Rates of metachronous adenoma after curative resection for left-sided or right-sided colon cancer

Background/Aims We determined the rates of metachronous colorectal neoplasm in colorectal cancer (CRC) patients after resection for right (R)-sided or left (L)-sided cancer. Methods Consecutive CRC patients who had undergone surgical resection for curative intent in our hospital between 2001 and 2004 were identified. R-sided colonic cancers refer to cancer proximal to splenic flexure whereas L-sided cancers include rectal cancers. Patients were included only if they had a clearing colonoscopy performed either before or within 6 months after the operation. Findings of surveillance colonoscopy performed up to 5 years after colonic resection were included in the analysis. Results Eight hundred and sixty-three CRC patients underwent curative surgical resection during the study period. Three hundred and twenty-seven patients (107 R-sided and 220 L-sided) fulfilled the inclusion criteria and had at least 1 postoperative surveillance colonoscopy performed. The proportion of patients who had polyp and adenoma on surveillance colonoscopy was significantly higher among patients with L-sided than R-sided cancers (polyps: 30.9% vs. 19.6%, P=0.03; adenomas: 25.5% vs. 13.1%, P=0.01). The mean number of adenoma per patient on surveillance colonoscopy was also higher for patients with L-sided than R-sided tumors (0.52; 95% confidence interval [CI], 0.37–0.68 vs. 0.22; 95% CI, 0.08–0.35; P<0.01). Multivariate analysis showed that L-sided cancers, age, male gender and longer follow-up were independent predictors of adenoma detection on surveillance colonoscopy. Conclusions Patients with Lsided cancer had a higher rate of metachronous polyps and adenoma than those with R-sided cancer on surveillance colonoscopy

Detection of microalbuminuria in non-insulin dependent diabetes mellitus (NIDDM) patients without overt proteinuria by a semiquantitative albumin-creatinine urine strips

AbstractMicroalbuminuria is the hallmark of the reversible stage of incipient diabetic nephropathy. A cost- effective and convenient bedside screening test is essential to detect this phase. We used Clinitek 50® which is a semiquantitative strip test to check spot urine sample from 81 patients with albustix one plus or less. The incidence of Clinitek 50® microalbuminuria was 17%, 18.2% and 75% in 47, 22 and 12 patients with albustix negative, trace or one plus respectively. Nineteen and 13 of the 21 Clinitek 50® positive patients were checked for spot urine DCA 2000® and two 12-hour urine collection for immunoassay respectively. Around 60% of these samples fell into the microalbuminuria range and 40% into the overt albuminuria range by either technique. There was no false positive of Clinitek 50®. The lowest range of microalbuminuria detected by Clinitek 50® was 27 μg/minute (38 mg/day). We concluded that Clinitek 50® is a useful screening test as it is nonexpensive, easily operated and has a sensitivity close to the lower range of microalbuminuria

Pegylated derivatives of recombinant human arginase (rhArg1) for sustained in vivo activity in cancer therapy: preparation, characterization and analysis of their pharmacodynamics in vivo and in vitro and action upon hepatocellular carcinoma cell (HCC)

<p>Abstract</p> <p>Background</p> <p>Protein used in medicine, e.g. interferon, are immunogenic and quickly broken down by the body. Pegylation is a recognized way of preserving their integrity and reducing immune reactions, and works well with enzymes used to degrade amino acids, a recent focus of attention in controlling cancer growth. Of the two arginine-degrading enzymes being explored clinically, arginine deiminase is a decidedly foreign mycoplasm-derived enzyme, whereas human arginase 1 is a native liver enzyme. Both have been pegylated, the former with adjuncts of 20 kD, the latter with 5 kD PEG. Pegylation is done by several different methods, not all of which are satisfactory or desirable.</p> <p>Methods</p> <p>The preparation of novel polyethylene glycol (PEG) derivatives for modifying proteins is described, but directed specifically at pegylation of recombinant human arginase 1 (rhArg1). rhArg1 expressed in <it>Escherichia coli </it>was purified and coupled in various ways with 5 different PEG molecules to compare their protective properties and the residual enzyme activity, using hepatocellular cell lines both in vitro and in vivo.</p> <p>Results</p> <p>Methoxypolyethylene glycol-succinimidyl propionate (mPEG-SPA 5,000) coupled with very high affinity under mild conditions. The resulting pegylated enzyme (rhArg1-peg_{5,000 mw}) had up to 6 PEG chains of 5K length which not only protected it from degradation and any residual immunogenicity, but most importantly let it retain >90% of its native catalytic activity. It remained efficacious in depleting arginine in rats after a single ip injection of 1,500 U of the conjugate as the native enzyme, plasma arginine falling to >0.05 μM from ~170 μM within 20 min and lasting 6 days. The conjugate had almost the same efficacy as unpegylated rhArg1 on 2 cultured human liver cancer (HCC) cell lines. It was considerably more effective than 4 other pegylated conjugates prepared.</p> <p>Conclusion</p> <p>Valuable data on the optimization of the pegylation procedure and choice of ligand that best stabilizes the enzyme arginase 1 are presented, a protocol that should equally fit many other enzymes and proteins. It is a long lasting arginine-depleting enzyme in vivo which will greatly improve its use in anti-cancer therapy.</p

The effects of a mindfulness-based family psychoeducation intervention for the caregivers of young adults with first-episode psychosis: A randomized controlled trial

Objective: In this study, we investigated the effects of a mindfulness-based family psychoeducation (MBFPE) program on the mental-health outcomes of both caregivers and young adults with first-episode psychosis with an onset in the past three years through a multi-site randomized controlled trial. We also studied the outcomes of three potential mediating effects of interpersonal mindfulness, expressed emotions, and non-attachment on the program. Method: We randomly assigned 65 caregivers of young adults with psychosis to MBFPE (n = 33) or an ordinary family psychoeducation (FPE) program (n = 32); among them, 18 young adults in recovery also participated in the evaluation of outcomes. Results: Intent-to-treat analyses were conducted. No significant time × group interaction effects of MBFPE and FPE programs were found in any of the caregivers’ outcomes. However, the young adults with psychosis reported higher levels of recovery after the MBFPE program than after the ordinary FPE program (F = 8.268, p = 0.012, d = 1.484). They also reported a larger reduction in over-involvement of their caregivers (F = 4.846, p = 0.044, d = 1.136), showing that MBFPE had a superior effect to FPE in promoting recovery and reducing over-involvement. Conclusions: A brief psychoeducation program may not reduce the burden on or improve the mental-health outcome of caregivers of individuals with recent-onset psychosis. However, integrating mindfulness into a conventional family psychoeducation program may reduce the expressed emotions of caregivers, especially over-involvement. Further studies should explore how psychoeducation programs can reduce the impact of psychosis on family through sustainable effects in terms of reducing their burden and expressed emotions, using a rigorous study and adequate sample size

Reactivation of Epstein–Barr virus by a dual-responsive fluorescent EBNA1-targeting agent with Zn2+-chelating function

EBNA1 is the only Epstein–Barr virus (EBV) latent protein responsible for viral genome maintenance and is expressed in all EBV-infected cells. Zn2+ is essential for oligomerization of the functional EBNA1. We constructed an EBNA1 binding peptide with a Zn2+ chelator to create an EBNA1-specific inhibitor (ZRL5P4). ZRL5P4 by itself is sufficient to reactivate EBV from its latent infection. ZRL5P4 is able to emit unique responsive fluorescent signals once it binds with EBNA1 and a Zn2+ ion. ZRL5P4 can selectively disrupt the EBNA1 oligomerization and cause nasopharyngeal carcinoma (NPC) tumor shrinkage, possibly due to EBV lytic induction. Dicer1 seems essential for this lytic reactivation. As can been seen, EBNA1 is likely to maintain NPC cell survival by suppressing viral reactivation

Complete Sequencing of pNDM-HK Encoding NDM-1 Carbapenemase from a Multidrug-Resistant Escherichia coli Strain Isolated in Hong Kong

BACKGROUND: The emergence of plasmid-mediated carbapenemases, such as NDM-1 in Enterobacteriaceae is a major public health issue. Since they mediate resistance to virtually all β-lactam antibiotics and there is often co-resistance to other antibiotic classes, the therapeutic options for infections caused by these organisms are very limited. METHODOLOGY: We characterized the first NDM-1 producing E. coli isolate recovered in Hong Kong. The plasmid encoding the metallo-β-lactamase gene was sequenced. PRINCIPAL FINDINGS: The plasmid, pNDM-HK readily transferred to E. coli J53 at high frequencies. It belongs to the broad host range IncL/M incompatibility group and is 88803 bp in size. Sequence alignment showed that pNDM-HK has a 55 kb backbone which shared 97% homology with pEL60 originating from the plant pathogen, Erwina amylovora in Lebanon and a 28.9 kb variable region. The plasmid backbone includes the mucAB genes mediating ultraviolet light resistance. The 28.9 kb region has a composite transposon-like structure which includes intact or truncated genes associated with resistance to β-lactams (bla(TEM-1), bla(NDM-1), Δbla(DHA-1)), aminoglycosides (aacC2, armA), sulphonamides (sul1) and macrolides (mel, mph2). It also harbors the following mobile elements: IS26, ISCR1, tnpU, tnpAcp2, tnpD, ΔtnpATn1 and insL. Certain blocks within the 28.9 kb variable region had homology with the corresponding sequences in the widely disseminated plasmids, pCTX-M3, pMUR050 and pKP048 originating from bacteria in Poland in 1996, in Spain in 2002 and in China in 2006, respectively. SIGNIFICANCE: The genetic support of NDM-1 gene suggests that it has evolved through complex pathways. The association with broad host range plasmid and multiple mobile genetic elements explain its observed horizontal mobility in multiple bacterial taxa

A Large Population Histology Study Showing the Lack of Association between ALT Elevation and Significant Fibrosis in Chronic Hepatitis B

OBJECTIVE: We determined the association between various clinical parameters and significant liver injury in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. METHODS: From 1994 to 2008, liver biopsy was performed on 319 treatment-naive CHB patients. Histologic assessment was based on the Knodell histologic activity index for necroinflammation and the Ishak fibrosis staging for fibrosis. RESULTS: 211 HBeAg-positive and 108 HBeAg-negative patients were recruited, with a median age of 31 and 46 years respectively. 9 out of 40 (22.5%) HBeAg-positive patients with normal ALT had significant histologic abnormalities (necroinflammation grading >/= 7 or fibrosis score >/= 3). There was a significant difference in fibrosis scores among HBeAg-positive patients with an ALT level within the Prati criteria (30 U/L for men, 19 U/L for women) and patients with a normal ALT but exceeding the Prati criteria (p = 0.024). Age, aspartate aminotransferase and platelet count were independent predictors of significant fibrosis in HBeAg-positive patients with an elevated ALT by multivariate analysis (p = 0.007, 0.047 and 0.045 respectively). HBV DNA and platelet count were predictors of significant fibrosis in HBeAg-negative disease (p = 0.020 and 0.015 respectively). An elevated ALT was not predictive of significant fibrosis for HBeAg-positive (p = 0.345) and -negative (p = 0.544) disease. There was no significant difference in fibrosis staging among ALT 1-2 x upper limit of normal (ULN) and > x 2 ULN for both HBeAg-positive (p = 0.098) and -negative (p = 0.838) disease. CONCLUSION: An elevated ALT does not accurately predict significant liver injury. Decisions on commencing antiviral therapy should not be heavily based on a particular ALT threshold.published_or_final_versio

Recent Progress in Steroid Synthesis Triggered by the Emergence of New Catalytic Methods

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154510/1/ejoc201901466_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154510/2/ejoc201901466.pd

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data