Search

Abstract Background Lipids are associated with atherosclerosis, and novel lipid indices have been recently identified to be closely linked to cardiovascular diseases. This study explored the association between four novel lipid indices and the white matter hyperintensities (WMHs) in patients diagnosed with cerebral small vessel disease (CSVD). Methods Between January 2023 and February 2024, 219 patients were recruited, including 165 patients with CSVD WMHs and 54 healthy controls. Based on WMHs severity, patients with CSVD were categorised into mild and moderate-to-severe cohorts using the Fazekas rating scale. The plasma levels of four novel lipid indices (low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio [LDL-C/HDL-C], triglyceride/high-density lipoprotein cholesterol ratio [TG/HDL-C], total cholesterol/high-density lipoprotein cholesterol ratio [TC/HDL-C], and non-high-density lipoprotein cholesterol [Non-HDL-C]), were rigorously monitored in the enrolled patients. Results A total of 165 patients with CSVD WMHs were enrolled, including 94 with mild WMHs and 71 with moderate-to-severe WMHs. Multivariable logistic regression analysis revealed that LDL-C/HDL-C, TG/HDL-C, TC/HDL-C, and Non-HDL-C levels were significantly associated with WMHs (all P ≤ 0.001). Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of plasma lipid levels for WMHs in patients with CSVD. The novel lipid indicators outperformed traditional lipid indicators in assessing the diagnostic capability of WMHs. The combined index of the four blood lipid indices had an optimal cutoff point (OCP) of 0.489, with 88.3% sensitivity and 60.6% specificity. The area under the curve (AUC) is 0.800 (95% confidence interval [CI], 0.731–0.869; P

Abstract Background Pain management is a critical but complex issue for the relief of acute pain, particularly for postoperative pain and severe pain in cancer patients. It also plays important roles in promoting quality of care. The introduction of pain management decision support systems (PM-DSS) is considered a potential solution for addressing the complex problems encountered in pain management. This study aims to investigate factors affecting acceptance of PM-DSS from a nurse anesthetist perspective. Methods A questionnaire survey was conducted to collect data from nurse anesthetists in a case hospital. A total of 113 questionnaires were distributed, and 101 complete copies were returned, indicating a valid response rate of 89.3%. Collected data were analyzed by structure equation modeling using the partial least square tool. Results The results show that perceived information quality (γ=.451, p2=.487) and perceived usefulness (β=.443, p2=.646) significantly affected nurse anesthetists’ PM-DSS acceptance (R2=.640). Thus, the critical role of information quality in the development of clinical decision support system is demonstrated. Conclusions The findings of this study enable hospital managers to understand the important considerations for nurse anesthetists in accepting PM-DSS, particularly for the issues related to the improvement of information quality, perceived usefulness and perceived ease of use of the system. In addition, the results also provide useful suggestions for designers and implementers of PM-DSS in improving system development.

Abstract Background Chronic soil-transmitted helminth (STH) infections have been associated with reduced physical fitness, but available evidence is limited. The aim of this cross-sectional survey was to assess the feasibility of measuring children's physical fitness and to relate it to STH infections. Our study was carried out among school-aged children of the Bulang ethnic group in rural southwest People's Republic of China (P.R. China). Standardized, quality-controlled methods were employed to determine STH infections (Kato-Katz technique), haemoglobin levels, anthropometry (body weight and height) and physical fitness (20-m shuttle run test). Results A compliance of 87% suggested good acceptance of the methods used. Among 69 children with complete data records, infection prevalence of Trichuris trichiura, Ascaris lumbricoides and hookworm were 81%, 44% and 6%, respectively. The maximum volume of oxygen that can be utilized within 1 min during exhaustive exercise (VO2 max estimate) of T. trichiura-infected children was 1.94 ml kg-1 min-1 lower than that of their non-infected counterparts (P = 0.005). Until exhaustion, T. trichiura-infected children had completed 6.14 20-m laps less (P = 0.004). Additionally, the mean VO2 max estimate of stunted children was lowered by 1.63 ml kg-1 min-1 (P = 0.002) and they completed 5.32 20-m laps less (P = 0.001) compared to children of normal stature. No significant association between stunting and infection with any STH species could be established. Conclusions Implementation of physical fitness tests in rural, resource-constraint settings is feasible. The physical fitness of children who are stunted or infected with STHs, particularly T. trichiura, is significantly impaired. We have launched a larger study and will determine the dynamics of school-aged children's physical fitness over a 7-month period after administration of anthelminthic drugs.

Abstract Background The ability to synthesize exopolysaccharides (EPS) is widespread among microorganisms, and microbial EPS play important roles in biofilm formation, pathogen persistence, and applications in the food and medical industries. Although it is well established that EPS synthesis is invariably in response to environmental cues, it remains largely unknown how various environmental signals trigger activation of the biochemical synthesis machinery. Results We report here the transcriptome profiling of Agrobacterium sp. ATCC 31749, a microorganism that produces large amounts of a glucose polymer known as curdlan under nitrogen starvation. Transcriptome analysis revealed a nearly 100-fold upregulation of the curdlan synthesis operon upon transition to nitrogen starvation, thus establishing the prominent role that transcriptional regulation plays in the EPS synthesis. In addition to known mechanisms of EPS regulation such as activation by c-di-GMP, we identify novel mechanisms of regulation in ATCC 31749, including RpoN-independent NtrC regulation and intracellular pH regulation by acidocalcisomes. Furthermore, we show evidence that curdlan synthesis is also regulated by conserved cell stress responses, including polyphosphate accumulation and the stringent response. In fact, the stringent response signal, pppGpp, appears to be indispensible for transcriptional activation of curdlan biosynthesis. Conclusions This study identifies several mechanisms regulating the synthesis of curdlan, an EPS with numerous applications. These mechanisms are potential metabolic engineering targets for improving the industrial production of curdlan from Agrobacterium sp. ATCC 31749. Furthermore, many of the genes identified in this study are highly conserved across microbial genomes, and we propose that the molecular elements identified in this study may serve as universal regulators of microbial EPS synthesis.

Abstract Background The mobility of female sex workers (FSWs) is a factor in the geographic spread of human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs). This study describes FSW mobility patterns in a high risk area of China to identify factors associated with increased mobility, and to study the incidence and prevalence of HIV/STIs in this group. Methods 270 FSWs recruited from a baseline cross-sectional study were invited to participate in a one-year monthly follow-up cohort study in Kaiyuan City, Yunnan Province, China from 2006 to 2007. Laboratory tests were conducted for HIV/STIs at baseline, 6 and 12 months. Results A total of 117 (43.3%) FSWs moved to another city during the year. Risk factors for increased mobility included being from another city within Yunnan (adjusted hazard ratio [AHR] 1.67, 95% confidence interval [CI] 1.09-2.56), being from outside Yunnan (AHR 1.58, 95% CI 1.04-2.54), and working in lower risk entertainment establishments (AHR 1.55, 95% CI 1.03-2.35). HIV-positive subjects, drug users and FSWs in higher risk venue were less likely to change residence, less likely to use condoms with clients, and earned less per client, but had more working locations and more clients each month. Conclusions The least mobile FSWs were from Kaiyuan, worked in higher risk venues, were more likely to use drugs and be HIV-infected. Because FSWs characteristics differ according to the venue at which they work, future prevention work should tailor programs according to venue with a particular focus on FSWs in higher risk venues.

Abstract In this article we summarize several recent major developments in human immunodeficiency virus treatment, prevention, outcome, and social policy change. Updated international guidelines endorse more aggressive treatment strategies and safer antiretroviral drugs. New antiretroviral options are being tested. Important lessons were learned in the areas of human immunodeficiency virus vaccines and microbicide gels from clinical studies, and additional trials in prevention, especially pre-exposure prophylaxis, are nearing completion. Insight into the role of the virus in the pathogenesis of diseases traditionally thought to be unrelated to acquired immunodeficiency syndrome has become a driving force for earlier and universal therapy. Lastly, we review important achievements of and future challenges facing China as she steps into her eighth year of the National Free Antiretroviral Treatment Program.

Abstract Background Oligosaccharides containing a terminal Gal-α1,3-Gal moiety are collectively known as α-Gal epitopes. α-Gal epitopes are integral components of several medical treatments under development, including flu and HIV vaccines as well as cancer treatments. The difficulty associated with synthesizing the α-Gal epitope hinders the development and application of these treatments due to the limited availability and high cost of the α-Gal epitope. This work illustrates the development of a whole-cell biocatalyst for synthesizing the α-Gal epitope, Gal-α1,3-Lac. Results Agrobacterium sp. ATCC 31749 was engineered to produce Gal-α1,3-Lac by the introduction of a UDP-galactose 4'-epimerase:α1,3-galactosyltransferase fusion enzyme. The engineered Agrobacterium synthesized 0.4 g/L of the α-Gal epitope. Additional metabolic engineering efforts addressed the factors limiting α-Gal epitope production, namely the availability of the two substrates, lactose and UDP-glucose. Through expression of a lactose permease, the intracellular lactose concentration increased by 60 to 110%, subsequently leading to an improvement in Gal-α1,3-Lac production. Knockout of the curdlan synthase gene increased UDP-glucose availability by eliminating the consumption of UDP-glucose for synthesis of the curdlan polysaccharide. With these additional engineering efforts, the final engineered strain synthesized approximately 1 g/L of Gal-α1,3-Lac. Conclusions The Agrobacterium biocatalyst developed in this work synthesizes gram-scale quantities of α-Gal epitope and does not require expensive cofactors or permeabilization, making it a useful biocatalyst for industrial production of the α-Gal epitope. Furthermore, the engineered Agrobacterium, with increased lactose uptake and improved UDP-glucose availability, is a promising host for the production of other medically-relevant oligosaccharides.

Abstract Background During the SARS epidemic, healthcare utilization and medical services decreased significantly. However, the long-term impact of SARS on hospital performance needs to be further discussed. Methods A municipal hospital in Taipei City was shut down for a month due to SARS and then became the designated SARS and infectious disease hospital for the city. This study collected the outpatient, inpatient and emergency service volumes for every year from April to March over four years. Average monthly service amount ± standard deviation were used to compare patient volume for the whole hospital, as well as the outpatient numbers accessing different departments. The ARIMA model of outpatient volume in the pre-SARS year was developed. Results The average monthly service volume of outpatient visits for the base year 2002 was 52317 ± 4204 visits per month, and number for 2003 and the following two years were 55%, 82% and 84% of the base year respectively. The average emergency service volume was 4382 ± 356 visits per month at the base year and this became 45%, 77% and 87% of the base year for the following three years respectively. Average inpatient service volume was 8520 ± 909 inpatient days per month at the base year becoming 43%, 81% and 87% of the base year for the following three years respectively. Only the emergency service volume had recovered to the level of a non-significant difference at the second year after SARS. In addition, the departments of family medicine, metabolism and nephrology reached the 2002 patient number in 2003. The ARIMA (2,1,0) model was the most suitable for outpatient volume in pre-SARS year. The MAPE of the ARIMA (2,1,0) model for the pre-SARS year was 6.9%, and 43.2%, 10.6%, 6.2% for following 3 years. Conclusion This study demonstrates that if a hospital is completely shut down due to SARS or a similar disease, the impact is longer than previous reported and different departments may experience different recover periods. The findings of this study identify subspecialties that are particularly vulnerable in an infectious disease designated hospital and such hospitals need to consider which subspecialties should be included in their medical structure.

Abstract Metabolic engineering has recently been embraced as an effective tool for developing whole-cell biocatalysts for oligosaccharide and polysaccharide synthesis. Microbial catalysts now provide a practical means to derive many valuable oligosaccharides, previously inaccessible through other methods, in sufficient quantities to support research and clinical applications. The synthesis process based upon these microbes is scalable as it avoids expensive starting materials. Most impressive is the high product concentrations (up to 188 g/L) achieved through microbe-catalyzed synthesis. The overall cost for selected molecules has been brought to a reasonable range (estimated $ 30–50/g). Microbial synthesis of oligosaccharides and polysaccharides is a carbon-intensive and energy-intensive process, presenting some unique challenges in metabolic engineering. Unlike nicotinamide cofactors, the required sugar nucleotides are products of multiple interacting pathways, adding significant complexity to the metabolic engineering effort. Besides the challenge of providing the necessary mammalian-originated glycosyltransferases in active form, an adequate uptake of sugar acceptors can be an issue when another sugar is necessary as a carbon and energy source. These challenges are analyzed, and various strategies used to overcome these difficulties are reviewed in this article. Despite the impressive success of the microbial coupling strategy, there is a need to develop a single strain that can achieve at least the same efficiency. Host selection and the manner with which the synthesis interacts with the central metabolism are two important factors in the design of microbial catalysts. Additionally, unlike in vitro enzymatic synthesis, product degradation and byproduct formation are challenges of whole-cell systems that require additional engineering. A systematic approach that accounts for various and often conflicting requirements of the synthesis holds the key to deriving an efficient catalyst. Metabolic engineering strategies applied to selected polysaccharides (hyaluronan, alginate, and exopolysaccharides for food use) are reviewed in this article to highlight the recent progress in this area and similarity to challenges in oligosaccharide synthesis. Many naturally occurring microbes possess highly efficient mechanisms for polysaccharide synthesis. These mechanisms could potentially be engineered into a microbe for oligosaccharide and polysaccharide synthesis with enhanced efficiency.