Patient Care Teams in treatment of diabetes and chronic heart failure in primary care: an observational networks study

Background

Patient care teams have an important role in providing medical care to patients with chronic disease, but insight into how to improve their performance is limited. Two potentially relevant determinants are the presence of a central care provider with a coordinating role and an active role of the patient in the network of care providers. In this study, we aimed to develop and test measures of these factors related to the network of care providers of an individual patient.

Methods

We performed an observational study in patients with type 2 diabetes or chronic heart failure, who were recruited from three primary care practices in The Netherlands. The study focused on medical treatment, advice on physical activity, and disease monitoring. We used patient questionnaires and chart review to measure connections between the patient and care providers, and a written survey among care providers to measure their connections. Data on clinical performance were extracted from the medical records. We used network analysis to compute degree centrality coefficients for the patient and to identify the most central health professional in each network. A range of other network characteristics were computed including network centralization, density, size, diversity of disciplines, and overlap among activity-specific networks. Differences across the two chronic conditions and associations with disease monitoring were explored.

Results

Approximately 50% of the invited patients participated. Participation rates of health professionals were close to 100%. We identified 63 networks of 25 patients: 22 for medical treatment, 16 for physical exercise advice, and 25 for disease monitoring. General practitioners (GPs) were the most central care providers for the three clinical activities in both chronic conditions. The GP's degree centrality coefficient varied substantially, and higher scores seemed to be associated with receiving more comprehensive disease monitoring. The degree centrality coefficient of patients also varied substantially but did not seem to be associated with disease monitoring.

Conclusions

Our method can be used to measure connections between care providers of an individual patient, and to examine the association between specific network parameters and healthcare received. Further research is needed to refine the measurement method and to test the association of specific network parameters with quality and outcomes of healthcare.

     

Interspecific protection against oxidative stress: green algae protect harmful cyanobacteria against hydrogen peroxide

Oceanographic studies have shown that heterotrophic bacteria can protect marine cyanobacteria against oxidative stress caused by hydrogen peroxide (H₂O₂). Could a similar interspecific protection play a role in freshwater ecosystems? In a series of laboratory experiments and two lake treatments, we demonstrate that freshwater cyanobacteria are sensitive to H₂O₂ but can be protected by less-sensitive species such as green algae. Our laboratory results show that green algae degrade H₂O₂ much faster than cyanobacteria. Consequently, the cyanobacterium Microcystis was able to survive at higher H₂O₂ concentrations in mixtures with the green alga Chlorella than in monoculture. Interestingly, even the lysate of destructed Chlorella was capable to protect Microcystis, indicating a two-component H₂O₂ degradation system in which Chlorella provided antioxidant enzymes and Microcystis the reductants. The level of interspecific protection provided to Microcystis depended on the density of Chlorella. These findings have implications for the mitigation of toxic cyanobacterial blooms, which threaten the water quality of many eutrophic lakes and reservoirs worldwide. In several lakes, H₂O₂ has been successfully applied to suppress cyanobacterial blooms. Our results demonstrate that high densities of green algae can interfere with these lake treatments, as they may rapidly degrade the added H₂O₂ and thereby protect the bloom-forming cyanobacteria.     

Functional YFP-tagging of the essential GDP-mannose transporter reveals an important role for the secretion related small GTPase SrgC protein in maintenance of Golgi bodies in Aspergillus niger

The addition of mannose residues to glycoproteins and glycolipids in the Golgi is carried out by mannosyltransferases. Their activity depends on the presence of GDP-mannose in the lumen of the Golgi. The transport of GDP-mannose (mannosyl donor) into the Golgi requires a specific nucleotide sugar transport present in the Golgi membrane. Here, we report the identification and functional characterization of the putative GDP-mannose transporter in Aspergillus niger, encoded by the gmtA gene (An17g02140). The single GDP-mannose transporter was identified in the A. niger genome and deletion analysis showed that gmtA is an essential gene. The lethal phenotype of the gmtA could be fully complemented by expressing an YFP-GmtA fusion protein from the endogenous gmtA promoter. Fluorescence studies revealed that, as in other fungal species, GmtA localized as punctate dots throughout the hyphal cytoplasm, representing Golgi bodies or Golgi equivalents. SrgC encodes a member of the Rab6/Ypt6 subfamily of secretion-related GTPases and is predicted to be required for the Golgi to vacuole transport. Loss of function of the srgC gene in A. niger resulted in strongly reduced growth and the inability to form conidiospores at 37°C and higher. Furthermore, the srgC disruption in the A. niger strain expressing the functional YFP-GmtA fusion protein led to an apparent 'disappearance' of the Golgi-like structures. The analysis suggests that SrgC has an important role in maintaining the integrity of Golgi-like structures in A. niger.     

中国朝鲜族DXS7132、DXS6854和GATA31E08基因座遗传多态性

利用复合PCR扩增、变性聚丙烯酰胺凝胶电泳和银染方法对261名中国朝鲜族人群3个X-STR基因座研究发现, 在DXS7132、DX6854和GATA31E08中分别检出8个、6个和10个等位基因; 基因频率分别分布在0.006~0.344、0.015~0.450和0.005~0.317之间; 分别检出19、17和21种基因型, 女性个体基因型频率分布均符合Hardy-Weinberg平衡(P>0.05); 观测杂合度分别为0.706, 0.743, 0.772; 多态信息含量分别为0.710, 0.730, 0.670;女性个人识别力分别为0.898, 0.911, 0.857; 男性个人识别力分别为0.766, 0.802, 0.734; 联体单倍型多样性大于0.988。结果表明, 3个基因座均具有较高的杂合度、多态信息量和个人识别力, 是较理想的遗传标记系统, 在研究中国朝鲜族起源和与其他民族之间的亲缘关系等方面具有较高的应用价值, 并且对中国朝鲜族群体的亲子鉴定和个人识别提供宝贵的基础资料。     

Insulin-like growth factor-binding protein-3 potentiates epidermal growth factor action in MCF-10A mammary epithelial cells. Involvement of p44/42 and p38 mitogen-activated protein kinases

Insulin-like growth factor-binding protein-3 (IGFBP-3) is inhibitory to the growth of many breast cancer cells in vitro; however, a high level of expression of IGFBP-3 in breast tumors correlates with poor prognosis, suggesting that IGFBP-3 may be associated with growth stimulation in some breast cancers. We have shown previously in MCF-10A breast epithelial cells that chronic activation of Ras-p44/42 mitogen-activated protein (MAP) kinase confers resistance to the growth-inhibitory effects of IGFBP-3 (Martin, J. L., and Baxter, R. C. (1999) J. Biol. Chem. 274, 16407-16411). Here we show that, in the same cell line, IGFBP-3 potentiates DNA synthesis and cell proliferation stimulated by epidermal growth factor (EGF), a potent activator of Ras. A mutant of IGFBP-3, which fails to translocate to the nucleus and has reduced ability to cell-associate, similarly enhanced EGF action in these cells. By contrast, the structurally related IGFBP-5, which shares many functional features with IGFBP-3, was slightly inhibitory to DNA synthesis in the presence of EGF. IGFBP-3 primes MCF-10A cells to respond to EGF because pre-incubation caused a similar degree of EGF potentiation as co-incubation. In IGFBP-3-primed cells, EGF-stimulated EGF receptor phosphorylation at Tyr-1068 was increased relative to unprimed cells, as was phosphorylation and activity of p44/42 and p38 MAP kinases, but not Akt/PKB. Partial blockade of the p44/42 and p38 MAP kinase pathways abolished the potentiation by IGFBP-3 of EGF-stimulated DNA synthesis. Collectively, these findings indicate that IGFBP-3 enhances EGF signaling and proliferative effects in breast epithelial cells via increased EGF receptor phosphorylation and activation of p44/42 and p38 MAP kinase signaling pathways.     

A new method for screening and isolation of hypersecretion mutants in Aspergillus niger

Although filamentous fungi have a unique property of secreting a large amount of homologous extracellular proteins, the use of filamentous fungi as hosts for the production of heterologous proteins is limited because of the low production levels that are generally reached. Here, we report a general screening method for the isolation of mutants with increased protein production levels. The screening method makes use of an Aspergillus niger strain that lacks the two major amylolytic enzymes, glucoamylase (GlaA) and acid amylase (AamA). The double-mutant strain grows poorly on starch and its growth is restored after reintroducing the catalytic part of the glucoamylase gene (GlaA₅₁₂). We show that the fusion of a heterologous protein, a laccase from Pleurotus ostreatus (Pox2), to the catalytic part of glucoamylase (GlaA₅₁₂–Pox2) severely hampers efficient production of the glucoamylase protein, resulting in a slow-growth phenotype on starch. Laccase-hypersecreting mutants were obtained by isolating mutants that displayed improved growth on starch plates. The mutant with the highest growth rate on starch displayed the highest laccase activity, indicating that increased glucoamylase protein levels are correlated with higher laccase production levels. In principle, our method can be applied to any low-produced heterologous protein that is secreted as a fusion with the glucoamylase protein.     

Environmental policy and the greenhouse effect

Emissions, resulting from human activity, are substantially increasing the atmospheric concentration of greenhouse gases. This, in turn, is causing an additional average warming of the Earth's surface. This article presents an overview of recent developments in the international discussion on climate change, taking into account the work of other organizations such as the Intergovernmental Panel on Climate Change (IPCC).The long term and global character of the climate change problem requires an international long term strategy based on internationally agreed principles such as sustainable development and the precautionary principle. Research is needed to further develop risk assessment and environmental quality standards, from which emission targets can be derived.As a first step, governments of many industrialized countries have already set provisional national CO₂ emission targets, aimed at stabilization at present levels by the year 2000 and, in some cases, reductions thereafter.Under the auspices of United Nations, negotiations have begun on an international framework climate convention and associated agreements, on, for example, greenhouse gas emissions, forestry and funding mechanisms. Obligations imposed on individual nations may be expected to reflect their responsibility for greenhouse warming; this paper presents some views on the equity of burden sharing.     

Construction of synthetic regulatory networks in yeast

Yeast species such as Saccharomyces cerevisiae have been exploited by humans for millennia and so it is therefore unsurprising that they are attractive cells to re-engineer for industrial use. Despite many beneficial traits yeast has for synthetic biology, it currently lags behind Escherichia coli in the number of synthetic networks that have been described. While the eukaryotic nature of yeast means that its regulation is not as simple to predict as it is for E. coli, once initial considerations have been made yeast is pleasingly tractable. In this review we provide a loose guide for constructing and implementing synthetic regulatory networks in S. cerevisiae using examples from previous research to highlight available resources, specific considerations and potential future advances.