Recent Insights into Clostridium perfringens Beta-Toxin

Clostridium perfringens beta-toxin is a key mediator of necrotizing enterocolitis and enterotoxemia. It is a pore-forming toxin (PFT) that exerts cytotoxic effect. Experimental investigation using piglet and rabbit intestinal loop models and a mouse infection model apparently showed that beta-toxin is the important pathogenic factor of the organisms. The toxin caused the swelling and disruption of HL-60 cells and formed a functional pore in the lipid raft microdomains of sensitive cells. These findings represent significant progress in the characterization of the toxin with knowledge on its biological features, mechanism of action and structure-function having been accumulated. Our aims here are to review the current progresses in our comprehension of the virulence of C. perfringens type C and the character, biological feature and structure-function of beta-toxin.     

Effectiveness of entecavir in preventing hepatocellular carcinoma development is genotype-dependent in hepatitis B virus-associated liver cirrhosis

BACKGROUND The oral nucleos(t)ide analogue,entecavir(ETV) was demonstrated to reduce the rate of hepatocellular carcinoma(HCC) in patients with hepatitis B virus(HBV)-associated liver cirrhosis.However,the reduction of HCC differs in various regions of the world.AIM To investigate the reduction of HCC development due to ETV therapy by metaanalysis.METHODS We surveyed the differences in HCC development following ETV treatment based on published articles using PubMed(2004-2019).RESULTS The regions with the most marked reduction in HCC development due to ETV therapy were Spain(1.0 %/year) and Canada(Southern part,1.3 %/year),and the most ineffective areas were South Korea(3.6 %-3.8 %/year),China(3.3 %/year),Taiwan(2.4 %-3.1 %/year),and Hong Kong(2.8 %/year).Following ETV administration,the incidence of HCC in genotype D regions(1.89 %±0.28 %/year,mean ± SE) was significantly lower than that in genotype C regions(2.91%±0.24%/year,P 0.01).With regard to the initial HBV-DNA level,in genotype C patients(average:5.61 Log_(10)IU/mL) this was almost the same as that in genotype D patients(average:5.46 Log_(10)IU/mL).Moreover,there was no association between the prevalence ratio of HBV and the incidence of HCC on ETV treatment.CONCLUSION The effectiveness of ETV in preventing HCC development in HBV-associated liver cirrhosis is genotype-dependent.     

Clinical significance of anti-phosphatidylserine-prothrombin complex antibodies in the diagnosis of anti-phospholipid syndrome

In this study, we clarified the clinical significance of IgG anti-phosphatidylserine-prothrombin complex (PS-PT) antibodies in the diagnosis of antiphospholipid syndrome (APS). The study population consisted of 113 patients with SLE and lupus-like disease. IgG anti-PS-PT antibodies were examined by ELISA. These antibodies were detected in 31% of the population, and were significantly associated with thrombosis and fetal loss. The frequency was significantly higher in patients who did not satisfy the Sapporo criteria, but met the Harris and Hughes diagnostic criteria (36%) than in non-APS patients (14%). The above findings suggest that IgG anti-PS-PT antibodies should be listed in the diagnostic criteria for APS.     

C-reactive protein and peripheral artery disease among Japanese elderly: the Tsurugaya Project.

We investigated the cross-sectional relationship between ankle brachial index and cardiovascular disease risk factors, including C-reactive protein (CRP), among Japanese elderly, a topic which has had little prior epidemiologic study. Our study population comprised 946 subjects aged at least 70 years in whom both CRP and ankle brachial index were measured. The participants were classified into a low (ankle brachial index<0.9) and normal ankle brachial index group. We found that current smoking, high-density lipoprotein cholesterol <40 mg/dl, a low body mass index (continuous variable), hypertension, diabetes and statin use were all significantly related to a lower ankle brachial index. Higher log-transformed CRP level was significantly related to a lower ankle brachial index after adjustment for the cardiovascular risk factors mentioned above (p <0.01). The odds ratios for low ankle brachial index compared to 0-1 risk factors were 5.79 (95% confidence interval [CI]: 2.99-11.20) for 2 risk factors and 17.45 (95% CI: 6.78-49.91) for 3 or more risk factors; independently of other risk factors, the odds ratio for CRP>1.0 mg/l was 2.10 (95% CI: 1.13-3.88) compared to lower CRP values. Thus, a high level of CRP is related to a low ankle brachial index among Japanese elderly as well as Western subjects. This is the first study to report the relationship between CRP and low ankle brachial index among Japanese elderly.     

Left ventricular shape index assessed by gated stress myocardial perfusion SPECT: initial description of a new variable.

BACKGROUND: Ventricular remodeling is predictive of congestive heart failure (CHF). We aimed to automatically quantify a new myocardial shape variable on gated myocardial perfusion single photon emission computed tomography (SPECT) (MPS) and to evaluate the association of this new SPECT parameter with the risk of hospitalization for CHF. METHODS AND RESULTS: A computer algorithm was used to measure the 3-dimensional (3D) left ventricular (LV) shape index (LVSI), derived as the ratio of maximum 3D short- and long-axis LV dimensions, for end systole and end diastole. LVSI normal limits were obtained from stress technetium 99m sestamibi MPS images of 186 patients (60% of whom were men) (control subjects) with a low likelihood of CAD (< 5%). These limits were tested in a consecutive series of 93 inpatients (85% of whom were men) having MPS less than 1 week after hospitalization, of whom 25 were hospitalized for CHF exacerbation. Variables associated with CHF hospitalization were tested by receiver operating characteristic curve and multivariate logistic regression analyses. LVSI repeatability was assessed in 52 patients with ischemic cardiomyopathy who had sequential stress MPS within 60 days after the initial MPS without clinical events in the interval between MPS studies. Control subjects had lower end-systolic and end-diastolic LVSIs compared with patients with CHF and those without CHF (P < .001). Receiver operating characteristic curve areas for the prediction of hospitalization as a result of CHF were similar for LV ejection fraction and end-systolic LVSI. End-systolic and end-diastolic LVSIs were independent predictors of CHF hospitalization by multivariate analysis; however, end-systolic LVSI had the greatest added value among all tested variables. Repeatability was excellent for both end-systolic LVSI (R2 = 0.85, P < .0001) and end-diastolic LVSI (R2 = 0.82, P < .001). CONCLUSION: LVSI is a promising new 3D variable derived automatically from gated MPS providing highly repeatable ventricular shape assessment. Preliminary findings suggest that LVSI might have clinical implications in patients with CHF.     

Lactobacillus GG-fermented milk prevents DSS-induced colitis and regulates intestinal epithelial homeostasis through activation of epidermal growth factor receptor

Background

Fermented milk is considered one of the best sources for efficient consumption of probiotic strains by hosts to promote good health. The purpose of this study was to investigate the effects of orally administering LGG-fermented milk (LGG milk) on intestinal inflammation and injury and to study the mechanisms of LGG milk’s action.

Methods

LGG milk and non-LGG-fermented milk (non-LGG milk) were administered through gavage to mice before and during dextran sodium sulfate (DSS)-induced intestinal injury and colitis. Inflammatory/injury score and colon length were assessed. Intestinal epithelial cells were treated with the soluble fraction of LGG milk to detect its effects on the epidermal growth factor receptor (EGFR) and its downstream target, Akt activation, cytokine-induced apoptosis, and hydrogen peroxide (H₂O₂)-induced disruption of tight junctions.

Results

LGG milk treatment significantly reduced DSS-induced colonic inflammation and injury, and colon shortening in mice, compared to that in non-LGG milk-treated and -untreated mice. The soluble fraction of LGG milk, but not non-LGG milk, stimulated the activation of EGFR and Akt in a concentration-dependent manner, suppressed cytokine-induced apoptosis, and attenuated H₂O₂-induced disruption of tight junction complex in the intestinal epithelial cells. These effects of LGG milk were blocked by the EGFR kinase inhibitor. LGG milk, but not non-LGG milk, contained two soluble proteins, p40 and p75, that have been reported to promote survival and growth of intestinal epithelial cells through the activation of EGFR. Depletion of p40 and p75 from LGG milk abolished the effects of LGG milk on prevention of cytokine-induced apoptosis and H₂O₂-induced disruption of tight junctions.

Conclusions

These results suggest that LGG milk may regulate intestinal epithelial homeostasis and potentially prevent intestinal inflammatory diseases through activation of EGFR by LGG-derived proteins.     

Dosimetric comparison of absolute and relative dose distributions between tissue maximum ratio and convolution algorithms for acoustic neurinoma plans in Gamma Knife radiosurgery

Background

The treatment planning for Gamma Knife (GK) stereotactic radiosurgery (SRS) that performs dose calculations based on tissue maximum ratio (TMR) algorithm has disadvantages in predicting dose in tissue heterogeneity. The latest version of the planning software is equipped with a convolution dose algorithm as an optional extra and the new algorithm is able to compensate for head inhomogeneity. However, the effect of this improved calculation method requires detailed validation in clinical cases. In this study, we compared absolute and relative dose distributions of treatment plans for acoustic neurinoma between TMR and the convolution calculation.

Methods

Twenty-nine clinically used plans created by TMR algorithm were recalculated by convolution method. Differences between TMR and convolution were evaluated in terms of absolute dose (beam-on time), dosimetric parameters including target coverage, selectivity, conformity index, gradient index, radical homogeneity index and the dose-volume relationship.

Results

The discrepancy in estimated absolute dose to the target ranged from 1 to 7 % between TMR and convolution. In addition, dosimetric parameters of the two methods achieved statistical significance. However, it was difficult to see the change of relative dose distribution by visual assessment on a monitor.

Conclusions

Convolution, heterogeneity correction calculation, and the algorithm are necessary to reduce the dosimetric uncertainty of each case in GK SRS.     

A prospective randomized controlled trial of subcutaneous passive drainage for the prevention of superficial surgical site infections in open and laparoscopic colorectal surgery

Introduction

A number of studies have evaluated the effects of subcutaneous drainage during digestive surgery. All of the previous studies assessed the usefulness of active-suctioning drain, including two randomized controlled studies which found no benefit for the placement of active-suctioning drains in digestive surgery. The utility of passive drainage has not been evaluated previously. The purpose of this study was to evaluate the efficacy of subcutaneous passive drainage system for preventing surgical site infections during major colorectal surgery.

Patients and methods

A total of 263 patients who underwent major colorectal surgery were enrolled in this study. Patients were randomly assigned to receive subcutaneous passive drainage or no drainage. The primary outcome measured was the incidence of superficial surgical site infections. The secondary outcomes measured were the development of hematomas, seromas, and wound dehiscence.

Results

Finally, a total of 246 patients (124 underwent passive drainage, and 122 underwent no drainage) were included in the analysis after randomization. There was a significant difference in the incidence of superficial surgical site infections between patients assigned to the passive drainage and no drainage groups (3.2 % vs 9.8 %, respectively, P?=?0.041). There were no cases that developed a hematoma, seroma, or wound dehiscence in either group. A subgroup analysis revealed that male gender, age ≥75 years, diabetes mellitus, American Society of Anesthesiologists (ASA) status ≥2, blood loss ≥100 ml, and open access were factors that were associated with a beneficial effect of subcutaneous passive drainage.

Conclusions

Subcutaneous passive drainage provides benefits over no drainage in patients undergoing major colorectal surgery.     

Low calcium intake is associated with high plasma homocysteine levels in postmenopausal women

Nutritional interventions targeting homocysteine remain controversial, and further nutritional research is warranted. We thus sought to explore the determinants of plasma homocysteine other than B-group vitamins. This cross-sectional study surveyed the nutritional status of 713 Japanese postmenopausal women using a semiquantitative food frequency questionnaire. Associations between total energy, protein, fat, carbohydrate, and vitamin A and K intakes and homocysteine were insignificant. Mean homocysteine in the second (536.1 ± 34.7 mg/day) and third (712.9 ± 115.6 mg/day) tertiles of calcium intake were lower than in the first tertile (379.6 ± 76.6 mg/day) by ?0.57 nmol/mL (95 % confidence interval, ?1.10 to ?0.04, p = 0.04) and ?1.18 nmol/mL (?1.76 to ?0.60, p < 0.01), respectively, after adjustment for lifestyle and clinical factors (trend p < 0.01). Mean homocysteine in those with dietary calcium intake above the median (>536 mg/day) were lower regardless of the folic acid concentration; the differences were ?1.59 nmol/mL (?2.33 to ?0.85, p = 0.02) and ?0.75 nmol/mL (?1.37 to ?0.12, p < 0.01) for the high (<7.8 ng/mL) and low folic acid groups, respectively. There was no significant association between calcium and folic acid (p = 0.08). In conclusion, further prospective research to confirm our findings is needed for the development of nutritional inventions targeting homocysteine.