Characterization of N-acetyltransferase 1 and 2 polymorphisms and haplotype analysis for inflammatory bowel disease and sporadic colorectal carcinoma

Background  

N-acetyltransferase 1 (NAT1) and 2 (NAT2) are polymorphic isoenzymes responsible for the metabolism of numerous drugs and carcinogens. Acetylation catalyzed by NAT1 and NAT2 are important in metabolic activation of arylamines to electrophilic intermediates that initiate carcinogenesis. Inflammatory bowel diseases (IBD) consist of Crohn's disease (CD) and ulcerative colitis (UC), both are associated with increased colorectal cancer (CRC) risk. We hypothesized that NAT1 and/or NAT2 polymorphisms contribute to the increased cancer evident in IBD.     

Coupled CH4 production and oxidation support CO2 supersaturation in a tropical flood pulse lake (Tonle Sap Lake,Cambodia)

Carbon dioxide (CO₂) supersaturation in lakes and rivers worldwide is commonly attributed to terrestrial–aquatic transfers of organic and inorganic carbon (C) and subsequent, in situ aerobic respiration. Methane (CH₄) production and oxidation also contribute CO₂ to freshwaters, yet this remains largely unquantified. Flood pulse lakes and rivers in the tropics are hypothesized to receive large inputs of dissolved CO₂ and CH₄ from floodplains characterized by hypoxia and reducing conditions. We measured stable C isotopes of CO₂ and CH₄, aerobic respiration, and CH₄ production and oxidation during two flood stages in Tonle Sap Lake (Cambodia) to determine whether dissolved CO₂ in this tropical flood pulse ecosystem has a methanogenic origin. Mean CO₂ supersaturation of 11,000 ± 9,000 μatm could not be explained by aerobic respiration alone. ¹³C depletion of dissolved CO₂ relative to other sources of organic and inorganic C, together with corresponding ¹³C enrichment of CH₄, suggested extensive CH₄ oxidation. A stable isotope-mixing model shows that the oxidation of ¹³C depleted CH₄ to CO₂ contributes between 47 and 67% of dissolved CO₂ in Tonle Sap Lake. ¹³C depletion of dissolved CO₂ was correlated to independently measured rates of CH₄ production and oxidation within the water column and underlying lake sediments. However, mass balance indicates that most of this CH₄ production and oxidation occurs elsewhere, within inundated soils and other floodplain habitats. Seasonal inundation of floodplains is a common feature of tropical freshwaters, where high reported CO₂ supersaturation and atmospheric emissions may be explained in part by coupled CH₄ production and oxidation.

Globally, most lakes and rivers are supersaturated with dissolved carbon dioxide (CO₂) relative to the atmosphere, highlighting their outsized role in transferring and transforming terrestrial carbon (C) (1–3). Terrestrial–aquatic transfers of C can include CO₂ dissolved in terrestrial ground and surface waters (3–6), dissolved inorganic carbon (DIC) from carbonate weathering (7, 8), or organic C from various sources that is subsequently respired in lakes and rivers (9, 10). Initially, oceanic export was thought to be the only fate for terrestrial–aquatic transfers of C, but a growing body of research on sediment burial of organic C and CO₂ emissions from freshwaters prompted the “active pipe” revision to this initial set of assumptions (11). Although freshwaters are now recognized as focal points for transferring and transforming C on the landscape, most of this research has been conducted within temperate freshwaters (2, 11, 12). Few studies focus on the mechanisms of CO₂ supersaturation in tropical lakes and rivers, with most conducted in just one watershed, the Amazon (4, 13–15).CO₂ supersaturation within tropical freshwaters is likely influenced by their unique flood pulse hydrology. The canonical flood pulse concept hypothesizes that annual flooding of riparian land will lead to organic C mobilization and respiration (16). Partial pressures of CO₂ (pCO₂) have been measured in excess of 44,000 μatm in the Amazon River (13), 16,000 μatm in the Congo River (17), and 12,000 μatm in the Lukulu River (17). Richey et al. (13), Borges et al. (18), and Zuidgeest et al. (17) have each shown that that riverine pCO₂ scales with the amount of land flooded in these watersheds. Yet it was only recently that Abril and Borges (19) proposed the importance of flooded land to the “active pipe.” These authors differentiate uplands that unidirectionally drain water downhill (via ground and surface water) from floodplains that bidirectionally exchange water with lakes and rivers (19). They conceptualize how floodplains combine high hydrologic connectivity, high rates of primary production, and high rates of respiration to transfer relatively large amounts of C to tropical freshwaters (19).Methanogenesis inevitably results on floodplains after dissolved oxygen (O₂) and other electron acceptors for anaerobic respiration such as iron and sulfate are consumed (16, 19). Horizontal gradients in dissolved O₂ and reducing conditions have been observed extending from the center of lakes and rivers through their floodplains in the Mekong (20, 21), Congo (22), Pantanal (23), and Amazon watersheds (4). CH₄ production and oxidation occur along such redox gradients (4, 16, 19, 23). CH₄ is produced by acetate fermentation (Eq. 1) and carbonate reduction (Eq. 2) within freshwaters (24, 25). CH₄ production coupled with aerobic oxidation results in CO₂ (Eq. 3 and ref. 25), yet no studies have quantified the relative contribution of coupled CH₄ production and oxidation to CO₂ supersaturation within tropical freshwaters.CH3COOH→CO2+CH4,[1]CO2+8H++8e−→CH4+2H2O,[2]CH4+2O2→CO2+2H2O.[3]The relative contribution of coupled CH₄ production and oxidation to CO₂ supersaturation within tropical freshwaters can be traced with stable C isotopes of CO₂ and CH₄. Methanogenesis results in CH₄ that is depleted in ¹³C (δ¹³C = −65 to −50‰ from acetate fermentation and −110 to −60‰ from carbonate reduction) compared to other potential sources of organic and inorganic C (δ¹³C = −37 to −7.7‰; see Materials and Methods) (24–26). The oxidation of this ¹³C-depleted CH₄ results in ¹³C-depleted CO₂ (24–26). At the same time, CH₄ oxidation enriches the ¹³C/¹²C of residual CH₄ as bacteria and archaea preferentially oxidize ¹²C-CH₄ (25). This means that the ¹³C/¹²C of CO₂ and CH₄ can serve as powerful tools to determine the source of CO₂ supersaturation within freshwaters.Tonle Sap Lake (TSL) is Southeast Asia’s largest lake and an understudied flood pulse ecosystem that supports a regionally important fishery (21, 22, 27). Each May through October, monsoonal rains and Himalayan snowmelt increase discharge in the Mekong River and cause one of its tributaries, the Tonle Sap River, to reverse course from southeast to northwest (21). During this course reversal, the Tonle Sap River floods TSL. The TSL flood pulse increases lake volume from 1.6 to 60 km³ and inundates 12,000 km² of floodplain for 3 to 6 mo per year (21, 27). Holtgrieve et al. (22) have shown that aerobic respiration is consistently greater than primary production in TSL (i.e., net heterotrophy), with the expectation of consistent CO₂ supersaturation. But, the partial pressures, C isotopic compositions, and ultimately the source of dissolved CO₂ in TSL remain unquantified.To quantify CO₂ supersaturation and its origins in TSL, we measured the partial pressures of CO₂ and CH₄ and compared their C isotopic composition to other potential sources of organic and inorganic C. We carried out these measurements in distinct lake environments during the high-water and falling-water stages of the flood pulse, hypothesizing that CH₄ production and oxidation on the TSL floodplain would support CO₂ supersaturation during the high-water stage. We found that coupled CH₄ production and oxidation account for a nontrivial proportion of the total dissolved CO₂ in all TSL environments and during both flood stages, showing that anaerobic degradation of organic C at aquatic–terrestrial transitions can support CO₂ supersaturation within tropical freshwaters.     

Three-dimensional light-field microendoscopy with a GRIN lens array

Optical endoscopy has emerged as an indispensable clinical tool for modern minimally invasive surgery. Most systems primarily capture a 2D projection of the 3D surgical field. Currently available 3D endoscopes can restore stereoscopic vision directly by projecting laterally shifted views of the operating field to each eye through 3D glasses. These tools provide surgeons with informative 3D visualizations, but they do not enable quantitative volumetric rendering of tissue. Therefore, advanced tools are desired to quantify tissue tomography for high precision microsurgery or medical robotics. Light-field imaging suggests itself as a promising solution to the challenge. The approach can capture both the spatial and angular information of optical signals, permitting the computational synthesis of the 3D volume of an object. In this work, we present GRIN lens array microendoscopy (GLAM), a single-shot, full-color, and quantitative 3D microendoscopy system. GLAM contains integrated fiber optics for illumination and a GRIN lens array to capture the reflected light field. The system exhibits a 3D resolution of ∼100 µm over an imaging depth of ∼22 mm and field of view up to 1 cm². GLAM maintains a small form factor consistent with the clinically desirable design, making the system readily translatable to a clinical prototype.     

Average and peak contact stress distribution evaluation of total knee arthroplasties

Seven total knee arthroplasty systems were tested to determine contact stress patterns and contact areas using a calibrated Fuji film stress analysis technique. Knees were loaded to 2,000 N (204 kg) at 15°, 60°, 90°, and 135° flexion at 24 and 37°C. Evaluation of stresses at 37°C at 15° and 60° using an average contact stress assessment technique indicated that the LCS meniscal bearing knee system, (DePuy, Warsaw, IN), the AMK knee with a constrained insert (DePuy), and the PFC knee with a posterior-lipped insert (Johnson and Johnson, Raynham, MA) had the lowest average contact stresses (near or below 10 MPa). The PFC with a regular insert (Johnson and Johnson), the Ortholoc II (Dow Corning Wright, Arlington, TN), and the AMK with a regular insert (DePuy) had intermediate contact stresses. The AMK with a Hylamer-M insert (DePuy) and the MG II (Zimmer, Warsaw, IN) had the highest average contact stresses (near or above 20 MPa). A stress-calibrated Fuji film measurement technique has shown that an assessment of ranges of contact stress provides much more information about regions of expected wear than an assessment of average contact stresses. Testing of the tibiofemoral articulation of artificial knees revealed that all knees had some areas of contact with maximum stresses in excess of 15 MPa. As the yield strength of ultrahigh-molecular-weight polyethylene is approximately 15 MPa, all tibial inserts could wear to some extent. Peak contact stresses at four test angles of the AMK, Series 7000 (Osteonics, Allendale, NJ:) Genesis (Smith & Nephew Orthopaedics, Memphis, TN), and MG II patellofemoral articulations were high (above 30 MPa). Contact areas varied from line-shaped to bilateral circular or elliptical shapes. The LCS knee system experienced substantially lower patellofemoral contact stresses and larger contact areas. Changes in conformity of knee designs are warranted to overcome wear problems. Peak contact stresses measured from the LCS meniscal bearing tibiofemoral and patellofemoral joint were in excess of 30 MPa in some areas at low flexion angles. This design does create large areas of contact at very low contact pressures, however, and for this reason is expected to wear less than other designs.     

How does peer teaching compare to faculty teaching? A systematic review and meta-analysis*

Purpose: In undergraduate medical education, peer-teaching has become an established and common method to enhance student learning. Evidence suggests that peer-teaching provides learning benefits for both learners and tutors. We aimed to describe the outcomes for medical students taught by peers through systematic review and meta-analysis of existing literature.

Methods: Seven databases were searched through 21 terms and their Boolean combinations. Studies reporting knowledge or skills outcomes of students taught by peers compared to those taught by faculty or qualified clinicians were included. Extracted data on students’ knowledge and skills outcomes were synthesised through a random effects model meta-analysis.

Results: The search yielded 2292 studies. Five hundred and fifty-three duplicates and 1611 irrelevant articles were removed during title-screening. The abstracts of 128 papers were screened against the inclusion and exclusion criteria. Ten studies have been included in the review. Meta-analyses showed no significant difference in peer-teaching compared to faculty teaching for knowledge or skills outcomes, standardised mean differences were 0.07 (95% CI: ?0.07, 0.21) and 0.11 (95% CI: ?0.07, 1.29), respectively.

Conclusion: Students taught by peers do not have significantly different outcomes to those taught by faculty. As the process of teaching helps to develop both tutor knowledge and teaching skills, peer-teaching should be supported.     

Application of DENSE‐MR‐elastography to the human heart

Typically, MR‐elastography (MRE) encodes the propagation of monochromatic acoustic waves in the MR‐phase images via sinusoidal gradients characterized by a detection frequency equal to the frequency of the mechanical vibration. Therefore, the echo time of a conventional MRE sequence is typically longer than the vibration period which is critical for heart tissue exhibiting a short T₂. Thus, fast acquisition techniques like the so‐called fractional encoding of harmonic motions were developed for cardiac applications. However, fractional encoding of harmonic motions is limited since it is two orders of magnitude less sensitive to motion than conventional MRE sequences for low‐frequency vibrations. Here, a new sequence is derived from the so‐called displacement encoding with stimulated echoes (DENSE) sequence. This sequence is more sensitive to displacement than fractional encoding of harmonic motions, and its spectral specificity is equivalent to conventional MRE sequences. The theoretical spectral properties of this new motion‐encoding technique are validated in a phantom and excised pork heart specimen. An excellent agreement is found for the measured displacement fields using classic MRE and displacement encoding with stimulated echoes MRE (8% maximum difference). In addition, initial in vivo results on a healthy volunteer clearly show propagating shear waves at 50 Hz. Thus, displacement encoding with stimulated echoes MRE is a promising technique for motion encoding within short T₂* materials. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Mortality,Morbidity, and Costs of Ruptured and Elective Abdominal Aortic Aneurysm Repairs in Nova Scotia,Canada

Ruptured abdominal aortic aneurysms (RAAA) have a 78-94% mortality rate. If cost-effectiveness of screening programs for abdominal aortic aneurysms (AAA) are to be assessed, direct costs for RAAA repairs and elective AAA (EAAA) repairs are required. This study reports mortality, morbidity, and direct costs for RAAA and EAAA repairs in Nova Scotia in 1997-1998 and also compares Nova Scotia and U.S. costs. We performed a retrospective study of 41 consecutive RAAA and 48 randomly selected EAAA patients. Average total costs for RAAA repair were significantly greater than those for EAAA repair (direct costs: $15,854 vs. $9673; direct plus overhead costs: $18,899 vs. $12,324 [pricing in 1998 Canadian dollars]). Intensive care unit length of stay and blood product usage were the most substantial direct cost differentials ($3593 and $2106). Direct cost for preoperative testing and surveillance was greater in the EAAA group ($839 vs. $33). Estimates of U.S. in-hospital RAAA and EAAA repair costs are more than 1.5 times Nova Scotia costs. Direct in-hospital RAAA repair costs are $6181 more than EAAA repair costs. These in-hospital cost data are key cost elements required to assess the cost-effectiveness of various screening strategies for earlier detection and monitoring of AAA within high-risk populations in Canada. Further studies are required to estimate cost per quality-adjusted-life-year gained for various AAA screening and monitoring strategies in Canada.