利用代谢网络模型和线性规划法在线预测谷氨酸发酵中产物浓度

在好氧型的谷氨酸发酵实验中发现，溶解氧（DO）对发酵性能有很大的影响，谷氨酸的生成方式也因此有很大不同：较低的DO水平能够延长产酸期、提高谷氨酸的最终浓度，但是代谢副产物——乳酸也有较大程度的积蓄；而DO水平过高，虽然代谢副产物不会生成积蓄，但菌体消亡过快导致产酸期缩短、谷氨酸的最终浓度降低．同时，谷氨酸的生成方式与发酵过程中摄氧率（OUR）和CO2的释放率（CER）有着非常紧密的关联．作者利用代谢网络模型并结合使用线性规划优化法，通过在线测定OUR和CER，比较准确地在线推定出发酵过程中谷氨酸的质量浓度变化。与传统的非构造式动力学模型相比，上述预测方法具有建模简单、模型物理意义明确、通用性能好等优点，为后续过程的在线控制和优化提供一种全新和有效的途径。     

On-line haemodiafiltration with and without acetate.

BACKGROUND: In patients on on-line convective treatments, given the considerable quantity of dialysis fluid re-infused, the small amount of acetate present in bicarbonate dialysis fluid as a pH stabilizing factor may allow a significant transfer of that anion to the patient, possibly inducing cytokine activation. METHODS: To verify this hypothesis, we performed on-line haemodiafiltration (OL-HDF) with (3 mmol/l) and without acetate in dialysis fluid in a cross-over randomized order on 12 prevalent patients. RESULTS: In comparison with the pre-treatment values, plasma acetate levels were unchanged during and after acetate-free OL-HDF, while they were 5-6 times higher in the course of OL-HDF containing acetate in dialysis fluid; plasma acetate levels returned to basal values 2 h after the end of the procedure. The total increase of bases in the patient attributable to acetate was 36%. Plasma bicarbonate values at the end of treatment were significantly lower in treatments without acetate, as compared to those with acetate. Interleukin-6 plasma levels were super-imposable at the beginning and in the course of the two methods compared, but there was a tendency towards a greater increase at an interval of 2 h following OL-HDF with acetate. CONCLUSIONS: Our preliminary results confirm the assumption that body gain of acetate is particularly high in convective treatments, while acetate-free OL-HDF slows down acetate burden. Clinical advantages due to these effects should be evaluated in properly designed prospective studies.     

SPPS of difficult sequences

The H-Ala-Arg-(Ala)₆-Lys-OH sequence is a biologically interesting ‘difficult sequence’ presenting N^α-Fmoc deprotection and coupling problems. Different chemical conditions and synthetic strategies have been tested in order to overcome the problems due to sequence-dependent interactions. In particular, it was confirmed that different solvents in the deprotection step did not provide any significant improvement, but the use of a more efficient base in the deprotection mixture avoided insufficient unblocking of N^α-protecting group; problems due to partial coupling in the last steps of the synthesis were solved by double coupling techniques. Moreover, the synthesis of the model peptide was carried out using both ‘continuous flow’ and ‘batch’ techniques. The present results demontrate that on-line monitoring of the deprotection step by absorbance measurements represents a very effective tool to detect the onset of internal aggregations during the synthesis. © Munksgaard 1997.     

双位点微透析-HPLC联用平台的构建与评价

目的:建立微透析-HPLC联用技术平台,以便自动取样与自动进样同步完成.方法:应用10孔自动进样阀将微透析取样与HPLC进行连接,以葛根素透析液为模型药物对仪器性能进行方法学评价.在线和离线微透析-HPLC联用装置相关指标采用SPSS 13.0统计软件进行t检验.结果:在所建立的HPLC色谱条件下葛根素在0.1～ 100 mg/L线性关系良好(r=1,n=5).低、中、高浓度葛根素对照品溶液日内精密度RSD分别为1.53％、0.60％、0.33％(n=5),日间精密度RSD分别为0.92％、0.52％、0.67％(n=5);重复性RSD=1.07％(n=5).葛根素对照品溶液在36 h内稳定性良好(RSD=1.05％);定量限为0.2 mg/L(S/N-10).建立的微透析-HPLC在线与离线装置进行比较,结果显示在线装置的日内、日间精密度和稳定性均显著优于离线装置(P＜0.05).结论:自行研制的双位点微透析-HPLC联用技术平台设备简便实用,可为药动学与代谢研究提供新的取样分析检测方法.     

Effect of a triage-based e-mail system on clinic resource use and patient and physician satisfaction in primary care

OBJECTIVES: E-mail communication between patients and their providers has diffused slowly in clinical practice. To address concerns about the use of this technology, we performed a randomized controlled trial of a triage-based e-mail system in primary care. DESIGN AND PATIENTS/PARTICIPANTS: Physicians in 2 university-affiliated primary care centers were randomized to a triage-based e-mail system promoted to their patients. E-mails from patients of intervention physicians were routed to a central account and parsed to the appropriate staff for response. Control group physicians and their patients did not have access to the system. We collected information on patient e-mail use, phone calls, and visit distribution by physician over the 10 months and performed physician and patient surveys to examine attitudes about communication. RESULTS: E-mail volume was greater for intervention versus control physicians (46 weekly e-mails per 100 scheduled visits vs 9 in the control group at the study midpoint; P <.01) but there were no between-group differences in phone volume (67 weekly phone calls per 100 scheduled visits vs 55 in the control group; P =.45) or rates of patient no-shows (5% in both groups; P =.77). Intervention physicians reported more favorable attitudes toward electronic communication than did control physicians but there were no differences in attitudes toward patient or staff communication in general. There were few between-group differences in patient attitudes toward electronic communication or communication in general. CONCLUSIONS: E-mail generated through a triage-based system did not appear to substitute for phone communication or to reduce visit no-shows in a primary care setting. Physicians' attitudes toward electronic communication were improved, but physicians' and patients' attitudes toward general communication did not change. Growth of e-mail communication in primary care settings may not improve the efficiency of clinical care.     

Mechanisms underlying syntactic comprehension deficits in vascular aphasia: new evidence from self-paced listening

Sixty-one people with aphasia (pwa) and 41 matched controls were tested for the ability to understand sentences that required the ability to process particular syntactic elements and assign particular syntactic structures. Participants paced themselves word-by-word through 20 examples of 11 spoken sentence types and indicated which of two pictures corresponded to the meaning of each sentence. Sentences were developed in pairs such that comprehension of the experimental version of a pair required an aspect of syntactic processing not required in the corresponding baseline sentence. The need for the syntactic operations required only in the experimental version was triggered at a “critical word” in the experimental sentence. Listening times for critical words in experimental sentences were compared to those for corresponding words in the corresponding baseline sentences. The results were consistent with several models of syntactic comprehension deficits in pwa: resource reduction, slowed lexical and/or syntactic processing, abnormal susceptibility to interference from thematic roles generated non-syntactically. They suggest that a previously unidentified disturbance limiting the duration of parsing and interpretation may lead to these deficits, and that this mechanism may lead to structure-specific deficits in pwa. The results thus point to more than one mechanism underlying syntactic comprehension disorders both across and within pwa.     

军事医学科学院在线教育系统的建立及应用

军事医学科学院在线教育系统的建立,坚持适用性与先进性相结合的原则,将教育资源进行整合,使之在研究生教育与学术交流工作中发挥重要作用.本文从用户模型、功能结构和技术实现等方面对系统进行了阐述,最后介绍了系统的应用效果,并提出进一步工作设想.     

Pre-dilution on-line haemofiltration vs low-flux haemodialysis: a randomized prospective study.

BACKGROUND: Accumulation of larger molecular weight uraemic toxins molecules may have a negative effect on the cardiovascular and nutritional state of dialysis patients and influence uraemic symptomatology. Their clearance can be enhanced by the use of haemofiltration (HF). METHODS: The effects of low-flux haemodialysis (HD) (ultrapure dialysate; polyamide membranes) and pre-dilution on-line HF (1:1 blood/substitution ratio; target filtration volume: 1.2 times body weight) on cardiovascular and nutritional parameters, interdialytic levels of uraemic toxins and quality of life (QOL; Laupacis questionnaire) were assessed during 1 year follow-up. Forty patients were randomized. RESULTS: After 1 year, 27 patients were eligible for analysis (HF: 13 patients; HD: 14 patients). Left ventricular mass index did not change in the HF patients (127+/-33 --> 131+/-36 g/m(2) after 12 months) or in the HD group (135+/-34 --> 138+/-32 g/m(2)). Also, there were no changes in pulse wave velocity, and 48 h systolic and diastolic blood pressures. Lean body mass, assessed by dual-energy X-ray absorptiometry, increased in the HF group (44.8+/-8.9 --> 46.2+/-9.6 kg; P<0.05), but not in the HD group (49.4+/-9.2 --> 50.6+/-8.8 kg), although differences between groups were not significant. Insulin-like growth factor-1 levels remained stable in the HF patients, but decreased in the HD group (P<0.05 between groups). QOL for physical symptoms improved in the HF group (4.2+/-1.2 --> 5.0+/-1.1; P<0.05 within the HF group and P = 0.06 between groups), but not in the HD group (4.0+/-1.0 --> 4.4+/-1.4). beta2-microglobulin, complement factor D and homocysteine decreased significantly in the HF but not in the HD group, whereas l-ADMA, leptin and advanced glycation end-products-related fluorescence did not change. CONCLUSIONS: No changes in cardiovascular parameters were observed during pre-dilution on-line HF compared with low-flux HD. Treatment with on-line HF resulted in marked changes in the uraemic toxicity profile, an improvement in physical well-being and a small improvement in nutritional state.     

Haemodialysis with on-line monitoring equipment: tools or toys?

BACKGROUND: On-line monitoring of chemical/physical signals during haemodialysis (HD) and bio-feedback represents the first step towards a 'physiological' HD system incorporating adaptive and logic controls in order to achieve pre-set treatment targets. METHODS: Discussions took place to achieve a consensus on key points relating to on-line monitoring and bio-feedback, focusing on the clinical applications. RESULTS: The relative blood volume (BV) reduction during HD can be monitored by optic devices detecting the variations in concentration of haemoglobin/haematocrit. BV changes result from an equilibrium between ultrafiltration and the refilling capacity. However, BV reduction has little power in predicting intra-HD hypotensive episodes, while the combination of the patient-dialysate sodium gradient, the relative BV reduction between the 20th and 40th minute of HD, the irregularity of the profile of BV reduction over time and the heart rate decrease from the start to the 20th minute of HD predict intra-HD hypotension with a sensitivity of 82%, a specificity of 73% and an accuracy of 80%. A bio-feedback system drives the relative BV reduction according to desired values by instantaneously changing the ultrafiltration rate and the dialysate conductivity. This system has proved to reduce the incidence of intra-HD hypotension episodes significantly. Ionic dialysance and the patient's plasma conductivity can be calculated easily from on-line inlet and outlet dialysate conductivity measurements at two different steps of dialysate conductivity. Ionic dialysance is equivalent to urea clearance corrected for recirculation and is a tool for continuously monitoring the dialysis efficiency and detecting early problems with the delivery of the prescribed dose of dialysis. Given the strict and linear relationship between conductivity and sodium content, the conductivity values replace the sodium concentration values and this permits the development of a conductivity kinetic model, by means of which sodium balance can be achieved at each dialysis session. The conductivity kinetic model has been demonstrated to improve intra-HD cardiovascular stability in hypotension-prone patients significantly. Ionic dialysance is also a useful tool to monitor vascular access function, as it can be used to obtain serial measurements of vascular access blood flow. On-line urea monitors provide detailed information on intra-HD urea kinetics and delivered dialysis dose, but they are not in widespread use because of the costs related to the disposable materials (e.g. urease cartridge). The body temperature monitor measures the blood temperature at the arterial and venous lines of the extra-corporeal circuit and, thanks to a bio-feedback system, is able to modulate the dialysate temperature in order to influence the patient's core body temperature, which can be kept at constant values. This is associated with improved intra-HD cardiovascular stability. The module can also be used to quantify total recirculation. CONCLUSIONS: On-line monitoring devices and bio-feedback systems have evolved from toys for research use to tools for routine clinical application, particularly in patients with clinical complications. Conductivity monitoring appears the most versatile tool, as it permits quantification of delivered dialysis dose, achievement of sodium balance and surveillance of vascular access function, potentially at each dialysis session and without extra cost.