Study on the effects of arm abduction angle and cushion support during sonographic examination on the stiffness of supraspinatus muscle of sonographers using shear wave elastography.

OBJECTIVES: The incidence of work-related musculoskeletal disorder remains high in sonography. The aims of this study are to determine the changes in muscle stiffness with different arm abduction angles, and to investigate the effect of cushion support on reducing muscle load in the supraspinatus when sonographers scan with the arm abducted to different angles. METHODS: This is a prospective crossover study. Twenty-three healthy female subjects aged between 20 and 23 years were included. Subjects were instructed to simulate performing standardized abdominal ultrasound scans. The changes in muscle stiffness of supraspinatus, measured as shear modulus, at rest and at 30°, 45°, and 60° arm abduction angles with and without cushion support were evaluated using shear-wave elastography. Styrofoam support was used for the cushion support. RESULTS: Mean shear moduli of supraspinatus were 27.77 ± 5.84 kPa at rest and 41.63 ± 7.09 kPa, 63.88 ± 14.43 kPa, and 89.76 ± 16.55 kPa for 30°, 45°, and 60° arm abduction respectively, which corresponds to 53%, 116% increase in muscle stiffness when scanning arm abducted from 30° to 45° and 60° (p < .001). After applying cushion support, shear moduli dropped to 24.04 ± 5.60 kPa, 31.98 ± 6.06 kPa, 37.47 ± 5.61 kPa for arm abducted to 30°, 45°, and 60° respectively (p < .001). The muscle stiffnesses between 30° abduction without support and 60° abduction with support had no significant difference (p > .05). CONCLUSIONS: Muscle stiffness of supraspinatus increased with increasing arm abduction angle during ultrasound scanning. Utilizing cushion support underneath the arm was effective in reducing muscle stiffness in supraspinatus. Our results provide scientific justification on postural modifications for sonographers.

Predicting Nash equilibria for microbial metabolic interactions.

MOTIVATION: Microbial metabolic interactions impact ecosystems, human health and biotechnology profoundly. However, their determination remains elusive, invoking an urgent need for predictive models seamlessly integrating metabolism with evolutionary principles that shape community interactions. RESULTS: Inspired by the evolutionary game theory, we formulated a bi-level optimization framework termed NECom for which any feasible solutions are Nash equilibria of microbial community metabolic models with/without an outer-level (community) objective function. Distinct from discrete matrix games, NECom models the continuous interdependent strategy space of metabolic fluxes. We showed that NECom successfully predicted several classical games in the context of metabolic interactions that were falsely or incompletely predicted by existing methods, including prisoner's dilemma, snowdrift and cooperation. The improved capability originates from the novel formulation to prevent 'forced altruism' hidden in previous static algorithms while allowing for sensing all potential metabolite exchanges to determine evolutionarily favorable interactions between members, a feature missing in dynamic methods. The results provided insights into why mutualism is favorable despite seemingly costly cross-feeding metabolites and demonstrated similarities and differences between games in the continuous metabolic flux space and matrix games. NECom was then applied to a reported algae-yeast co-culture system that shares typical cross-feeding features of lichen, a model system of mutualism. 488 growth conditions corresponding to 3221 experimental data points were simulated. Without training any parameters using the data, NECom is more predictive of species' growth rates given uptake rates compared with flux balance analysis with an overall 63.5% and 81.7% reduction in root-mean-square error for the two species respectively. AVAILABILITY AND IMPLEMENTATION: Simulation code and data are available at https://github.com/Jingyi-Cai/NECom.git. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Bacterial colonization reprograms the neonatal gut metabolome.

Initial microbial colonization and later succession in the gut of human infants are linked to health and disease later in life. The timing of the appearance of the first gut microbiome, and the consequences for the early life metabolome, are just starting to be defined. Here, we evaluated the gut microbiome, proteome and metabolome in 88 African-American newborns using faecal samples collected in the first few days of life. Gut bacteria became detectable using molecular methods by 16 h after birth. Detailed analysis of the three most common species, Escherichia coli, Enterococcus faecalis and Bacteroides vulgatus, did not suggest a genomic signature for neonatal gut colonization. The appearance of bacteria was associated with reduced abundance of approximately 50 human proteins, decreased levels of free amino acids and an increase in products of bacterial fermentation, including acetate and succinate. Using flux balance modelling and in vitro experiments, we provide evidence that fermentation of amino acids provides a mechanism for the initial growth of E. coli, the most common early colonizer, under anaerobic conditions. These results provide a deep characterization of the first microbes in the human gut and show how the biochemical environment is altered by their appearance.

Metabolic Analyses of Nitrogen Fixation in the Soybean Microsymbiont Sinorhizobium fredii Using Constraint-Based Modeling.

Rhizobia are soil bacteria able to establish symbiosis with diverse host plants. Specifically, Sinorhizobium fredii is a soil bacterium that forms nitrogen-fixing root nodules in diverse legumes, including soybean. The strain S. fredii CCBAU45436 is a dominant sublineage of S. fredii that nodulates soybeans in alkaline-saline soils in the Huang-Huai-Hai Plain region of China. Here, we present a manually curated metabolic model of the symbiotic form of Sinorhizobium fredii CCBAU45436. A symbiosis reaction was defined to describe the specific soybean-microsymbiont association. The performance and quality of the reconstruction had a 70% score when assessed using a standardized genome-scale metabolic model test suite. The model was used to evaluate in silico single-gene knockouts to determine the genes controlling the nitrogen fixation process. One hundred forty-one of 541 genes (26%) were found to influence the symbiotic process, wherein 121 genes were predicted as essential and 20 others as having a partial effect. Transcriptomic profiles of CCBAU45436 were used to evaluate the nitrogen fixation capacity in cultivated versus in wild soybean inoculated with the microsymbiont. The model quantified the nitrogen fixation activities of the strain in these two hosts and predicted a higher nitrogen fixation capacity in cultivated soybean. Our results are consistent with published data demonstrating larger amounts of ureides and total nitrogen in cultivated soybean than in wild soybean. This work presents the first metabolic network reconstruction of S. fredii as an example of a useful tool for exploring the potential benefits of microsymbionts to sustainable agriculture and the ecosystem.IMPORTANCE Nitrogen is the most limiting macronutrient for plant growth, and rhizobia are important bacteria for agriculture because they can fix atmospheric nitrogen and make it available to legumes through the establishment of a symbiotic relationship with their host plants. In this work, we studied the nitrogen fixation process in the microsymbiont Sinorhizobium fredii at the genome level. A metabolic model was built using genome annotation and literature to reconstruct the symbiotic form of S. fredii Genes controlling the nitrogen fixation process were identified by simulating gene knockouts. Additionally, the nitrogen-fixing capacities of S. fredii CCBAU45436 in symbiosis with cultivated and wild soybeans were evaluated. The predictions suggested an outperformance of S. fredii with cultivated soybean, consistent with published experimental evidence. The reconstruction presented here will help to understand and improve nitrogen fixation capabilities of S. fredii and will be beneficial for agriculture by reducing the reliance on fertilizer applications.

Creation and analysis of biochemical constraint-based models using the COBRA Toolbox v.3.0.

Constraint-based reconstruction and analysis (COBRA) provides a molecular mechanistic framework for integrative analysis of experimental molecular systems biology data and quantitative prediction of physicochemically and biochemically feasible phenotypic states. The COBRA Toolbox is a comprehensive desktop software suite of interoperable COBRA methods. It has found widespread application in biology, biomedicine, and biotechnology because its functions can be flexibly combined to implement tailored COBRA protocols for any biochemical network. This protocol is an update to the COBRA Toolbox v.1.0 and v.2.0. Version 3.0 includes new methods for quality-controlled reconstruction, modeling, topological analysis, strain and experimental design, and network visualization, as well as network integration of chemoinformatic, metabolomic, transcriptomic, proteomic, and thermochemical data. New multi-lingual code integration also enables an expansion in COBRA application scope via high-precision, high-performance, and nonlinear numerical optimization solvers for multi-scale, multi-cellular, and reaction kinetic modeling, respectively. This protocol provides an overview of all these new features and can be adapted to generate and analyze constraint-based models in a wide variety of scenarios. The COBRA Toolbox v.3.0 provides an unparalleled depth of COBRA methods.

When Community Calls, We Collaborate! Community-Based Participatory Research With the Multilanguage Montagnard Refugee Community.

BACKGROUND: Montagnard refugees, an indigenous multilingual tribal people from Vietnam, experience lifestyle changes and post-resettlement challenges in the United States that contribute to chronic health conditions. Foundational research and health data are lacking. OBJECTIVES: We describe the Montagnard Hypertension Study, a community-based participatory research (CBPR) project documenting chronic disease risk. METHODS: We developed a Montagnard dictionary of hypertension-specific terminology and conducted two focus group discussions (FGD), 131 biological assessments (blood pressure, height, weight, waist circumference, scalp hair and saliva sample collection), and 127 behavioral surveys. We implemented two health fairs that offered services to the community. LESSONS LEARNED: This is the first study to examine chronic disease using a CBPR framework for Montagnard health. We highlight lessons learned specific to constituents and their capacities, historical and current conflicts, and the iterative processes in CBPR design. CONCLUSIONS: CBPR is a practically achievable approach to studying chronic disease risk within indigenous, tribal communities, with implications for future research with Asian American subgroups and other minority populations.

Accelerating flux balance calculations in genome-scale metabolic models by localizing the application of loopless constraints.

Background: Genome-scale metabolic network models and constraint-based modeling techniques have become important tools for analyzing cellular metabolism. Thermodynamically infeasible cycles (TICs) causing unbounded metabolic flux ranges are often encountered. TICs satisfy the mass balance and directionality constraints but violate the second law of thermodynamics. Current practices involve implementing additional constraints to ensure not only optimal but also loopless flux distributions. However, the mixed integer linear programming problems required to solve become computationally intractable for genome-scale metabolic models. Results: We aimed to identify the fewest needed constraints sufficient for optimality under the loopless requirement. We found that loopless constraints are required only for the reactions that share elementary flux modes representing TICs with reactions that are part of the objective function. We put forth the concept of localized loopless constraints (LLCs) to enforce this minimal required set of loopless constraints. By combining with a novel procedure for minimal null-space calculation, the computational time for loopless flux variability analysis (ll-FVA) is reduced by a factor of 10-150 compared to the original loopless constraints and by 4-20 times compared to the current fastest method Fast-SNP with the percent improvement increasing with model size. Importantly, LLCs offer a scalable strategy for loopless flux calculations for multi-compartment/multi-organism models of large sizes, for example, shortening the CPU time for ll-FVA from 35 h to less than 2 h for a model with more than104 reactions. Availability and implementation: Matlab functions are available in the Supplementary Material or at https://github.com/maranasgroup/lll-FVA. Supplementary information: Supplementary data are available at Bioinformatics online.

Differences in clinical outcome between docetaxel and abiraterone acetate as the first-line treatment in chemo-naïve metastatic castration-resistant prostate cancer patients with or without the ineligible clinical factors of the COU-AA-302 study.

BACKGROUND: This study aimed to compare the efficacy of abiraterone acetate (AA) versus docetaxel (T) as first-line treatment in chemo-naïve metastatic castration-resistant prostate cancer (mCRPC) patients with or without the ineligible factors of the COU-AA-302 study (presence of visceral metastases, symptomatic disease, and/or Eastern Cooperative Oncology Group performance status ≥ 2). MATERIALS AND METHODS: The clinical records of chemo-naïve mCRPC patients who received AA in six public oncology centers or T in two of these centers between 2003 and 2014 were reviewed. The survival time was compared among four subgroups of patients: those with ineligible factors administered AA (Group Ineligible-AA) or T (Group Ineligible-T), and those without ineligible factors and administered AA (Group Eligible-AA) or T (Group Eligible-T). RESULTS: During the study period, we identified 115 mCRPC patients who received AA or T, among whom 29, 36, 29, and 21 patients were classified as Groups Ineligible-AA, Ineligible-T, Eligible-AA, and Eligible-T, respectively. Both Group Ineligible-AA and Group Eligible-AA had significantly longer progression-free survival (PFS) and similar overall survival (OS) as Group Ineligible-T and Group Eligible-T (Ineligible, PFS: 6.3 vs. 5.9 months, P = 0.0234, OS: 7.8 vs. 15.7 months, P = 0.1601; Eligible, PFS: 9.8 vs. 5.6 months, P = 0.0437, OS: 20.5 vs. 18.2 months, P = 0.7820). CONCLUSIONS: Compared to T, AA treatment resulted in longer PFS and similar OS in chemo-naïve mCRPC patients, irrespective of the presence of ineligible factors, suggesting that the initial treatment by AA may still be beneficial to those with the aforementioned ineligible factors.

Standardizing biomass reactions and ensuring complete mass balance in genome-scale metabolic models.

MOTIVATION: In a genome-scale metabolic model, the biomass produced is defined to have a molecular weight (MW) of 1 g mmol-1. This is critical for correctly predicting growth yields, contrasting multiple models and more importantly modeling microbial communities. However, the standard is rarely verified in the current practice and the chemical formulae of biomass components such as proteins, nucleic acids and lipids are often represented by undefined side groups (e.g. X, R). RESULTS: We introduced a systematic procedure for checking the biomass weight and ensuring complete mass balance of a model. We identified significant departures after examining 64 published models. The biomass weights of 34 models differed by 5-50%, while 8 models have discrepancies >50%. In total 20 models were manually curated. By maximizing the original versus corrected biomass reactions, flux balance analysis revealed >10% differences in growth yields for 12 of the curated models. Biomass MW discrepancies are accentuated in microbial community simulations as they can cause significant and systematic errors in the community composition. Microbes with underestimated biomass MWs are overpredicted in the community whereas microbes with overestimated biomass weights are underpredicted. The observed departures in community composition are disproportionately larger than the discrepancies in the biomass weight estimate. We propose the presented procedure as a standard practice for metabolic reconstructions. AVAILABILITY AND IMPLEMENTATION: The MALTAB and Python scripts are available in the Supplementary Material. CONTACT: costas@psu.edu or joshua.chan@connect.polyu.hk. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

A prospective interventional study to examine the effect of a silver alloy and hydrogel-coated catheter on the incidence of catheter-associated urinary tract infection.

INTRODUCTION: Catheter-associated urinary tract infection is a major hospital-acquired infection. This study aimed to analyse the effect of a silver alloy and hydrogel-coated catheter on the occurrence of catheter-associated urinary tract infection. METHODS: This was a 1-year prospective study conducted at a single centre in Hong Kong. Adult patients with an indwelling urinary catheter for longer than 24 hours were recruited. The incidence of catheter-associated urinary tract infection in patients with a conventional latex Foley catheter without hydrogel was compared with that in patients with a silver alloy and hydrogel-coated catheter. The most recent definition of urinary tract infection was based on the latest surveillance definition of the National Healthcare Safety Network managed by Centers for Disease Control and Prevention. RESULTS: A total of 306 patients were recruited with a similar ratio between males and females. The mean (standard deviation) age was 81.1 (10.5) years. The total numbers of catheter-days were 4352 and 7474 in the silver-coated and conventional groups, respectively. The incidences of catheter-associated urinary tract infection per 1000 catheter-days were 6.4 and 9.4, respectively (P=0.095). There was a 31% reduction in the incidence of catheter-associated urinary tract infection per 1000 catheter-days in the silver-coated group. Escherichia coli was the most commonly involved pathogen (36.7%) of all cases. Subgroup analysis revealed that the protective effect of silver-coated catheter was more pronounced in long-term users as well as female patients with a respective 48% (P=0.027) and 42% (P=0.108) reduction in incidence of catheter-associated urinary tract infection. The mean catheterisation time per person was the longest in patients using a silver-coated catheter (17.0 days) compared with those using a conventional (10.8 days) or both types of catheter (13.6 days) [P=0.01]. CONCLUSIONS: Silver alloy and hydrogel-coated catheters appear to be effective in preventing catheter-associated urinary tract infection based on the latest surveillance definition. The effect is perhaps more prominent in long-term users and female patients.

A hospital-wide screening programme to control an outbreak of vancomycin-resistant enterococci in a large tertiary hospital in Hong Kong.

INTRODUCTION: Apart from individual small-scale outbreaks, infections with vancomycin-resistant enterococci are uncommon in Hong Kong. A major outbreak of vancomycin-resistant enterococci, however, occurred at a large tertiary hospital in 2013. We describe the successful control of this outbreak and share the lessons learned. METHODS: In 2013, there was an abnormal increase in the incidence of vancomycin-resistant enterococci carriage compared with baseline in multiple clinical departments at Queen Elizabeth Hospital. A multipronged approach was adopted that included a 10-week hospital-wide active screening programme, which aimed to identify and isolate hidden vancomycin-resistant enterococci carriers among all in-patients. The identified carriers were completely segregated in designated wards where applicable. Other critical infection control measures included directly observed hand hygiene and environmental hygiene. A transparent and open disclosure approach was adopted throughout the outbreak. RESULTS: The infection control measures were successfully implemented. The active screening of vancomycin-resistant enterococci was conducted between 30 September and 10 November 2013. A total of 7053 rectal swabs were collected from patients in 46 hospital wards from 11 departments. The overall carriage rate of vancomycin-resistant enterococci was 2.8% (201/7053). Pulsed-field gel electrophoresis showed a predominant outbreak clone. We curbed the outbreak and kept the colonisation of vancomycin-resistant enterococci among patients at a pre-upsurge low level. CONCLUSIONS: We report the largest cohesive effort to control spread of vancomycin-resistant enterococci in Hong Kong. Coupled with other infection control measures, we successfully controlled vancomycin-resistant enterococci to the pre-outbreak level. We have demonstrated that the monumental tasks can be achieved with meticulous planning, and thorough communication and understanding between all stakeholders.

Farnesoid X Receptor Signaling Shapes the Gut Microbiota and Controls Hepatic Lipid Metabolism.

The gut microbiota modulates obesity and associated metabolic phenotypes in part through intestinal farnesoid X receptor (FXR) signaling. Glycine-ß-muricholic acid (Gly-MCA), an intestinal FXR antagonist, has been reported to prevent or reverse high-fat diet (HFD)-induced and genetic obesity, insulin resistance, and fatty liver; however, the mechanism by which these phenotypes are improved is not fully understood. The current study investigated the influence of FXR activity on the gut microbiota community structure and function and its impact on hepatic lipid metabolism. Predictions about the metabolic contribution of the gut microbiota to the host were made using 16S rRNA-based PICRUSt (phylogenetic investigation of communities by reconstruction of unobserved states), then validated using 1H nuclear magnetic resonance-based metabolomics, and results were summarized by using genome-scale metabolic models. Oral Gly-MCA administration altered the gut microbial community structure, notably reducing the ratio of Firmicutes to Bacteroidetes and its PICRUSt-predicted metabolic function, including reduced production of short-chain fatty acids (substrates for hepatic gluconeogenesis and de novo lipogenesis) in the ceca of HFD-fed mice. Metabolic improvement was intestinal FXR dependent, as revealed by the lack of changes in HFD-fed intestine-specific Fxr-null (FxrΔIE) mice treated with Gly-MCA. Integrative analyses based on genome-scale metabolic models demonstrated an important link between Lactobacillus and Clostridia bile salt hydrolase activity and bacterial fermentation. Hepatic metabolite levels after Gly-MCA treatment correlated with altered levels of gut bacterial species. In conclusion, modulation of the gut microbiota by inhibition of intestinal FXR signaling alters host liver lipid metabolism and improves obesity-related metabolic dysfunction. IMPORTANCE The farnesoid X receptor (FXR) plays an important role in mediating the dialog between the host and gut microbiota, particularly through modulation of enterohepatic circulation of bile acids. Mounting evidence suggests that genetic ablation of Fxr in the gut or gut-restricted chemical antagonism of the FXR promotes beneficial health effects, including the prevention of nonalcoholic fatty liver disease in rodent models. However, questions remain unanswered, including whether modulation of FXR activity plays a role in shaping the gut microbiota community structure and function and what metabolic pathways of the gut microbiota contribute in an FXR-dependent manner to the host phenotype. In this report, new insights are gained into the metabolic contribution of the gut microbiota to the metabolic phenotypes, including establishing a link between FXR antagonism, bacterial bile salt hydrolase activity, and fermentation. Multiple approaches, including unique mouse models as well as metabolomics and genome-scale metabolic models, were employed to confirm these results.

Sleep Duration and Insomnia Symptoms as Risk Factors for Suicidal Ideation in a Nationally Representative Sample.

OBJECTIVE: Suicidal behavior (suicidal ideation, suicide attempts, and suicide completion) has been increasingly linked with difficulty initiating sleep, maintaining sleep, and early morning awakenings. However, the relationship between suicidal behavior and sleep duration abnormalities is unclear, especially at the population level. The present study used a nationally representative sample to examine the association of suicidal ideation with extreme sleep durations and insomnia symptoms. METHOD: Cross-sectional data from adult respondents (≥ 18 years of age, N = 6,228) were extracted from the 2007-2008 wave of the National Health and Nutritional Examination Survey. Ordinal logistic regression analyses were used to evaluate the relationship of suicidal ideation with sleep duration, global insomnia, and individual insomnia symptoms in models adjusted for sociodemographic, socioeconomic, and health-related covariates. RESULTS: Suicidal ideation was associated with abnormalities of sleep duration. This relationship ceased to exist once the model was adjusted for depressive symptoms. As expected, an increased level of suicidal ideation was consistently associated with insomnia. Of the insomnia symptoms, difficulty maintaining sleep was found to be the most predictive of suicidal ideation, followed by difficulty initiating sleep (P< .05). CONCLUSIONS: Abnormalities of sleep duration and continuity should prompt a clinical assessment for suicide risk.

Antimicrobial susceptibility in hospitals in Hong Kong: The current status 2009-2011.

Hospitals in Hong Kong, like many hospitals in the world, are constantly challenged by the increasing rate of non-susceptible and multidrug-resistant organisms (MDROs). Accurate and timely surveillance is essential for effective control. The Hospital Authority of Hong Kong has developed a comprehensive antimicrobial susceptibility monitoring system that utilises data obtained from all of its 38 hospitals. In this review, the susceptibility pattern of more than 320000 isolates covering the period 2009-2011 will be discussed. Special attention will be paid to MDROs.

Synthetic archaeosome vaccines containing triglycosylarchaeols can provide additive and long-lasting immune responses that are enhanced by archaetidylserine.

The relation between archaeal lipid structures and their activity as adjuvants may be defined and explored by synthesizing novel head groups covalently linked to archaeol (2,3-diphytanyl-sn-glycerol). Saturated archaeol, that is suitably stable as a precursor for chemical synthesis, was obtained in high yield from Halobacterium salinarum. Archaeosomes consisting of the various combinations of synthesized lipids, with antigen entrapped, were used to immunize mice and subsequently determine CD8(+) and CD4(+)-T cell immune responses. Addition of 45 mol% of the glycolipids gentiotriosylarchaeol, mannotriosylarchaeol or maltotriosylarchaeol to an archaetidylglycerophosphate-O-methyl archaeosome, significantly enhanced the CD8(+) T cell response to antigen, but diminished the antibody titres in peripheral blood. Archaeosomes consisting of all three triglycosyl archaeols combined with archaetidylglycerophosphate-O-methyl (15/15/15/55 mol%) resulted in approximately additive CD8(+) T cell responses and also an antibody response not significantly different from the archaetidylglycerophosphate-O-methyl alone. Synthetic archaetidylserine played a role to further enhance the CD8(+) T cell response where the optimum content was 20-30 mol%. Vaccines giving best protection against solid tumor growth corresponded to the archaeosome adjuvant composition that gave highest immune activity in immunized mice.

Correlation of pulse wave velocity with left ventricular mass in patients with hypertension once blood pressure has been normalized.

Vascular stiffness has been proposed as a simple method to assess arterial loading conditions of the heart which induce left ventricular hypertrophy (LVH). There is some controversy as to whether the relationship of vascular stiffness to LVH is independent of blood pressure, and which measurement of arterial stiffness, augmentation index (AI) or pulse wave velocity (PWV) is best. Carotid pulse wave contor and pulse wave velocity of patients (n=20) with hypertension whose blood pressure (BP) was under control (<140/90 mmHg) with antihypertensive drug treatment medications, and without valvular heart disease, were measured. Left ventricular mass, calculated from 2D echocardiogram, was adjusted for body size using two different methods: body surface area and height. There was a significant (P<0.05) linear correlation between LV mass index and pulse wave velocity. This was not explained by BP level or lower LV mass in women, as there was no significant difference in PWV according to gender (1140.1+67.8 vs 1110.6+57.7 cm/s). In contrast to PWV, there was no significant correlation between LV mass and AI. In summary, these data suggest that aortic vascular stiffness is an indicator of LV mass even when blood pressure is controlled to less than 140/90 mmHg in hypertensive patients. The data further suggest that PWV is a better proxy or surrogate marker for LV mass than AI and the measurement of PWV may be useful as a rapid and less expensive assessment of the presence of LVH in this patient population.

Occupational rehabilitation in Hong Kong: current status and future needs.

INTRODUCTION: This paper reviews the development of occupational rehabilitation in Hong Kong, both in terms of the science as well as the service for injured workers. Besides, it also reviews the existing Employees' Compensation Ordinance for work injury to illustrate how the policy could influence the success and development of the discipline. METHODS: Five experienced occupational rehabilitation providers, including 1 occupational medicine specialist, 3 occupational therapists, and 1 physiotherapist critically reviewed the past and current development of occupational rehabilitation in Hong Kong as well as the local contextual factors, which could influence its future development. RESULTS: Since the enactment of the Employees' Compensation Ordinance in the 1950s, there have been progressive improvements in the field of occupational rehabilitation in Hong Kong. Services in the early years were mostly based on the biomedical model, where doctors and patients tended to focus on clinical symptoms and physical pathology when making clinical decisions. Since then, remarkable academic achievements have been made in the field locally, from the validation of clinical instruments for assessment of work capacity, assessment of employment readiness to the evaluation of efficacy of interventional programs for injured workers focusing on work related outcomes. However, there has been a relatively lack of progress in the development of related policies and implementation of related programs for occupational rehabilitation. There is no built in linkage between rehabilitation, compensation and prevention in the current system in Hong Kong, and there is no rehabilitation policy specific to those workers with occupational diseases and injuries. CONCLUSIONS: There are still deficiencies in the development and provision of occupational rehabilitation services in Hong Kong. Incorporation of requirements for occupational rehabilitation at the legislation and policy levels should be seriously considered in the future. Besides, the development of the Occupational Medicine subspecialty in the public hospital system in Hong Kong is considered a facilitator to the future development of occupational rehabilitation in Hong Kong.

Isopranoid- and dipalmitoyl-aminophospholipid adjuvants impact differently on longevity of CTL immune responses.

The success of lipid membranes as cytotoxic T-cell (CTL) adjuvants requires targeted uptake by antigen-presenting cells (APCs) and delivery of the antigen cargo to the cytosol for processing. To target the phosphatidylserine (PS) receptor of APCs, we prepared antigen-loaded liposomes containing dipalmitoylphosphatidylserine and archaeal lipid liposomes (archaeosomes), containing an equivalent amount of archaetidylserine, and compared their ability to promote short and long-term CTL activity in animals. CTL responses were enhanced by the incorporation of PS into phosphatidylcholine/cholesterol liposomes and, to a lesser extent, into phosphatidylglycerol/cholesterol liposomes, that correlated to the amount of surface amino groups reactive with trinitrobenzoyl sulfonate. Archaeosomes contrasted to the liposome adjuvants by exhibiting higher amounts of surface amino groups and inducing superior shorter and, especially, longer-term CTL responses. The incorporation of dipalmitoyl lipids into archaeosomes induced instability and prevented long-term, but not short-term, CTL responses in mice. The importance of glycero-lipid cores (isopranoid versus dipalmitoyl) to the longevity of the CTL response achieved was shown further by incorporating dipalmitoyl phosphatidylethanolamine (DPPE) or equivalent amounts of synthetic archaetidylethanolamine (AE) into archaeosome adjuvants. Both DPPE and AE at equivalent (5 mol%) concentrations enhanced the rapidity of CTL responses in mice, indicating the importance of the head group in the short term. In the longer term, 5% of DPPE (but not 5% of AE) was detrimental. In addition to head-group effects critical to the potency of short-term CTL responses, the longer term CTL adjuvant properties of archaeosomes may be ascribed to stability imparted by the archaeal isopranoid core lipids.

Development of new glycosylation methodologies for the synthesis of archaeal-derived glycolipid adjuvants.

To commercialize the production of glycolipid adjuvants, their synthesis needs to be both robust and inexpensive. Herein we describe a semi-synthetic approach where the lipid acceptor is derived from the biomass of the archaeon Halobacterium salinarum, and the glycosyl donors are chemically synthesized. This work presents some preliminary results using the promoter system N-iodosuccinimide (NIS) and a stable 0.25 M solution of boron trifluoride-trifluoroethanol (BF(3) x TFE(2)) in dichloromethane. This promoter system allows for the use of peracetyl alkyl(aryl)thioglycosides that are available in high yield from inexpensive disaccharide starting materials by promoting clean glycosylation reactions from which pure product can be easily isolated. Conventional glycosylation using NIS-silver trifluoromethanesulfonate (AgOTf) leads to extensive acetyl transfer to the archaeol acceptor and numerous byproducts that make purification complicated. As part of preliminary structure-adjuvant activity studies, we describe the one-pot synthesis of a gentiobiose beta-Glcp-(1-->6)-Glcp-SEt donor with an O-2 benzoyl group, which can be used to prepare a disaccharide attached to archaeol in 85% overall yield, and the related glycolipid trisaccharide beta-Glcp-(1-->6)-beta-Glcp-(1-->6)-beta-Glcp-(1-->O)-archaeol. The synthesis of the isomeric beta-Glcp-(1-->6)-alpha-Glcp-(1-->O)-archaeol featuring a >10:1 alpha/beta alpha-selective glycosylation using the promoter system N-phenylselenylphthalimide-trifluoromethanesulfonic acid (TfOH) is also presented, along with the adjuvant properties of the corresponding archaeosomes (liposomes comprised entirely of combinations of isoprenoid archaeal-like lipids). These new vaccine formulations extend previous observations that glycolipids are integral to the activation of MHC type I pathways via CD8(+) antigen-specific T-cells. The beta-Glcp-(1-->6)-beta-Glcp-(1-->6)-beta-Glcp-(1-->O)-archaeol trisaccharide is shown to be more active than the Glcp-(1-->6)-beta-Glcp-(1-->O)-archaeol disaccharide.