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A nematode sterol C4{alpha}-methyltransferase catalyzes a new methylation reaction responsible for sterol diversity [Research Articles]

Primitive sterol evolution plays an important role in fossil record interpretation and offers potential therapeutic avenues for human disease resulting from nematode infections. Recognizing that C4-methyl stenol products [8(14)-lophenol] can be synthesized in bacteria while C4-methyl stanol products (dinosterol) can be synthesized in dinoflagellates and preserved as sterane biomarkers in ancient sedimentary rock is key to eukaryotic sterol evolution. In this regard, nematodes have been proposed to convert dietary cholesterol to 8(14)-lophenol by a secondary metabolism pathway that could involve sterol C4 methylation analogous to the C2 methylation of hopanoids (radicle-type mechanism) or C24 methylation of sterols (carbocation-type mechanism). Here, we characterized dichotomous cholesterol metabolic pathways in Caenorhabditis elegans that generate 3-oxo sterol intermediates in separate paths to lophanol (4-methyl stanol) and 8(14)-lophenol (4-methyl stenol). We uncovered alternate C3-sterol oxidation and 7 desaturation steps that regulate sterol flux from which branching metabolite networks arise, while lophanol/8(14)-lophenol formation is shown to be dependent on a sterol C4α-methyltransferse (4-SMT) that requires 3-oxo sterol substrates and catalyzes a newly discovered 3-keto-enol tautomerism mechanism linked to S-adenosyl-l-methionine-dependent methylation. Alignment-specific substrate-binding domains similarly conserved in 4-SMT and 24-SMT enzymes, despite minimal amino acid sequence identity, suggests divergence from a common, primordial ancestor in the evolution of methyl sterols. The combination of these results provides evolutionary leads to sterol diversity and points to cryptic C4-methyl steroidogenic pathways of targeted convergence that mediate lineage-specific adaptations.­­




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Worming our way toward multiple evolutionary origins of convergent sterol pathways [Commentary]




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Deficiency in ZMPSTE24 and resulting farnesyl-prelamin A accumulation only modestly affect mouse adipose tissue stores [Research Articles]

Zinc metallopeptidase STE24 (ZMPSTE24) is essential for the conversion of farnesyl–prelamin A to mature lamin A, a key component of the nuclear lamina. In the absence of ZMPSTE24, farnesyl–prelamin A accumulates in the nucleus and exerts toxicity, causing a variety of disease phenotypes. By ~4 months of age, both male and female Zmpste24–/– mice manifest a near-complete loss of adipose tissue, but it has never been clear whether this phenotype is a direct consequence of farnesyl–prelamin A toxicity in adipocytes. To address this question, we generated a conditional knockout Zmpste24 allele and used it to create adipocyte-specific Zmpste24–knockout mice. To boost farnesyl–prelamin A levels, we bred in the "prelamin A–only" Lmna allele. Gene expression, immunoblotting, and immunohistochemistry experiments revealed that adipose tissue in these mice had decreased Zmpste24 expression along with strikingly increased accumulation of prelamin A. In male mice, Zmpste24 deficiency in adipocytes was accompanied by modest changes in adipose stores (an 11% decrease in body weight, a 23% decrease in body fat mass, and significantly smaller gonadal and inguinal white adipose depots). No changes in adipose stores were detected in female mice, likely because prelamin A expression in adipose tissue is lower in female mice. Zmpste24 deficiency in adipocytes did not alter the number of macrophages in adipose tissue, nor did it alter plasma levels of glucose, triglycerides, or fatty acids. We conclude that ZMPSTE24 deficiency in adipocytes, and the accompanying accumulation of farnesyl–prelamin A, reduces adipose tissue stores, but only modestly and only in male mice.




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Lithium ion adduction enables UPLC-MS/MS-based analysis of multi-class 3-hydroxyl group-containing keto-steroids [Methods]

Steroids that contain a 3-hydroxyl group (3-OH steroids) are widely distributed in nature. During analysis with ESI-MS, they easily become dehydrated while in the protonated form, resulting in the production of several precursor ions and leading to low sensitivity of detection. To address this analytical challenge, here, we developed a method for the quantitation of 3-OH steroids by LC-MS/MS coupled with post-column addition of lithium (Li) ions to the mobile phase. The Li ion has a high affinity for the keto group of steroids, stabilizing their structures during ionization and permitting detection of analytes exclusively as the lithiated form. This not only improved the intensities of the precursor ions, but also promoted the formation of typical lithiated fragment ions. This improvement made the quantitation by multiple reaction monitoring more sensitive and reliable, as evidenced by 1.53–188 times enhanced detection sensitivity of 13 steroids that contained at least one keto and two hydroxyl groups or one keto and one 5-olefinic double bond, among 16 different 3-OH steroids. We deployed our newly developed method for profiling steroids in mouse brain tissue and identified six steroids in one tissue sample. Among these, 16-hydroxyestrone, tetrahydrocorticosterone, and 17α-hydroxypregnenolone were detected for the first time in the mouse brain. In summary, the method described here enables the detection of lithiated steroids by LC-MS/MS, including three 3-OH steroids not previously reported in the mouse brain. We anticipate that this new method may allow the determination of 3-OH steroids in different brain regions.




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Heritability of 596 lipid species and genetic correlation with cardiovascular traits in the Busselton Family Heart Study [Patient-Oriented and Epidemiological Research]

CVD is the leading cause of death worldwide, and genetic investigations into the human lipidome may provide insight into CVD risk. The aim of this study was to estimate the heritability of circulating lipid species and their genetic correlation with CVD traits. Targeted lipidomic profiling was performed on 4,492 participants from the Busselton Family Heart Study to quantify the major fatty acids of 596 lipid species from 33 classes. We estimated narrow-sense heritabilities of lipid species/classes and their genetic correlations with eight CVD traits: BMI, HDL-C, LDL-C, triglycerides, total cholesterol, waist-hip ratio, systolic blood pressure, and diastolic blood pressure. We report heritabilities and genetic correlations of new lipid species/subclasses, including acylcarnitine (AC), ubiquinone, sulfatide, and oxidized cholesteryl esters. Over 99% of lipid species were significantly heritable (h2: 0.06–0.50) and all lipid classes were significantly heritable (h2: 0.14–0.50). The monohexosylceramide and AC classes had the highest median heritabilities (h2 = 0.43). The largest genetic correlation was between clinical triglycerides and total diacylglycerol (rg = 0.88). We observed novel positive genetic correlations between clinical triglycerides and phosphatidylglycerol species (rg: 0.64–0.82), and HDL-C and alkenylphosphatidylcholine species (rg: 0.45–0.74). Overall, 51% of the 4,768 lipid species-CVD trait genetic correlations were statistically significant after correction for multiple comparisons. This is the largest lipidomic study to address the heritability of lipids and their genetic correlation with CVD traits. Future work includes identifying putative causal genetic variants for lipid species and CVD using genome-wide SNP and whole-genome sequencing data.




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Dynamics of sphingolipids and the serine palmitoyltransferase complex in rat oligodendrocytes during myelination [Research Articles]

Myelin is a unique lipid-rich membrane structure that accelerates neurotransmission and supports neuronal function. Sphingolipids are critical myelin components. Yet sphingolipid content and synthesis have not been well characterized in oligodendrocytes, the myelin-producing cells of the CNS. Here, using quantitative real-time PCR, LC-MS/MS-based lipid analysis, and biochemical assays, we examined sphingolipid synthesis during the peak period of myelination in the postnatal rat brain. Importantly, we characterized sphingolipid production in isolated oligodendrocytes. We analyzed sphingolipid distribution and levels of critical enzymes and regulators in the sphingolipid biosynthetic pathway, with focus on the serine palmitoyltransferase (SPT) complex, the rate-limiting step in this pathway. During myelination, levels of the major SPT subunits increased and oligodendrocyte maturation was accompanied by extensive alterations in the composition of the SPT complex. These included changes in the relative levels of two alternative catalytic subunits, SPTLC2 and -3, in the relative levels of isoforms of the small subunits, ssSPTa and -b, and in the isoform distribution of the SPT regulators, the ORMDLs. Myelination progression was accompanied by distinct changes in both the nature of the sphingoid backbone and the N-acyl chains incorporated into sphingolipids. We conclude that the distribution of these changes among sphingolipid family members is indicative of a selective channeling of the ceramide backbone toward specific downstream metabolic pathways during myelination. Our findings provide insights into myelin production in oligodendrocytes and suggest how dysregulation of the biosynthesis of this highly specialized membrane could contribute to demyelinating diseases.




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Nanodomains can persist at physiologic temperature in plasma membrane vesicles and be modulated by altering cell lipids [Research Articles]

The formation and properties of liquid-ordered (Lo) lipid domains (rafts) in the plasma membrane are still poorly understood. This limits our ability to manipulate ordered lipid domain-dependent biological functions. Giant plasma membrane vesicles (GPMVs) undergo large-scale phase separations into coexisting Lo and liquid-disordered lipid domains. However, large-scale phase separation in GPMVs detected by light microscopy is observed only at low temperatures. Comparing Förster resonance energy transfer-detected versus light microscopy-detected domain formation, we found that nanodomains, domains of nanometer size, persist at temperatures up to 20°C higher than large-scale phases, up to physiologic temperature. The persistence of nanodomains at higher temperatures is consistent with previously reported theoretical calculations. To investigate the sensitivity of nanodomains to lipid composition, GPMVs were prepared from mammalian cells in which sterol, phospholipid, or sphingolipid composition in the plasma membrane outer leaflet had been altered by cyclodextrin-catalyzed lipid exchange. Lipid substitutions that stabilize or destabilize ordered domain formation in artificial lipid vesicles had a similar effect on the thermal stability of nanodomains and large-scale phase separation in GPMVs, with nanodomains persisting at higher temperatures than large-scale phases for a wide range of lipid compositions. This indicates that it is likely that plasma membrane nanodomains can form under physiologic conditions more readily than large-scale phase separation. We also conclude that membrane lipid substitutions carried out in intact cells are able to modulate the propensity of plasma membranes to form ordered domains. This implies lipid substitutions can be used to alter biological processes dependent upon ordered domains.




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Problem Notes for SAS®9 - 65852: The PANEL procedure produces incorrect results for certain models when the NOINT and RANONE options are specified

The estimation results might be incorrect in PROC PANEL when the RANONE and NOINT options are specified in the MODEL statement.




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Problem Notes for SAS®9 - 65834: PROC METADATA returns various errors when the input contains certain multi-byte characters

The METADATA procedure might return an error similar to one of the following:

  • ERROR: Missing root element definition.
  • Full Article


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    Problem Notes for SAS®9 - 65922: Trying to read a Google BigQuery table that contains a variable defined as an array might result in a panic error and SAS shutting down

    Trying to read a Google BigQuery table that contains a variable that is defined as an array of records might result in an error and cause SAS to shut down. This issue occurs when one of the variables contained in




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    Problem Notes for SAS®9 - 65916: Accessing a Google BigQuery table without including the SCHEMA= option in the LIBNAME statement might result in an error

    When you issue a LIBNAME statement for a Google BigQuery database without including the SCHEMA= option, all tables in the project are shown when the libref is expanded. However, if you try to acces




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    Problem Notes for SAS®9 - 65886: Trying to bulk load data into a Google BigQuery database might result in an error

    When you bulk load data into a Google BigQuery database, you might encounter this error: "Error while reading data, error message: CSV table encountered too many errors, giving up...Error detected while parsing row starting at position: 0...Data




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    Problem Notes for SAS®9 - 65597: An SQL procedure query with a WHERE clause that contains multiple subselects might return incorrect results

    An issue occurs when code contains a complex SQL procedure query with a WHERE clause that contains multiple subselects. Incorrect results might be returned. Click the Hot Fix tab in this note to




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    Problem Notes for SAS®9 - 65869: SAS Visual Data Builder does not enable you to schedule with multiple time-event triggers

    SAS Visual Data Builder might not enable you to create multiple time-event triggers. The + button to add another trigger is not available to select, as shown in the following display: imgalt="" src="{fusion_658




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    MtrP, a putative methyltransferase in Corynebacteria, is required for optimal membrane transport of trehalose mycolates [Lipids]

    Pathogenic bacteria of the genera Mycobacterium and Corynebacterium cause severe human diseases such as tuberculosis (Mycobacterium tuberculosis) and diphtheria (Corynebacterium diphtheriae). The cells of these species are surrounded by protective cell walls rich in long-chain mycolic acids. These fatty acids are conjugated to the disaccharide trehalose on the cytoplasmic side of the bacterial cell membrane. They are then transported across the membrane to the periplasm where they act as donors for other reactions. We have previously shown that transient acetylation of the glycolipid trehalose monohydroxycorynomycolate (hTMCM) enables its efficient transport to the periplasm in Corynebacterium glutamicum and that acetylation is mediated by the membrane protein TmaT. Here, we show that a putative methyltransferase, encoded at the same genetic locus as TmaT, is also required for optimal hTMCM transport. Deletion of the C. glutamicum gene NCgl2764 (Rv0224c in M. tuberculosis) abolished acetyltrehalose monocorynomycolate (AcTMCM) synthesis, leading to accumulation of hTMCM in the inner membrane and delaying its conversion to trehalose dihydroxycorynomycolate (h2TDCM). Complementation with NCgl2764 normalized turnover of hTMCM to h2TDCM. In contrast, complementation with NCgl2764 derivatives mutated at residues essential for methyltransferase activity failed to rectify the defect, suggesting that NCgl2764/Rv0224c encodes a methyltransferase, designated here as MtrP. Comprehensive analyses of the individual mtrP and tmaT mutants and of a double mutant revealed strikingly similar changes across several lipid classes compared with WT bacteria. These findings indicate that both MtrP and TmaT have nonredundant roles in regulating AcTMCM synthesis, revealing additional complexity in the regulation of trehalose mycolate transport in the Corynebacterineae.




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    Necrostatin-1 Mitigates Cognitive Dysfunction in Prediabetic Rats With no Alteration in Insulin Sensitivity

    Previous studies show that 12-week of high-fat diet (HFD) consumption caused not only prediabetes, but also cognitive decline and brain pathologies. Recently, necrostatin-1 (nec-1), a necroptosis inhibitor, showed beneficial effects in brain against stroke. However, the comparative effects of nec-1 and metformin on cognition and brain pathologies in prediabetes have not been investigated. We hypothesized that nec-1 and metformin equally attenuated cognitive decline and brain pathologies in prediabetic rats. Rats (n=32) were fed with either normal diet (ND) or high-fat diet (HFD) for 20 weeks. At week 13, ND-fed rats were given a vehicle (n=8) and HFD-fed rats were randomly assigned into 3 subgroups (n=8/subgroup) with vehicle, nec-1 or metformin for 8 weeks. Metabolic parameters, cognitive function, brain insulin receptor function, synaptic plasticity, dendritic spine density, microglial morphology, brain mitochondrial function, Alzheimer’s protein, and cell death were determined. HFD-fed rats exhibited prediabetes, cognitive decline, and brain pathologies. Nec-1 and metformin equally improved cognitive function, synaptic plasticity, dendritic spine density, microglial morphology, brain mitochondrial function, reduced hyperphosphorylated-tau and necroptosis in HFD-fed rats. Interestingly metformin, but not nec-1, improved brain insulin sensitivity in those rats. In conclusion, necroptosis inhibition directly improved cognition in prediabetic rats without alteration in insulin sensitivity.




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    Erratum. Multiethnic Genome-Wide Association Study of Diabetic Retinopathy Using Liability Threshold Modeling of Duration of Diabetes and Glycemic Control. Diabetes 2019;68:441--456




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    Inhibition of glycosphingolipid biosynthesis reverts multidrug resistance by differentially modulating ABC transporters in chronic myeloid leukemias [Cell Biology]

    Multidrug resistance (MDR) in cancer arises from cross-resistance to structurally- and functionally-divergent chemotherapeutic drugs. In particular, MDR is characterized by increased expression and activity of ATP-binding cassette (ABC) superfamily transporters. Sphingolipids are substrates of ABC proteins in cell signaling, membrane biosynthesis, and inflammation, for example, and their products can favor cancer progression. Glucosylceramide (GlcCer) is a ubiquitous glycosphingolipid (GSL) generated by glucosylceramide synthase, a key regulatory enzyme encoded by the UDP-glucose ceramide glucosyltransferase (UGCG) gene. Stressed cells increase de novo biosynthesis of ceramides, which return to sub-toxic levels after UGCG mediates incorporation into GlcCer. Given that cancer cells seem to mobilize UGCG and have increased GSL content for ceramide clearance, which ultimately contributes to chemotherapy failure, here we investigated how inhibition of GSL biosynthesis affects the MDR phenotype of chronic myeloid leukemias. We found that MDR is associated with higher UGCG expression and with a complex GSL profile. UGCG inhibition with the ceramide analog d-threo-1-(3,4,-ethylenedioxy)phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (EtDO-P4) greatly reduced GSL and monosialotetrahexosylganglioside levels, and co-treatment with standard chemotherapeutics sensitized cells to mitochondrial membrane potential loss and apoptosis. ABC subfamily B member 1 (ABCB1) expression was reduced, and ABCC-mediated efflux activity was modulated by competition with nonglycosylated ceramides. Consistently, inhibition of ABCC-mediated transport reduced the efflux of exogenous C6-ceramide. Overall, UGCG inhibition impaired the malignant glycophenotype of MDR leukemias, which typically overcomes drug resistance through distinct mechanisms. This work sheds light on the involvement of GSL in chemotherapy failure, and its findings suggest that targeted GSL modulation could help manage MDR leukemias.




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    Genetic lineage tracing with multiple DNA recombinases: A user's guide for conducting more precise cell fate mapping studies [Methods and Resources]

    Site-specific recombinases, such as Cre, are a widely used tool for genetic lineage tracing in the fields of developmental biology, neural science, stem cell biology, and regenerative medicine. However, nonspecific cell labeling by some genetic Cre tools remains a technical limitation of this recombination system, which has resulted in data misinterpretation and led to many controversies in the scientific community. In the past decade, to enhance the specificity and precision of genetic targeting, researchers have used two or more orthogonal recombinases simultaneously for labeling cell lineages. Here, we review the history of cell-tracing strategies and then elaborate on the working principle and application of a recently developed dual genetic lineage-tracing approach for cell fate studies. We place an emphasis on discussing the technical strengths and caveats of different methods, with the goal to develop more specific and efficient tracing technologies for cell fate mapping. Our review also provides several examples for how to use different types of DNA recombinase–mediated lineage-tracing strategies to improve the resolution of the cell fate mapping in order to probe and explore cell fate–related biological phenomena in the life sciences.




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    The streptococcal multidomain fibrillar adhesin CshA has an elongated polymeric architecture [Microbiology]

    The cell surfaces of many bacteria carry filamentous polypeptides termed adhesins that enable binding to both biotic and abiotic surfaces. Surface adherence is facilitated by the exquisite selectivity of the adhesins for their cognate ligands or receptors and is a key step in niche or host colonization and pathogenicity. Streptococcus gordonii is a primary colonizer of the human oral cavity and an opportunistic pathogen, as well as a leading cause of infective endocarditis in humans. The fibrillar adhesin CshA is an important determinant of S. gordonii adherence, forming peritrichous fibrils on its surface that bind host cells and other microorganisms. CshA possesses a distinctive multidomain architecture comprising an N-terminal target-binding region fused to 17 repeat domains (RDs) that are each ∼100 amino acids long. Here, using structural and biophysical methods, we demonstrate that the intact CshA repeat region (CshA_RD1–17, domains 1–17) forms an extended polymeric monomer in solution. We recombinantly produced a subset of CshA RDs and found that they differ in stability and unfolding behavior. The NMR structure of CshA_RD13 revealed a hitherto unreported all β-fold, flanked by disordered interdomain linkers. These findings, in tandem with complementary hydrodynamic studies of CshA_RD1–17, indicate that this polypeptide possesses a highly unusual dynamic transitory structure characterized by alternating regions of order and disorder. This architecture provides flexibility for the adhesive tip of the CshA fibril to maintain bacterial attachment that withstands shear forces within the human host. It may also help mitigate deleterious folding events between neighboring RDs that share significant structural identity without compromising mechanical stability.




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    Structural basis of substrate recognition and catalysis by fucosyltransferase 8 [Protein Structure and Folding]

    Fucosylation of the innermost GlcNAc of N-glycans by fucosyltransferase 8 (FUT8) is an important step in the maturation of complex and hybrid N-glycans. This simple modification can dramatically affect the activities and half-lives of glycoproteins, effects that are relevant to understanding the invasiveness of some cancers, development of mAb therapeutics, and the etiology of a congenital glycosylation disorder. The acceptor substrate preferences of FUT8 are well-characterized and provide a framework for understanding N-glycan maturation in the Golgi; however, the structural basis of these substrate preferences and the mechanism through which catalysis is achieved remain unknown. Here we describe several structures of mouse and human FUT8 in the apo state and in complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80–2.50 Å resolution. These structures provide insights into a unique conformational change associated with donor substrate binding, common strategies employed by fucosyltransferases to coordinate GDP, features that define acceptor substrate preferences, and a likely mechanism for enzyme catalysis. Together with molecular dynamics simulations, the structures also revealed how FUT8 dimerization plays an important role in defining the acceptor substrate-binding site. Collectively, this information significantly builds on our understanding of the core fucosylation process.




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    The Histone Methyltransferase MLL1 Directs Macrophage-Mediated Inflammation in Wound Healing and Is Altered in a Murine Model of Obesity and Type 2 Diabetes

    Andrew S. Kimball
    Sep 1, 2017; 66:2459-2471
    Immunology and Transplantation




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    A Variation on the Theme: SGLT2 Inhibition and Glucagon Secretion in Human Islets

    David J. Hodson
    May 1, 2020; 69:864-866
    Commentaries




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    Pancreas Pathology of Latent Autoimmune Diabetes in Adults (LADA) in Patients and in a LADA Rat Model Compared With Type 1 Diabetes

    Anne Jörns
    Apr 1, 2020; 69:624-633
    Islet Studies




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    Evidence Against an Important Role of Plasma Insulin and Glucagon Concentrations in the Increase in EGP Caused by SGLT2 Inhibitors

    Mariam Alatrach
    Apr 1, 2020; 69:681-688
    Pathophysiology




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    The Multiple Actions of GLP-1 on the Process of Glucose-Stimulated Insulin Secretion

    Patrick E. MacDonald
    Dec 1, 2002; 51:S434-S442
    Section 5: Beta-Cell Stimulus-Secretion Coupling: Hormonal and Pharmacological Modulators




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    Latent Autoimmune Diabetes in Adults: Definition, Prevalence, {beta}-Cell Function, and Treatment

    Gunnar Stenström
    Dec 1, 2005; 54:S68-S72
    Section II: Type 1-Related Forms of Diabetes




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    Enhanced Health in Care Homes during Covid19




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    Re: Mitigating the wider health effects of covid-19 pandemic response




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    US adults are more likely to have poor health than those in 10 similar countries, survey finds




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    Engage China to Uphold Multilateralism – But Not at Any Cost

    12 June 2019

    Harriet Moynihan

    Senior Research Fellow, International Law Programme
    Where China’s interests align with those of the international community, there are opportunities for the country’s influence and economic power to strengthen the rules-based international order. Where they do not, states that traditionally support that order should join together to push back.

    2019-02-01-China.jpg

    Students holding Chinese national flags watch the live broadcast of the 40th anniversary celebration of China's reform and opening-up at Huaibei Normal University on 18 December. Photo: Getty Images.

    China’s adherence to the rules-based international system is selective, prioritizing certain rules in favour of others. States supportive of that ‘system’ – or, as some argue, systems[1] – should identify areas of mutual strategic interest so that they can draw China further into the global rules-based order and leverage China as a constructive player that potentially also contributes to improvements in such areas. This is particularly apposite at a time when the US is in retreat from multilateralism and Russia seems bent on disrupting the rules-based international order.

    Supportive player

    There are many reasons for actively engaging with China on mutual areas of interest. China is a committed multilateralist in many areas, recognizing that often international cooperation and frameworks hold the key to its domestic problems, for example in the fields of environmental sustainability and financial regulation.

    China’s economic power is valuable in upholding international institutions: China is the UN’s third-largest donor (after the US and Japan) at a time when the UN is facing budgetary shortfalls. China is also the second-highest contributor to the UN peacekeeping budget, and the largest contributor of peacekeeping forces among the five permanent members of the UN Security Council.

    China also has a valuable role to play in the settlement of international disputes over trade and investment. China is a big supporter of the World Trade Organization (WTO)’s dispute settlement mechanism, and one of its most active participants;[2] China is currently playing an active role in negotiations to save the WTO’s appellate mechanism from folding in the wake of the US’s refusal to nominate new judges.

    The last 15 years have also seen a major shift in Chinese attitudes to investment arbitration, from a general suspicion and limitation of arbitration rights to broad acceptance and incorporation of such rights in China’s trade and investment treaties. China is actively engaged in multilateral negotiations through the UN Commission on International Trade Law (UNCITRAL) on reforms to investor–state dispute settlement.

    China has shown leadership on global climate change diplomacy, urging nations to remain committed to the Paris Agreement in the wake of the US decision to pull out, and has been an important interlocutor with the UK and the EU on these issues. As a strong supporter of the Paris Agreement, but also as the world’s top emitter of carbon dioxide, China has a crucial role to play in pushing forward implementation of the Paris targets. Despite its high emissions, China remains one of the few major economies on track to meet its targets,[3] giving it greater leverage to peer review other parties’ efforts.

    A recent report by the UK parliament’s Foreign Affairs Committee (FAC), on China and the rules-based international order, noted that where a body of trust and goodwill is developed with China, there is the possibility of discovering interests that coincide and the ability to work together on issues mutually regarded as of global importance. The report refers to a number of success stories from UK partnership with China in multilateral forums, including in counterproliferation and global health.[4]

    Developing areas of global governance

    As well as working with the current system, China is increasingly involved in the shaping of newer areas of international law – whether it be submissions to the International Tribunal for the Law of the Sea (ITLOS) on procedural rules for the emerging deep-sea mining regime or pitching for a greater role in Arctic governance.[5]

    This enthusiasm should be harnessed to promote the international rule of law, but at the same time there needs to be recognition of the strategic goals that drive China’s engagement. China’s interest in the Arctic, while including the desire to protect its ecology and environment, is also about access to marine resources, as well as about the Arctic’s strategic potential for China’s military.

    China’s submissions to ITLOS on the rules of procedure for deep-sea mining are constructive, but also reflect an ambition to secure first-mover advantage when commercial mining eventually takes place. Like other major powers working in this policy area, China’s actions are guided by self-interest, but that doesn’t mean its goals can’t be pursued through multilateral rules.

    China is also interested in creating new international structures and instruments that further its strategic aims. For example, with Russia (through the Shanghai Cooperation Organisation) it has proposed an International Code of Conduct for Information Security in the UN.[6]

    China is also pondering an array of options for dispute-resolution mechanisms for its Belt and Road projects, including the possibility of an Asian version of the international Convention on the Settlement of Investment Disputes, which might sit under the auspices of the Asian Infrastructure Investment Bank (AIIB).[7]

    The creation of new instruments and institutions need not be a threat to the rules-based international order in itself. We have already seen a combination of the creation of parallel complementary regimes alongside the reform of existing institutions, for example in development financing through the AIIB or the New Development Bank (often referred to as the ‘BRICS Bank’); these two banks are relatively conventionally structured along the lines of Western-dominated institutions, albeit with greater Chinese control. Based on these examples, selective adaptation seems more likely than a hostile ‘Eastphalian’ takeover.[8]

    Risks

    There is, however, a real risk that in certain areas China may promote a rival authoritarian model of governance, assisted by an opportunistic convergence with Russia on issues such as human rights, development and internet governance. In areas where China’s core interests clash with those of the rules-based international order, China has shown itself to be unbending, as in its refusal to abide by the July 2016 decision of the Permanent Court of Arbitration in its dispute with the Philippines over the South China Sea.[9]

    China is becoming more assertive at the UN, but while it seeks to project itself there as a responsible emerging global leader, it is promoting a vision that weakens international norms of human rights, transparency and accountability,[10] while also carrying out practices domestically that raise serious human rights concerns (not least the detention of hundreds of thousands of Uighurs in re-education camps in Xinjiang).[11]

    China’s increased dominance geographically and geopolitically through its Belt and Road infrastructure projects carries with it a number of social and economic risks, including smaller states becoming trapped in unsustainable financial debts to China.

    But at a recent Chatham House conference on Asia and international law, participants highlighted the limitations on how far China can shape an alternative governance model.[12] China currently lacks soft power, cultural power and language power, all of which are needed in order to embed an alternative model abroad. China also currently lacks capacity and confidence to build coalitions with other states in the UN.

    Where it has tried to get buy-in from the international community for its new institutions, such as the China International Commercial Court (CICC) announced in July 2018, there has been scepticism about the standards to be applied.[13] Unless the court can demonstrate sufficient due process, international parties are likely to prefer other centres with a strong reputation for upholding the rule of law, such as those in London, Dubai and Singapore.

    Where China does promote its own governance model at the expense of the rules-based international order, states are starting to push back, often in concert. EU member states so far have adopted a joined-up approach to the Belt and Road Initiative. With the exception of Italy, they have refused to sign a Memorandum of Understanding on participation unless China provides much greater transparency on its compliance with international standards.

    The EU also recently presented a coordinated response to China on the situation in Xinjiang.[14] Similarly, members of the so-called ‘Five Eyes’ intelligence-sharing alliance (comprising Australia, Canada, New Zealand, the UK and the US) have acted together in relation to certain incidents of cyber interference attributed to China.[15]

    There are also signs of pushback from smaller states closer to home in relation to challenges to national sovereignty, debt diplomacy and financial viability arising from Belt and Road projects. The Sri Lankan government recently reversed the award of a $300 million housing deal to China, instead opting for a joint venture with an Indian company.

    China has been downscaling its investments as a way to counter some of the backlash it has received: the most recent Belt and Road summit put forward a more modest set of aspirations. This suggests that there is some scope for states to stand up to China and use leverage to secure better deals.

    Many international institutions have been Western-dominated for years;[16] China, together with many emerging and middle powers, has felt for some time that the international architecture does not reflect the world we live in. Given that context, states that champion the rules-based international order should acknowledge China’s desire to update the international order to reflect greater multipolarity, globalization and technological change, while being clear-eyed about their engagement with China. This involves investing in a proper understanding of China and how it works.[17]

    Where possible, cooperation with China should lead to outcomes that are backed up by international standards and transparency. The above-mentioned FAC report cites evidence that the UK’s support, and that of other developed countries, had a positive impact in shaping the governance and standards of the AIIB.[18] China has brought in international experts to advise on disputes before the CIIC, which may reassure would-be litigants.

    China’s relationship with the rules-based international order needs to be assessed pragmatically and dynamically. China can be a valuable partner in many areas where its objectives are closely aligned with those of the international community – from trade to climate change to peacekeeping.

    But where the country’s core interests are at odds with those of the wider international community, an increasingly confident China will strongly resist pressure, including on the South China Sea and human rights. In these areas, states supportive of international law can most powerfully push back through alliances and by ensuring that their own core values are not compromised in the interests of economic benefits.

    What needs to happen

    • China’s rising power and selective commitment to multilateralism make it a potentially influential ally in modernizing international governance.
    • China is increasingly involved in shaping newer areas of international law. This enthusiasm could be harnessed in the service of institutional development and reform.
    • Other states should identify areas of mutual strategic interest where China may offer a constructive role, including dispute settlement, health and climate change.
    • However, engagement must not ignore the strategic calculations that drive China’s agenda, or its poor record on civil and political rights, transparency and accountability.
    • Cooperation with China should lead to outcomes that are backed up by international standards and transparency.
    • Where China’s actions undermine the rules-based international order, coordinated action by states supportive of that order is likely to be more effective than acting individually.

    Notes

    [1] Chalmers, M. (2019), Which Rules? Why There is No Single ‘Rules-Based International System’, RUSI Occasional Paper, April 2019, London: Royal United Services Institute, https://rusi.org/occasional-papers/Which-Rules-Why-There-Is-No-Single-Rules-Based-International-System.

    [2] See, for example, Moynihan, H. (2017), China’s Evolving Approach to International Dispute Settlement, Briefing, London: Royal Institute of International Affairs, https://www.chathamhouse.org/publication/chinas-evolving-approach-international-dispute-settlement.

    [3] UN Environment (2018), Emissions Gap Report 2018, p. XVII, https://www.unenvironment.org/resources/emissions-gap-report-2018.

    [4] House of Commons Foreign Affairs Committee (2019), China and the Rules-Based International System: Sixteenth Report of Session 2017–19, p. 32, https://publications.parliament.uk/pa/cm201719/cmselect/cmfaff/612/612.pdf.

    [5] Moynihan, H. (2018), ‘China Expands Its Global Governance Ambitions in the Arctic’, Expert Comment, 15 October 2018, https://www.chathamhouse.org/expert/comment/china-expands-its-global-governance-ambitions-arctic.

    [6] Updated version proposed 9 January 2015.

    [7] Moynihan, H. (2018), ‘Exploring Public International Law Issues with Chinese Scholars – Part Four’, Meeting Summary, 3 June 2018, https://www.chathamhouse.org/publication/exploring-public-international-law-issues-chinese-scholars-part-four.

    [8] Chatham House (2019, forthcoming, ‘Security and Prosperity in the Asia-Pacific: The Role of International Law’, conference summary, https://www.chathamhouse.org/event/security-and-prosperity-asia-pacific-role-international-law.

    [9] Permanent Court of Arbitration Case No. 2013-19 (Philippines v China), Award of 12 July 2016, https://pca-cpa.org/wp-content/uploads/sites/6/2016/07/PH-CN-20160712-Award.pdf.

    [10] Piccone, T. (2018), China’s Long Game on Human Rights at the United Nations, Washington, DC: Brookings Institution, https://www.brookings.edu/wp-content/uploads/2018/09/FP_20181009_china_human_rights.pdf.

    [11] Wye, R. (2018), ‘‘The entire Uyghur population is seemingly being treated as suspect’: China’s persecution of its Muslim minority’, LSE Religion and Global Society blog, 18 September 2018, https://blogs.lse.ac.uk/religionglobalsociety/2018/09/the-entire-uyghur-population-is-seemingly-being-treated-as-suspect-chinas-persecution-of-its-muslim-minority/.

    [12] Chatham House (2019, forthcoming, ‘Security and Prosperity in the Asia-Pacific: The Role of International Law’.

    [13] Walters, M. (2018), ‘Jury is out over China’s new commercial court, say lawyers’, Law Society Gazette, 1 November 2018, https://www.lawgazette.co.uk/law/jury-is-out-over-chinas-new-commercial-court-say-lawyers/5068125.article.

    [14] The Economist (2019), ‘Hope remains for Western solidarity. Look at embassies in Beijing’, 17 April 2019, https://www.economist.com/china/2019/04/20/hope-remains-for-western-solidarity-look-at-embassies-in-beijing.

    [15] In December 2018, the Five Eyes attributed the activities of a Chinese cyber espionage group targeting intellectual property and sensitive commercial property to China’s Ministry of State Security.

    [16] Roberts, A. (2017), Is International Law International?, Oxford: Oxford University Press.

    [17] Parton, C. (2019), China–UK Relations: Where to Draw the Border Between Influence and Interference?, RUSI Occasional Paper, February 2019, London: Royal United Services Institute, p. 30, https://rusi.org/publication/occasional-papers/china-uk-relations-where-draw-border-between-influence-and.

    [18] House of Commons Foreign Affairs Committee (2019), China and the Rules-Based International System, p. 15.

    This essay was produced for the 2019 edition of Chatham House Expert Perspectives – our annual survey of risks and opportunities in global affairs – in which our researchers identify areas where the current sets of rules, institutions and mechanisms for peaceful international cooperation are falling short, and present ideas for reform and modernization.




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    Crimea’s Occupation Exemplifies the Threat of Attacks on Cultural Heritage

    4 February 2020

    Kateryna Busol

    Robert Bosch Stiftung Academy Fellow, Russia and Eurasia Programme
    Societies, courts and policymakers should have a clearer awareness that assaults against cultural heritage constitute a creeping encroachment on a people’s identity, endangering its very survival.

    2020-02-04-Bakhchysarai.jpg

    'The destructive reconstruction of the 16th-century Bakhchysarai Palace is being conducted by a team with no experience of cultural sites, in a manner that erodes its authenticity and historical value.' Photo: Getty Images.

    Violations against cultural property – such as archaeological treasures, artworks, museums or historical sites – can be no less detrimental to the survival of a nation than the physical persecution of its people. These assaults on heritage ensure the hegemony of some nations and distort the imprint of other nations in world history, sometimes to the point of eradication.

    As contemporary armed conflicts in Syria, Ukraine and Yemen demonstrate, cultural property violations are not only a matter of the colonial past; they continue to be perpetrated, often in new, intricate ways.

    Understandably, from a moral perspective, it is more often the suffering of persons, rather than any kind of ‘cultural’ destruction, that receives the most attention from humanitarian aid providers, the media or the courts. Indeed, the extent of the damage caused by an assault on cultural property is not always immediately evident, but the result can be a threat to the survival of a people. This is strikingly exemplified by what is currently happening in Crimea.

    Ukraine’s Crimean peninsula has been occupied by Russia since February 2014, meaning that, under international law, the two states have been involved in an international armed conflict for the last six years.

    While much attention has been paid to the alleged war crimes perpetrated by the occupying power, reports by international organizations and the International Criminal Court (ICC) have been less vocal on the issue of cultural property in Crimea. Where they do raise it, they tend to confine their findings to the issue of misappropriation.

    However, as part of its larger policy of the annexation and Russification of the peninsula and its history, Russia has gone far beyond misappropriation.

    Crimean artefacts have been transferred to Russia – without security justification or Ukrainian authorization as required by the international law of occupation – to be showcased at exhibitions celebrating Russia’s own cultural heritage. In 2016, the Tretyakov Gallery in Moscow staged its record-breaking Aivazovsky exhibition, which included 38 artworks from the Aivazovsky Museum in the Crimean town of Feodosia.

    Other ‘cultural’ violations in the region include numerous unsanctioned archaeological excavations, whose findings are often unlawfully exported to Russia or end up on the black market.

    There is also the example of Russia’s plan to establish a museum of Christianity in Ukraine’s UNESCO World Heritage site, the Ancient City of Tauric Chersonese. This is an indication of Russia’s policy of asserting itself as a bastion of Orthodox Christianity and culture in the Slavic world, with Crimea as one of the centres.

    The harmful effects of Russia’s destructive cultural property policy can be seen in the situation of the Crimean Tatars, Ukraine’s indigenous Muslim people. Already depleted by a Stalin-ordered deportation in 1944 and previously repressed by the Russian Empire, the Crimean Tatars are now facing the destruction of much of the remainder of their heritage.

    For example, Muslim burial grounds have been demolished to build the Tavrida Highway, which leads to the newly built Kerch Bridge connecting the peninsula to Russia.

    The destructive reconstruction of the 16th-century Bakhchysarai Palace – the only remaining complete architectural ensemble of the indigenous people, included in the UNESCO World Heritage Tentative List – is another example of how the very identity of the Crimean Tatars is being threatened. This reconstruction is being conducted by a team with no experience of cultural sites, in a manner that erodes its authenticity and historical value – which is precisely as Russia intends.

    There is a solid body of international and domestic law covering Russia’s treatment of Crimea’s cultural property.

    Under the 1954 Hague Convention for the Protection of Cultural Property in the Event of Armed Conflict – ratified by both Ukraine and Russia – the occupying power must facilitate the safeguarding efforts of the national authorities in occupied territories. States parties must prevent any vandalism or misappropriation of cultural property, and, according to the first protocol of the convention, the occupying power is required to prevent any export of artefacts from the occupied territory.

    The 1907 Hague Regulations and the 1949 Fourth Geneva Convention confirm that the authentic domestic legislation continues to apply in occupied territories. This leaves Russia with no excuse for non-compliance with Ukraine’s cultural property laws and imposing its own rules unless absolutely necessary.

    Besides, both Ukrainian and Russian criminal codes penalise pillage in occupied territory, as well as unsanctioned archaeological excavations. As an occupying power, Russia must not just abstain from such wrongdoings in Crimea, but also duly investigate and prosecute the alleged misconduct.

    The clarity of the international legal situation demonstrates that no exhibitions in continental Russia and no archaeological excavations which are not sanctioned by Ukraine can be justified. Likewise, any renovation or use of cultural sites, especially those on permanent or tentative UNESCO lists, must only be conducted pursuant to consultancy with and approval of the Ukrainian authorities.

    But the resonance of the Crimean case goes beyond law and touches on issues of the very survival of a people. The Soviet deportation of the Crimean Tatars in 1944 did not only result in the deaths of individuals. Their footprints in Crimea have been gradually erased by baseless treason charges, the long exile of the indigenous community from their native lands and ongoing persecution.

    First the Soviet Union and now Russia have targeted the Crimean Tatars’ cultural heritage to undermine their significance in the general historical narrative, making attempts to preserve or celebrate this culture seem futile. Russia is thus imposing its own historical and political hegemony at the expense of the Crimean Tatar and Ukrainian layers of Crimean history.

    As exemplified by occupied Crimea, the manipulation and exploitation of cultural heritage can serve an occupying power’s wider policies of appropriating history and asserting its own dominance. Domestic cultural property proceedings are challenging due to the lack of access to the occupied territory, but they should still be pursued.

    More effort is needed in the following areas: case prioritization; informing the documenters of alleged violations about the spectrum of cultural property crimes; developing domestic investigative and prosecutorial capacity, including by involving foreign expert consultancy; more proactively seeking bilateral and multilateral cooperation in art crime cases; liaising with auction houses (to track down objects originating from war-affected areas) and museums (to prevent the exhibition of the artefacts from occupied territories).

    When possible, cultural property crimes should also be reported to the ICC.

    Additionally, more international – public, policy, media and jurisprudential – attention to such violations is needed. Societies, courts and policymakers should have a clearer awareness that assaults against cultural heritage constitute a creeping encroachment on a people’s identity, endangering its very survival.




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    The Morass of Central American Migration: Dynamics, Dilemmas and Policy Alternatives

    Invitation Only Research Event

    22 November 2019 - 8:15am to 9:30am

    Chatham House | 10 St James's Square | London | SW1Y 4LE

    Event participants

    Anita Isaacs, Professor of Political Science, Haverford College; Co-Director, Migration Encounters Project
    Juan Ricardo Ortega, Principal Advisor for Central America, Inter-American Development Bank
    Chair: Amy Pope, Associate Fellow, Chatham House; US Deputy Homeland Security Adviser for the Obama Administration (2015-17)

    2019 has seen a record number of people migrating from Central America’s Northern Triangle – an area that covers El Salvador, Guatemala and Honduras. Estimates from June 2019 have placed the number of migrants at nearly double of what they were in 2018 with the increase in numbers stemming from a lack of economic opportunity combined with a rise in crime and insecurity in the region. The impacts of migration can already be felt within the affected states as the exodus has played a significant role in weakening labour markets and contributing to a ‘brain drain’ in the region. It has also played an increasingly active role in the upcoming US presidential election with some calling for more security on the border to curb immigration while others argue that a more effective strategy is needed to address the sources of migration. 

    What are the core causes of Central American migration and how have the US, Central American and now also Mexican governments facilitated and deterred migration from the region? Can institutions be strengthened to alleviate the causes of migration? And what possible policy alternatives and solutions are there that could alleviate the pressures individuals and communities feel to migrate?   

    Anita Isaacs, professor of Political Science at Haverford College and co-director of the Migration Encounters Project, and Juan Ricard Ortega, principal advisor for Central America at the Inter-American Development Bank, will join us for a discussion on the core drivers of migration within and across Central America.

    Attendance at this event is by invitation only. 

    Event attributes

    Chatham House Rule

    Department/project

    US and Americas Programme




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    Diabetes Core Update: Covid-19 and Diabetes – Considerations for Health Care Professionals - April 2019

    Diabetes Core Update: Covid-19 and Diabetes – Considerations for Health Care Professionals - April 2019

    This special issue is an audio version of the American Diabetes Associations Covid-19 leadership team discussing a range of issues on Covid-19 and Diabetes.

    Recorded March 31, 2020.

    Topics include:

    1. Access to medications
    2. Effect on Diabetes Self-management
    3. Can Patients take their own Supplies if they are an inpatient in the hospital – particularly insulin pumps and CGM
    4. Considerations for Specific Hypoglycemic Medications during Inpatient Hospitalization
    5. Differences in Management for Persons with Type 1 and Type 2 Diabetes
    6. SGLT-2 inhibitors and GLP-1 Receptor Agonists use During Covid-19 Infection
    7. Diabetes and Cardiovascular Disease during Covid-19
    8. ACEs and ARBs
    9. Stress among Healthcare Professionals

    Intended for practicing physicians and health care professionals, Diabetes Core Update discusses how the latest research and information published in journals of the American Diabetes Association are relevant to clinical practice and can be applied in a treatment setting.

    Presented by:

    Robert Eckel, MD
    ADA President, Medicine & Science
    University of Colorado

    Mary de Groot, PhD
    ADA President, Health Care & Education
    Indiana University

    Irl Hirsch, MD
    University of Washington

    Anne Peters, MD
    University of Southern California    

    Louis Philipson, MD, PhD
    ADA Past President, Medicine & Science
    University of Chicago

    Neil Skolnik, MD
    Abington Jefferson Health




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    Diabetes Core Update: COVID-19 – Telehealth and COVID-19 , April 2019

    This special issue focuses on Telehealth and COVID-19.

    Recorded March 31, 2020.

    Intended for practicing physicians and health care professionals, Diabetes Core Update discusses how the latest research and information published in journals of the American Diabetes Association are relevant to clinical practice and can be applied in a treatment setting.

    Presented by:

    Neil Skolnik, MD
    Sidney Kimmel Medical College, Thomas Jefferson University

    Eric Johnson, MD
    University of North Dakota School of Medicine and Health Sciences




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    Diabetes Core Update: COVID-19 – Older Adults with Diabetes and Covid-19 April 2019

    This special issue focuses on Older Adults with Diabetes and Covid-19.

    Recorded April 20, 2020.

    This podcast will cover:

    1. Risk of COVID-19 in Older Adults
    2. What are the recommendations for glucose control during the pandemic
    3. Telemedicine
    4. Challenges to home care
    5. Long-term care settings

    Intended for practicing physicians and health care professionals, Diabetes Core Update discusses how the latest research and information published in journals of the American Diabetes Association are relevant to clinical practice and can be applied in a treatment setting.

    Presented by:

    Irl Hirsch, MD
    University of Washington
     
    Elbert Huang, MD, MPH, FACP
    University of Chicago
     
    Stacie Levine, MD
    University of Chicago

     




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    Trust boss gave misleading information to GMC about consultant who was unfairly dismissed




    lt

    Covid-19: Lack of capacity led to halting of community testing in March, admits deputy chief medical officer




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    Covid-19: Health needs of sex workers are being sidelined, warn agencies




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    Med Treatments India | Medical Tourism in India | Healthcare India

    Med Treatments India offers one stop solution for medical healthcare services and most affordable treatments facility with best hospitals & alternative treatments in India.



    • Sports and Health

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    Building a solution - UWI Faculty of Engineering answering COVID-19 call

    THE FACULTY of Engineering at The University of the West Indies (UWI), Mona campus, is stepping up to the plate in the fight against the new coronavirus (COVID-19) through its final-year projects and commercial arm, Mona-Tech Engineering Services....




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    Climate Change: Raising Ambition, Delivering Results

    Conference

    3 November 2014 - 9:30am to 4 November 2014 - 1:15pm

    Chatham House, London

    Overview

    Agenda

    Speakers

    Pricing

    Media partners

    Sponsors

    Audience profile

    Venue and accommodation

    Press registration

    Climate change is climbing the political agenda. Extreme weather has raised questions in public discourse about the role of anthropogenic warming and concerns about its future impacts; slowdowns in emerging economies and sluggish recoveries in the developed world mean debates about the impact of climate policies on energy bills and competitiveness have assumed particular significance. Against this background, governments are gearing up for a crucial series of agreements in 2015 with climate change at their core. The international community must agree new global sustainable development goals, a new framework on disaster risk reduction and, at the 21st UN Framework Convention on Climate Change (UNFCCC) meeting of the Conference of Parties (COP 21) in Paris, a new global deal on climate change. 

    The 18th Annual Chatham House Conference on Climate Change will take stock of developments in 2014, including the latest science, the findings of high-level commissions, initiatives from the business community and the UN Secretary-General’s High Level Summit at the end of September. Looking forward to COP 20 in Lima and beyond, this conference will examine opportunities to raise ambition and convert this into results.

    In particular, it will:

    • Review the latest science on climate risk and the implications for business, society and politics 
       
    • Examine the benefits of a low carbon economy, and assess the costs of climate action and where they fall 
       
    • Discuss concrete measures to decarbonize key sectors and the barriers to action
       
    • Identify the critical path to the UNFCCC’s Conference of the Parties (COP 21) in 2015, and look at whether, and how, support for ambitious action can be built among publics, business and politicians


    The Chatham House Rule
    To enable as open a debate as possible, this conference will be held under the Chatham House Rule.

    Twitter
    Suggested hashtag: #CHclimate

    DAY ONE
    Monday 3 November

    Session One
    Taking Stock and Mapping the Road Ahead
    09:30-11:15

    • What was achieved at the UN Secretary General’s High Level Summit in September? 
    • What is the outlook for COP 20 in Lima, and how can ambition be increased?
    • How will success at COP 21 in Paris be defined?

    Chair
    Rob Bailey, Acting Research Director, Energy, Environment and Resources, Chatham House

    Keynote Address
    Manuel Pulgar-Vidal, Minister of State for the Environment, Peru; President, COP 20, UN Framework for the Convention on Climate Change (UNFCCC) (on the record)

    Amber Rudd MP, Parliamentary Under Secretary of State, Department of Energy and Climate Change, United Kingdom (on the record)

    Questions and Discussion

    Chair
    Jennifer Morgan, Director, Climate and Energy Programme, World Resources Institute (WRI) 

    Speakers

    Selwin Hart, Director, Secretary-General's Climate Change Support Team, United Nations

    Dr Halldór Thorgeirsson, Director for Strategy, UN Framework for the Convention on Climate Change (UNFCCC)

    Leena Srivastava, Executive Director, The Energy and Resource Institute (TERI) 

    Paul Watkinson, Head of Climate Negotiation Team, Ministry of Ecology, Sustainable Development and Energy, France

    Questions and Discussion

    11:15-11:45 Refreshments

    Session Two
    Low Carbon Economy: Costs and Benefits
    11:45-13:00 

    • What are the economic and social opportunities and benefits of a low carbon economy? Where do these occur? How much are they worth?
    • What are examples of leadership among governments and business? What is needed to accelerate the transition and translate ambition into results?
    • What has been the impact of climate policies on economic competitiveness? Which economies and sectors have been most affected? How has this influenced national and international climate politics?
    Chair's Opening Remarks
    Marianne Fay, Chief Economist, Climate Change Group, The World Bank
    Keynote Panel Discussion

    Jeremy Oppenheim, Programme Director, New Climate Economy, Global Commission on the Economy and Climate 

    Jos Delbeke, Director General for Climate Action, European Commission 

    Dr Qi Ye, Director, Brookings-Tsinghua Center for Public Policy; Professor of Environmental Policy and Management at Tsinghua University’s School of Public Policy and Management

    Jeremy Bentham, Vice President, Global Business Environment, Shell

    Questions and Discussion

    13:00-14:00 Lunch

    Session Three
    Concrete Steps to Action: Finance and Achieving Net Zero 

    There is growing interest in the concept of net zero carbon emissions, for businesses, sectors and even countries. This session will examine the feasibility of net zero for the power and transport sectors, and for buildings and cities.

    Chair
    Shane Tomlinson, Senior Research Fellow, Energy, Environment and Resources, Chatham House

    Opening Discussion
    Manfred Konukiewitz, Co-Chair, the Green Climate Fund 

    Matthew Kotchen, Professor of Economics, Yale University 

    Farhana Yamin, Associate Fellow, Chatham House

    Power and Transport
    14:45-15:45

    • What do decarbonization roadmaps for the power and transport sectors look like? Is net zero feasible? If so, by when and how? What are the challenges posed by increasing renewable penetration, and how can they be managed? What are the implications of vehicle electrification for the power sector?
    • What are the implications for infrastructure and investment?

    Chair
    Shane Tomlinson, Senior Research Fellow, Energy, Environment and Resources, Chatham House

    Speakers
    Abyd Karmali, Managing Director, Climate Finance, Bank of America Merrill Lynch

    Dries Acke, Policy Manager, European Climate Foundation (Belgium) 

    Olivier Paturet, General Manager,  Zero Emissions Strategy, Nissan Europe

    Stefan Raubenheimer, Co-Founder and Director, South South North;  Co-Director, MAPS Programme 

    Questions and Discussion

    15:45-16:15 Refreshments

    Buildings and Cities
    16:15-17:15

    • What is the state of the art for low carbon building; how can this be rolled out at scale? 
    • How can decarbonization objectives be incorporated into urban planning and regulation?
    • How are the challenges and needs different for developed and developing countries? 

    Chair
    Farhana Yamin, Associate Fellow, Energy, Environment and Resources, Chatham House

    Speakers
    Ed Mazria, Founder and CEO, Architecture 2030

    Tony Mallows, Director, Masdar City 

    Questions and Discussion

    17:15 Close of day and drinks reception

    DAY TWO
    Tuesday 4 November

    Session Four 
    Climate Impacts
    9:30-11:15 

    Chair
    Sir David King, Foreign Secretary's Special Representative for Climate Change, United Kingdom

    Keynote Addresses
    HE Belete Tafere, Minister, Ministry of Environment Protection and Forestry, Ethiopia (on the record)

    Professor Hans Joachim Schellnhuber, Founding Director, Potsdam Institute for Climate Impact Research (on the record)

    • What climate impacts are already being witnessed? Are these in line with expectations? What is the current state of attribution analysis?
    • What are the implications for climate politics?
    • What are the expected social, economic and environmental impacts under different climate scenarios? What is the most recent science since the deadline for Working Group II of the Intergovernmental Panel on Climate Change’s Fifth Assessment Report?  
    • Which countries and sectors are most vulnerable? What are governments and businesses doing to adapt?


    Chair
    Sir David King, Foreign Secretary's Special Representative for Climate Change, United Kingdom

    Speakers
    Chris Field, Founding Director, Department of Global Ecology, Carnegie Institution of Science, Co-Chair of Working Group II of the IPCC’s Fifth Assessment Report 

    Professor Myles Allen, Leader of ECI Climate Research Programme and Professor of Geosystem Science, University of Oxford 

    Nick Mabey, Director, E3G 

    Oilver Bettis, Chair, Resource and Environment Board, Institute and Faculty of Actuaries

    Questions and Discussion

    11:15 - 11.45 Refreshments

    Session Five
    The Conditions for Action
    11:45 - 13:00

    • What is the current state of public support for climate action? What shapes attitudes and beliefs? How does this vary by country? 
    • What can create political ambition, nationally and internationally?
    • What role can different stakeholders play in catalysing climate action?
    • What immediate obstacles need to be overcome and what lessons can be learned from recent success? 
    Chair
    Simon Maxwell, Executive Chair, Climate Development Knowledge Network
    Keynote Address
    Bill McKibben, President and Co-Founder, 350.org (on the record)

    Panel Discussion
    Antonio Hill, Executive Director, Global Campaign for Climate Action

    Michael Jacobs, Senior Adviser on International Climate Policy, The Institute for Sustainable Development and International Relations  

    Jennifer Morgan, Director, Climate and Energy Programme, World Resources Institute (WRI) 

    Sergio Margulis, National Secretary of Sustainable Development, Secretariat of Strategic Affairs of the Presidency of Brazil 

    Sir David King, Foreign Secretary's Special Representative for Climate Change, United Kingdom

    Questions and Discussion

    Closing remarks
    Rob Bailey, Acting Research Director, Energy, Environment and Resources, Chatham House

    1
    3:10 End of conference and lunch

     © The Royal Institute of International Affairs 2014

    Keynote Speakers

    Speakers

    Dries Acke

    Policy Manager, European Climate Foundation (Belgium)

    Myles Allen

    Coordinating Lead Author, Intergovernmental Panel on Climate Change Special Report on Global Warming of 1.5 °C; Professor of Geosystem Science, University of Oxford

    Oliver Bettis

    Chair, Institute and Faculty of Actuaries' Resource and Environment Board

    Marianne Fay

    Chief Economist, Climate Change Group, The World Bank

    Chris Field

    Founding Director, Department of Global Ecology, Carnegie Institution of Science

    Selwin Hart

    Director, Secretary-General's Climate Change Support Team, United Nations

    Antonio Hill

    Executive Director, Global Campaign for Climate Action

    Michael Hogan

    Senior Adviser, Regulatory Assistance Project

    Professor Michael Jacobs

    Senior Adviser on International Climate Policy, The Institute for Sustainable Development and International Relations

    Abyd Karmali

    Managing Director, Climate Finance, Bank of America Merrill Lynch

    Sir David King

    Foreign Secretary’s Special Representative for Climate Change

    Manfred Konukiewitz

    Co-Chair, The Green Climate Fund

    Matthew Kotchen

    Professor of Economics, Yale University

    Nick Mabey

    Co-Founding Director and Chief Executive, E3G

    Antony Mallows

    Director, Masdar City

    Sergio Margulis

    National Secretary of Sustainable Development, Secretariat of Strategic Affairs of the Presidency, Brazil

    Simon Maxwell

    Executive Chairman, Climate and Development Knowledge Network

    Edward Mazria

    Founder and CEO, Architecture 2030

    Jennifer Morgan

    Executive Director, Greenpeace International

    Olivier Paturet

    General Manager, Zero Emissions Strategy, Nissan Europe

    Stefan Raubenheimer

    Co-Founder and Director, South South North; Co-Director, MAPS Programme

    Jose-Manuel Sanoval

    Coordinator, Colombian Low Carbon Development Strategy (CLCDS) and Mitigation Action Plans and Scenarios (MAPS)

    Leena Srivastava

    Hony. Executive Director (Operations), The Energy and Resources Institute (TERI)

    Halldór Thorgeirsson

    Director for Strategy, UN Framework for the Convention on Climate Change

    Paul Watkinson

    Head of Climate Negotiation Team, Ministry of Ecology, Sustainable Development and Energy, France

    Farhana Yamin

    Associate Fellow, Energy, Environment and Resources Programme

    [node:event_chair]

    Pricing

    For any questions about rates, please call +44 (0)20 7314 2782.

                          FULL RATE
    EXCL. VATINCL. VAT
    Major corporate member rates
    All organizations£595£714 
    Corporate member rates
    Commercial organizations£1,295£1,554
    Government departments£775£930
    NGOs and academics£495£594
    Standard rates
    Commercial organizations£1,445£1,734 
    Government departments£845£1,014
    NGOs and academics£550£660

    This conference will offer a unique opportunity to network with senior officials from businesses, government, NGO's and academic institutions.

    Our previous Climate Change conferences saw delegates from companies and institutions such as:

    Accenture
    AEA Energy & Environment
    Agulhas
    ArcelorMittal
    Association of Asia Pacific Airlines (AAPA)
    Atkins Ltd
    Bank of America Merrill Lynch
    BASF plc
    Bayerngas Norge AS
    Beetle Capital
    BG Group plc
    BHP Billiton
    BIRA-IASB
    BirdLife
    Booz & Co
    BP plc
    British Council
    BT Group plc
    CAFOD
    Cairn Energy plc
    Cambridge Centre for Energy Studies
    Cambridge Programme for Sustainable Leadership
    Carbon Capture and Storage Association
    Carbon Leapfrog
    Carbon Trust
    Caritas Internationalis
    Catholic Fund for Overseas Development (CAFOD)
    CH2M Hill
    Chevron Ltd
    Chubu Electric Power Co Inc
    City of London
    ClientEarth
    Clifford Chance LLP
    Climate & Development Knowledge Network (CDKN)
    Climate Action Network (CAN)
    Climate and Health Council
    Climate Secure
    Coalition for an International Court for the Environment (ICE Coalition)
    Compassion in World Farming (CIWF)
    Conocophillips (UK) Ltd
    Control Risks
    Co-operative Group
    Cranfield University
    Deloitte Consulting LLP
    Department for Business, Innovation & Skills (BIS)
    Department for International Development (DFID)
    Department of Energy and Climate Change (DECC)
    Ecofys UK Ltd
    Ecologic Institute
    EDF Energy
    Energy Charter Secretariat
    Energy Technologies Institute
    Eni S.p.A
    Environment Agency
    Environmental Law Foundation (ELF)
    Environmental Protection Agency (EPA)
    Environmental Resources Management (ERM)
    ENWORKS
    Ernst & Young
    Ethical Investment Research Services Ltd (EIRIS)
    European Bank For Reconstruction & Development
    European Commission (Directorate General for Enterprise and Industry)
    European Parliament
    ExxonMobil International Ltd
    Fauna & Flora International
    FIA Foundation for the Automobile and Society
    Finnish Forest Association
    Foreign and Commonwealth Office (FCO)
    Forestry Commission
    Friends of the Earth
    Genesis Investment Management LLP
    GLG Partners LP
    Global CCS Institute
    Global Humanitarian Forum
    Global Sustainability Institute
    Global Witness
    Globeleq Ltd
    Grantham Research Institute on Climate Change and the Environment, LSE
    Greater Manchester Chamber of Commerce
    Greenpeace International
    Herbert Smith Freehills LLP
    HM Treasury
    Imperial College London
    INPEX Corporation
    Institute for Public Policy Research (IPPR)
    Institutional Investors Group on Climate Change (IIGCC)
    International Association of Oil & Gas Producers
    International Council on Mining and Metals
    International Finance Corporation (IFC)
    International Institute for Environment and Development (IIED)
    International Organization for Standardization (ISO)
    Japan External Trade Organization (JETRO)
    Joseph Rowntree Foundation
    JPMorgan
    King's College London
    KPMG
    Kuwait Petroleum Corporation
    London Assembly
    London Metropolitan University
    London School of Economics and Political Science (LSE)
    Maersk Group
    Massey University
    McKinsey & Company
    Met Office
    METREX
    Ministere des Affaires Etrangeres, France
    Ministry of Defence (Development, Concepts and Doctrine Centre)
    Ministry of Foreign Affairs, Netherlands
    Ministry of Foreign Affairs, Finland
    Ministry of Foreign Affairs, Poland
    Ministry of Infrastructure and the Environment
    Mitsubishi Corporation
    National Farmers' Union
    National Round Table on the Environment and the Economy
    Netherlands Development Finance Company (FMO)
    NEXUS Singapore
    Nordic Council
    Office of National Assessments
    Ogilvy
    Open Society Foundation
    Overseas Development Institute (ODI)
    Oxford University
    Plan UK
    PricewaterhouseCoopers LLP
    Privy Council Office
    Progressio
    Quaker Peace and Social Witness
    Québec Government Office
    Renewable Energy and Energy Efficiency Partnership (REEEP)
    Renewable Energy Systems Ltd (RES)
    Rolls-Royce International Ltd
    RWE Power AG
    Save the Children UK
    SCA, Svenska Cellulosa Aktiebolaget
    School of Oriental and African Studies (SOAS)
    Shell
    Standard Chartered Bank plc
    Statoil (UK) Ltd
    SustainAbility Ltd
    Swedish Defence Research Agency (FOI)
    Swiss Agency for Development and Cooperation SDC
    Task Consult
    Texas A&M University
    The 40 Foundation
    The Climate Group
    The Gold Standard Foundation
    The Norwegian Institute for Nature Research
    The Open University
    The Prince of Wales Corporate Leader Group
    The Royal Society
    The Saudi Fund For Development
    Tokyo Electric Power Company
    Total Holdings UK Ltd
    UK Chamber of Shipping
    UK Collaborative on Development Sciences (UKCDS)
    United Nations Environment Programme (UNEP)
    University College London (UCL)
    University of Cambridge
    University of East Anglia (School of Environmental Sciences)
    University of Edinburgh
    University of Oxford (Department of Politics and International Relations)
    US Department of State
    USAID
    Warwick Business School
    WaterAid
    World Coal Association
    World Coal Institute
    World Economic Forum
    World Society for the Protection of Animals (WSPA)
    World Vision UK
    WWF-UK
    Xynteo Ltd
    Yorkshire Forward

    Venue

    Chatham House
    10 St James's Square
    London
    SW1Y 4LE
    UK

    conferences@chathamhouse.org

    Telephone: +44 (0)20 7957 5729
    Fax: +44 (0)20 7957 5710

    If you wish to book the venue for your event please phone +44 (0)20 7314 2764


    Directions

    The nearest tube station is Piccadilly Circus which is on the Piccadilly and the Bakerloo Underground lines. From Piccadilly follow Regent Street southwards towards Pall Mall and take the first road on the right called Jermyn Street. Duke of York Street is the second road on the left and leads to St James's Square. Chatham House is immediately on your right.

    Map

    Accommodation

    Although we cannot book accommodation for delegates, we have arranged a reduced rate at some nearby hotels, where you can book your own accommodation. Please inform the hotel that you will be attending a conference at Chatham House (The Royal Institute of International Affairs) to qualify for the Institute's reduced rate.

    Please note all rates are subject to availability.

    Flemings Mayfair
    Half Moon Street
    Mayfair
    London W1J 7BH
    Tel: + 44 (0)20 7499 2964
    Fax: + 44 (0)20 7499 1817
    Standard Single from £199 + VAT

    The Cavendish London
    81 Jermyn Street
    London
    SW1Y 6JF
    Tel: + 44 (0)20 7930 2111
    Fax: + 44 (0)20 7839 2125
    Standard Single £205 + VAT

    To book The Cavendish online

    The Stafford London by Kempinski
    St James's Place
    London
    SW1A 1NJ
    Tel: 020 7518 1125
    Fax: 020 7493 7121
    Standard Single £230 +VAT

    This conference will be held under the Chatham House Rule. Information for journalists
    Press can request a press pass.


    Chatham House Conferences

    +44 (0)20 7957 5729




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    Why wealthy countries must not drop nuclear energy: coal power, climate change and the fate of the global poor

    12 March 2015 , Volume 91, Number 2

    Reinhard Wolf




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    Douglas Orane | Cultural attitudes to enhance productivity - Case Studies numbers five and six

    In this article, I share my two final case studies, which examine changing our cultural attitudes to enhance productivity. Case study #5 – The role of punctuality An entrepreneur named Michael Fairbanks, who specialises in developing...




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    G. Anthony Hylton | A glimpse of a post-COVID-19 world

    The lessons of COVID-19 are yet to crystallise, but the evidence so far has yielded some early insights of developments that are likely to shape the national and global agenda for the immediate future. The speed and scale of the spread of the...




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    Maintaining health with simple lifestyle changes

    Let’s face it, ladies: boosting your health is not always your primary priority, but it needs to be. It doesn’t require a long, overbearing and spine-chilling regime. Simple lifestyle changes can get the job done! In the end you’ll be left with a...




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    Serotonin Regulates Adult {beta}-Cell Mass by Stimulating Perinatal {beta}-Cell Proliferation

    A sufficient β-cell mass is crucial for preventing diabetes, and perinatal β-cell proliferation is important in determining the adult β-cell mass. However, it is not yet known how perinatal β-cell proliferation is regulated. Here, we report that serotonin regulates β-cell proliferation through serotonin receptor 2B (HTR2B) in an autocrine/paracrine manner during the perinatal period. In β-cell–specific Tph1 knockout (Tph1 βKO) mice, perinatal β-cell proliferation was reduced along with the loss of serotonin production in β-cells. Adult Tph1 βKO mice exhibited glucose intolerance with decreased β-cell mass. Disruption of Htr2b in β-cells also resulted in decreased perinatal β-cell proliferation and glucose intolerance in adulthood. Growth hormone (GH) was found to induce serotonin production in β-cells through activation of STAT5 during the perinatal period. Thus, our results indicate that GH-GH receptor-STAT5-serotonin-HTR2B signaling plays a critical role in determining the β-cell mass by regulating perinatal β-cell proliferation, and defects in this pathway affect metabolic phenotypes in adults.




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    Lipid Droplet Accumulation in Human Pancreatic Islets Is Dependent On Both Donor Age and Health

    Human but not mouse islets transplanted into immunodeficient NSG mice effectively accumulate lipid droplets (LDs). Because chronic lipid exposure is associated with islet β-cell dysfunction, we investigated LD accumulation in the intact human and mouse pancreas over a range of ages and states of diabetes. Very few LDs were found in normal human juvenile pancreatic acinar and islet cells, with numbers subsequently increasing throughout adulthood. While accumulation appeared evenly distributed in postjuvenile acinar and islet cells in donors without diabetes, LDs were enriched in islet α- and β-cells from donors with type 2 diabetes (T2D). LDs were also found in the islet β-like cells produced from human embryonic cell–derived β-cell clusters. In contrast, LD accumulation was nearly undetectable in the adult rodent pancreas, even in hyperglycemic and hyperlipidemic models or 1.5-year-old mice. Taken together, there appear to be significant differences in pancreas islet cell lipid handling between species, and the human juvenile and adult cell populations. Moreover, our results suggest that LD enrichment could be impactful to T2D islet cell function.




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    Pancreas Pathology of Latent Autoimmune Diabetes in Adults (LADA) in Patients and in a LADA Rat Model Compared With Type 1 Diabetes

    Approximately 10% of patients with type 2 diabetes suffer from latent autoimmune diabetes in adults (LADA). This study provides a systematic assessment of the pathology of the endocrine pancreas of patients with LADA and for comparison in a first rat model mimicking the characteristics of patients with LADA. Islets in human and rat pancreases were analyzed by immunohistochemistry for immune cell infiltrate composition, by in situ RT-PCR and quantitative real-time PCR of laser microdissected islets for gene expression of proinflammatory cytokines, the proliferation marker proliferating cell nuclear antigen (PCNA), the anti-inflammatory cytokine interleukin (IL) 10, and the apoptosis markers caspase 3 and TUNEL as well as insulin. Human and rat LADA pancreases showed differences in areas of the pancreas with respect to immune cell infiltration and a changed ratio between the number of macrophages and CD8 T cells toward macrophages in the islet infiltrate. Gene expression analyses revealed a changed ratio due to an increase of IL-1β and a decrease of tumor necrosis factor-α. IL-10, PCNA, and insulin expression were increased in the LADA situation, whereas caspase 3 gene expression was reduced. The analyses into the underlying pathology in human as well as rat LADA pancreases provided identical results, allowing the conclusion that LADA is a milder form of autoimmune diabetes in patients of an advanced age.




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    Healthy Donaldson could be force for Braves

    When the Braves open Spring Training next week, their bid to defend their National League East crown will be significantly influenced by whether Josh Donaldson is capable of reestablishing himself as one of baseball's elite superstars.