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Central {alpha}-Klotho Suppresses NPY/AgRP Neuron Activity and Regulates Metabolism in Mice

α-Klotho is a circulating factor with well-documented anti-aging properties; however, the central role of α-klotho in metabolism remains largely unexplored. The current study investigated the potential role of central α-klotho to modulate NPY/AgRP neurons, energy balance, and glucose homeostasis. Intracerebroventricular (ICV) administration of α-klotho suppressed food intake, improved glucose profiles, and reduced body weight in mouse models of Type I and II diabetes. Furthermore, central α-klotho inhibition via an anti-α-klotho antibody impaired glucose tolerance. Ex vivo patch clamp electrophysiology and immunohistochemical analysis revealed that α-klotho suppresses NPY/AgRP neuron activity, at least in part, by enhancing mIPSC’s. Experiments in hypothalamic GT1-7 cells observed α-klotho induces phosphorylation of AKTser473, ERKthr202/tyr204, and FOXO1ser256, as well as blunts AgRP gene transcription. Mechanistically, fibroblast growth factor 1 (FGFR1) inhibition abolished the downstream signaling of α-klotho, negated its ability to modulate NPY/AgRP neurons, and blunted its therapeutic effects. PI3 kinase inhibition also abolished α-klotho’s ability to suppress food intake and improve glucose clearance. These results indicate a prominent role of hypothalamic α-klotho/FGFR1/PI3K signaling in the modulation of NPY/AgRP neuron activity and maintenance of energy homeostasis, thus providing new insight into the pathophysiology of metabolic disease.




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Acute Hyperglycemia Increases Brain Pregenual Anterior Cingulate Cortex Glutamate Concentrations in Type 1 Diabetes Mellitus

The brain mechanisms underlying the association of hyperglycemia with depressive symptoms are unknown. We hypothesized that disrupted glutamate metabolism in pregenual anterior cingulate cortex (ACC) in type 1 diabetes (T1D) without depression affects emotional processing. Using proton magnetic resonance spectroscopy (MRS), we measured glutamate concentrations in ACC and occipital cortex (OCC) in 13 T1D without major depression (HbA1c=7.1±0.7% [54±7mmol/mol]) and 11 healthy non-diabetic controls (HbA1c=5.5±0.2% [37±3mmol/mol]) during fasting euglycemia (EU) followed by a 60-minute +5.5mmol/l hyperglycemic clamp (HG). Intrinsic neuronal activity was assessed using resting-state blood oxygen level dependent functional MRI to measure the fractional amplitude of low frequency fluctuations in slow-band 4 (fALFF4). Emotional processing and depressive symptoms were assessed using emotional tasks (Emotional-Stroop, Self-Referent-Encoding-Task SRET) and clinical ratings (HAM-D, SCL-90-R), respectively. During HG, ACC glutamate increased (1.2mmol/kg, +10%, p=0.014) while ACC fALFF4 was unchanged (-0.007, -2%, p=0.449) in T1D; in contrast, glutamate was unchanged (-0.2mmol/kg, -2%, p=0.578) while fALFF4 decreased (-0.05, -13%, p=0.002) in controls. OCC glutamate and fALFF4 were unchanged in both groups. T1D had longer SRET negative-word response-times (p=0.017) and higher depression-rating scores (HAM-D p=0.020; SCL-90-R-depression p=0.008). Higher glutamate change tended to associate with longer Emotional-Stroop response-times in T1D only. Brain glutamate must be tightly controlled during hyperglycemia due to the risk for neurotoxicity with excessive levels. Results suggest that ACC glutamate control mechanisms are disrupted in T1D, which affects glutamatergic neurotransmission related to emotional or cognitive processing. Increased prefrontal glutamate during acute hyperglycemic episodes could explain our previous findings of associations between chronic hyperglycemia, cortical thinning and depressive symptoms in T1D.




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Central KATP Channels Modulate Glucose Effectiveness in Humans and Rodents

Hyperglycemia is a potent regulator of endogenous glucose production (EGP). Loss of this ‘glucose effectiveness’ is a major contributor to elevated plasma glucose concentrations in type 2 diabetes (T2D). ATP-sensitive potassium channels (KATP channels) in the central nervous system (CNS) have been shown to regulate EGP in humans and rodents. We examined the contribution of central KATP channels to glucose effectiveness. Under fixed hormonal conditions (‘pancreatic clamp’ studies), hyperglycemia suppressed EGP by ~50% in both non-diabetic humans and normal Sprague Dawley rats. By contrast, antagonism of KATP channels with glyburide significantly reduced the EGP-lowering effect of hyperglycemia in both humans and rats. Furthermore, the effects of glyburide on EGP and gluconeogenic enzymes in rats were abolished by intracerebroventricular (ICV) administration of the KATP channel agonist diazoxide. These findings indicate that about half of EGP suppression by hyperglycemia is mediated by central KATP channels. These central mechanisms may offer a novel therapeutic target for improving glycemic control in T2D.




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The Metabolic Responses to 24-h Fasting and Mild Cold Exposure in Overweight Individuals are Correlated and Accompanied by Changes in FGF21 Concentration

A greater decrease in 24-h energy expenditure (24EE) during 24h fasting defines a thriftier metabolic phenotype prone to weight gain during overfeeding and resistant to weight loss during caloric restriction. As the thermogenic response to mild cold exposure (COLD) may similarly characterize this human phenotype identified by acute fasting conditions, we analyzed changes in 24EE and sleeping metabolic rate (SLEEP) in a whole-room indirect calorimeter during 24h fasting at thermoneutrality (24°C) and during energy balance both at thermoneutrality (24°C) and mild cold (19°C) in 20 healthy volunteers (80% male, age: 36.6±11.4y, percentage body fat: 34.8±10.5%). Greater decrease in 24EE during fasting (thriftier phenotype) was associated with less increase in 24EE during COLD, i.e. less cold-induced thermogenesis. Greater decreases in plasma fibroblast growth factor 21 (FGF21) after 24h fasting and after COLD were highly correlated and associated with greater decreases in SLEEP in both conditions. We conclude that the metabolic responses to short-term fasting and COLD are associated and mediated by the liver-derived hormone FGF21. Thus, the 24EE response to COLD further identifies the thrifty versus spendthrift phenotype, providing an additional setting to investigate the physiological mechanisms underlying the human metabolic phenotype and characterizing the individual susceptibility to weight change.




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Effect of a Sustained Reduction in Plasma Free Fatty Acid Concentration on Intramuscular Long-Chain Fatty Acyl-CoAs and Insulin Action in Type 2 Diabetic Patients

Mandeep Bajaj
Nov 1, 2005; 54:3148-3153
Metabolism




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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 Rise of Childhood Type 1 Diabetes in the 20th Century

Edwin A.M. Gale
Dec 1, 2002; 51:3353-3361
Perspectives in Diabetes




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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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Kazakhstan: Reaching Out to Central Asian Neighbours

4 December 2019

Annette Bohr

Associate Fellow, Russia and Eurasia Programme
Despite its regional outreach, Kazakhstan’s diplomatic priority will remain Russia, China, and Europe.

2019-12-04-Kaz.jpg

Kazakhstan's President Kassym-Jomart Tokayev, Kazakh Majilis Chairman Nurlan Nigmatulin and ex-president Nursultan Nazarbayev at an inauguration ceremony in parliament. Photo: Pavel AleksandrovTASS via Getty Images.

Leaders of the resource-rich Central Asian region have the propensity to remain in power until mortality dictates otherwise. Much like the UK and Brexit, however, few wanted to see Central Asia’s longest reigning ruler, Kazakhstan’s septuagenarian president Nursultan Nazarbayev, crash out without a deal.

The sudden departure of the country’s official leader of the nation with no clear succession plan could have led to investment chaos, intra-elite fighting and the unravelling in a matter of months of a system he had built over decades, à la Uzbekistan following the death of long-serving autocrat Islam Karimov in 2016.

In order to avoid just such a ‘no-deal’ scenario and ensure the continuity of his policies, in March Nazarbayev carefully choreographed his own resignation and the election of a hand-picked successor, President Kassym-Jomart Tokayev, while retaining plum positions and powers for himself.

Tokayev’s assumption of the presidency was accompanied by protesters in the streets, increasing wealth inequality, rising Sinophobia among rank-and-file Kazakhstanis, a hard-to-kick economic dependence on oil revenues and a lack of clarity as to which leader—the old or the new president—would actually be calling the shots. But, amidst this plethora of concerns, as argued in a recent Chatham House report, Kazakhstan: Tested by Transition, one bright spot has been the tangible growth of intra-Central Asian cooperation, with the Nazarbayev-Tokayev ruling duo appearing eager to improve the regional dialogue.

Kazakhstan has long shaped its identity as a Eurasian state that has acted as more of an intermediary between Russia and Central Asia than as an integral part of the Central Asian region. But since 2017, in particular, Kazakhstan has been increasingly looking for opportunities to boost hitherto weak cooperation with its Central Asian neighbours. While this is first and foremost owing to the liberalization of Uzbekistan’s large market, there are other factors at work that get less airplay.

One such factor is a perceptible disentangling from the Kremlin’s policy directions as Kazakhstan has come to view Russia’s foreign policy as increasingly neo-colonial. The example of the Russia-led Eurasian Economic Union is in many respects more off-putting than inspiring, and Nur-Sultan does not want to be locked tightly into the union’s economic orbit. And in distancing itself slightly from Moscow in order to limit Russian leverage in its affairs, Nur-Sultan has shown itself to be more open to Central Asian regional initiatives.

As part of the leadership’s plan to offset oil dependence, Kazakhstan aspires to become the transport, telecommunications and investment hub for Eurasian integration. The intense focus on connectivity and the development of logistical arteries and infrastructure could have the knock-on effect of boosting trade within the Central Asian region and reducing transit times, which are currently greater than in most other parts of the globe.

In addition, demographic trends and educational shifts that favour ethnic Kazakhs, together with a growing ethno-nationalist narrative, have allowed the state’s leadership to identify more closely with Kazakhstan’s common Central Asian heritage and, by extension, a common Central Asian region—although Kazakhstan’s leadership still remains eager to demonstrate that the country is not just another ‘stan’. The coming to power of President Mirziyoyev in Uzbekistan appears to have made Kazakhstan more aware of the interconnectedness of the two countries in terms of geographical location and potential economic complementarities, as well as culture and history.

Not least, there is a growing recognition among the Central Asian states themselves—including isolationist Turkmenistan to a degree—that deepening regional trade is mutually beneficial, especially given the constraints associated with Russia’s economic problems. The strengthening of Kazakhstan’s ties with Uzbekistan has slowly kick-started regional cooperation as a whole: trade turnover between the Central Asian states in 2018 grew by 35 per cent on the previous year.

But both Kazakhstan and Uzbekistan are keen to stress that there is no discussion of integration or institutionalization, not least because previous attempts at integration have been overtaken by Russia, leaving Central Asia without its own coordinating body.

The official consensus in Kazakhstan is that Uzbekistan’s economic reforms after years of isolation will spur ‘a healthy rivalry’ and ultimately boost Kazakhstan’s own economy, in so far as the competition for foreign investment will require both countries to work harder to improve their respective business and regulatory environments.

At the unofficial level, however, some Kazakhstani analysts view Uzbekistan’s rise as potentially unprofitable, given the possible diversion of some investments and market activity from Kazakhstan to Uzbekistan. Moreover, Uzbekistan has the advantage of having undergone a clear change of executive, while it remains unclear which developments await Kazakhstan once First President Nazarbayev leaves the scene for good.

It can certainly be argued that Uzbekistan does pose a potential threat in the long-term to Kazakhstan’s entrenched position as Central Asia’s economic powerhouse: Uzbekistan’s population is one-and-a-half times bigger, even if its nominal GDP is three times smaller. Uzbekistan has a bigger market and a well-developed industrial sector, and is already the regional leader in terms of security. But it is not as though the world’s interest is moving from Kazakhstan to Uzbekistan; rather, Uzbekistan is in the process of trying to catch up.

Despite this relatively upbeat picture, Kazakhstan’s combined trade with the other Central Asian states accounts for less than 5 per cent of its total volume of foreign trade—a figure that cannot begin to equal its trade with Russia, China, and Europe. As a result, Kazakhstan will continue to give greater importance to positioning itself as a global player than as a regional leader.

This article was originally published in The Diplomat.




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Analysing the Recent Changes in Russia

Invitation Only Research Event

17 February 2020 - 10:30am to 12:00pm

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

Event participants

Leonid Gozman, President, Perspective Foundation

The scale of the changes in Russia’s political system is yet to be fully understood, as new suggestions for revising the constitution appear almost daily. This event will discuss the risks of President Putin’s 15 January announcement, and what strategies Russia’s non-systemic opposition might now deploy in response.

Event attributes

Chatham House Rule

Anna Morgan

Administrator, Ukraine Forum
+44 (0)20 7389 3274




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Venerable but vulnerable: Centenarians hit hard by virus

BOSTON (AP) — Centenarians have always been a rare breed. Now they’re an endangered species. The 100-plus crowd — those most venerable of human beings — is succumbing rapidly and heartbreakingly to the coronavirus...




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Patient spotlight - How can we get better at providing patient centred care?

Participants in our discussion on person centred care in January agreed that a change in culture and better use of technology could benefit both patients and doctors. At the roundtable: Fiona Godlee (chair), editor in chief, The BMJ Tessa Richards, senior editor, patient partnership, The BMJ Rosamund Snow, patient editor, The BMJ Navjoyt Ladher,...




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Should doctors boycott working in Australia’s immigration detention centres?

However well intentioned, working in detention centres amounts to complicity in torture, says David Berger, a district medical officer in emergency medicine at Broome Hospital in Australia. However, Steven Miles, chair in bioethics at the University of Minnesota thinks that they play an important role in telling the world about conditions in...




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PPAR{gamma} Ligands Increase Expression and Plasma Concentrations of Adiponectin, an Adipose-Derived Protein

Norikazu Maeda
Sep 1, 2001; 50:2094-2099
Pathophysiology




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Interplay of Placental DNA Methylation and Maternal Insulin Sensitivity in Pregnancy

The placenta participates in maternal insulin sensitivity changes during pregnancy; however, mechanisms remain unclear. We investigated associations between maternal insulin sensitivity and placental DNA methylation markers across the genome. We analyzed data from 430 mother-offspring dyads in the Gen3G cohort. All women underwent 75-g oral glucose tolerance tests at ~26 weeks of gestation; we used glucose and insulin measures to estimate insulin sensitivity (Matsuda index). At delivery, we collected samples from placenta (fetal side) and measured DNA methylation using Illumina EPIC arrays. Using linear regression models to quantify associations at 720,077 cytosine-guanine dinucleotides (CpGs), with adjustment for maternal age, gravidity, smoking, BMI, child sex, and gestational age at delivery, we identified 188 CpG sites where placental DNA methylation was associated with Matsuda index (P < 6.94 x 10–8). Among genes annotated to these 188 CpGs, we found enrichment in targets for miRNAs, in histone modifications, and in parent-of-origin DNA methylation including the H19/MIR675 locus (paternally imprinted). We identified 12 known placenta imprinted genes, including KCNQ1. Mendelian randomization analyses revealed five loci where placenta DNA methylation may causally influence maternal insulin sensitivity, including the maternally imprinted gene DLGAP2. Our results suggest that placental DNA methylation is fundamentally linked to the regulation of maternal insulin sensitivity in pregnancy.




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Downswell reaches out to Central Village - Carry Me singer delivers care packages to community

The wet weather last Saturday (May 2) could not dampen the spirits of award-winning gospel artiste and ordained evangelist Kevin Downswell as he ventured into the St Catherine community of Central Village, where he spent some of his formative years...




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St Vincent denies US-based airline from landing with stranded nationals

KINGSTOWN, St Vincent, CMC – The St Vincent and the Grenadines Government has denied a United States-based airline permission to land, dashing hopes that an estimated 300 nationals employed with a US-based cruise line would have arrived home...




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Vincentian students in Jamaica told to pay over US$1,000 to return home

KINGSTOWN, St Vincent, CMC – St Vincent and the Grenadines students in Jamaica wanting to return home amid the coronavirus (COVID-19, including locked borders, must each pay an estimated US$1,3339 for a return flight. In a letter to the...




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20 questions that will define the NL Central

It was only five years ago that the Cardinals won the National League Central with only 90 wins. Heck, it was only 12 years ago that the Cubs won it with 85, and 13 that the Cardinals won it with 83. Point is: There have been times in recent baseball history that the NL Central was not exactly the toughest gauntlet in the sport. But in 2019, it looks like the scariest division in baseball.




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Prospective Evaluation of 18F-DCFPyL PET/CT in Biochemically Recurrent Prostate Cancer in an Academic Center: A Focus on Disease Localization and Changes in Management

18F-DCFPyL (2-(3-{1-carboxy-5-[(6-18F-fluoropyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) is a promising PET radiopharmaceutical targeting prostate-specific membrane antigen (PSMA). We present our experience with this single-academic-center prospective study evaluating the positivity rate of 18F-DCFPyL PET/CT in patients with biochemical recurrence (BCR) of prostate cancer (PC). Methods: We prospectively enrolled 72 men (52–91 y old; mean ± SD, 71.5 ± 7.2) with BCR after primary definitive treatment with prostatectomy (n = 42) or radiotherapy (n = 30). The presence of lesions compatible with PC was evaluated by 2 independent readers. Fifty-nine patients had scans concurrent with at least one other conventional scan: bone scanning (24), CT (21), MR (20), 18F-fluciclovine PET/CT (18), or 18F-NaF PET (14). Findings from 18F-DCFPyL PET/CT were compared with those from other modalities. Impact on patient management based on 18F-DCFPyL PET/CT was recorded from clinical chart review. Results: 18F-DCFPyL PET/CT had an overall positivity rate of 85%, which increased with higher prostate-specific antigen (PSA) levels (ng/mL): 50% (PSA < 0.5), 69% (0.5 ≤ PSA < 1), 100% (1 ≤ PSA < 2), 91% (2 ≤ PSA < 5), and 96% (PSA ≥ 5). 18F-DCFPyL PET detected more lesions than conventional imaging. For anatomic imaging, 20 of 41 (49%) CT or MRI scans had findings congruent with 18F-DCFPyL, whereas 18F-DCFPyL PET was positive in 17 of 41 (41%) cases with negative CT or MRI findings. For bone imaging, 26 of 38 (68%) bone or 18F-NaF PET scans were congruent with 18F-DCFPyL PET, whereas 18F-DCFPyL PET localized bone lesions in 8 of 38 (21%) patients with negative results on bone or 18F-NaF PET scans. In 8 of 18 (44%) patients, 18F-fluciclovine PET had located the same lesions as did 18F-DCFPyL PET, whereas 5 of 18 (28%) patients with negative 18F-fluciclovine findings had positive 18F-DCFPyL PET findings and 1 of 18 (6%) patients with negative 18F-DCFPyL findings had uptake in the prostate bed on 18F-fluciclovine PET. In the remaining 4 of 18 (22%) patients, 18F-DCFPyL and 18F-fluciclovine scans showed different lesions. Lastly, 43 of 72 (60%) patients had treatment changes after 18F-DCFPyL PET and, most noticeably, 17 of these patients (24% total) had lesion localization only on 18F-DCFPyL PET, despite negative results on conventional imaging. Conclusion: 18F-DCFPyL PET/CT is a promising diagnostic tool in the work-up of biochemically recurrent PC, given the high positivity rate as compared with Food and Drug Administration–approved currently available imaging modalities and its impact on clinical management in 60% of patients.




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18F-FET PET Imaging in Differentiating Glioma Progression from Treatment-Related Changes: A Single-Center Experience

In glioma patients, differentiation between tumor progression (TP) and treatment-related changes (TRCs) remains challenging. Difficulties in classifying imaging alterations may result in a delay or an unnecessary discontinuation of treatment. PET using O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) has been shown to be a useful tool for detecting TP and TRCs. Methods: We retrospectively evaluated 127 consecutive patients with World Health Organization grade II–IV glioma who underwent 18F-FET PET imaging to distinguish between TP and TRCs. 18F-FET PET findings were verified by neuropathology (40 patients) or clinicoradiologic follow-up (87 patients). Maximum tumor-to-brain ratios (TBRmax) of 18F-FET uptake and the slope of the time–activity curves (20–50 min after injection) were determined. The diagnostic accuracy of 18F-FET PET parameters was evaluated by receiver-operating-characteristic analysis and 2 testing. The prognostic value of 18F-FET PET was estimated using the Kaplan–Meier method. Results: TP was diagnosed in 94 patients (74%) and TRCs in 33 (26%). For differentiating TP from TRCs, receiver-operating-characteristic analysis yielded an optimal 18F-FET TBRmax cutoff of 1.95 (sensitivity, 70%; specificity, 71%; accuracy, 70%; area under the curve, 0.75 ± 0.05). The highest accuracy was achieved by a combination of TBRmax and slope (sensitivity, 86%; specificity, 67%; accuracy, 81%). However, accuracy was poorer when tumors harbored isocitrate dehydrogenase (IDH) mutations (91% in IDH-wild-type tumors, 67% in IDH-mutant tumors, P < 0.001). 18F-FET PET results correlated with overall survival (P < 0.001). Conclusion: In our neurooncology department, the diagnostic performance of 18F-FET PET was convincing but slightly inferior to that of previous reports.




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Manual acupuncture versus sham acupuncture and usual care for prophylaxis of episodic migraine without aura: multicentre, randomised clinical trial




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Infectious diseases in children and adolescents in China: analysis of national surveillance data from 2008 to 2017




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Association between maternal and paternal mental illness and risk of injuries in children and adolescents: nationwide register based cohort study in Sweden




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Lack of evidence for interventions offered in UK fertility centres




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Generics have a chequered recent history




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Trends in Unaccompanied Child and Family Migration from Central America

This fact sheet uses U.S. and Mexican apprehensions data to trace the evolving trends in unaccompanied child and family migration from Central America through Mexico and to the United States, and discusses the push factors and pull factors responsible for the increase in flows seen in recent years, as well as the growing role of smuggling organizations.




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Central American Development: Two Decades of Progress and Challenges for the Future

This report summarizes the economic and social development policy achievements of Central American countries over the past 20 years, as well as the notable obstacles to development that remain. The author identifies long-term challenges and outlines how they can be incorporated into a new development agenda.




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Children on the Run: An Analysis of First-Hand Accounts from Children Fleeing Central America

This event with UN High Commissioner for Refugees António Guterres includes a discussion on the state of citizen security in Central America and the resulting humanitarian impact, featuring findings from Children on the Run, a UNHCR report based on interviews with more than 400 unaccompanied children from the region.




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Building Skills in North and Central America: Barriers and Policy Options toward Harmonizing Qualifications in Nursing

Amid aging populations and the growth of chronic diseases, the demand for skilled health-care professionals is on the rise in the United States, Canada, and Mexico. This report explores the policy implications, benefits, and challenges of harmonizing nursing qualifications in the region, suggesting that a more collaborative approach could result in greater supply and quality of nurses.




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Reception and Reintegration Services in Central America: Ending the Deportee Revolving Door

A webinar releasing a report examining deportations to Central America and reception and reintegration services in El Salvador, Guatemala, and Honduras.




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Stopping the Revolving Door: Reception and Reintegration Services for Central American Deportees

For a growing population of migrants deported from Mexico and the United States to Central America, the conditions upon return typically are worse than when they left, setting up a revolving-door cycle of migration, deportation, and remigration. This report provides a detailed profile of reception and reintegration services offered in El Salvador, Guatemala, and Honduras to deported migrants, examining their challenges and opportunities for improvement. 




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Reception and Reintegration Services in Central America: Ending the Deportee Revolving Door

A webinar releasing a report examining deportations to Central America and reception and reintegration services in El Salvador, Guatemala, and Honduras.




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Inmigrantes Centroamericanos en los Estados Unidos

La migración centroamericana a los Estados Unidos comenzó en gran números en los años ochenta, impulsada por la inestabilidad política, los desastres naturales y las dificultades económicas. Aproximadamente 3,4 millones de centroamericanos vivieron en los Estados Unidos en 2015, principalmente de El Salvador, Guatemala y Honduras. Dónde viven en los Estados Unidos, su competencia en inglés, su estado legal, las vías de inmigración, y más, están cubiertos en este artículo.




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Temporary Protected Status at Risk: Implications for Central America and U.S. Policy

As the Trump administration weighs the future of Temporary Protected Status (TPS) for Salvadorans, this teleconference focuses on the legal framework for TPS (particularly for Hondurans and Salvadorans) and profile of current TPS holders; the capacity of El Salvador and Honduras to receive and meaningfully reintegrate returnees; and the implications of TPS termination for broader U.S. policy goals in Central America.




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Promising Strategies for Reintegration of Migrants Returning to Mexico and Central America

Authors of a year-long study of reception and reintegration services in Mexico and the Northern Triangle discuss the findings of their fieldwork, including the differing reintegration needs of individual migrant groups, promising reception and reintegration programs, ongoing challenges for origin communities, and policy recommendations to improve reintegration strategies. 




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As Lesvos Battles Migration Crisis Fatigue, the Value of Centralized Migration Decision-Making Is Questioned

As Greece's Aegean islands continue to grapple with migrants arriving on their shores, decisions regarding the needs of newcomers are negotiated in Brussels and Athens, far removed from the situation on the ground. Meanwhile, local communities have had successes in hosting migrants, as this article drawing on observations from the hospitality center and refugee camp on Lesvos explores.




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Excess BMI Accelerates Islet Autoimmunity in Older Children and Adolescents

OBJECTIVE

Sustained excess BMI increases the risk of type 1 diabetes (T1D) in autoantibody-positive relatives without diabetes of patients. We tested whether elevated BMI also accelerates the progression of islet autoimmunity before T1D diagnosis.

RESEARCH DESIGN AND METHODS

We studied 706 single autoantibody–positive pediatric TrialNet participants (ages 1.6–18.6 years at baseline). Cumulative excess BMI (ceBMI) was calculated for each participant based on longitudinally accumulated BMI ≥85th age- and sex-adjusted percentile. Recursive partitioning analysis and multivariable modeling defined the age cut point differentiating the risk for progression to multiple positive autoantibodies.

RESULTS

At baseline, 175 children (25%) had a BMI ≥85th percentile. ceBMI range was –9.2 to 15.6 kg/m2 (median –1.91), with ceBMI ≥0 kg/m2 corresponding to persistently elevated BMI ≥85th percentile. Younger age increased the progression to multiple autoantibodies, with age cutoff of 9 years defined by recursive partitioning analysis. Although ceBMI was not significantly associated with progression from single to multiple autoantibodies overall, there was an interaction with ceBMI ≥0 kg/m2, age, and HLA (P = 0.009). Among children ≥9 years old without HLA DR3-DQ2 and DR4-DQ8, ceBMI ≥0 kg/m2 increased the rate of progression from single to multiple positive autoantibodies (hazard ratio 7.32, P = 0.004) and conferred a risk similar to that in those with T1D-associated HLA haplotypes. In participants <9 years old, the effect of ceBMI on progression to multiple autoantibodies was not significant regardless of HLA type.

CONCLUSIONS

These data support that elevated BMI may exacerbate islet autoimmunity prior to clinical T1D, particularly in children with lower risk based on age and HLA. Interventions to maintain normal BMI may prevent or delay the progression of islet autoimmunity.




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Day and Night Home Closed-Loop Insulin Delivery in Adults With Type 1 Diabetes: Three-Center Randomized Crossover Study

Lalantha Leelarathna
Jul 1, 2014; 37:1931-1937
Emerging Technologies and Therapeutics




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Serum 25-Hydroxyvitamin D3 Concentrations and Prevalence of Cardiovascular Disease Among Type 2 Diabetic Patients

Massimo Cigolini
Mar 1, 2006; 29:722-724
BR Cardiovascular and Metabolic Risk




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Depressive Symptoms in Children and Adolescents With Type 1 Diabetes: Association with diabetes-specific characteristics

Korey K. Hood
Jun 1, 2006; 29:1389-1389
BR Epidemiology/Health Services/Psychosocial Research




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Relationship Between {beta}-Cell Mass and Fasting Blood Glucose Concentration in Humans

Robert A. Ritzel
Mar 1, 2006; 29:717-718
BR Pathophysiology/Complications




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Update on Prevention of Cardiovascular Disease in Adults With Type 2 Diabetes Mellitus in Light of Recent Evidence: A Scientific Statement From the American Heart Association and the American Diabetes Association

Caroline S. Fox
Sep 1, 2015; 38:1777-1803
Scientific Statement




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Concentrations of Serum Vitamin D and the Metabolic Syndrome Among U.S. Adults

Earl S. Ford
May 1, 2005; 28:1228-1230
BR Metabolic Syndrome/Insulin Resistance Syndrome/Pre-Diabetes




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Coronary Heart Disease Incidence and Cardiovascular Mortality in Busselton with Reference to Glucose and Insulin Concentrations

T A Welborn
Mar 1, 1979; 2:154-160
Proceedings of the Kroc Foundation International Conference on Epidemiology of Diabetes and its Macrovascular Complications




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Impact of Recent Increase in Incidence on Future Diabetes Burden: U.S., 2005-2050

K.M. Venkat Narayan
Sep 1, 2006; 29:2114-2116
BR Epidemiology/Health Services/Psychosocial Research




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Bank of England: British economy could decline 14 percent

A Bank of England report said Thursday the British economy could fall as much as 14 percent this year, which would be its worst showing in more than 300 years.




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Table 1--Systeme International (SI) units for plasma, serum, or blood concentrations


Apr 1, 1994; 17:360-361
Syst[egrave]me International (SI) Units




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Table 1--Systeme International (SI) units for plasma, serum, or blood concentrations


Nov 1, 1995; 18:1524-1525
Syst[egrave]me International (SI) Units




cent

Effects of Coffee Consumption on Fasting Blood Glucose and Insulin Concentrations: Randomized controlled trials in healthy volunteers

Rob M. van Dam
Dec 1, 2004; 27:2990-2992
Brief Reports