Controlling transmembrane protein concentration and orientation in supported lipid bilayers.

The trans-membrane protein - proteorhodopsin (pR) has been incorporated into supported lipid bilayers (SLB). In-plane electric fields have been used to manipulate the orientation and concentration of these proteins, within the SLB, through electrophoresis leading to a 25-fold increase concentration of pR.

Anatomical pulmonary magnetic resonance imaging segmentation for regional structure-function measurements of asthma.

PURPOSE: Pulmonary magnetic-resonance-imaging (MRI) and x-ray computed-tomography have provided strong evidence of spatially and temporally persistent lung structure-function abnormalities in asthmatics. This has generated a shift in their understanding of lung disease and supports the use of imaging biomarkers as intermediate endpoints of asthma severity and control. In particular, pulmonary (1)H MRI can be used to provide quantitative lung structure-function measurements longitudinally and in response to treatment. However, to translate such biomarkers of asthma, robust methods are required to segment the lung from pulmonary (1)H MRI. Therefore, their objective was to develop a pulmonary (1)H MRI segmentation algorithm to provide regional measurements with the precision and speed required to support clinical studies. METHODS: The authors developed a method to segment the left and right lung from (1)H MRI acquired in 20 asthmatics including five well-controlled and 15 severe poorly controlled participants who provided written informed consent to a study protocol approved by Health Canada. Same-day spirometry and plethysmography measurements of lung function and volume were acquired as well as (1)H MRI using a whole-body radiofrequency coil and fast spoiled gradient-recalled echo sequence at a fixed lung volume (functional residual capacity + 1 l). We incorporated the left-to-right lung volume proportion prior based on the Potts model and derived a volume-proportion preserved Potts model, which was approximated through convex relaxation and further represented by a dual volume-proportion preserved max-flow model. The max-flow model led to a linear problem with convex and linear equality constraints that implicitly encoded the proportion prior. To implement the algorithm, (1)H MRI was resampled into ∼3 × 3 × 3 mm(3) isotropic voxel space. Two observers placed seeds on each lung and on the background of 20 pulmonary (1)H MR images in a randomized dataset, on five occasions, five consecutive days in a row. Segmentation accuracy was evaluated using the Dice-similarity-coefficient (DSC) of the segmented thoracic cavity with comparison to five-rounds of manual segmentation by an expert observer. The authors also evaluated the root-mean-squared-error (RMSE) of the Euclidean distance between lung surfaces, the absolute, and percent volume error. Reproducibility was measured using the coefficient of variation (CoV) and intraclass correlation coefficient (ICC) for two observers who repeated segmentation measurements five-times. RESULTS: For five well-controlled asthmatics, forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) was 83% ± 7% and FEV1 was 86 ± 9%pred. For 15 severe, poorly controlled asthmatics, FEV1/FV C = 66% ± 17% and FEV1 = 72 ± 27%pred. The DSC for algorithm and manual segmentation was 91% ± 3%, 92% ± 2% and 91% ± 2% for the left, right, and whole lung, respectively. RMSE was 4.0 ± 1.0 mm for each of the left, right, and whole lung. The absolute (percent) volume errors were 0.1 l (∼6%) for each of right and left lung and ∼0.2 l (∼6%) for whole lung. Intra- and inter-CoV (ICC) were <0.5% (>0.91%) for DSC and <4.5% (>0.93%) for RMSE. While segmentation required 10 s including ∼6 s for user interaction, the smallest detectable difference was 0.24 l for algorithm measurements which was similar to manual measurements. CONCLUSIONS: This lung segmentation approach provided the necessary and sufficient precision and accuracy required for research and clinical studies.

Multilayered tissue mimicking skin and vessel phantoms with tunable mechanical, optical, and acoustic properties.

PURPOSE: This paper describes the design, fabrication, and characterization of multilayered tissue mimicking skin and vessel phantoms with tunable mechanical, optical, and acoustic properties. The phantoms comprise epidermis, dermis, and hypodermis skin layers, blood vessels, and blood mimicking fluid. Each tissue component may be individually tailored to a range of physiological and demographic conditions. METHODS: The skin layers were constructed from varying concentrations of gelatin and agar. Synthetic melanin, India ink, absorbing dyes, and Intralipid were added to provide optical absorption and scattering in the skin layers. Bovine serum albumin was used to increase acoustic attenuation, and 40 µm diameter silica microspheres were used to induce acoustic backscatter. Phantom vessels consisting of thin-walled polydimethylsiloxane tubing were embedded at depths of 2-6 mm beneath the skin, and blood mimicking fluid was passed through the vessels. The phantoms were characterized through uniaxial compression and tension experiments, rheological frequency sweep studies, diffuse reflectance spectroscopy, and ultrasonic pulse-echo measurements. Results were then compared to in vivo and ex vivo literature data. RESULTS: The elastic and dynamic shear behavior of the phantom skin layers and vessel wall closely approximated the behavior of porcine skin tissues and human vessels. Similarly, the optical properties of the phantom tissue components in the wavelength range of 400-1100 nm, as well as the acoustic properties in the frequency range of 2-9 MHz, were comparable to human tissue data. Normalized root mean square percent errors between the phantom results and the literature reference values ranged from 1.06% to 9.82%, which for many measurements were less than the sample variability. Finally, the mechanical and imaging characteristics of the phantoms were found to remain stable after 30 days of storage at 21 °C. CONCLUSIONS: The phantoms described in this work simulate the mechanical, optical, and acoustic properties of human skin tissues, vessel tissue, and blood. In this way, the phantoms are uniquely suited to serve as test models for multimodal imaging techniques and image-guided interventions.

Experiences and meanings of integration of TCAM (Traditional, Complementary and Alternative Medical) providers in three Indian states: results from a cross-sectional, qualitative implementation research study.

OBJECTIVES: Efforts to engage Traditional, Complementary and Alternative Medical (TCAM) practitioners in the public health workforce have growing relevance for India's path to universal health coverage. We used an action-centred framework to understand how policy prescriptions related to integration were being implemented in three distinct Indian states. SETTING: Health departments and district-level primary care facilities in the states of Kerala, Meghalaya and Delhi. PARTICIPANTS: In each state, two or three districts were chosen that represented a variation in accessibility and distribution across TCAM providers (eg, small or large proportions of local health practitioners, Homoeopaths, Ayurvedic and/or Unani practitioners). Per district, two blocks or geographical units were selected. TCAM and allopathic practitioners, administrators and representatives of the community at the district and state levels were chosen based on publicly available records from state and municipal authorities. A total of 196 interviews were carried out: 74 in Kerala, and 61 each in Delhi and Meghalaya. PRIMARY AND SECONDARY OUTCOME MEASURES: We sought to understand experiences and meanings associated with integration across stakeholders, as well as barriers and facilitators to implementing policies related to integration of Traditional, Complementary and Alternative (TCA) providers at the systems level. RESULTS: We found that individual and interpersonal attributes tended to facilitate integration, while system features and processes tended to hinder it. Collegiality, recognition of stature, as well as exercise of individual personal initiative among TCA practitioners and of personal experience of TCAM among allopaths enabled integration. The system, on the other hand, was characterised by the fragmentation of jurisdiction and facilities, intersystem isolation, lack of trust in and awareness of TCA systems, and inadequate infrastructure and resources for TCA service delivery. CONCLUSIONS: State-tailored strategies that routinise interaction, reward individual and system-level individual integrative efforts, and are fostered by high-level political will are recommended.

Mean bone mineral density and frequency of occurrence of osteopenia and osteoporosis in patients on hemodialysis: a single-center study.

Chronic renal disease changes both quality and quantity of bone through multi-factorial influences on bone metabolism, leading to osteopenia, osteoporosis and increased risk of fracture. The objectives of our present cross-sectional study were to determine the mean bone mineral density (BMD) and frequency of occurrence of osteoporosis and osteopenia in Saudi patients on hemodialysis (HD) for longer than 1 year. Forty-two male and 78 female patients with age between 20 and 50 years were enrolled in this study. The BMD of the lumbar vertebral spine (LV) and the neck of femur (FN) were measured in all patients. Data were analyzed using SPSS version 17.0 software and the level of significance was considered as P <0.05. The mean BMD in the LV (L2-L4) was 1.155 ± 0.026 g/cm 2 in male and 1.050 ± 0.025 g/cm 2 in female patients (P = 0.016). The mean BMD in the FN was 1.010 ± 0.023 g/cm 2 in male and 0.784 ± 0.020 g/cm 2 in female patients (P = 0.00). Based on the World Health Organization criteria, 73.8% of the male and 44.9% of the female patients in our study had normal BMD (P = 0.002); 16.7% male and 28.2% female patients had osteopenia (P = 0.14), while 9.5% male and 26.9% female patients had osteoporosis (P = 0.01). This study showed a marked decrease in mean BMD in the cortical bone (FN) compared with trabecular bone (LV) (P = 0.00) as well as in female patients on HD compared with male patients (P = 0.016 for LV and P = 0.00 for FN).

Response of native soil microbial functions to the controlled mycorrhization of an exotic tree legume, Acacia holosericea in a Sahelian ecosystem.

Fifty years of overexploitation have disturbed most forests within Sahelian areas. Exotic fast growing trees (i.e., Australian Acacia species) have subsequently been introduced for soil improvement and fuelwood production purposes. Additionally, rhizobial or mycorrhizal symbioses have sometimes been favored by means of controlled inoculations to increase the performance of these exotic trees in such arid and semiarid zones. Large-scale anthropogenic introduction of exotic plants could also threaten the native biodiversity and ecosystem resilience. We carried out an experimental reforestation in Burkina Faso in order to study the effects of Acacia holosericea mycorrhizal inoculation on the soil nutrient content, microbial soil functionalities and mycorrhizal soil potential. Treatments consisted of uninoculated A. holosericea, preplanting fertilizer application and arbuscular mycorrhizal inoculation with Glomus intraradices. Our results showed that (i) arbuscular mycorrhizal (AM) inoculation and prefertilizer application significantly improved A. holosericea growth after 4 years of plantation and (ii) the introduction of A. holosericea trees significantly modified soil microbial functions. The results clearly showed that the use of exotic tree legume species should be directly responsible for important changes in soil microbiota with great disturbances in essential functions driven by microbial communities (e.g., catabolic diversity and C cycling, phosphatase activity and P availability). They also highlighted the importance of AM symbiosis in the functioning of soils and forest plantation performances. The AM effect on soil functions was significantly correlated with the enhanced mycorrhizal soil potential recorded in the AM inoculation treatment.

Influence of hydration state and homologue composition of magnesium stearate on the physical chemical properties of liquid paraffin lipogels.

Lipogels were prepared by dispersing mixed (60:40 C(16)-C(18)) and pure (C(18)) homologue magnesium stearate (MgSt) in liquid paraffin, using three methods of preparation, i.e. addition of water at 95 °C during cooling cycle (method 1), homogenisation upon cooling (method 2) or cooling without addition of water or homogenisation (method 3). The systems were characterised by physical inspection, polarised, hot stage and scanning electron microscopy (SEM), differential scanning calorimetry (DSC), rheology, and X-ray diffraction (XRD). Systems formed stable semisolid lipogels (no syneresis), unstable solids showing syneresis or structured fluids, depending on the type of magnesium stearate used and the preparation technique. The stable semisolid lipogels containing mixed homologue MgSt (commercial-as received, anhydrous or dihydrate) prepared by methods 1 (∼ 1-2% water) and 2 contained α-crystalline lamellar structure. These were not present in the unstable solids formed with method 3 or in systems prepared from pure homologue MgSt which were generally structured fluids rather than semisolids. In addition, semisolid lipogels of pure homologue trihydrate MgSt prepared by method 3 showed plate-like crystals, implying pressure sensitivity. There is significantly more amorphous MgSt in the unstable solids compared to the stable semisolid lipogels, which are mainly crystalline (confirmed by XRD).

Colorectal cancer detection: time to abandon barium enema?

OBJECTIVES: To assess the sensitivity of double contrast barium enema (DCBE) for diagnosing colorectal cancer (CRC). DESIGN: Retrospective evaluation of DCBE performed in the 2 years prior to diagnosis of CRC. SETTING: Teaching hospital in Cambridge, UK. PATIENTS: 1310 consecutive cases of CRC identified from cancer registry data. INTERVENTIONS: DCBE and colonoscopy. MAIN OUTCOME MEASURES: Sensitivity of DCBE for diagnosing CRC. RESULTS: 215 patients had undergone a DCBE within the 2 years prior to diagnosis with CRC. After excluding those reported as inadequate, 37 of these were reported as normal, giving a sensitivity of 83% (81-85%). CONCLUSIONS: The performance of DCBE is inadequate for the exclusion of CRC. Expansion of colonoscopy and CT colonography capacity is urgently required nationally so that DCBE can finally be abandoned as a firstline test in patients at risk of CRC.

Undergraduate medical education in the Gulf Cooperation Council: a multi-countries study (Part 1).

BACKGROUND: The Gulf Cooperation Council (GCC) countries have witnessed over the last 40 years a rapid and major social, cultural, and economic transformation. The development of medical education in the region is relatively new, dating from the late 1960s. An important goal among the medical colleges in the region is to graduate national physicians who can populate the healthcare service of each country. AIM: The aim of this study is to provide understanding of undergraduate medical education in each of the six GCC countries and the challenges that each face. METHODS: This is a descriptive cross-sectional study. Fourteen senior medical faculty were requested to submit information about undergraduate medical education in their own countries, focusing on its historical background, student selection, curriculum, faculty, and challenges. RESULTS: The information provided was about 27 medical colleges: 16 from the Kingdom of Saudi Arabia (KSA), five from the United Arab Emirates (UAE), two from the Kingdom of Bahrain, two from Sultanate of Oman, one from Kuwait, and one from the State of Qatar. It was found that older colleges are reviewing their curriculum while new colleges are developing their programs following current trends in medical education, particularly problem-based learning and integrated curricula. The programs as described 'on paper' look good but what needs to be evaluated is the curriculum 'in action'. Faculty development in medical education is taking place in most of the region's medical colleges. CONCLUSION: The challenges reported were mainly related to shortages of faculty, availability of clinical training facilities and the need to more integration with the National Health Care services. Attention to quality, standards, and accreditation is considered essential by all colleges.

Management of biliary ascariasis in children living in an endemic area.

BACKGROUND: One quarter of the world's population is known to be infected with ascariasis. It is endemic in various parts of the Indian subcontinent with a high incidence in the Kashmir valley. Although intestinal obstruction is the commonest complication of ascariasis in children, biliary ascariasis remains the second most common complication. We aimed to study the various types of clinical presentations, complications and different diagnostic tools and to assess various options for the management of biliary ascariasis. MATERIALS AND METHODS: Sixty-one cases of ultrasound documented hepatobiliary ascariasis were studied prospectively over a period of 3 years from Jan 2003 to Dec 2005 at the Sheri-Kashmir Institute of Medical Sciences in Srinagar, Kashmir. All patients were children aged between 3 and 14 years. All patients were admitted to hospital and put on intravenous fluids, nothing per os until patients were symptom-free, broadspectrum antibiotics and antispasmodics. All patients received antihelminthics in the form of albendazole 400 mg as soon as patients could accept oral medication. Conservative management was continued until the patients were symptom-free. Endoscopic extraction was deferred until 3 weeks later except in patients with pyogenic cholangitis where urgent endoscopic intervention was carried out. Surgical intervention was carried out if both conservative management and endoscopic extraction failed or ERCP could not be performed for technical reasons or complications developed. RESULTS: The most common presentation was upper abdominal pain in 36 (59%) patients followed by vomiting of worms in 20 (33.3%) cases. Complications included cholangitis in 8 (13.1%), obstructive jaundice in 7 (11.4%), acute pancreatitis in 1 (1.6%) and hepatic abscess in 1 (1.6%) patient. Spontaneous passage of worms from the biliary ducts was observed in 44 (72.1%) patients. ERCP was successful in 8 (13.1%) patients, and 9 (14.7%) patients needed surgical intervention. CONCLUSION: In endemic countries, ascariasis should be suspected in patients with biliary disease. Most patients respond to conservative management although a few may need surgical intervention. Although this disease is prevalent in developing countries, because of increased travel and migration, clinicians elsewhere should be aware of the problems associated with ascariasis.

Anti-ganglioside antibody-mediated neuronal cytotoxicity and its protection by intravenous immunoglobulin: implications for immune neuropathies.

Antibodies against GD1a, GM1 and related gangliosides are frequently present in patients with the motor variant of Guillain-Barré syndrome (GBS), and their pathological role in this variant of GBS is now widely accepted. However, two basic issues related to anti-ganglioside antibody-mediated neural injury are not completely resolved: (i) some anti-ganglioside antibodies can cross-react with glycoproteins and therefore the nature of antigens targeted by these antibodies is not well established; and (ii) although pathological studies suggest that complement activation occurs in GBS, experimental data for the role of complement remain inconclusive. To address these issues, we developed and characterized a simple anti-ganglioside antibody-mediated cytotoxicity assay. Our results demonstrate first, that both GBS sera containing anti-ganglioside antibodies and monoclonal anti-ganglioside antibodies cause neuronal cell lysis by targeting specific cell surface gangliosides, and secondly, that this cell lysis is complement dependent. In this assay, the GD1a cell membrane pool appears to be more susceptible to anti-ganglioside antibody-mediated injury than the GM1 pool. Further, human intravenous immunoglobulin (i.v.Ig), now a standard treatment for GBS, significantly decreased cytotoxicity in this assay. Our data indicate that the mechanisms of i.v.Ig-mediated protection in this assay include anti-idiotypic antibodies and downregulation of complement activation. This simple cytotoxicity assay can potentially be used for screening of (i) pathogenic anti-ganglioside antibodies in patients with immune-mediated neuropathies; and (ii) new/experimental therapies to prevent anti-ganglioside antibody-mediated neural injury.

Localization of major gangliosides in the PNS: implications for immune neuropathies.

Antibodies targeting major gangliosides that are broadly distributed in the nervous system are sometimes associated with clinical symptoms that imply selective nerve damage. For example, anti-GD1a antibodies are associated with acute motor axonal neuropathy (AMAN), a form of Guillain-Barré syndrome that selectively affects motor nerves, despite reports that GD1a is present in human axons and myelin and is not expressed differentially in motor versus sensory roots. We used a series of high-affinity monoclonal antibodies (mAbs) against the major nervous system gangliosides GM1, GD1a, GD1b and GT1b to test whether any of them bind motor or sensory fibres differentially in rodent and human peripheral nerves. The following observations were made. (i) Some of the anti-GD1a antibodies preferentially stained motor fibres, supporting the association of human anti-GD1a antibodies with predominant motor neuropathies such as AMAN. (ii) A GD1b antibody preferentially stained the large dorsal root ganglion (DRG) neurones, in keeping with the proposed role of human anti-GD1b antibodies in sensory ataxic neuropathies. (iii) Two mAbs with broad structural cross-reactivity bound to both gangliosides and peripheral nerve proteins. (iv) Myelin was poorly stained; all clones stained axons nearly exclusively. Our findings suggest that anti-ganglioside antibody fine specificity as well as differences in ganglioside accessibility in axons and myelin influence the selectivity of injury to different fibre systems and cell types in human autoimmune neuropathies.

Utility of provider volume as an indicator of medical care quality and for policy decisions.

Associations between hospital volume or physician caseload and patient outcome have been used to assess the performance of health care providers. Although most studies have focused on major surgical procedures, in-hospital or 30-day mortality from many nonsurgical conditions and procedures has also been examined. Although high volume may be a surrogate for the provider's skill and experience, and better outcomes may attract greater volumes, aggregate data on provider volume show many outliers indicating that the outcome for some low-volume providers is better than that for high-volume providers. Mortality is only one measure of medical care quality. Although high volume may not always be indicative of favorable outcome, referral of patients from low-volume to high-volume providers has been recommended. It has also been suggested that patients choose health care providers on the basis of physician caseload. It is unclear how such recommendations could be implemented in practice; furthermore, they would deprive many patients from access to, as well as disrupt the provision of, adequate health care in many areas. An alternative to requiring patients to receive care from high-volume providers is to adopt other measures for improving outcomes, such as improving the quality of care provided by low-volume providers and attracting better providers to low-volume areas.

Urban-rural differences in the quality of care for medicare patients with acute myocardial infarction.

BACKGROUND: There are urban-rural differences in health care utilization in Kansas. This study was conducted to determine if similar differences exist in the quality of inpatient care provided for patients with acute myocardial infarction (AMI). METHODS: All acute care hospitals in the state were stratified into 12 urban, 31 semirural, and 76 rural hospitals according to their location. Data from medical records of 2521 Medicare patients 65 years and older who had survived AMI and were discharged alive from hospitals during an 8-month period in 1994/1995 were abstracted. The measures of the quality of care (quality indicators [QIs]) were the use of aspirin (during hospital stay and at discharge) and the administration of beta-blockers, intravenous (IV) nitroglycerin, heparin, and reperfusion by thrombolytic therapy or primary angioplasty. RESULTS: A significantly higher proportion of ideal candidates for the use of aspirin during hospital stay and at discharge, heparin, and IV nitroglycerin received these medications in urban hospitals, and a lower proportion of similar patients received these medications in rural hospitals compared with the patients in semirural hospitals (P<.001). Similar trends in each of the 6 QIs were observed for less than ideal patients (P<.05). Patient age was associated with a relatively poor quality of care in terms of the 6 QIs. Except for the administration of IV nitroglycerine to less than ideal patients, age adjustments did not change the observed urban-rural differences in the QI measures. CONCLUSION: Relatively poor quality of care for patients with AMI was provided by rural hospitals where greater opportunity for improvement exists.

Management of Guillain-Barré syndrome.

Guillain-Barré syndrome is now the most common cause of acute flaccid paralysis. Although modern intensive care facilities have significantly reduced the mortality associated with this monophasic immune mediated neuropathy, up to 5% of patients do not survive and 10% are left unable to walk unaided. Supportive medical care remains the most important aspect of management but both plasmapheresis and iv. immunoglobulin have been shown to hasten recovery when given in the early stages of the illness. This article summarizes the current management of Guillain-Barré syndrome, including both supportive measures and immune modulating therapy.