Impact of Community Based Peer Support in Type 2 Diabetes: A Cluster Randomised Controlled Trial of Individual and/or Group Approaches

Background

Diabetes peer support, where one person with diabetes helps guide and support others, has been proposed as a way to improve diabetes management. We have tested whether different diabetes peer support strategies can improve metabolic and/or psychological outcomes.

Methods

People with type 2 diabetes (n = 1,299) were invited to participate as either ‘peer’ or ‘peer support facilitator’ (PSF) in a 2x2 factorial randomised cluster controlled trial across rural communities (130 clusters) in England. Peer support was delivered over 8–12 months by trained PSFs, supported by monthly meetings with a diabetes educator. Primary end point was HbA1c. Secondary outcomes included quality of life, diabetes distress, blood pressure, waist, total cholesterol and weight. Outcome assessors and investigators were masked to arm allocation. Main factors were 1:1 or group intervention. Analysis was by intention-to-treat adjusting for baseline.

Results

The 4 arms were well matched (Group n = 330, 1:1(individual) n = 325, combined n = 322, control n = 322); 1035 (79•7%) completed the mid-point postal questionnaire and 1064 (81•9%) had a final HbA1c. A limitation was that although 92.6% PSFs and peers were in telephone contact, only 61.4% of intervention participants attended a face to face session. Mean baseline HbA1c was 57 mmol/mol (7•4%), with no significant change across arms. Follow up systolic blood pressure was 2•3mm Hg (0.6 to 4.0) lower among those allocated group peer-support and 3•0mm Hg (1.1 to 5.0) lower if the group support was attended at least once. There was no impact on other outcomes by intention to treat or significant differences between arms in self-reported adherence or medication.

Conclusions

Group diabetes peer support over 8–12 months was associated with a small improvement in blood pressure but no other significant outcomes. Long term benefits should be investigated.

Trial Registration

ISRCTN.com ISRCTN6696362166963621     

Cuticular lipids correlate with age and insemination status in queen honeybees

Eusocial insects exhibit reproductive division of labour, in which one or a few queens perform almost all of the reproduction, while the workers are largely sterile and assist in rearing their siblings. Consequently, many of the colony’s tasks (e.g. nest construction and brood rearing) should be modulated depending on whether the queen is fertile. Here, we tested whether queens’ cuticular lipids could provide reliable signals of fertility in the honeybee Apis mellifera, as they do in other social Hymenoptera. Specifically, we tested whether cuticular lipids differ between virgin queens of different ages, and between queens exposed to different artificial insemination treatments being semen (sperm and seminal fluid), seminal fluid only or saline control. Using gas chromatography–mass spectrometry, we found 27 lipids: 21 different hydrocarbons, namely alkanes, alkenes and dienes, as well as six wax esters. The lipid profile changed dramatically in the first 10 days after eclosion, and there were differences in lipid composition between virgin and artificially inseminated queens. Insemination with semen, seminal fluid or saline did not result in distinct chemical profiles. Our findings indicate that the physical stimulus of insemination was responsible for the observed changes in the cuticular profile in honeybee queens. Our results demonstrate that cuticular lipid profiles encode information on queen age, fertility and mating status, which could in principle be utilised by workers and rival queens.     

Imaging Cell Wall Architecture in Single Zinnia elegans Tracheary Elements

The chemical and structural organization of the plant cell wall was examined in Zinnia elegans tracheary elements (TEs), which specialize by developing prominent secondary wall thickenings underlying the primary wall during xylogenesis in vitro. Three imaging platforms were used in conjunction with chemical extraction of wall components to investigate the composition and structure of single Zinnia TEs. Using fluorescence microscopy with a green fluorescent protein-tagged Clostridium thermocellum family 3 carbohydrate-binding module specific for crystalline cellulose, we found that cellulose accessibility and binding in TEs increased significantly following an acidified chlorite treatment. Examination of chemical composition by synchrotron radiation-based Fourier-transform infrared spectromicroscopy indicated a loss of lignin and a modest loss of other polysaccharides in treated TEs. Atomic force microscopy was used to extensively characterize the topography of cell wall surfaces in TEs, revealing an outer granular matrix covering the underlying meshwork of cellulose fibrils. The internal organization of TEs was determined using secondary wall fragments generated by sonication. Atomic force microscopy revealed that the resulting rings, spirals, and reticulate structures were composed of fibrils arranged in parallel. Based on these combined results, we generated an architectural model of Zinnia TEs composed of three layers: an outermost granular layer, a middle primary wall composed of a meshwork of cellulose fibrils, and inner secondary wall thickenings containing parallel cellulose fibrils. In addition to insights in plant biology, studies using Zinnia TEs could prove especially productive in assessing cell wall responses to enzymatic and microbial degradation, thus aiding current efforts in lignocellulosic biofuel production.The organization and molecular architecture of plant cell walls represent some of the most challenging problems in plant biology. Although much is known about general aspects of assembly and biosynthesis of the plant cell wall, the detailed three-dimensional molecular cell wall structure remains poorly understood. The highly complex and dynamic nature of the plant cell wall has perhaps limited the generation of such detailed structural models. This information is pivotal for the successful implementation of novel approaches for conversion of biomass to liquid biofuels, given that one of the critical processing steps in biomass conversion involves systematic deconstruction of cell walls. Therefore, a comprehensive understanding of the architecture and chemical composition of the plant cell wall will not only help develop molecular-scale models, but will also help improve the efficiency of biomass deconstruction.The composition and molecular organization of the cell wall is species and cell type dependent (Vorwerk et al., 2004). Thus, the development of a model plant system, which utilizes a single cell type, has enhanced our capacity to understand cell wall architecture. The ability to generate a population of single Zinnia elegans plant cells that were synchronized throughout cell wall deposition during xylogenesis was developed in the 1980s (Fukuda and Komamine, 1980). Mesophyll cells isolated from the leaves of Zinnia and cultured in the presence of phytohormones will transdifferentiate into tracheary elements (TEs), which are individual components of the xylem vascular tissue (Fukuda and Komamine, 1980). During this transdifferentiation process, TEs gradually develop patterned secondary wall thickenings, commonly achieving annular, spiral, reticulate, scalariform, and pitted patterns (Bierhorst, 1960; Falconer and Seagull, 1988; Roberts and Haigler, 1994). These secondary wall thickenings serve as structural reinforcements that add strength and rigidity to prevent the collapse of the xylem under the high pressure created by fluid transport. During the final stages of transdifferentiation, TEs accumulate lignin in their secondary walls and undergo programmed cell death, which results in the removal of all cell contents, leaving behind a “functional corpse” (Roberts and McCann, 2000; Fukuda, 2004).In broad terms, the primary cell wall of higher plants is mainly composed of three types of polysaccharides: cellulose, hemicelluloses, and pectins (Cosgrove, 2005). Cellulose is composed of unbranched β-1,4-Glc chains that are packed together into fibrils by intermolecular and intramolecular hydrogen bonding. Hemicelluloses and pectins are groups of complex polysaccharides that are primarily composed of xyloglucans/xylans and galacturonans, respectively. Hemicelluloses are involved in cross-linking and associating with cellulose microfibrils, while pectins control wall porosity and help bind neighboring cells together. The patterned deposits of secondary wall in Zinnia TEs primarily consist of cellulose microfibrils, along with hemicelluloses, and also lignin, a complex aromatic polymer that is characteristic of secondary walls and provides reinforcement (Turner et al., 2007). All the molecular components in the cell wall correspond to a multitude of different polysaccharides, phenolic compounds, and proteins that become arranged and modified in muro, yielding a structure of great strength and resistance to degradation.Currently, electron microscopy is the primary tool for structural studies of cell walls and has provided remarkable information regarding wall organization. Fast-freeze deep-etch electron microscopy in combination with chemical and enzymatic approaches have generated recent models of the architecture of the primary wall (McCann et al., 1990; Carpita and Gibeaut, 1993; Nakashima et al., 1997; Fujino et al., 2000; Somerville et al., 2004). Direct visualization of secondary wall organization has been focused toward the examination of multiple wall layers in wood cells (Fahlen and Salmen, 2005; Zimmermann et al., 2006). However, few studies have examined the secondary wall, so our knowledge regarding the higher order architecture of this type of wall is limited. Over the past few decades, atomic force microscopy (AFM) has provided new opportunities to probe biological systems with spatial resolution similar to electron microscopy techniques (Kuznetsov et al., 1997; Muller et al., 1999), with additional ease of sample preparation and the capability to probe living native structures. AFM has been successfully applied to studies of the high-resolution architecture, assembly, and structural dynamics of a wide range of biological systems (Hoh et al., 1991; Crawford et al., 2001; Malkin et al., 2003; Plomp et al., 2007), thus enabling the observation of the ultrastructure of the plant cell wall, which is of particular interest to us (Kirby et al., 1996; Morris et al., 1997; Davies and Harris, 2003; Yan et al., 2004; Ding and Himmel, 2006).To generate more detailed structural models, knowledge about the structural organization of the cell wall can be combined with spatial information about chemical composition. Instead of utilizing chromatography techniques to analyze cell wall composition by extracting material from bulk plant samples (Mellerowicz et al., 2001; Pauly and Keegstra, 2008), Fourier transform infrared (FTIR) spectromicroscopy can be used to directly probe for polysaccharide and aromatic molecules in native as well as treated plant material (Carpita et al., 2001; McCann et al., 2001). FTIR spectromicroscopy is not only able to identify chemical components in a specific system but also can determine their distribution and relative abundance. This technique also improves the sensitivity and spatial resolution of cellular components without the derivatization needed by chemical analysis using chromatography. Polysaccharide-specific probes, such as carbohydrate-binding modules (CBMs), can also be used to understand the chemical composition of the plant cell wall. CBMs are noncatalytic protein domains existing in many glycoside hydrolases. Based on their binding specificities, CBMs are generally categorized into three groups: surface-binding CBMs specific for insoluble cellulose surfaces, chain-binding CBMs specific for single chains of polysaccharides, and end-binding CBMs specific for the ends of polysaccharides or oligosaccharides. A surface-binding CBM with high affinity for the planar faces of crystalline cellulose (Tormo et al., 1996; Lehtio et al., 2003) has been fluorescently labeled and used to label crystals as well as plant tissue (Ding et al., 2006; Porter et al., 2007; Liu et al., 2009; Xu et al., 2009). The binding capacity of the CBM family has been further exploited for the detection of different polysaccharides, such as xylans and glucans, and can thus be used for the characterization of plant cell wall composition (McCartney et al., 2004, 2006).In this study, we used a combination of AFM, synchrotron radiation-based (SR)-FTIR spectromicroscopy, and fluorescence microscopy using a cellulose-specific CBM to probe the cell wall of Zinnia TEs. The Zinnia TE culture system proved ideal for observing the structure and chemical composition of the cell wall because it comprises a single homogeneous cell type, representing a simpler system compared with plant tissues, which may contain multiple cell types. Zinnia TEs were also advantageous because they were analyzed individually, and population statistics were generated based on specific conditions. Furthermore, cultured Zinnia TEs were used for the consistent production of cell wall fragments for analysis of the organization of internal secondary wall structures. In summary, we have physically and chemically dissected Zinnia TEs using a combination of imaging techniques that revealed primary and secondary wall structures and enabled the reconstruction of TE cell wall architecture.     

Effect of mutation type and location on clinical outcome in 1,013 probands with Marfan syndrome or related phenotypes and FBN1 mutations: an international study

Mutations in the fibrillin-1 (FBN1) gene cause Marfan syndrome (MFS) and have been associated with a wide range of overlapping phenotypes. Clinical care is complicated by variable age at onset and the wide range of severity of aortic features. The factors that modulate phenotypical severity, both among and within families, remain to be determined. The availability of international FBN1 mutation Universal Mutation Database (UMD-FBN1) has allowed us to perform the largest collaborative study ever reported, to investigate the correlation between the FBN1 genotype and the nature and severity of the clinical phenotype. A range of qualitative and quantitative clinical parameters (skeletal, cardiovascular, ophthalmologic, skin, pulmonary, and dural) was compared for different classes of mutation (types and locations) in 1,013 probands with a pathogenic FBN1 mutation. A higher probability of ectopia lentis was found for patients with a missense mutation substituting or producing a cysteine, when compared with other missense mutations. Patients with an FBN1 premature termination codon had a more severe skeletal and skin phenotype than did patients with an inframe mutation. Mutations in exons 24-32 were associated with a more severe and complete phenotype, including younger age at diagnosis of type I fibrillinopathy and higher probability of developing ectopia lentis, ascending aortic dilatation, aortic surgery, mitral valve abnormalities, scoliosis, and shorter survival; the majority of these results were replicated even when cases of neonatal MFS were excluded. These correlations, found between different mutation types and clinical manifestations, might be explained by different underlying genetic mechanisms (dominant negative versus haploinsufficiency) and by consideration of the two main physiological functions of fibrillin-1 (structural versus mediator of TGF beta signalling). Exon 24-32 mutations define a high-risk group for cardiac manifestations associated with severe prognosis at all ages.     

Thrifty Tbc1d1 and Tbc1d4 proteins link signalling and membrane trafficking pathways

Establishing a complete pathway which links occupancy of the insulin receptor to GLUT4 translocation has been particularly elusive because of the complexities involved in studying both signalling and membrane trafficking processes. However, Lienhard's group has now discovered two related molecules that could function in this linking role. These proteins, Tbc1d4 (also known as AS160) and now Tbc1d1, as reported in this issue of the Biochemical Journal, have been demonstrated to be Rab GAPs (GTPase-activating proteins) that link upstream to Akt (protein kinase B) and phosphoinositide 3-kinase and downstream to Rabs involved in trafficking of GLUT4 vesicles. The data from Leinhard and colleagues suggest that high levels of Rab GAP activity lead to suppression of GLUT4 translocation and this observation has wide significance and is likely to be relevant to the recent discovery that mutations in the Tbc1d1 gene lead to some cases of severe human obesity.     

小黄皮叶挥发油的化学成分

利用水蒸气蒸馏法提取小黄皮叶挥发油,运用毛细管气相色谱-质谱联用法对挥发油进行了分析,分离出40个峰,鉴定了其中的37种成分,所鉴定成分占挥发油总量的99.87%,其主要化学成分为单萜及倍半萜类化合物。     

Dia-interacting protein modulates formin-mediated actin assembly at the cell cortex

BACKGROUND: Mammalian Diaphanous (mDia)-related formins and the N-WASP-activated Arp2/3 complex initiate the assembly of filamentous actin. Dia-interacting protein (DIP) binds via its amino-terminal SH3 domain to the proline-rich formin homology 1 (FH1) domain of mDia1 and mDia2 and to the N-WASp proline-rich region. RESULTS: Here, we investigated an interaction between a conserved leucine-rich region (LRR) in DIP and the mDia FH2 domain that nucleates, processively elongates, and bundles actin filaments. DIP binding to mDia2 was regulated by the same Rho-GTPase-controlled autoinhibitory mechanism modulating formin-mediated actin assembly. DIP was previously shown to interact with and stimulate N-WASp-dependent branched filament assembly via Arp2/3. Despite direct binding to both mDia1 and mDia2 FH2 domains, DIP LRR inhibited only mDia2-dependent filament assembly and bundling in vitro. DIP expression interfered with filopodia formation, consistent with a role for mDia2 in assembly of these structures. After filopodia retraction into the cell body, DIP expression induced excessive nonapoptotic membrane blebbing, a physiological process involved in both cytokinesis and amoeboid cell movement. DIP-induced blebbing was dependent on mDia2 but did not require the activities of either mDia1 or Arp2/3. CONCLUSIONS: These observations point to a pivotal role for DIP in the control of nonbranched and branched actin-filament assembly that is mediated by Diaphanous-related formins and activators of Arp2/3, respectively. The ability of DIP to trigger blebbing also suggests a role for mDia2 in the assembly of cortical actin necessary for maintaining plasma-membrane integrity.     

Discovery of platelet-type 12-human lipoxygenase selective inhibitors by high-throughput screening of structurally diverse libraries

Human lipoxygenases (hLO) have been implicated in a variety of diseases and cancers and each hLO isozyme appears to have distinct roles in cellular biology. This fact emphasizes the need for discovering selective hLO inhibitors for both understanding the role of specific lipoxygenases in the cell and developing pharmaceutical therapeutics. To this end, we have modified a known lipoxygenase assay for high-throughput (HTP) screening of both the National Cancer Institute (NCI) and the UC Santa Cruz marine extract library (UCSC-MEL) in search of platelet-type 12-hLO (12-hLO) selective inhibitors. The HTP screen led to the characterization of five novel 12-hLO inhibitors from the NCI repository. One is the potent but non-selective michellamine B, a natural product, anti-viral agent. The other four compounds were selective inhibitors against 12-hLO, with three being synthetic compounds and one being alpha-mangostin, a natural product, caspase-3 pathway inhibitor. In addition, a selective inhibitor was isolated from the UCSC-MEL (neodysidenin), which has a unique chemical scaffold for a hLO inhibitor. Due to the unique structure of neodysidenin, steady-state inhibition kinetics were performed and its mode of inhibition against 12-hLO was determined to be competitive (K(i)=17microM) and selective over reticulocyte 15-hLO-1 (K(i) 15-hLO-1/12-hLO>30).     

Ten days of darkness causes temporary blindness during an early critical period in felines

Extended periods of darkness have long been used to study how the mammalian visual system develops in the absence of any instruction from vision. Because of the relative ease of implementation of darkness as a means to eliminate visually driven neural activity, it has usually been imposed earlier in life and for much longer periods than was the case for other manipulations of the early visual input used for study of their influences on visual system development. Recently, it was shown that following a very brief (10 days) period of darkness imposed at five weeks of age, kittens emerged blind. Although vision as assessed by measurements of visual acuity eventually recovered, the time course was very slow as it took seven weeks for visual acuity to attain normal levels. Here, we document the critical period of this remarkable vulnerability to the effects of short periods of darkness by imposing 10 days of darkness on nine normal kittens at progressively later ages. Results indicate that the period of susceptibility to darkness extends only to about 10 weeks of age, which is substantially shorter than the critical period for the effects of monocular deprivation in the primary visual cortex, which extends beyond six months of age.