 (20.7%) and 388 (79.3%) patients were classified in the CRE and non-CRE groups, respectively. The non-CRE group included 91 (18.6%) and 297 (60.7%) patients in the CSE and control groups, respectively. In multivariate analysis between the CRE and non-CRE groups, exposure to other CRE-acquired patients (P = 0.018), abbreviated burn severity index score ≥9 (P = 0.012), and mechanical ventilation (P < 0.001) were associated with CRE acquisition. In multivariate analysis between the CRE and CSE groups, exposure to other CRE-acquired patients was associated with CRE acquisition (P = 0.048). CONCLUSION: Considering the limitation of controlling the burn severity in hospitalized patients, enhanced infection control measures for preventing in-hospital CRE transmission among patients with severe burns should be emphasized.

Association between urine cotinine levels, continuous performance test variables, and attention deficit hyperactivity disorder and learning disability symptoms in school-aged children.

BACKGROUND: We examined the cross-sectional relationship between environmental tobacco smoke exposure, continuous performance test (CPT) measures, and attention deficit hyperactivity disorder (ADHD) or learning disability symptoms in school-aged children. METHOD: In total, 989 children (526 boys, mean age 9.1 ± 0.7 years), recruited from five South Korean cities participated in this study. We used urine cotinine as a biomarker for environmental tobacco smoke exposure, and obtained the children's scores on a CPT. Parents completed the Korean versions of the ADHD rating scale-IV (ADHD-RS) and learning disability evaluation scale (LDES). Using generalized linear mixed model (GLMM), we assessed the associations between urine cotinine concentrations, neuropsychological variables, and symptoms of ADHD and learning disabilities. Additionally, we conducted structural equation models to explore the effects' pathways. RESULTS: After adjusting for a range of relevant covariates, GLMM showed urinary cotinine levels were significantly and positively associated with CPT scores on omission errors, commission errors, response time, and response time variability, and with parent- and teacher-rated ADHD-RS scores. In addition, urine cotinine levels were negatively associated with LDES scores on spelling and mathematical calculations. The structural equation model revealed that CPT variables mediated the association between urine cotinine levels and parental reports of symptoms of ADHD and learning disabilities. CONCLUSIONS: Our data indicate that environmental exposure to tobacco smoke is associated with ADHD and learning disabilities in children, and that impairments in attention and inhibitory control probably mediate the effect.

Higher levels of small dense low-density lipoprotein (LDL) are associated with cardiac autonomic neuropathy in patients with type 2 diabetes.

AIM: To investigate the relationship between small dense LDL cholesterol and cardiac autonomic neuropathy among patients with Type 2 diabetes. METHODS: A total of 175 patients who had not taken lipid-lowering agents previously were enrolled consecutively in this study. Small dense LDL cholesterol level was measured using polyacrylamide tube gel electrophoresis, which fractionates LDL cholesterol into seven components according to particle size and charge. We analysed the mean LDL cholesterol particle size and the proportion of small dense LDL cholesterol. RESULTS: The mean (± sd) patient age was 56 (± 14) years, the mean (± sd) duration of diabetes was 10.3 (± 8.3) years, the mean (± sd) proportion of small dense LDL cholesterol was 21.3 (± 17.6)% and the mean (± sd) LDL cholesterol size was 26.33 (± 0.8) nm. Men with cardiac autonomic neuropathy had a longer duration of diabetes compared with those without cardiac autonomic neuropathy. Women with cardiac autonomic neuropathy had a larger waist circumference, higher plasma triglyceride levels, smaller mean (± sd) LDL cholesterol size [26.8 (± 4.3) nm vs 26.4 (± 6.9) nm; P < 0.01] and larger mean (± sd) proportion of small dense LDL cholesterol [10.1 (± 9.9)% vs 19.1 (± 16.8)%; P < 0.01] compared with those without cardiac autonomic neuropathy. After adjusting for other confounding risk factors, the triglyceride/ HDL cholesterol ratio (odds ratio = 1.698, 95% CI: 1.07-2.69; P = 0.025) and mean LDL cholesterol size (odds ratio = 0.873, 95% CI: 0.77-0.99; P = 0.038) remained as independent risk factors for cardiac autonomic neuropathy in women. CONCLUSIONS: A more atherogenic lipid profile such as the triglyceride: HDL cholesterol ratio and a smaller mean LDL cholesterol particle size were related to the prevalence of cardiac autonomic neuropathy in women with Type 2 diabetes.

Central nervous system endoplasmic reticulum stress in a murine model of type 2 diabetes.

AIMS/HYPOTHESIS: Type 2 diabetes is associated with complications in the central nervous system (CNS), including learning and memory, and an increased risk for neurodegenerative diseases. The mechanism underlying this association is not understood. The aim of this study was to gain greater insight into the possible mechanisms of diabetes-induced cognitive decline. METHODS: We used microarray technology to identify and examine changes in gene expression in the hippocampus of a murine model of type 2 diabetes, the db/db mouse. Bioinformatics approaches were then used to investigate the biological significance of these genes. To validate the biological significance we evaluated mRNA and protein levels. RESULTS: At 8 and 24 weeks, 256 and 822 genes, respectively, were differentially expressed in the db/db mice. The most significantly enriched biological functions were related to mitochondria, heat shock proteins, or the endoplasmic reticulum (ER), the majority of which were downregulated. The ER-enriched cluster was one of the clusters that contained the highest number of differentially expressed genes. Several of the downregulated genes that were differentially expressed at 24 but not at 8 weeks are directly involved in the unfolded protein response (UPR) pathway and include two heat shock proteins (encoded by Hspa5 and Hsp90b1), a transcriptional factor (x-box binding protein 1, encoded by Xbp1), and an apoptotic mediator (DNA-damage inducible transcript 3, encoded by Ddit3). CONCLUSIONS/INTERPRETATION: The changes that we observed in the UPR pathway due to ER stress may play a role in the pathogenesis of CNS complications in diabetes. The results of this study are a foundation for the development of pharmacological targets to reduce ER stress in diabetic hippocampi.

Use of parenteral colistin for the treatment of multiresistant Gram-negative organisms in major burn patients in South Korea.

PURPOSE: To assess the therapeutic effect and toxicity of intravenous colistin in the treatment of multidrug-resistant (MDR) Gram-negative bacteria in patients with severe burns. METHODS: The medical records of 930 patients admitted to the Burn Intensive Care Unit (ICU) at Hallym University Hangang Sacred Heart Hospital, Seoul, South Korea between April 2007 and December 2009 were retrospectively reviewed. Of these, the 104 patients who had received intravenous colistin treatments (104 courses) during this period were enrolled in the study. Changes in creatinine level were analyzed in three groups: all patients receiving colistin (n = 104), patients with undergoing continuous renal replacement therapy (CRRT group; n = 38), and patients not undergoing CRRT (non-CRRT group; n = 66). RESULTS: Among these patients, the burnt body surface area ranged from 5 to 96% (mean 49.7%). Thirty-five patients (33.7%) suffered inhalation injury, and CRRT was administered to 38 patients. The mean duration of colistin treatment was 14.7 (range 4-71) days. The total dose of colistin was 3,045.7 mg (range 100-13,800). The length of ICU stay was 48.9 (range 7-154) days. Forty patients (38.5%) died. The mean pre-colistin creatinine level of all patients was 1.04 mg/dL, and the mean post-colistin level was 1.34 mg/dL. The mean pre-colistin creatinine level of the CRRT group and non-CRRT group was 1.68 and 0.66 mg/dL, and the mean post-colistin level was 1.68 and 1.14 mg/dL, respectively. CONCLUSIONS: Colistin appears to be a relatively safe and effective treatment for major burn patients with infections caused by MDR Gram-negative bacteria when no other drug is available. Additionally, we found no statistically significant impairment of creatinine levels.

Relationship between the expression of fibulin-3 and anterior vaginal wall prolapse.

Anterior vaginal wall prolapse is the most common type of pelvic organ prolapse. Vaginal wall samples were obtained from women with (n =12) and without (n =12) anterior vaginal wall prolapse. No reports have been published on the content of fibulin-3 in the vaginal walls of patients with prolapse; thus, we compared the expression of fibulin-3 in the vaginal walls of women with and without anterior vaginal wall prolapse. RT-PCR was performed to measure mRNA expression and the expression of protein was assessed by immunohistochemistry. Statistical analysis was performed to determine differences between the two groups of women. Age, parity and menopausal status did not differ between women with and without prolapse. The expressions of fibulin-3 mRNA and protein were not different between the prolapse and no prolapse groups. It is unlikely that abnormal expression of fibulin-3 has a major role in the pathogenesis of anterior vaginal wall prolapse.

Hematological Responses, Survival, and Respiratory Exchange in the Olive Flounder, Paralichthys olivaceus, during Starvation.

A 12-wk experiment was conducted to examine the hematological changes, survival, and respiratory exchange in the olive flounder, Paralichthys olivaceus, during starvation. The growth, survival and respiratory exchange rates of the starved group were lower than those of the fed group during the experiment. Blood analysis, including hematocrit, hemoglobin, red blood cells, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and mean corpuscular volume, did not differ significantly (p>0.05) between the fed and starved groups at the end of the experiment. There were no significant differences in plasma cortisol, glucose, Na(+), Cl(-), K(+), or aspartate aminotransferase between the fed and starved groups (p>0.05). Alanine aminotransferase levels were higher in the starved group than in the fed group, whereas plasma osmolality was lower in the starved group than in the fed group. It was shown that starved fish had various problems after four weeks, which did not occur in the fed group. Long-term starvation is infrequent in aquaculture farms. However, starvation studies of this kind are very useful for a basic understanding of how physiological changes affect fish health, life expectancy, and growth.

Toll-like receptors and inflammation in metabolic neuropathy; a role in early versus late disease?

Neuropathy is a common, morbid complication of the metabolic syndrome, prediabetes, and diabetes. Recent studies have indicated a potential role for the immune system in the development of neuropathy. In particular, toll-like receptors (TLR) 2 and 4 have been linked to metabolic dysfunction, and blocking TLR4 is proposed as a treatment for neuropathic pain. In the current study, we investigated the role of the immune system, particularly TLRs 2 and 4, in the pathogenesis and progression of neuropathy. Sural or sciatic nerve gene expression arrays from humans and murine neuropathy models of prediabetes and diabetes were first analyzed to identify differentially expressed TLR2- and TLR4-associated genes within the KEGG (Kyoto Encyclopedia of Genes and Genomes) database. We observed that genes associated with TLRs 2 and 4, particularly lipopolysaccharide binding protein (LPB) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta (PIK3CB), were dysregulated across species and across multiple murine models of prediabetic and diabetic neuropathy. To further understand the role of these pathways in vivo, TLR 2 and 4 global knockout mice placed on a 60% high fat diet (HFD-TLR2/4-/-) were compared with wild type (WT) mice on a high fat diet (HFD-WT) and WT controls on a standard diet (CON). Mice then underwent metabolic, neuropathic, and immunological phenotyping at two time points to assess the impact of TLR signaling on neuropathy and immunity during metabolic dysfunction over time. We found that HFD-TLR2/4-/- and HFD-WT mice weighed more than CON mice but did not have increased fasting blood glucose levels. Despite normal blood glucose levels, HFD-TLR2/4-/- mice eventually developed neuropathy at the later time point (28 wks of age) but were somewhat protected from neuropathy at the early time point (16 wks of age) as measured by shorter hind paw withdraw latencies. This is in contrast to HFD-WT mice which developed neuropathy within 11 wks of being placed on a high fat diet and were neuropathic by all measures at both the early and late time points. Finally, we immunophenotyped all three mouse groups at the later time point and found differences in the number of peripheral blood Ly6C-myeloid cells as well as F4/80+ expression. These results indicate that TLR signaling influences early development of neuropathy in sensory neurons, potentially via immune modulation and recruitment.

Age-and region-dependent changes in three-dimensional microstructural properties of proximal femoral trabeculae.

UNLABELLED: This study investigated regional variations in the 3D microstructure of trabecular bone in human proximal femur, with respect to aging. The results demonstrate that age-related changes in trabecular microstructure significantly varied from different sub-regions of the proximal femur. INTRODUCTION: We hypothesize that the age-related changes in trabecular bone microstructure appear to be varied from specific anatomic sub-regions of the proximal femur followed by non-uniform bone loss. The purpose of this study was therefore to explore regional variations in the 3D microstructure of trabecular bone in human proximal femur, with respect to aging. METHODS: A total of 162 trabecular bone cores from six regions of 27 femora of male cadaver donors were scanned using micro-computed tomography (micro-CT). The following microstructural parameters were calculated: bone volume fraction (BV/TV), trabecular number (Tb.N), thickness (Tb.Th) and separation (Tb.Sp), structure model index (SMI), and degree of anisotropy (DOA). RESULTS: Age-related changes in trabecular microstructure varied from different regions of the proximal femur. There was a significant decrease in bone volume fraction and an almost identical decrease in trabecular thickness associated with aging at any region. Regional analysis demonstrated a significant difference in BV/TV, Tb.Th, Tb.Sp, Tb.N and DOA between superior and inferior neck, as well as a significant difference in BV/TV, Tb.Sp, Tb.N, SMI and DOA between superior and inferior trochanter. CONCLUSIONS: Age-related changes in bone loss and trabecular microstructure within the male proximal femur are not uniform in this cadaveric population.

Infectious complications in living-donor liver transplant recipients: a 9-year single-center experience.

BACKGROUND: Infectious complications following living-donor liver transplantation (LDLT) remain a major cause of morbidity and mortality. We analyzed the frequency and type of infectious complications according to the post-transplantation period, and their risk factors with regard to morbidity and mortality. METHODS: We retrospectively analyzed 208 subjects who had undergone LDLT during a 9-year period. RESULTS: The rate of infection was 1.69 per patient during the study period. The predominant infections were intra-abdominal infections (37.6%), primary bacteremia (17.4%), and pneumonia (14.5%). Within the first post-transplant month, 140 (39.9%) infections were detected, and catheter-related coagulase-negative staphylococci (44) were the most common infectious agents. During the 2-6-month post-transplant period, 109 infectious episodes occurred (31.1%), and Enterococcus sp. (n=16) related to biliary infection was the most frequent isolate. After the sixth month, 96 infectious episodes (29%) occurred, and biliary tract-related Escherichia coli (n=19) was the major causative organism. The overall mortality was 24.5% (51/208); 1-year survival rate was 88% (196/208). Post-transplant infection-related mortality was 52.9% (27/51). Biliary tract complications, such as biliary stenosis or leakage, significantly increased the mortality (P=0.01); however, reoperation (retransplantation or resurgery for biliary tract obstruction/leakage or to control bleeding) significantly reduced the mortality (P=0.01). CONCLUSIONS: Our data showed that early catheter removal would mainly aid in reducing infectious complications in the 1-month post-transplantation period. Aggressive management, including reoperation, would lower the mortality in the LDLT recipients.

Comparative study of fluorodeoxyglucose positron emission tomography and magnetic resonance imaging for the detection of spinal bone marrow infiltration in untreated patients with multiple myeloma.

BACKGROUND: The presence and extent of osteolytic bone lesions in untreated patients with multiple myeloma are important factors in the staging of the disease, and the extent of bone lesions in multiple myeloma cases significantly influences decisions regarding therapy. Recently, fluorodeoxyglucose positron emission tomography (FDG-PET) and magnetic resonance imaging (MRI) have been used to detect bone marrow involvement in patients with multiple myeloma. PURPOSE: To compare the efficacy of FDG-PET and MRI for the detection of bone marrow infiltration into the spine in untreated patients with multiple myeloma. MATERIAL AND METHODS: Twenty-two patients with multiple myeloma underwent both FDG-PET and spine MRI. The examined spinal regions by MRI included 21 thoracic and lumbar spines, one lumbar spine, and 12 cervical spines. The following imaging sequences were performed: T1-weighted spin-echo MRI with and without fat suppression, and T2-weighted spin-echo MRI in the sagittal plane. In the patients with bone marrow abnormalities, an additional contrast-enhanced T1-weighted spin-echo MR image and a fat-suppressed T1-weighted spin-echo MR image were obtained. Patients were divided into three groups on the basis of the criteria defined by Durie and Salmon: stage I (n=9), stage II (n=3), and stage III (n=10). The number and location of lesions detected in both FGD-PET and MRI were recorded, and the lesions were compared using the McNemar test. Bone marrow biopsy results, the patient's clinical examinations, and other imaging findings (MRI, FDG-PET, etc.) were used as references. RESULTS: In stages I and II (37 lesions in 12 patients), FDG-PET and MRI detected lesions in 78% (29 of 37 lesions) and 86% (32 of 37 lesions), respectively. However, the difference between the abilities of FDG-PET and MRI to detect lesions was not statistically significant (P=0.317). In stage III (101 lesions in 10 patients), FDG-PET and MRI detected lesions in 80% (81 of 101 lesions) and 92% (93 of 101 lesions), respectively. The difference between the abilities of FDG-PET and MRI to detect lesions was statistically significant (P=0.038). CONCLUSION: MRI is superior to FDG-PET in detecting bone marrow involvement in the spine of patients with advanced multiple myeloma.

Use of synchronous fluorescence spectra to estimate biochemical oxygen demand (BOD) of urban rivers affected by treated sewage.

Synchronous fluorescence spectra and the first derivative spectra of urban rivers affected by treated sewage were studied to find the optimum index for biochemical oxygen demand (BOD) estimation. In addition, various sample treatment methods as well as the multiple regression method using available monitoring parameters were examined to improve the BOD estimation capability of the indices. From July to November 2006, grab samples were collected from three rivers in the city of Seoul, Korea, which included one receiving effluent from a municipal wastewater treatment facility. The BOD values of the samples ranged from 0.4 to 28.0 mg l(-1). Out of the many fluorescence characteristics observed, the relative fluorescence intensity at 283 nm to 245 nm from the synchronous spectra was selected as the optimum fluorescence estimation index because it had the highest positive correlations with the BOD values (r = 0.910). The filtration process, using GF/F filter prior to the fluorescence measurement, resulted in an enhanced correlation demonstrating that the removal of suspended solids from the samples helps alleviate, to some extent, the interference of light scattering. In contrast, the same correlation was not enhanced by the pH adjustment of the sample to minimize the complexation of organic matter with cations. The multiple regression method, using either light scattering intensity at 633nm or turbidity, greatly enhanced the correlation between measured and predicted BOD values. The correlation was even higher than that obtained for filtered samples, thus suggesting that the multiple regression method based on the original sample is more effective than sample treatment in enhancing BOD estimation.

Administration of Cripto in GRP78 overexpressed human MSCs enhances stem cell viability and angiogenesis during human MSC transplantation therapy.

OBJECTIVES: The purpose of this study was to explore the effectiveness of concurrent GRP78 overexpression combined with Cripto on hMSC proliferation and migration both in vitro and in vivo. Specifically, we explored whether the treatment enhances effectiveness of hMSC transplantation in ischaemic tissue. MATERIALS AND METHODS: Human MSCs obtained from human adipose tissue were cultured in α-minimum essential medium (Hyclone, Logan, UT, USA) supplemented with 10% (v/v) foetal bovine serum (Hyclone), 100 U mL-1 penicillin and 100 µg mL-1 streptomycin. Murine hindlimb ischaemic model was generated with 8-week-old male nude BALB/c mice (Biogenomics, Seoul, Korea) maintained under a 12-h light/dark cycle following the established protocol with minor modification. Cellular injection was performed no later than 3 hour after surgery. Lipofectamine transfection, single-cell cultivation assay, transwell assay, scratch wound-healing migration assay, immunohistochemistry and western blotting assays were performed. RESULTS: Overexpression of GRP78 along with Cripto enhanced hMSC proliferation, migration and invasion. It increased interaction of surface GRP78 receptor with Cripto via JAK2/STAT3 pathway. We confirmed our proposed mechanism by showing that treatment with GRP78 antibody blocks the enhancement in vitro. In vivo, we observed that Cripto induced by the hypoxic environment in hindlimb ischaemic model interacts with the overexpressed GRP78 and increases hMSC proliferation, migration and invasion potentials as well as angiogenesis around transplanted ischaemic site via cytokine secretions. CONCLUSIONS: These results demonstrate supporting evidences that GRP78-Cripto combination technique offers novel strategy to enhance MSC proliferation, migration and invasion potentials as well as angiogenesis around ischaemic site, ultimately facilitating MSC-based transplantation therapy in ischaemic conditions.

Endophytic and endolichenic fungal diversity in maritime Antarctica based on cultured material and their evolutionary position among Dikarya.

Fungal endophytes comprise one of the most ubiquitous groups of plant symbionts. They live asymptomatically within vascular plants, bryophytes and also in close association with algal photobionts inside lichen thalli. While endophytic diversity in land plants has been well studied, their diversity in lichens and bryophytes are poorly understood. Here, we compare the endolichenic and endophytic fungal communities isolated from lichens and bryophytes in the Barton Peninsula, King George Island, Antarctica. A total of 93 fungal isolates were collected from lichens and bryophytes. In order to determine their identities and evolutionary relationships, DNA sequences of the nuclear internal transcribed spacer (ITS), nuclear ribosomal small subunit (nuSSU), nuclear large subunit (nuLSU), and mitochondrial SSU (mtSSU) rDNA were obtained and protein coding markers of the two largest subunit of RNA polymerase II (RPB1 and RPB2) were generated. Multilocus phylogenetic analyses revealed that most of the fungal isolates were distributed in the following six classes in the phylum Ascomycota: Dothideomycetes, Eurotiomycetes, Lecanoromycetes, Leotiomycetes, Pezizomycetes and Sordariomycetes. For the first time we report the presence of subphylum Mortierellomycotina that may belong to an undescribed order in endophytic fungi. Taken together, our results imply that lichens and bryophytes provide similar niches and harbour a selection of these fungi, indicating generalists within the framework of evolutionary adaptation.

Abnormal RNA stability in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) share key features, including accumulation of the RNA-binding protein TDP-43. TDP-43 regulates RNA homeostasis, but it remains unclear whether RNA stability is affected in these disorders. We use Bru-seq and BruChase-seq to assess genome-wide RNA stability in ALS patient-derived cells, demonstrating profound destabilization of ribosomal and mitochondrial transcripts. This pattern is recapitulated by TDP-43 overexpression, suggesting a primary role for TDP-43 in RNA destabilization, and in postmortem samples from ALS and FTD patients. Proteomics and functional studies illustrate corresponding reductions in mitochondrial components and compensatory increases in protein synthesis. Collectively, these observations suggest that TDP-43 deposition leads to targeted RNA instability in ALS and FTD, and may ultimately cause cell death by disrupting energy production and protein synthesis pathways.