Ethnicity and OPRM variant independently predict pain perception and patient-controlled analgesia usage for post-operative pain

<p>Abstract</p> <p>Background</p> <p>Morphine consumption can vary widely between individuals even for identical surgical procedures. As mu-opioid receptor (OPRM1) is known to modulate pain perception and mediate the analgesic effects of opioid compounds in the central nervous system, we examined the influence of two OPRM polymorphisms on acute post-operative pain and morphine usage in women undergoing elective caesarean delivery.</p> <p>Results</p> <p>Data on self-reported pain scores and amount of total morphine use according to patient-controlled analgesia were collected from 994 women from the three main ethnic groups in Singapore. We found statistically significant association of the OPRM 118A>G with self-administered morphine during the first 24-hour postoperative period both in terms of total morphine (p = 1.7 × 10^-5) and weight-adjusted morphine (p = 6.6 × 10^-5). There was also significant association of this OPRM variant and time-averaged self-rated pain scores (p = 0.024). OPRM 118G homozygotes used more morphine and reported higher pain scores than 118A carriers. Other factors which influenced pain score and morphine usage include ethnicity, age and paying class.</p> <p>Conclusion</p> <p>Our results suggest that ethnicity and OPRM 118A>G genotype are independent and significant contributors to variation in pain perception and postoperative morphine use in patients undergoing cesarean delivery.</p

Identification of Tuberculosis Susceptibility Genes with Human Macrophage Gene Expression Profiles

Although host genetics influences susceptibility to tuberculosis (TB), few genes determining disease outcome have been identified. We hypothesized that macrophages from individuals with different clinical manifestations of Mycobacterium tuberculosis (Mtb) infection would have distinct gene expression profiles and that polymorphisms in these genes may also be associated with susceptibility to TB. We measured gene expression levels of >38,500 genes from ex vivo Mtb-stimulated macrophages in 12 subjects with 3 clinical phenotypes: latent, pulmonary, and meningeal TB (n = 4 per group). After identifying differentially expressed genes, we confirmed these results in 34 additional subjects by real-time PCR. We also used a case-control study design to examine whether polymorphisms in differentially regulated genes were associated with susceptibility to these different clinical forms of TB. We compared gene expression profiles in Mtb-stimulated and unstimulated macrophages and identified 1,608 and 199 genes that were differentially expressed by >2- and >5-fold, respectively. In an independent sample set of 34 individuals and a subset of highly regulated genes, 90% of the microarray results were confirmed by RT-PCR, including expression levels of CCL1, which distinguished the 3 clinical groups. Furthermore, 6 single nucleotide polymorphisms (SNPs) in CCL1 were found to be associated with TB in a case-control genetic association study with 273 TB cases and 188 controls. To our knowledge, this is the first identification of CCL1 as a gene involved in host susceptibility to TB and the first study to combine microarray and DNA polymorphism studies to identify genes associated with TB susceptibility. These results suggest that genome-wide studies can provide an unbiased method to identify critical macrophage response genes that are associated with different clinical outcomes and that variation in innate immune response genes regulate susceptibility to TB

Pathogens and host immunity in the ancient human oral cavity.

Calcified dental plaque (dental calculus) preserves for millennia and entraps biomolecules from all domains of life and viruses. We report the first, to our knowledge, high-resolution taxonomic and protein functional characterization of the ancient oral microbiome and demonstrate that the oral cavity has long served as a reservoir for bacteria implicated in both local and systemic disease. We characterize (i) the ancient oral microbiome in a diseased state, (ii) 40 opportunistic pathogens, (iii) ancient human-associated putative antibiotic resistance genes, (iv) a genome reconstruction of the periodontal pathogen Tannerella forsythia, (v) 239 bacterial and 43 human proteins, allowing confirmation of a long-term association between host immune factors, 'red complex' pathogens and periodontal disease, and (vi) DNA sequences matching dietary sources. Directly datable and nearly ubiquitous, dental calculus permits the simultaneous investigation of pathogen activity, host immunity and diet, thereby extending direct investigation of common diseases into the human evolutionary past

A 2-year open-label study of galantamine therapy in Chinese Alzheimer's disease patients in Hong Kong

There was no long-term clinical study on galantamine in Alzheimer's disease (AD) in the Asian population. The objectives of this study were to evaluate the efficacy of galantamine on cognitive function, daily functioning, behavioural symptoms and its safety in Chinese AD patients. This was a 2-year open-label clinical trial. The inclusion criteria were patients with probable AD by the NINCDS-ADRDA criteria. A historical control group (n = 19) of AD patients with no galantamine or other cholinesterase inhibitor therapy was employed. In the galantamine group, 33 and 32 subjects had completed a 1-year and 2-year follow up, respectively. Within the galantamine group and at a 6-month follow up, the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-cog score) showed an improvement of 2.9 +/- 1.18 (p = 0.019, paired t-test) but remained the same at 1 and 2 years. The Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL) deteriorated by 4.31 +/- 2.06 (p = 0.044, paired t-test) at 6 months but showed no significant decline at 1 and 2 years vs. baseline. The Neuropsychiatric Inventory (NPI) score also showed a significant deterioration of 5 +/- 1.99 (p = 0.017, paired t-test) at 6 months, 8.06 +/- 1.97 (p < 0.001, paired t-test) at 1 year and 7.31 +/- 1.76 at 2 years. Comparison between the two groups showed a statistically significant improvement in the 1-year ADAS-cog score but decline in the NPI score in the galantamine vs. control groups. Adverse effects were commonly mild. In Chinese mild-moderate AD patients, galantamine showed beneficial effects mainly on the cognitive function

A modelling method for conjugate heat transfer and fluid flow in building spaces

Computational fluid dynamics (CFD) has been used extensively for the prediction of air movement in buildings. In many cases buoyancy forces generated at heated surfaces that dissipate their energy by an interactive process of convection, radiation and conduction dominate air movement. In this work a new method for calculating conjugate fluxes at surfaces involving coupled short-wave and long-wave radiation, convection and conduction is developed as part of the CFD eld problem. The method is based on translating surface radiant exchanges into local volumetric fluxes. Results for a test room with a heated surface compared with data generated within the framework of IEA Annex 20 show that the method produces better results than might be expected from conventional models that use simplified radiant treatments