Western Diet Promotes Intestinal Colonization by Collagenolytic Microbes and Promotes Tumor Formation After Colorectal Surgery.

BACKGROUND & AIMS: The Western diet, which is high in fat, is a modifiable risk factor for colorectal recurrence after curative resection. We investigated the mechanisms by which the Western diet promotes tumor recurrence, including changes in the microbiome, in mice that underwent colorectal resection. METHODS: BALB/c male mice were fed either standard chow diet or Western-type diet (characterized by high fat, no fiber, and decreased minerals and vitamins) for 4 weeks; some mice were given antibiotics or ABA-PEG20k-Pi20 (Pi-PEG), which inhibits collagenase production by bacteria, but not bacterial growth, in drinking water. Colorectal resections and anastomoses were then performed. The first day after surgery, mice were given enemas containing a collagenolytic rodent-derived strain of Enterococcus faecalis (strain E2), and on the second day they were given mouse colon carcinoma cells (CT26). Twenty-one days later, distal colons were removed, and colon contents (feces, distal colon, and tumor) were collected. Colon tissues were analyzed by histology for the presence of collagenolytic colonies and by 16S ribosomal RNA sequencing, which determined the anatomic distribution of E faecalis at the site of the anastomosis and within tumors using in situ hybridization. Mouse imaging analyses were used to identify metastases. RESULTS: Colorectal tumors were found in 88% of mice fed the Western diet and given antibiotics, surgery, and E faecalis compared with only 30% of mice fed the standard diet followed by the same procedures. Colon tumor formation correlated with the presence of collagenolytic E faecalis and Proteus mirabilis. Antibiotics eliminated collagenolytic E faecalis and P mirabilis but did not reduce tumor formation. However, antibiotics promoted emergence of Candida parapsilosis, a collagenase-producing microorganism. Administration of a Pi-PEG reduced tumor formation and maintained diversity of the colon microbiome. CONCLUSIONS: We identified a mechanisms by which diet and antibiotic use can promote tumorigenesis by colon cancer cells at the anastomosis after colorectal surgery. Strategies to prevent emergence of these microbe communities or their enzymatic activities might be used to reduce the risk of tumor recurrence in patients undergoing colorectal cancer surgery.

Solar background noise mitigation using the orbital angular momentum mode in vertical FSO downlink transmissions.

Free-space optical communication (FSO) is used to provide network configuration flexibility. A network-flying platform-based vertical FSO connection can be employed to enhance mobile network coverage and capacity. Solar background noise can be a potential risk that disrupts the seamless connection in the vertical FSO downlink channel. In this paper, we propose signal transmission using an orbital angular momentum (OAM) beam. The OAM demodulation process can filter sunlight out of the optical receiver except for the signal corresponding to the azimuthal state. We experimentally verified that most of the solar background noise could be reduced. To verify the feasibility of the proposed scheme in a vertical FSO channel, we modeled a FSO vertical downlink with an OAM modulation/demodulation process.

Combining stool and stories: exploring antimicrobial resistance among a longitudinal cohort of international health students.

BACKGROUND: Antimicrobial resistance (AMR) is a global public health concern that requires transdisciplinary and bio-social approaches. Despite the continuous calls for a transdisciplinary understanding of this problem, there is still a lack of such studies. While microbiology generates knowledge about the biomedical nature of bacteria, social science explores various social practices related to the acquisition and spread of these bacteria. However, the two fields remain disconnected in both methodological and conceptual levels. Focusing on the acquisition of multidrug resistance genes, encoding extended-spectrum betalactamases (CTX-M) and carbapenemases (NDM-1) among a travelling population of health students, this article proposes a methodology of 'stool and stories' that combines methods of microbiology and sociology, thus proposing a way forward to a collaborative understanding of AMR. METHODS: A longitudinal study with 64 health students travelling to India was conducted in 2017. The study included multiple-choice questionnaires (n = 64); a collection of faecal swabs before travel (T0, n = 45), in the first week in India (T1, n = 44), the second week in India (T2, n = 41); and semi-structured interviews (n = 11). Stool samples were analysed by a targeted metagenomic approach. Data from semi-structured interviews were analysed using the method of thematic analysis. RESULTS: The incidence of ESBL- and carbapenemase resistance genes significantly increased during travel indicating it as a potential risk; for CTX-M from 11% before travel to 78% during travel and for NDM-1 from 2% before travel to 11% during travel. The data from semi-structured interviews showed that participants considered AMR mainly in relation to individual antibiotic use or its presence in a clinical environment but not to travelling. CONCLUSION: The microbiological analysis confirmed previous research showing that international human mobility is a risk factor for AMR acquisition. However, sociological methods demonstrated that travellers understand AMR primarily as a clinical problem and do not connect it to travelling. These findings indicate an important gap in understanding AMR as a bio-social problem raising a question about the potential effectiveness of biologically driven AMR stewardship programs among travellers. Further development of the 'stool and stories' approach is important for a transdisciplinary basis of AMR stewardship.

Risk factors and renal outcomes of low bone mineral density in patients with non-dialysis chronic kidney disease.

Bone disorder is a common complication of chronic kidney disease (CKD). The clinical usefulness of bone mineral density (BMD) in CKD is not well known. Our study shows that low BMD is associated with physical activity and dietary Na/K intake ratio and can predict poor renal outcome in non-dialysis CKD. PURPOSE: Despite evidence of a link between bone mineral disorders and chronic kidney disease (CKD), the clinical implications of bone mineral density (BMD) in CKD are not well established. We investigated risk factors and renal outcomes of low BMD in CKD. METHODS: We analyzed data from the KNOW-CKD. BMD measured by dual-energy x-ray absorptiometry was classified by T score: normal (T score ≥ - 1.0), osteopenia (- 1.0 > T score > - 2.5), and osteoporosis (T score ≤ - 2.5) of the lumbar spine, hip, or femoral neck. Logistic regression analysis to assess risk factors of low BMD (T score < - 1.0) and Cox proportional hazards models to estimate risk of incident end-stage renal disease (ESRD). RESULTS: Low BMD was prevalent (osteopenia 33%; osteoporosis 8%) in 2128 adults with CKD (age 54 ± 12 years; male 61%). Over a median follow-up of 4.3 years, there were 521 cases of incident ESRD. Lower BMD was associated with female sex, older age, low eGFR, low BMI, and lifestyle factors of physical activity (odds ratio (OR) = 0.62, 95% confidence interval (0.49-0.77)) and spot urine Na/K ratio (1.07 (1.00-1.15)). In adjusted Cox models, low BMD was associated with increased incident ESRD (hazard ratio (HR) = 1.14 (0.92-1.41) for osteopenia; 1.43 (1.01-2.04) for osteoporosis, P for trend < 0.05) compared with the reference of normal BMD. The association between low BMD and ESRD was similar according to T score discordance classification. CONCLUSIONS: Low BMD was associated with modifiable lifestyle factors including low physical activity and high dietary Na/K intake ratio. The presence of low BMD is associated with poor renal outcomes in non-dialysis CKD.

Low hydration status may be associated with insulin resistance and fat distribution: analysis of the Korea National Health and Nutrition Examination Survey (KNHANES) 2008-2010.

We aimed to identify the association of hydration status with insulin resistance (IR) and body fat distribution. A total of 14 344 adults participated in the Korea National Health and Nutrition Examination Survey 2008-2010. We used urine specific gravity (USG) to indicate hydration status, and HOMA-IR (homoeostasis model assessment of IR) and trunk:leg fat ratio (TLR) as primary outcomes. In multivariate logistic regression, the OR per 0·01 increase in USG for high IR was 1·303 (95 % CI 1·185, 1·433; P < 0·001). In multivariate generalised additive model plots, increased USG showed a J-shaped association with logarithmic HOMA-IR, with the lowest Akaike's information criterion score of USG 1·030. Moreover, increased USG was independently associated with increased trunk fat, decreased leg fat and increased TLR. In mediation analysis, the proportion of mediation effects of USG on TLR via IR was 0·193 (95 % CI 0·132, 0·285; P < 0·001), while the proportion of mediation effects of USG on IR via TLR was 0·130 (95 % CI 0·086, 0·188; P < 0·001). Increased USG, a sign of low hydration status and presumably high vasopressin, was associated with IR and poor fat distribution. Direct effect of low hydration status may be more dominant than indirect effect via IR or fat distribution. Further studies are necessary to confirm our findings.

Equol, a Blood-Brain Barrier Permeable Gut Microbial Metabolite of Dietary Isoflavone Daidzein, Exhibits Neuroprotective Effects against Neurotoxins Induced Toxicity in Human Neuroblastoma SH-SY5Y Cells and Caenorhabditis elegans.

Emerging data support that plant food based isoflavones have ameliorating effects on a variety of neurodegenerative diseases including Parkinson's disease (PD). Our previous investigation revealed that dietary isoflavones including genistein (GEN), daidzein (DAI), and equol (EQL; a gut microbial metabolite of DAI) showed promising blood-brain barrier permeability and anti-neuroinflammatory activity in murine microglial BV2 cells. However, the neuroprotective effects of EQL against neurotoxins induced toxicity in PD related models remains unclear. Herein, EQL, along with GEN and DAI, were evaluated for their cytoprotective effect in a non-contact co-culture model with LPS-BV2-conditioned media and human neuroblastoma SH-SY5Y cells. In addition, their neuroprotective effects against PD related neurotoxins including 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP+) induced cytotoxicity were evaluated in SH-SY5Y cells. Furthermore, EQL was evaluated for its neuroprotective effects against MPP+ induced neurotoxicity using in vivo PD model including Caenorhabditis elegans lifespan assay. DAI (10 µM) and EQL (10 and 20 µM) showed cytoprotective effects by decreasing LPS-BV2-conditioned media induced cytotoxicity in SH-SY5Y cells by 29.2, 32.4 and 27.2%, respectively. EQL (10 and 20 µM) also showed neuroprotective effects by decreasing 6-OHDA and MPP+ induced cytotoxicity in SH-SY5Y cells by 30.6-34.5 and 17.9-18.9%, respectively. Additionally, data from the in vivo assay supported EQL's neuroprotective effect as it increases survival of C. elegans exposed to MPP+ from 72 to 108 h. Our findings support a growing body of evidence of the neuroprotective effects of dietary isoflavones and further studies are warranted to elucidate their mechanisms of action.

Effects of quorum-sensing inhibition on experimental periodontitis induced by mixed infection in mice.

This study aimed to verify, in in vivo settings, whether quorum-sensing inhibition molecules could attenuate alveolar bone loss induced by Porphyromonas gingivalis/Fusobacterium nucleatum co-infection and reduce the bacterial colonization of periodontal tissues. In BALB/c mice, periodontitis was induced through oral inoculation with P. gingivalis and F. nucleatum six times during a 42-d period. Quorum sensing inhibitors (a furanone compound and D-ribose) were administered simultaneously with bacterial infection. Linear and volumetric modifications of interproximal alveolar bone levels were compared between groups using micro-computed tomography. Total bacteria, and P. gingivalis and F. nucleatum DNA in periodontal tissues, were quantified using real-time PCR. Radiographic linear measurements demonstrated a significant reduction of alveolar bone loss, of approximately 40%, in mice treated with quorum sensing inhibitors when compared with the co-infection group. This was confirmed by a significant increase of residual bone volume in the test group. While total bacterial genes in the treatment group significantly decreased by 93% in periodontal tissue samples when quorum sensing inhibitors were administered, no significant differences of P. gingivalis DNA were found. Quorum sensing inhibitors reduced periodontal breakdown and bacterial infection in periodontal tissues after co-infection with P. gingivalis and F. nucleatum.

Neuroprotective effects of a novel poly (ADP-ribose) polymerase-1 inhibitor, JPI-289, in hypoxic rat cortical neurons.

Excessive activation of poly (ADP-ribose) polymerase-1 (PARP-1) is known to develop neuronal apoptosis, necrosis and inflammation after ischaemic brain injury. Therefore, PARP-1 inhibition after ischaemic stroke has been attempted in successful animal studies. The purpose of present work was to develop a novel water soluble PARP-1 inhibitor (JPI-289) and explore its neuroprotective effect on ischaemic injury in an in vitro model. The half-life of JPI-289 after intravenous or oral administration in rats was relatively long (1.4-1.5 hours) with 65.6% bioavailability. The inhibitor strongly inhibited PARP-1 activity (IC50 =18.5 nmol/L) and cellular PAR formation (IC50 =10.7 nmol/L) in the nanomolar range. In rat cortical neuronal cells, JPI-289 did not affect cell viability up to 1 mmol/L as assayed by Trypan blue staining (TBS) and lactate dehydrogenase (LDH) assay. Treatment of JPI-289 for 2 hours after 2 hours of oxygen glucose deprived (OGD) rat cortical neuron attenuated PARP activity and restored ATP and NAD+ levels. Apoptosis-associated molecules such as apoptosis inducing factor (AIF), cytochrome C and cleaved caspase-3 were reduced after JPI-289 treatment in the OGD model. The present findings suggest that the novel PARP-1 inhibitor, JPI-289, is a potential neuroprotective agent which could be useful as a treatment for acute ischaemic stroke.

Chronic kidney disease and high eGFR according to body composition phenotype in adults with normal BMI.

BACKGROUND AND AIMS: Body composition contributes to the risk of chronic kidney disease (CKD) and glomerular hyperfiltration. In adults with normal body mass index (BMI), the relationships of body composition with CKD and high estimated glomerular filtration rate (eGFR) are largely unknown. METHODS AND RESULTS: We analyzed 10,734 adults from the Korean National Health and Nutrition Examination Survey (KNHANES), whose body mass index (BMI) was within the normal range (18.5-24.9 kg/m2). Body composition was categorized into four phenotypes (normal, sarcopenia alone, obesity alone, and sarcopenic obesity) based on appendicular lean mass index (ALMI) and total body fat percentage (TBF%) measured by dual-energy X-ray absorptiometry (DXA). We examined the relationship of CKD and high eGFR (eGFR ≥ 120 ml/min per 1.73 m2) with body composition phenotypes. Sarcopenia alone (14.3%), obesity alone (16.0%), and sarcopenic obesity (10.7%) were prevalent. The association between sarcopenia alone and eGFR was J-shaped, while that between sarcopenic obesity and eGFR was U-shaped. In multivariate logistic regression analysis compared with the normal phenotype, sarcopenic obesity had an elevated odds ratio (OR) for CKD (OR: 1.59, 95% CI: 1.16-2.19). Sarcopenia alone (OR: 1.87; 95% CI: 1.41-2.47) and sarcopenic obesity (OR: 2.37, 95% CI: 1.68-3.36) had elevated OR for high eGFR. CONCLUSION: These findings suggest that decreased muscle mass and coexistence with excess adiposity show associations with CKD and high eGFR even in adults with normal BMI. Body composition measured by DXA could provide information on the relationship of body composition with CKD and high eGFR.

A cohort study of MFN2 mutations and phenotypic spectrums in Charcot-Marie-Tooth disease 2A patients.

Charcot-Marie-Tooth disease 2A (CMT2A) is the most common axonal form of peripheral neuropathy caused by a defect in the mitofusin 2 (MFN2) gene, which encodes an outer mitochondrial membrane GTPase. MFN2 mutations result in a large range of phenotypes. This study analyzed the prevalence of MFN2 mutation in Korean families with their assorted phenotypes (607 CMT families and 160 CMT2 families). Direct sequencing of the MFN2 coding exons or whole-exome sequencing has been applied to identify causative mutations. A total of 21 mutations were found in 36 CMT2 families. Comparative genotype-phenotype correlations impacting severity, onset age, and specific symptoms were assessed. Most mutations were seen in the GTPase domain (∼86%). A deletion mutation found in the transmembrane helices is reported for the first time, as well as five novel mutations at other domains. MFN2 mutations made up 5.9% of total CMT families, whereas 22.9% in CMT2 families, of which 27.8% occurred de novo. Interestingly, patient phenotypes ranged from mild to severe even for the same mutation, suggesting other factors influenced phenotype and penetrance. This CMT2A cohort study will be useful for molecular diagnosis and treatment of axonal neuropathy.

Identification of novel mutations in the VPS33B gene involved in arthrogryposis, renal dysfunction, and cholestasis syndrome.

Arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome is an autosomal recessive disorder caused by mutations in the VPS33B and VIPAS39. Here, we report novel mutations identified in four patients with ARC syndrome. We analyzed the entire coding regions of the VPS33B and VIPAS39 genes by direct sequencing. To detect novel splice site mutations, mRNA transcripts were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and sequencing. All four patients had compound heterozygous variants in the VPS33B gene. One patient had a previously reported splice site variant with unknown significance, c.239+5G>A, and a novel nonsense mutation, c.621G>A. The other three patients had the c.403+2T>A mutation, and each of them carried one of the splice site variants, c.239+5G>A or c.499-11G>A. c.239+5G>A and c.499-11G>A created novel splice sites which resulted in abnormal transcripts. No significant VIPAS39 mutation was detected in all patients. In patients suspected with ARC syndrome, mutation analysis of the VPS33B gene should be employed as a primary diagnostic test before performing invasive testing procedures such as organ biopsies. Performing mRNA analysis can be useful in predicting the pathogenic phenotype when the mutation seems to affect a normal splicing mechanism.

Low serum magnesium is associated with coronary artery calcification in a Korean population at low risk for cardiovascular disease.

BACKGROUND AND AIMS: Previous studies suggested an association between low serum magnesium levels and metabolic or cardiovascular disease. Additionally, several studies have shown that low serum magnesium is associated with vascular calcification, but there are no studies exploring its relation to coronary artery calcification (CAC). We investigated the relationship between low serum magnesium and CAC by using health examination data. METHODS AND RESULTS: We cross-sectionally analyzed 34,553 participants who underwent coronary multi-detector computed tomography and serum magnesium level measurement in 2010-2012 as part of a health examination program at a tertiary hospital in Korea. CAC was defined as a coronary artery calcium score > 100. Participants were divided into three groups according to their serum magnesium level as follows: low < 1.9 mg/dL (n = 931), normal = 1.9-2.3 mg/dL (n = 32,341), and high > 2.3 mg/dL (n = 1281). The percentages of participants with CAC were 3.7, 1.5, and 2.3 in each group, respectively. According to multivariate analysis, low serum magnesium was associated with CAC after adjustment for age, sex, BMI, diabetes, hypertension, cardiovascular disease, systolic BP, LDL cholesterol, HDL cholesterol, eGFR, serum calcium and phosphorus, hsCRP, current smoking status, alcohol intake and vigorous exercise frequency. The odds ratio for CAC in the low serum magnesium group compared to the normal group was 2.10 (1.40-3.15, P < 0.001). CONCLUSION: Low serum magnesium level is associated with CAC in a Korean population at low risk for cardiovascular disease. Further studies are needed to generalize this finding and to verify the causal relationship between low serum magnesium and CAC.

Clinical and histopathological study of Charcot-Marie-Tooth neuropathy with a novel S90W mutation in BSCL2.

The objective of the study was to investigate the disease-causing mutation in an autosomal dominant Charcot-Marie-Tooth disease type 2 family and examine the clinical and histopathological evaluation. We enrolled a family of Korean origin with axonal Charcot-Marie-Tooth disease neuropathy (FC305; 13 males, six females) and applied genome-wide linkage analysis. Whole exome sequencing was performed for two patients. In addition, sural nerve biopsies were obtained from two patients. Through whole exome sequencing, we identified an average of 20,336 coding variants from two patients. We also found evidence of linkage mapped to chromosome 11p11-11q13.3 (LOD score of 3.6). Among these variants in the linkage region, we detected a novel p.S90W mutation in the Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) gene, after filtering 31 Korean control exomes. Our p.S90W patients had frequent sensory disturbances, pyramidal tract signs, and predominant right thenar muscle atrophy in comparison with reported p.S90L patients. The phenotypic spectra were wide and demonstrated intrafamilial variability. Two patients with different clinical features underwent sural nerve biopsies; the myelinated fiber densities were increased slightly in both patients, which differed from two previous case reports of BSCL2 mutations (p.S90L and p.N88S). This report expands the variability of the clinical spectrum associated with the BSCL2 gene and describes the first family with the p.S90W mutation.

Recruiting African American Prostate Cancer Survivors for a Population-based Biobank Study.

BACKGROUND: Prostate cancer affects African American men disproportionately compared with men of other racial/ethnic groups. To identify biological bases for this health disparity, we sought to create a state-wide biobank of African American prostate cancer survivors in Florida. METHODS: African American men diagnosed with prostate cancer between 2013 and 2017 and living in Florida at diagnosis were identified through the State of Florida's cancer registry. Individuals were approached via mail and telephone, assessed for eligibility, and asked for informed consent. χ2 and t tests were conducted to identify differences between eligible and reachable individuals (i.e., had valid contact information) versus consented participants. RESULTS: Of the 5,960 eligible and reachable individuals, 3,904 were eligible and contacted at least once, and 578 consented [overall consent rate = 10% (578/5,960); adjusted consent rate = 15% (578/3,904)]. Statistically significant (Ps < 0.05) but small differences in demographic and clinical variables were observed. Consented participants were less likely to be older than 64 (35% vs. 41%) and less likely to have received radiotherapy (36% vs. 41%) and hormone therapy (16% vs. 21%), but more likely to have regional prostate cancer (13% vs. 11%) and have undergone surgery (44% vs. 39%). Consented participants did not differ from reachable individuals on other demographic and clinical factors (Ps > 0.05). CONCLUSIONS: Recruiting African American prostate cancer survivors to biobanking research through a cancer registry is feasible. However, the consent rate was low, and existing challenges limit consent and participation. IMPACT: Strategies for overcoming barriers to informed consent and increasing participation in biospecimen research are needed to address cancer disparities.

Enterococcus faecalis promotes a migratory and invasive phenotype in colon cancer cells.

Much about the role of intestinal microbes at the site of colon cancer development and tumor progression following curative resection remains to be understood. We have recently shown that collagenolytic bacteria such as Enterococcus faecalis predominate within the colon postoperatively, particularly at the site of the colon reconnection (i.e. anastomosis) in the early period of post-surgical recovery. The presence of collagenolytic bacteria at this site correlates with the tumor progression in a mouse model of post-surgical tumor development. In the present study we hypothesized, that collagenolytic bacteria, such as E. faecalis, play an important yet to be discovered role in tumor formation and progression. Therefore the aims of this study were to assess the role of collagenolytic E. faecalis on the migration and invasion of a murine colon cancer cell line. Results demonstrated that both migration and invasion were induced by E. faecalis with collagenolytic activity being required for only invasion. Bidirectional signaling in the E. faecalis-cancer cell interaction was observed by the discovering that the expression of gelE in E. faecalis, the gene required for collagenase production, is expressed in response to exposure to CT26 cells. The mechanism by which migration enhancement via E. faecalis occurs appears to be dependent on its ability to activate pro-uPA, a key element of the urokinase-plasminogen system, a pathway that is well - known to be important in cancer cell invasion and migration. Finally, we demonstrated that collagenase producing microbes preferentially colonize human colon cancer specimens.

Translational Genomic Research: The Association between Genetic Profiles and Cognitive Functioning or Cardiac Function Among Breast Cancer Survivors Completing Chemotherapy.

Introduction: Emerging evidence suggests that Chemotherapy (CT) treated breast cancer survivors (BCS) who have "risk variants" in genes may be more susceptible to cognitive impairment (CI) and/or poor cardiac phenotypes. The objective of this preliminary study was to examine whether there is a relationship between genetic variants and objective/subjective cognitive or cardiac phenotypes. Methods and Analysis: BCS were recruited from Moffitt Cancer Center, Morsani College of Medicine, AdventHealth Tampa and Sarasota Memorial Hospital. Genomic DNA were collected at baseline for genotyping analysis. A total of 16 single nucleotide polymorphisms (SNPs) from 14 genes involved in cognitive or cardiac function were evaluated. Three genetic models (additive, dominant, and recessive) were used to test correlation coefficients between genetic variants and objective/subjective measures of cognitive functioning and cardiac outcomes (heart rate, diastolic blood pressure, systolic blood pressure, respiration rate, and oxygen saturation). Results: BCS (207 participants) with a mean age of 56 enrolled in this study. The majority were non-Hispanic white (73.7%), married (63.1%), and received both CT and radiation treatment (77.3%). Three SNPs in genes related to cognitive functioning (rs429358 in APOE, rs1800497 in ANKK1, rs10119 in TOMM40) emerged with the most consistent significant relationship with cognitive outcomes. Among five candidate SNPs related to cardiac functioning, rs8055236 in CDH13 and rs1801133 in MTHER emerged with potential significant relationships with cardiac phenotype. Conclusions: These preliminary results provide initial targets to further examine whether BCS with specific genetic profiles may preferentially benefit from interventions designed to improve cognitive and cardiac functioning following CT.

Cloning and characterization of α-L-arabinofuranosidase and bifunctional α-L-arabinopyranosidase/ß-D-galactopyranosidase from Bifidobacterium longum H-1.

AIMS: This study focused on the cloning, expression and characterization of recombinant α-l-arabinosidases from Bifidobacterium longum H-1. METHODS AND RESULTS: α-l-Arabinofuranosidase (AfuB-H1) and bifunctional α-l-arabinopyranosidase/ß-d-galactosidase (Apy-H1) from B. longum H-1 were identified by Southern blotting, and their recombinant enzymes were overexpressed in Escherichia coli BL21 (DE3). Recombinant AfuB-H1 (rAfuB-H1) was purified by single-step Ni(2+) -affinity column chromatography, whereas recombinant Apy-H1 (rApy-H1) was purified by serial Q-HP and Ni(2+) -affinity column chromatography. Enzymatic properties and substrate specificities of the two enzymes were assessed, and their kinetic constants were calculated. According to the results, rAfuB-H1 hydrolysed p-nitrophenyl-α-l-arabinofuranoside (pNP-αL-Af) and ginsenoside Rc, but did not hydrolyse p-nitrophenyl-α-l-arabinopyranoside (pNP-αL-Ap). On the other hand, rApy-H1 hydrolysed pNP-αL-Ap, p-nitrophenyl-ß-d-galactopyranoside (pNP-ßD-Ga) and ginsenoside Rb2. CONCLUSIONS: Ginsenoside-metabolizing bifidobacterial rAfuB-H1 and rApy-H1 were successfully cloned, expressed, and characterized. rAfuB-H1 specifically recognized the α-l-arabinofuranoside, whereas rApy-H1 had dual functions, that is, it could hydrolyse both ß-d-galactopyranoside and α-l-arabinopyranoside. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings suggest that the biochemical properties and substrate specificities of these recombinant enzymes differ from those of previously identified α-l-arabinosidases from Bifidobacterium breve K-110 and Clostridium cellulovorans.

Carcinoma of müllerian origin presenting as colorectal cancer: a clinicopathologic study of 13 Cases.

Carcinomas of müllerian origin involving colorectum in women with no concurrent or history of gynecologic malignancies are diagnostically challenging, and its histogenetic origin is uncertain. We reviewed 13 cases of carcinoma of müllerian origin with clinical presentation mimicking primary colorectal carcinoma. The patients' average age was 63.9 years. All except 2 patients presented with mass lesions in rectosigmoid colon or rectovaginal septum. The major presenting symptoms were rectal bleeding (4/13), rectosigmoid mass (6/13), vaginal mass (1/13), and abdominal pain or constipation (2/13). The average size of tumor was 4.2 cm (range, 2.4-15.0 cm). Among the 10 patients who underwent preoperative biopsy, 5 were diagnosed to have moderately and poorly differentiated colorectal carcinoma. All tumors were surgically resected with final diagnoses of moderately differentiated endometrioid carcinoma in 6 cases, mixed serous and endometrioid carcinoma in 4 cases, malignant mixed müllerian tumor in 2 cases, and undifferentiated carcinoma in 1 case. In 9 of 13 cases, foci of endometriosis were identified adjacent to or within the tumor. One case had endosalpingiosis. Immunohistochemical stains showed, after positive results, the following: cytokeratin 7 (CK7; 13/13), estrogen receptor (13/13), progesterone receptor (10/13), cytokeratin 20 (CK20; 0/13), and CDX-2 (0/13). In conclusion, carcinoma of müllerian origin often presents as bulky mass in rectosigmoid or rectovaginal septum clinically mimicking primary colorectal cancer. Endometriosis might be an important etiologic factor. Familiarities of this unusual clinicopathologic entity, careful morphologic evaluation, and immunohistochemical stain with a panel of markers (CK7, CK20, estrogen receptor, progesterone receptor, CDX-2) will be helpful for the correct diagnosis.

Effects of exercise program on appetite-regulating hormones, inflammatory mediators, lipid profiles, and body composition in healthy men.

AIM: Exercise can improve appetite, inflammatory mediators, lipid profiles, and body composition in overweight or obese patients. However, it has not yet been clearly elucidated how exercise affects healthy people in relation to these variables. Thus, we investigated the effects of an exercise program on appetite-regulating hormones, inflammatory mediators, lipid profiles, and body composition in healthy men. METHODS: Thirty sedentary men were recruited and randomly assigned to two groups (exercise group, EG, N.=15 and control group, CG, N.=15). Total plasma ghrelin, leptin, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were determined by radioimmunoassay and immunoassay. Total cholesterol (TC), triglyceride (TG), high- and low-density lipoprotein cholesterol (HDL-C and LDL-C) were determined by enzymatic assay. Body composition was determined by bioelectrical impedance analysis. RESULTS: After 8 weeks, the ghrelin and leptin levels of CG showed a tendency to increase, whereas those of EG were significantly decreased. Although TNF-α and CRP, except for IL-6, showed a tendency to increase in CG, all three tended to decrease in EG after 8 weeks. TG and LDL-C were significantly increased in CG. The TC, TG, and LDL-C levels of EG were remarkably decreased, whereas HDL-C was significantly increased. In EG, body weight, fat mass, percent fat, and waist/hip ratio were significantly decreased, whereas muscle mass was significantly increased after 8 weeks. CONCLUSION: The present study results have demonstrated the beneficial effects of an exercise program by altering appetite-regulating hormones, decreasing inflammatory factors, and improving lipid profiles and body composition in healthy young men.

High performance Ω-gated Ge nanowire MOSFET with quasi-metallic source/drain contacts.

Ge nanowires (NWs) about 2 µm long and 35 nm in diameter are grown heteroepitaxially on Si(111) substrates in a hot wall low-pressure chemical vapor deposition (LP-CVD) system using Au as a catalyst and GeH(4) as precursor. Individual NWs are contacted to Cu pads via e-beam lithography, thermal evaporation and lift-off techniques. Self-aligned and atomically sharp quasi-metallic copper-germanide source/drain contacts are achieved by a thermal activated phase formation process. The Cu(3)Ge segments emerge from the Cu contact pads through axial diffusion of Cu which was controlled in situ by SEM, thus the active channel length of the MOSFET is adjusted without any restrictions from a lithographic process. Finally the conductivity of the channel is enhanced by Ga(+) implantation leading to a high performance Ω-gated Ge-NW MOSFET with saturation currents of a few microamperes.