正常人左心室功能指标的参考值及其预计公式的初步研究报告*

目的: 当前评估左心室容量和功能仍常用正常值范围,个体化分析也仅使用体表面积进行校正。尚缺少个体化因素相关的大样本参考值和预计公式。方法: 本研究纳入美国加州洛杉矶县南湾地区1200名健康志愿者,其中男807女393,年龄20岁-94岁,心脏CT造影（CTA）,经过高精度三维成像技术处理,计算左心室容积在收缩和舒张过程中的连续动态变化,测定左心室（LV）容量和功能指标：舒张末期容积（EDV)、收缩末期容积(ESV)、每搏输出量(SV)、射血分数(EF)和心输出量(CO)。将以上指标与一般特征指标进行多因素相关分析,以探索正常人预计值计算公式。结果: 男性除LVEF小于女性外（P<0.001）,其余各指标均大于女性（P<0.001）。多元线性回归分析提示, 性别、年龄、身高和体质量均为EDV、ESV、SV的独立影响因子(P<0.001); 而CO仅受年龄、性别、体质量显著影响(P<0.001),但与身高无关(P>0.05)。CO的预测公式CO (L·min^-1)= 6.963+0.446(Male) -0.037×年龄(yr)+0.013×体质量(kg)。结论: 性别、年龄、身高、体质量均影响左心室容量和功能,建立预测值计算公式,对心血管疾病的无创评估和个体化精准医疗具有重要参考价值。     

Initial screening transferrin saturation values, serum ferritin concentrations, and HFE genotypes in whites and blacks in the Hemochromatosis and Iron Overload Screening Study

We compared initial screening data of 44,082 white and 27,124 black Hemochromatosis and Iron Overload Screening (HEIRS) Study participants. Each underwent serum transferrin saturation (TfSat) and ferritin (SF) measurements without regard to fasting, and HFE C282Y and H63D genotyping. Elevated measurements were defined as: TfSat more than 50% (men), more than 45% (women); and SF more than 300 ng/ml (men), more than 200 ng/ml (women). Mean TfSat and percentages of participants with elevated TfSat were significantly greater in whites than in blacks. Mean SF and percentages of participants with elevated SF were significantly greater in blacks than in whites. TfSat and SF varied by gender and age in whites and blacks. Prevalences of genotypes that included either C282Y or H63D were significantly greater in whites than in blacks. The prevalence of elevated TfSat and SF plus genotypes C282Y/C282Y, C282Y/H63D, or H63D/H63D was 0.006 in whites and 0.0003 in blacks. Among whites with HFE C282Y homozygosity, 76.8% of men and 46.9% of women had elevated TfSat and SF values. Three black participants had HFE C282Y homozygosity; one had elevated TfSat and SF values. Possible explanations for differences in TfSat and SF in whites and blacks and pertinence to the detection of hemochromatosis, iron overload, and other disorders with similar phenotypes are discussed.     

Crop biotechnology provides an opportunity to develop a sustainable future

The current reliance on petro-based fuels and chemicals is not sustainable. New technologies typically take approximately 25 years to penetrate the market; consequently, the development of viable alternatives is required in the near future. Plant-based systems capture solar energy and can be produced in a renewable manner. However, the harvestable parts are not well optimized for energy transfer and this has been a significant limitation to the development of economically viable and sustainable biomass energy systems. Biotechnology has provided a new toolset that can be used to design and optimize the capture of solar energy through crops. Further development of biotechnology and genomics tools will enable the development of crops with specific traits that are optimized for biofuels and bioenergy. The implementation of such a system will enable a sustainable platform for centuries to come and should be given a high priority in society.     

Human embryonic stem cell lines: socio-legal concerns and therapeutic promise

Stem cell lines would be very valuable for the repair of diseased or damaged organs. Stem cells derived from adult tissues raise few ethical problems, and would not be rejected if derived from the patient. They show considerable plasticity and might be appropriate for some clinical conditions, but they tend not to grow well in culture. Stem cells derived from the early human embryo proliferate indefinitely in culture and can give rise to many different tissues, but their derivation requires destruction of the embryo, which is not ethically acceptable in some countries. Other countries allow strictly regulated destructive research on human embryos, usually those that have been produced for infertile couples in infertility clinics. Embryos that are no longer required for the couple's own reproductive project could be donated for research rather than just discarded. Different approaches are being developed to avoid immunological rejection of embryonic stem cells used for therapy. Derivation of embryonic stem cell lines by somatic cell nuclear transfer ('cloning') from the patients themselves might be one possible approach, but is unlikely to be used in routine clinical practice if more cost-effective methods are available.     

OXBench: A benchmark for evaluation of protein multiple sequence alignment accuracy

Background  

The alignment of two or more protein sequences provides a powerful guide in the prediction of the protein structure and in identifying key functional residues, however, the utility of any prediction is completely dependent on the accuracy of the alignment. In this paper we describe a suite of reference alignments derived from the comparison of protein three-dimensional structures together with evaluation measures and software that allow automatically generated alignments to be benchmarked. We test the OXBench benchmark suite on alignments generated by the AMPS multiple alignment method, then apply the suite to compare eight different multiple alignment algorithms. The benchmark shows the current state-of-the art for alignment accuracy and provides a baseline against which new alignment algorithms may be judged.     

Abstract and associatively based representations in human sequence learning

We give an analysis of performance in an artificial neural network for which the claim had been made that it could learn abstract representations. Our argument is that this network is associative in nature, and cannot develop abstract representations. The network thus converges to a solution that is solely based on the statistical regularities of the training set. Inspired by human experiments that have shown that humans can engage in both associative (statistical) and abstract learning, we present a new, hybrid computational model that combines associative and more abstract, cognitive processes. To cross-validate the model we attempted to predict human behaviour in further experiments. One of these experiments reveals some evidence for the use of abstract representations, whereas the others provide evidence for associatively based performance. The predictions of the hybrid model stand in line with our empirical data.     

A reinvestigation of the multisite phosphorylation of the transcription factor c-Jun

We have used phospho-specific antibodies to re-examine the multisite phosphorylation of c-Jun in murine RAW macrophages and embryonic fibroblasts. Our results indicate that JNK isoforms are required and sufficient for the phosphorylation of Thr91 and Thr93, as well as the phosphorylation of Ser63 and Ser73, in response to LPS or anisomycin in macrophages and TNFalpha or anisomycin in fibroblasts. However, the phorbol ester (TPA) and EGF-induced phosphorylation of Ser63 and Ser73 is mediated by ERK1/ERK2, as well as JNK1/JNK2, in fibroblasts from wild-type mice and by ERK1/ERK2 alone in fibroblasts from JNK-deficient mice. The phosphorylation of Thr239 is catalysed by GSK3 and the phosphorylation of Ser243 by an as yet unidentified protein kinase. The inhibition of GSK3 is not required for the dephosphorylation of Thr239 in response to LPS, and nor is the phosphorylation of Thr91 and Thr93 required for the TPA- or EGF-induced dephosphorylation of Thr239 in fibroblasts. The agonist-induced dephosphorylation of Thr239 may involve a conformational change that exposes Thr239 to dephosphorylation and/or the activation of a Thr239 phosphatase.     

Special considerations in the treatment of patients with bipolar disorder and medical co-morbidities

BACKGROUND: The pharmacological treatment of bipolar disorder has dramatically improved with multiple classes of agents being used as mood-stabilizers, including lithium, anticonvulsants, and atypical antipsychotics. However, the use of these medications is not without risk, particularly when a patient with bipolar disorder also has comorbid medical illness. As the physician who likely has the most contact with patients with bipolar disorder, psychiatrists must have a high index of suspicion for medical illness, as well as a basic knowledge of the risks associated with the use of medications in this patient population. METHODS: A review of the literature was conducted and papers addressing this topic were selected by the authors. RESULTS AND DISCUSSION: Common medical comorbidities and treatment-emergent illnesses, including obesity, diabetes mellitus, dyslipidemia, cardiac disease, hepatic disease, renal disease, pulmonary disease and cancer are reviewed with respect to concomitant use of mood stabilizers. Guidance to clinicians regarding effective monitoring and treatment is offered. CONCLUSIONS: Mood-stabilizing medications are necessary in treating patients with bipolar disorder and often must be used in the face of medical illness. Their safe use is possible, but requires increased vigilance in monitoring for treatment-emergent illnesses and effects on comorbid medical illness.