Myocardial tissue Doppler-based indexes to distinguish right ventricular volume overload from right ventricular pressure overload

The objective of this study was to develop tissue Doppler parameters that could be used to differentiate right ventricular (RV) volume overload from RV pressure overload. The RV-pressure-overload group consisted of 40 patients with severe pulmonary hypertension, and the RV-volume-overload group consisted of 40 patients who had an atrial septal defect without evidence of right-to-left shunt, significant pulmonary hypertension, or Eisenmenger's complex. Another 40 healthy subjects were enrolled and served as a control group. Routine echocardiography and tissue Doppler imaging were performed. RV myocardial performance index was determined based on data collected during tissue Doppler imaging over the lateral tricuspid annulus. In patients with RV pressure overload, tissue Doppler parameters showed characteristically lower systolic velocity over the tricuspid annulus (RV myocardial systolic wave [Sm]) and longer isovolumic relaxation time (RV-IVRT). Nevertheless, in patients with RV volume overload, RV-Sm increased significantly, but early-diastolic velocity over tricuspid annulus was relatively low. In conclusion, RV-MPI, RV-Sm/early-diastolic velocity over tricuspid annulus, and RV-IVRT/RV-Sm were all useful to differentiate RV pressure overload from volume overload, although RV-IVRT/RV-Sm was the best parameter, with excellent sensitivity and specificity.     

Residues Distal to the Active Site Contribute to Enhanced Catalytic Activity of Variant and Hybrid β-Lactamases Derived from CTX-M-14 and CTX-M-15

A variety of CTX-M-type extended-spectrum β-lactamases (ESBLs), including hybrid ones, have been reported in China that are uncommon elsewhere. To better characterize the substrate profiles and enzymatic mechanisms of these enzymes, we performed comparative kinetic analyses of both parental and hybrid CTX-M enzymes, including CTX-M-15, -132, -123, -64, -14 and -55, that are known to confer variable levels of β-lactam resistance in the host strains. All tested enzymes were susceptible to serine β-lactamase inhibitors, with sulbactam exhibiting the weakest inhibitory effects. CTX-M-55, which differs from CTX-M-15 by one substitution, A⁷⁷V, displayed enhanced catalytic activity (k_cat/K_m) against expanded-spectrum cephalosporins (ESCs). CTX-M-55 exhibits higher structure stability, most likely by forming hydrophobic interactions between A⁷⁷V and various key residues in different helices, thereby stabilizing the core architecture of the helix cluster, and indirectly contributes to a more stable active site conformation, which in turn shows higher catalytic efficiency and is more tolerant to temperature change. Analyses of the hybrids and their parental prototypes showed that evolution from CTX-M-15 to CTX-M-132, CTX-M-123, and CTX-M-64, characterized by gradual enhancement of catalytic activity to ESCs, was attributed to introduction of different substitutions to amino acids distal to the active site of CTX-M-15. Similarly, the increased hydrolytic activities against cephalosporins and sensitivity to β-lactamase inhibitors, clavulanic acid and sulbactam, of CTX-M-64 were partly due to the amino acids that were different from CTX-M-14 and located at both the C and N termini of CTX-M-64. These data indicate that residues distal to the active site of CTX-Ms contributed to their enhanced catalytic activities to ESCs.     

Can we predict pathologic complete response before surgery for locally advanced rectal cancer treated with preoperative chemoradiation therapy?

Background

Pathologic complete response has been proven to have oncological benefits for locally advanced rectal cancer treated with chemoradiation therapy. The aims of this study are to analyze and determine the factors to predict pathologic complete response for patients treated with preoperative neoadjuvant therapy.

Methods

Patients with biopsy-proven, locally advanced rectal cancer were treated neoadjuvantly followed by radical surgical resection. Tumors were re-assessed after completing chemoradiation, including pelvic magnetic resonance images, colonoscopic examination, and re-biopsy. The results of examination were compared with the final pathologic status.

Results

A retrospective chart review of 166 patients was conducted. Twenty-five patients (15.1%) had pathologic complete response after chemoradiation. The 5-year overall survival rates were better in the complete response group than the residual tumor group (91.1% vs. 70.8%; P?=?0.047), and there were also significant differences in the 5-year disease-free survival rates between these two groups (91.1% vs. 70.2%; P?=?0.027). The prediction rates for pathologic complete response by re-biopsy, magnetic resonance images, and colonoscopy were 21.4%, 33.3%, and 53.8%, respectively. In addition, when we further combine the results of colonoscopic findings and re-biopsy, the prediction rate for pathologic complete response reached 77.8% (P?=?0.009).

Conclusions

Combining the results of the re-biopsy and post-treatment colonoscopic findings, we can achieve a good prediction rate for pathologic complete response. Post-treatment magnetic resonance images are not useful tools in predicting tumor clearance following chemoradiation.     

Developmental enamel defects in the primary dentition: aetiology and clinical management

Developmental enamel defects, presenting as enamel hypoplasia or opacities are caused by damage or disruption to the developing enamel organ as a result of inherited and acquired systemic conditions. The high prevalence of these defects in the primary dentition demonstrates the vulnerability of the teeth to changes in the pre‐ and postnatal environment. The presence of enamel hypoplasia increases the risk of primary teeth to early childhood caries and tooth wear as the defective enamel is thinner, more plaque retentive and less resistant to dissolution in acid compared to normal enamel. The purpose of this paper was to critically review the aetiology and clinical complications of developmental enamel defects in the primary dentition and propose recommendations for the clinical management of affected teeth.     

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.