An enzymatic approach to configurationally rare trans‐androsteronyl‐α‐glucoside and Its potential anticancer application

Enzymatic glycosylation of sterols/steroids with glycosyltransferase HP0421 shows protein plasticity on generation of configurationally rare steryl‐α‐glucosides. Investigation of trans‐androsteronyl‐α‐glucoside on tamoxifen‐treated MCF‐7 breast cancer cells shows dose‐dependent depression of cell viability and enhanced drug effectiveness, illustrating a new avenue for the production of novel steryl‐α‐glucosides with useful biological activities.     

A program of cell death and extracellular matrix degradation is activated in the amnion before the onset of labor.

Fetal membranes usually rupture during the process of labor. Premature fetal membrane rupture occurs not infrequently and is associated with significant fetal and maternal morbidity. The mechanisms of normal and pathologic fetal membrane rupture are not well understood. We have examined structural and biochemical changes in the rat amnion as labor approaches in order to characterize this process in normal pregnancy. Here we report that before the onset of active labor the amnion epithelial cells undergo apoptotic cell death which encompasses degradation of 28S ribosomal subunit RNA and associated P proteins and fragmentation of nuclear DNA. Concurrent with these cellular changes, the amnion type I collagen matrix is degraded with the accumulation of three-quarter length type I collagen fragments in extraembryonic fluid, characteristic of the cleavage of fibrillar collagen by interstitial collagenase. Western blot and immunohistochemical analyses confirmed that interstitial collagenase protein appears in association with the loss of amnion type I collagen. We conclude that amnion epithelial cells undergo a process of programmed cell death associated with orchestrated extracellular matrix degradation which begins before the onset of active labor. Thus, fetal membrane rupture is likely to be the result of biochemical changes as well as physical forces.     

Vascular stiffness in familial hypercholesterolaemia is associated with C-reactive protein and cholesterol burden

BACKGROUND: Familial hypercholesterolaemia (FH) is characterized by very high serum cholesterol and premature coronary atherosclerosis. Arterial stiffness and atherosclerosis are two major underlying pathophysiologies of arterial disease that are predictive of future cardiovascular events. The aims of this study were to quantify atherosclerosis and arterial stiffness and to evaluate their relationship with high sensitive C-reactive protein (hs-CRP) and the level of exposure to high serum cholesterol in FH patients. Materials AND METHODS: We measured traditional risk factors, hs-CRP, intima-media thickness (IMT) of carotid artery, and brachial-ankle pulse wave velocity (baPWV) in 35 heterozygous FH subjects and 17 healthy control subjects. Cholesterol-year score (CYS) was calculated to estimate the lifetime cholesterol burden in FH subjects. RESULTS: FH subjects had significantly elevated total cholesterol, low-density lipoprotein cholesterol, and carotid IMT compared with those without mutations. Among FH patients, the baPWV and carotid IMT were higher in cases with high cholesterol burden than those without. Similarly, the baPWV and carotid IMT were also higher in cases with elevated hs-CRP (> 1 mg L(-1)) than those without. Multiple linear regression analysis demonstrated CYS and hs-CRP were significant independent predictors of baPWV and IMT in FH patients. CONCLUSIONS: Both high cholesterol burden and vascular inflammation are not only associated with atherosclerosis, but also contribute to the development of arterial stiffness in FH patients. Early detection of hypercholesterolaemia in FH patients is warranted to prevent the untoward pathophysiologies.     

Suitable restriction enzymes for pulsed-field gel electrophoresis analysis of Candida tropicalis

This study was designed to pursue the identification of optimal restriction enzyme for pulsed-field gel electrophoresis (PFGE) analysis of Candida tropicalis. Twelve restriction enzymes were tested on C. tropicalis strains. Our results indicate that BssHII, NaeI, and RsrII were useful enzymes for PFGE analysis, and NaeI was the best for PFGE analysis of C. tropicalis isolates.     

Foot care knowledge,attitudes and practices among patients with diabetic foot and amputation in St. Kitts and Nevis

About one‐third of admissions to the surgical unit annually are diabetes foot infections in need of amputation In St. Kitts and Nevis. However, the risk factors related to diabetes foot and amputation remain unknown. This study investigated factors associated with diabetic foot and amputation (DFA). Retrospective case control study design, and purposive and quota sampling method was used to recruit the participants. Patients with and without DFA were interviewed at two main hospitals, several primary health centres, and a private doctor's office during July and August 2018. Self‐development questionnaires were applied to assess patients' demographic, physical and behaviour, foot care knowledge, attitudes, and practices related to DFA. Chi‐square, t‐test, and multiple logistic regressions were used to analyse the data. A total of 210 patients were evaluated, 89 had DFA, while 121 did not, with a mean age of 61.10 (SD = 11.85). Participants' responses indicated good knowledge, favourable attitudes, and adequate practices related to foot care. The two items of the questionnaire, ways to maintain blood flow in the lower extremities and wash their feet daily, had significant lower score in DFA group. In multiple logistic regression, knowledge, attitudes, and practices related to foot care were not a significant predictor of DFA. Being male was a predictor of DFA than female (OR = 3.53; 95% CI = 1.65‐7.57; P < .01). Participants who were currently unemployed were less likely to have DFA than those who were employed (OR = 0.38; 95% Cl = 0.17‐0.86; P < .05). Comparing patients with the longest experience of diabetes mellitus (31 years or more) with those who had diabetes for the shortest period of time (between 1 and 10 years) was less likely to have DFA (OR = 0.38; 95% CI = 0.15‐0.97; P = <.05). The combination of these independent variables could explain 29% of the variance in DFA. Based on these findings, strategies to prevent diabetic foot and amputation should focus on male and outdoor heavy worker, and longer duration of diabetes patients which are identified in this study.     

Sodium chloride or plasmalyte-148 for patients presenting to emergency departments with diabetic ketoacidosis: A nested cohort study within a multicentre,cluster, crossover,randomised, controlled trial

Objective

To test the hypothesis that fluid resuscitation in the ED with plasmalyte-148 (PL) compared with 0.9% sodium chloride (SC) would result in a lower proportion of patients with diabetic ketoacidosis (DKA) requiring intensive care unit (ICU) admission.

Methods

We performed a prespecified nested cohort study at two hospitals within a cluster, crossover, open label, randomised, controlled trial comparing the effects of PL versus SC as fluid therapy for patients who presented to the ED with DKA. All patients presenting within a fixed recruitment period were included. The primary outcome was the proportion of patients admitted to ICU.

Results

Eighty-four patients were enrolled (SC n = 38, PL n = 46). The SC group had a lower median pH on admission (SC: 7.09 [interquartile range (IQR) 7.01–7.21], PL: 7.17 [IQR 6.99–7.26]). The median volume of intravenous fluids administered in ED was 2150 mL (IQR 2000–3200 mL; SC) and 2200 mL (IQR 2000–3450; PL); respectively. A higher proportion of patients in the SC group, 19 (50%), was admitted to ICU compared with PL group, 18 (39.1%); however, after adjustment for pH at presentation and diabetes type in a multivariable logistic regression model, the PL group did not have a significantly different rate of ICU admission compared with the SC group (odds ratio for ICU admission 0.73, 95% confidence interval 0.13–3.97, P = 0.71).

Conclusion

Patients with DKA treated with PL compared with SC in the EDs had similar rates of requiring ICU admission.     

Surgical Resection Versus Transarterial Chemoembolization for Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis: A Propensity Score Analysis

Background

The long-term survival in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) who received surgical resection (SR) or transarterial chemoembolization (TACE) remains unclear. We compared the efficacy of SR and TACE by using a propensity score analysis.

Methods

A total of 247 and 181 HCC patients with PVTT undergoing SR and TACE, respectively, were evaluated. One hundred eight pairs of matched patients were selected from each treatment arm by using a propensity score analysis.

Results

Of all patients, the estimated 1-, 3-, and 5-year survival rates of patients receiving SR and TACE were 85 versus 60 %, 68 versus 42 %, and 61 versus 33 %, respectively (p < 0.001). Patients selected for SR were significantly younger and had better liver functional reserve, performance status, and smaller tumor burden. In the propensity model, the survival benefit of SR remained significant. The estimated 1-, 3-, and 5-year survival rates of patients receiving SR and TACE were 84 versus 71 %, 69 versus 50 %, and 59 versus 35 %, respectively (p = 0.004). The two groups of patients in the propensity score analysis were similar in baseline characteristics. In the Cox proportional hazards model, patients receiving TACE had a 2.044-fold increased risk of mortality compared with patients receiving SR (95 % confidence interval: 1.284–3.252, p = 0.003).

Conclusions

For either unselected patients or patients in the propensity model, SR provides significantly better long-term survival than TACE. SR should be considered as a priority treatment in this subgroup of HCC patients.