Trial MVA85A - monkey trials for a booster vaccine for BCG, developed by researchers at Oxford University, is the subject of an investigation published on bmj.com. Experts warn that today’s investigation is just one example of “a systematic failure” afflicting preclinical research and call for urgent action “to make animal research more fit for...

Patients who are depressed and prescribed antidepressants may report weight gain, but there has been limited research into the association between the two. However new observational research published on bmj.com aims to identify that association. Rafael Gafoor, a psychiatrist and researcher at Kings College London, and one of the authors of that...

Markus Tiedge
Nov 1, 1997; 46:1733-1742
Original Article

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

During some Reds pitchers fielding practice, or PFP drills, on Friday, Amir Garrett was playing first base. Alex Wood was at shortstop and Brandon Finnegan was flashing some skills all over the infield.

Incretin hormone dysregulation contributes to reduced insulin secretion and hyperglycemia in patients with type 2 diabetes mellitus (T2DM). Resistance to glucose-dependent insulinotropic polypeptide (GIP) action may occur through desensitization or downregulation of β-cell GIP receptors (GIP-R). Studies in rodents and cell lines show GIP-R expression can be regulated through peroxisome proliferator–activated receptor (PPAR) response elements (PPREs). Whether this occurs in humans is unknown. To test this, we conducted a randomized, double-blind, placebo-controlled trial of pioglitazone therapy on GIP-mediated insulin secretion and adipocyte GIP-R expression in subjects with well-controlled T2DM. Insulin sensitivity improved, but the insulinotropic effect of infused GIP was unchanged following 12 weeks of pioglitazone treatment. In parallel, we observed increased GIP-R mRNA expression in subcutaneous abdominal adipocytes from subjects treated with pioglitazone. Treatment of cultured human adipocytes with troglitazone increased PPAR binding to GIP-R PPREs. These results show PPAR agonists regulate GIP-R expression through PPREs in human adipocytes, but suggest this mechanism is not important for regulation of the insulinotropic effect of GIP in subjects with T2DM. Because GIP has antilipolytic and lipogenic effects in adipocytes, the increased GIP-R expression may mediate accretion of fat in patients with T2DM treated with PPAR agonists.

Insulin-mediated microvascular recruitment (IMVR) regulates delivery of insulin and glucose to insulin-sensitive tissues. We have previously proposed that perivascular adipose tissue (PVAT) controls vascular function through outside-to-inside communication and through vessel-to-vessel, or "vasocrine," signaling. However, direct experimental evidence supporting a role of local PVAT in regulating IMVR and insulin sensitivity in vivo is lacking. Here, we studied muscles with and without PVAT in mice using combined contrast-enhanced ultrasonography and intravital microscopy to measure IMVR and gracilis artery diameter at baseline and during the hyperinsulinemic-euglycemic clamp. We show, using microsurgical removal of PVAT from the muscle microcirculation, that local PVAT depots regulate insulin-stimulated muscle perfusion and glucose uptake in vivo. We discovered direct microvascular connections between PVAT and the distal muscle microcirculation, or adipomuscular arterioles, the removal of which abolished IMVR. Local removal of intramuscular PVAT altered protein clusters in the connected muscle, including upregulation of a cluster featuring Hsp90ab1 and Hsp70 and downregulation of a cluster of mitochondrial protein components of complexes III, IV, and V. These data highlight the importance of PVAT in vascular and metabolic physiology and are likely relevant for obesity and diabetes.

Inflammation contributes to ventricular remodeling after myocardial ischemia, but its role in nonischemic heart failure is poorly understood. Local tissue inflammation is difficult to assess serially during pathogenesis. Although ¹⁸F-FDG accumulates in inflammatory leukocytes and thus may identify inflammation in the myocardial microenvironment, it remains unclear whether this imaging technique can isolate diffuse leukocytes in pressure-overload heart failure. We aimed to evaluate whether inflammation with ¹⁸F-FDG can be serially imaged in the early stages of pressure-overload–induced heart failure and to compare the time course with functional impairment assessed by cardiac MRI. Methods: C57Bl6/N mice underwent transverse aortic constriction (TAC) (n = 22), sham surgery (n = 12), or coronary ligation as an inflammation-positive control (n = 5). MRI assessed ventricular geometry and contractile function at 2 and 8 d after TAC. Immunostaining identified the extent of inflammatory leukocyte infiltration early in pressure overload. ¹⁸F-FDG PET scans were acquired at 3 and 7 d after TAC, under ketamine-xylazine anesthesia to suppress cardiomyocyte glucose uptake. Results: Pressure overload evoked rapid left ventricular dilation compared with sham (end-systolic volume, day 2: 40.6 ± 10.2 μL vs. 23.8 ± 1.7 μL, P < 0.001). Contractile function was similarly impaired (ejection fraction, day 2: 40.9% ± 9.7% vs. 59.2% ± 4.4%, P < 0.001). The severity of contractile impairment was proportional to histology-defined myocardial macrophage density on day 8 (r = –0.669, P = 0.010). PET imaging identified significantly higher left ventricular ¹⁸F-FDG accumulation in TAC mice than in sham mice on day 3 (10.5 ± 4.1 percentage injected dose [%ID]/g vs. 3.8 ± 0.9 %ID/g, P < 0.001) and on day 7 (7.8 ± 3.7 %ID/g vs. 3.0 ± 0.8 %ID/g, P = 0.006), though the efficiency of cardiomyocyte suppression was variable among TAC mice. The ¹⁸F-FDG signal correlated with ejection fraction (r = –0.75, P = 0.01) and ventricular volume (r = 0.75, P < 0.01). Western immunoblotting demonstrated a 60% elevation of myocardial glucose transporter 4 expression in the left ventricle at 8 d after TAC, indicating altered glucose metabolism. Conclusion: TAC induces rapid changes in left ventricular geometry and contractile function, with a parallel modest infiltration of inflammatory macrophages. Metabolic remodeling overshadows inflammatory leukocyte signal using ¹⁸F-FDG PET imaging. More selective inflammatory tracers are requisite to identify the diffuse local inflammation in pressure overload.

Faced with a lack of employment opportunities and recurrent poverty, Albanian youth migrate to Italy alone in the hopes of improving their educational prospects or making money for their families. Yet upon arrival, they face many vulnerabilities. While some protections for unaccompanied minors exist in the Italy, the system is greatly fragmented and challenges, including how to return them to Albania, remain persistent.

The Trump administration has been steadily building a case to penalize "sanctuary" cities—those jurisdictions that in some way limit their cooperation with federal immigration authorities—after threatening to cut federal funding. Despite court rulings that seemed to strike a blow against these efforts, the Justice Department is moving forward with its strategy, relying on a broad interpretation of a federal statute, as this article explores.

Ideological differences in the Democratic Party over immigration that were once masked by unity against President Trump’s border wall and immigration agenda are now being exposed as Democratic presidential candidates seek to stand out in a crowded field and amid controversy over an emergency border spending bill. As the 2020 electoral calendar accelerates, how the party navigates the gulf between its most liberal and conservative wings will become a greater challenge for its leaders.

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

Dario Giugliano
Oct 1, 1993; 16:1387-1390
Short Report

Anna Solini
Aug 1, 2016; 39:S234-S243
VI. Cardiovascular Risk and Diabetes

The ADA is partnering with the Organization for Safety, Asepsis and Prevention in providing a free on-demand webinar on Friday, March 20, with content for the program based on questions the ADA has received from members looking for guidance while navigating the novel coronavirus pandemic.

OBJECTIVE

Although blood pressure variability is increasingly appreciated as a risk factor for cardiovascular disease, its relationship with heart failure (HF) is less clear. We examined the relationship between blood pressure variability and risk of HF in two cohorts of type 2 diabetes participating in trials of glucose and/or other risk factor management.

OBJECTIVE

To examine whether low baseline diastolic blood pressure (DBP) modifies the effects of intensive systolic blood pressure (SBP) lowering on cardiovascular outcomes in type 2 diabetes mellitus (T2DM).

OBJECTIVE

Despite evidence of a relationship among obstructive sleep apnea (OSA), metabolic dysregulation, and diabetes, it is uncertain whether OSA treatment can improve metabolic parameters. We sought to determine effects of long-term continuous positive airway pressure (CPAP) treatment on glycemic control and diabetes risk in patients with cardiovascular disease (CVD) and OSA.

Presidential press secretary Kayleigh McEnany said Friday the Trump administration is confident in a major economic recovery after several weeks of closures due to the coronavirus pandemic.

Since its launch in 2015, the Express Entry system has changed how economic immigration to Canada happens and how it fits into public and political debates. And while it has proven successful in cutting through application backlogs, some challenges remain. This report looks at how and why this points-based system was introduced, what its impact has been, and how it could be further finetuned.

The role of motherhood is complex and profound. Psychology and development experts agree — the role of the mother is critical to child development, for better or worse. This role...

Good or bad? Better or worse than Huckabee?

In his starting section, "Path", Macfarlane admits that not all walkers are benign or appealing. While I think he is a little hard on Morris Dancers and people who walk in sandals (p. 23) he does mention that trampers can have more sinister motives than mere enjoyment of nature and movement. He mentions people who walk because they are delusional or racist.

He also discusses two writers who walked to stave off depression -  19th-century walker George Borrow and poet Edward Thomas, who was killed in World War I. Borrow, who rode around on a black Arab stallion when at home, walked over not only England but also France, Spain, Portugal, Russia, and Morocco. He knew twelve languages and was acquainted with another forty. The activity of walking exposed him to new people and allowed him to exercise his mind as he exercised his body.

Edward Thomas and his poetry had the most influence over Macfarlane. The author admits that Thomas is the guiding spirit of his book (p. 24) and his first walk in The Old Ways is one that Thomas took a hundred years earlier. Macfarlane says that while Thomas

"was drawn to the romantic figure of the self-confident solitary walker, he was more interestingly alert to how we are scattered, as well as affirmed, by the places through which we move" (p. 25).

Thomas appears throughout The Old Ways, and Macfarlane gradually tells the story of Thomas's life in the "Ghost" section of the book. Thomas suffered badly from depression and moved frequently in the hopes that his new house would help him battle it; walking was a similar way to stave it off.

Interestingly enough, American poet Robert Frost knew Thomas. The famous Frost poem, "The Road Not Taken", was inspired by a walk that Frost and Thomas took together. When Frost sent Thomas a draft of the poem, Thomas decided that it was a sign that he should enlist in the British army. He was later killed in France in 1917.

honeycomb 40 g (11/2 oz) honey 70 g (21/2 oz) glucose syrup 200 g (7 oz) caster (superfine) sugar 1 teaspoon bicarbonate of soda (baking soda), sifted mousse 200 g (7 oz/11/3 cups) chopped good-quality dark chocolate, such as couverture (see note, page 235) 40 g (11/2 oz) unsalted butter, chopped 4 eggs, separated 150 g (51/2 oz/2/3 heaped cup) sugar espresso sauce 250 ml (9 fl oz/1 cup) espresso coffee 100 g (31/2 oz/1/2 cup) sugar 2 tablespoons kahlua

OBJECTIVE

This study aimed to reveal the associations between the risk of new-onset type 2 diabetes and the duration of antidepressant use and the antidepressant dose, and between antidepressant use after diabetes onset and clinical outcomes.

Paul Ciechanowski
Apr 1, 2011; 29:43-49
Feature Articles

Depression is one of the most common mental health issues in the United States. In fact, according to the National Institutes of Mental Health, 1 in 14 Americans experienced an episode of major depression in the last year alone. Given the circumstances surrounding the current COVID-19 coronavirus pandemic, many in the mental health community predict that the number will be even higher this year because these circumstances are creating a “perfect storm” of depression risks. The widespread prevalence of depression has a lot of implications for our lives, even if we don’t personally have depression ourselves. Many of us will have loved ones, such as a romantic partner, who develops depression at some point. In these situations, it’s common for people to wonder how they can help their partner most effectively. So what should they do?

The federal office of special education programs said the state failed to ensure that students were properly evaluated for special education, as required by the Individuals with Disabilities Education Act.

Parents Unified for Local School Education New Jersey is calling for community-driven schools and opposes the One Newark reorganization plan.

Musée d'Orsay -- Exhibitions.

Self-help techniques.

Depression, Mental -- Etiology.

[S.i.] : [publisher not identified]

Ubiquity Press is an open access publisher of peer-reviewed, academic journals and books. It was founded by researchers at University College London (UCL) in 2012.

This is the delivery platform that provides online access to the full text of individual Edinburgh Univeristy Press journals. The Wellcome Library offers access to selected titles from this publisher.

Delivery platform that provides online access to the full text of individual University of Texas Press journals. The Wellcome Library offers access to selected titles from this publisher.

Paris : Société d’éditions scientifiques, 1895.

London : J. & A. Churchill, 1879.

London : Chemist and Druggist, 1898.

London : John J. Griffin, 1851.

London (No. 4, Hanover Street) : Published ... for the proprietor by T.G. March ; [London] (Threadneedle Street) : Sold also by F. G. Moon ; [London] (Strand) : [Sold also by] Ackermann & Co., April 10, 1842 ([London?] : Printed by R. Lloyd)

Bruxelles (rue de l'Industrie) : Félix Callewaert père, éditeur, 1875.