Empirical treatment of community-acquired pneumonia and the development of fluoroquinolone-resistant tuberculosis.

Unlabelled: BACKGROUND" Fluoroquinolone (FLQ) antibiotics are not uncommonly prescribed for community-acquired pneumonia that is later proven to be pulmonary tuberculosis (TB). Such FLQ monotherapy may result in FLQ-resistant pulmonary TB.

Methods: To assess outpatient FLQ use by patients with culture-proven pulmonary TB before diagnosis, TB registries in Alberta and Saskatchewan, Canada, were linked with provincial and federal drug benefit plans.

Development of an indirect enzyme immunoassay using monoclonal antibodies for the measurement of 17alpha-hydroxyprogesterone in human serum.

An indirect enzyme immunoassay for the measurement of total 17alpha-hydroxyprogesterone (17OHP) in serum using monoclonal antibodies generated in our laboratory was developed. Here, (a) instead of extraction with solvents, serum was heated to free protein-bound 17OHP and assay was performed at pH 9.6, (b) to ensure uniform assay conditions for both standards and samples, buffer for standards contained charcoal-stripped pre-heated pooled cord serum.

Regulation of epithelial-mesenchymal IL-1 signaling by PPARbeta/delta is essential for skin homeostasis and wound healing.

Skin morphogenesis, maintenance, and healing after wounding require complex epithelial-mesenchymal interactions. In this study, we show that for skin homeostasis, interleukin-1 (IL-1) produced by keratinocytes activates peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) expression in underlying fibroblasts, which in turn inhibits the mitotic activity of keratinocytes via inhibition of the IL-1 signaling pathway. In fact, PPARbeta/delta stimulates production of the secreted IL-1 receptor antagonist, which leads to an autocrine decrease in IL-1 signaling pathways and consequently decreases production of secreted mitogenic factors by the fibroblasts.

Validation study of the Mini-Mental State Examination in a Malay-speaking elderly population in Malaysia.

Background/aims: In view of the differing sensitivity and specificity of the Mini-Mental State Examination (MMSE) in the non-English-speaking populations, we conducted the first validation study of the Malay version (M-MMSE) in Malaysia among 300 subjects (from the community and outpatient clinics).

Methods: Three versions were used: M-MMSE-7 (serial 7), M-MMSE-3 (serial 3) and M-MMSE-S (spell 'dunia' backwards). Dementia was assessed using the criteria of the Diagnostic and Statistical Manual of Mental Disorders IV.

Stable aziridinium salts as versatile intermediates: isolation and regio- and stereoselective ring-opening and rearrangement.

Rock trapping and exploration: Aziridinium bromide salts were discovered serendipitously during bromination of N,N-dicarboxymethylated beta-amino alcohols. Regiospecific ring-opening and rearrangement of the isolated, surprisingly stable aziridinium salts produces useful molecules including C-functionalized oxomorpholines and alpha,beta-unsaturated amines.

Recombinant human arginase inhibits proliferation of human hepatocellular carcinoma by inducing cell cycle arrest.

Human hepatocellular carcinoma (HCC) has an elevated requirement for arginine in vitro, and pegylated recombinant human arginase I (rhArg-PEG), an arginine-depleting enzyme, can inhibit the growth of arginine-dependent tumors. While supplementation of the culture medium with ornithine failed to rescue Hep3B cells from growth inhibition induced by rhArg-PEG, citrulline successfully restored cell growth. The data support the roles previously proposed for ornithine transcarbamylase (OTC) in the arginine auxotrophy and rhArg-PEG sensitivity of HCC cells.

Use of permeability surface area-product to differentiate intracranial tumours from abscess.

Background And Purpose: Clinical and radiological findings of intracranial abscesses may mimic the findings of brain tumours and vice versa. However, the discrimination is of great clinical importance in planning treatment and in following prognosis and response to therapy. This study evaluates the Computed Tomography (CT) perfusion parameters, especially the permeability index, with the aim of evaluating the usefulness of dynamic CT perfusion imaging as an alternative tool to differentiate necrotic brain tumours and intracerebral abscesses.

Neuroendocrine tumour of the cystic duct: a case report and literature review.

This is a case report of a neuroendocrine tumour of the cystic duct which is extremely rare and was an incidental finding during laparoscopic surgery. A literature review of similar cases is also provided.

ERP correlates of item recognition memory: effects of age and performance.

Decline in episodic memory is a common feature of healthy aging. Event-related potential (ERP) studies in young adults have consistently reported several modulations thought to index memory retrieval processes, but relatively limited work has explored the impact of aging on them. Further, work with functional imaging has demonstrated differential neural recruitment in elderly subjects depending on their level of cognitive performance which may reflect compensatory or, alternatively, inefficient processing.

Synthesis and biological evaluation of a novel decadentate ligand DEPA.

An efficient and short synthetic route to a novel decadentate ligand 7-[2-(bis-carboxymethyl-amino)-ethyl]-4,10-bis-carboxymethyl-1,4,7,10-tetraaza-cyclododec-1-yl-acetic acid (DEPA) with both macrocyclic and acyclic binding moieties is reported. A reproducible and scalable synthetic method to a precursor molecule of DEPA, 1,4,7-tris(tert-butoxycarbonylmethyl)tetraazacyclododecane was developed. DEPA was evaluated as a chelator of (177)Lu, (212)Bi, and (213)Bi for potential use in an antibody-targeted cancer therapy, radioimmunotherapy (RIT) using Arsenazo III based spectroscopic complexation kinetics, in vitro serum stability, and in vivo biodistribution studies.

Novel bimodal bifunctional ligands for radioimmunotherapy and targeted MRI.

The structurally novel bifunctional ligands C-NETA and C-NE3TA, each possessing both acyclic and macrocyclic moieties, were prepared and evaluated as potential chelates for radioimmunotherapy (RIT) and targeted magnetic resonance imaging (MRI). Heptadentate C-NE3TA was fortuitously discovered during the preparation of C-NETA. An optimized synthetic method to C-NETA and C-NE3TA including purification of the polar and tailing reaction intermediates, tert-butyl C-NETA (2) and tert-butyl C-NE3TA (3) using semiprep HPLC was developed.

Peri-articular steroid injection improves the outcome after unicondylar knee replacement: a prospective, randomised controlled trial with a two-year follow-up.

We have performed a prospective double-blind, randomised controlled trial over two years to evaluate the efficacy and safety of an intra-operative peri-articular injection of triamcinolone acetonide in patients undergoing medial unicondylar knee replacement. We randomised 90 patients into two equal groups. The study group received an injection of triamcinolone acetonide, bupivacaine, and epinephrine into the peri-articular tissues at the end of the operation.

Continuous femoral nerve block in total knee arthroplasty: immediate and two-year outcomes.

We conducted a prospective study to investigate the immediate and 2-year outcomes of total knee arthroplasty patients who received continuous femoral nerve block (FNB) for analgesia. Sixty patients undergoing unilateral total knee arthroplasty were randomized into 3 groups and received high-dose continuous FNB, low-dose continuous FNB, or no FNB. In the immediate postoperative period, we studied their pain scores, cumulative morphine use, any FNB-related complications, time of first ambulation, and patient satisfaction.

Efficient synthesis and evaluation of bimodal ligand NETA.

The efficient and short synthetic route to the structurally novel bimodal ligand NETA for antibody-targeted radiation therapy (radioimmunotherapy, RIT) of cancer was developed. The structure of NETA was determined by X-ray crystallography. The arsenazo-based UV spectroscopic complexation kinetics data suggest that NETA is a promising chelator for use in RIT applications of (212)Bi, (213)Bi, and (177)Lu.

Synthesis and evaluation of novel polyaminocarboxylate-based antitumor agents.

Iron depletion, using iron chelators targeting transferrin receptor (TfR) and ribonucleotide reductase (RR), is proven to be effective in the treatment of cancer. We synthesized and evaluated novel polyaminocarboxylate-based chelators NETA, NE3TA, and NE3TA-Bn and their bifunctional versions C-NETA, C-NE3TA, and N-NE3TA for use in iron depletion tumor therapy. The cytotoxic activities of the novel polyaminocarboxylates were evaluated in the HeLa and HT29 colon cancer cell lines and compared to the clinically available iron depletion agent DFO and the frequently explored polyaminocarboxylate DTPA.

A novel cholic acid-based contrast enhancement agent for targeted MRI.

The novel Gd(III) complexes of heptadentate ligands NE3TA and NE3TA-Bn were prepared, and their relaxivities were measured and favorably compared to the commercially available MRI contrast enhancement agent Gd(DOTA). NE3TA was conjugated with cholic acid (CA) to produce CA-NE3TA. TEM images of Gd(CA-NE3TA) indicate that the complex self-assembles forming nano-sized micelles and displays an over threefold increased relaxivity compared to Gd(DOTA).

Genetic and neutralization properties of HIV-1 env clones from subtype B/BC/AE infections in China.

Background: As HIV vaccines move into preclinical and clinical trials in China, pseudovirion-based neutralization assays, especially those using env genes of Chinese origin, are widely required to evaluate the ability of HIV vaccines to induce neutralizing antibody (nAb) responses.

Materials And Methods: Functional gp160 genes from plasma samples from Chinese HIV-infected patients were cloned and sequenced and then used to establish a pseudovirus-based neutralization assay. The neutralization phenotypes of the Env-pseudotyped viruses were characterized with known nAbs (4E10, 2F5, IgG1b12, and 2G12) and 43 plasma samples from patients infected with different HIV subtypes.

Computer-assisted minimally invasive total knee arthroplasty compared with standard total knee arthroplasty. A prospective, randomized study.

Background: There is little information on the feasibility of computer navigation when using a minimally invasive approach for total knee arthroplasty, during which the anatomic landmarks for registration may be obscured. The purpose of the present study was to determine the radiographic accuracy of this technique and to compare the rate of functional recovery between patients who underwent computer-assisted minimally invasive arthroplasty and those who underwent conventional total knee arthroplasty.

Methods: One hundred and eight consecutive patients were randomized to undergo computer-assisted minimally invasive total knee arthroplasty or conventional total knee arthroplasty.

Induction of hsp70-mediated Th17 autoimmunity can be exploited as immunotherapy for metastatic prostate cancer.

A close connectivity between autoimmune and tumor rejection responses is known to exist in the case of melanoma immunotherapy. However, relatively little is known about self-antigens on other types of normal cells, their relation to the development of autoimmune disease, and their possible coexistence as potential tumor rejection antigens on associated tumors. In the current study, we induced inflammatory killing of normal prostate tissue in situ using a fusogenic membrane glycoprotein along with the immune adjuvant hsp70.

Rational design and generation of a bimodal bifunctional ligand for antibody-targeted radiation cancer therapy.

An antibody-targeted radiation therapy (radioimmunotherapy, RIT) employs a bifunctional ligand that can effectively hold a cytotoxic metal with clinically acceptable complexation kinetics and stability while being attached to a tumor-specific antibody. Clinical exploration of the therapeutic potential of RIT has been challenged by the absence of adequate ligand, a critical component for enhancing the efficacy of the cancer therapy. To address this deficiency, the bifunctional ligand C-NETA in a unique structural class possessing both a macrocyclic cavity and a flexible acyclic moiety was designed.

Impact of HIV-1 genetic diversity in China on the measurement of viral load.

In this study, 190 HIV-positive samples were collected from different regions of China. The HIV clades of 153 samples were determined successfully based on env sequencing. Specifically, 48, 5, 87, and 13 isolates belonged to clades B', B, BC, and AE, respectively.

Compensatory neural activity distinguishes different patterns of normal cognitive aging.

Most cognitive neuroscientific research exploring the nature of age-associated compensatory mechanisms has compared old adults (high vs. average performers) to young adults (not split by performance), leaving ambiguous whether findings are truly age-related or reflect differences between high and average performers throughout the life span. Here, we examined differences in neural activity (as measured by ERPs) that were generated by high vs.

To ignore or explore: top-down modulation of novelty processing.

Abstract Attending to novelty is a critical element of human behavior and learning. Novel events can serve as task-irrelevant distracters or as potential sources of engagement by interesting or important aspects of one's environment. An optimally functioning brain should have the capacity to respond differentially to novel events depending on the circumstances in which they occur.

Novel synthetic ligands for targeted PET imaging and radiotherapy of copper.

Novel ligands, NBEA, NBPA, NETA, NE3TA, and NE3TA-Bn, were synthesized and evaluated as potential chelators of copper radioisotopes for use in targeted positron emission tomography (PET) imaging or radiation therapy. The new ligands were radiolabeled with (64)Cu, and in vitro stability of the radiolabeled complexes was assessed in rat serum. Serum stability results suggest that among the ligands tested, NETA, NE3TA, and NE3TA-Bn form stable complexes with (64)Cu.