Lifestyle Therapy for the Treatment of Youth with Type 2 Diabetes

Type 2 diabetes (T2D) in youth is a relatively novel condition facing paediatric health care providers. Few experimental trials exist to guide clinical management in this population. Supporting and prescribing modifiable lifestyle behaviours is cornerstone in the management of T2D in adults. Clinical trials in obese adolescents suggest that intensive lifestyle interventions that include both dietary changes and increased physical activity elicit clinically meaningful reductions in weight and improve cardiovascular risk profiles. Observational studies in youth with T2D suggest that better diet quality and increased physical activity are associated with better metabolic control; however, the limited experimental data available does not support these observations. Trials evaluating lifestyle monotherapy for the treatment of hyperglycaemia in youth with T2D do not exist, and the only study evaluating combined lifestyle and pharmacologic therapy did not show additional benefit over pharmacologic treatment with metformin alone. Physiological and psychosocial differences between youth and adults with T2D likely contribute to the differences in the effectiveness of lifestyle therapy for improving glycaemic control. The current review describes these topics in detail and provides recommendations for paediatric health care providers for the promotion of lifestyle therapy for the management of hyperglycaemia and cardiovascular risk factors for youth with T2DM.     

Synthesis and evaluation of (18)F labeled alanine derivatives as potential tumor imaging agents

IntroductionThis paper reports the synthesis and labeling of ¹⁸F alanine derivatives. We also investigate their biological characteristics as potential tumor imaging agents mediated by alanine–serine–cysteine preferring (ASC) transporter system.MethodsThree new ¹⁸F alanine derivatives were prepared from corresponding tosylate-precursors through a two-step labeling reaction. In vitro uptake studies to evaluate and to compare these three analogs were carried out in 9L glioma and PC-3 prostate cancer cell lines. Potential transport mechanisms, protein incorporation and stability of 3-(1-[¹⁸F]fluoromethyl)-L-alanine (L-[¹⁸F]FMA) were investigated in 9L glioma cells. Its biodistribution was determined in a rat-bearing 9L tumor model. PET imaging studies were performed on rat bearing 9L glioma tumors and transgenic mouse carrying spontaneous generated M/tomND tumor (mammary gland adenocarcinoma).ResultsNew ¹⁸F alanine derivatives were prepared with 7%–34% uncorrected radiochemical yields, excellent enantiomeric purity (> 99%) and good radiochemical purity (> 99%). In vitro uptake of the L-[¹⁸F]FMA in 9L glioma and PC-3 prostate cancer cells was higher than that observed for the other two alanine derivatives and [¹⁸F]FDG in the first 1 h. Inhibition of cell uptake studies suggested that L-[¹⁸F]FMA uptake in 9L glioma was predominantly via transport system ASC. After entering into cells, L-[¹⁸F]FMA remained stable and was not incorporated into protein within 2 h. In vivo biodistribution studies demonstrated that L-[¹⁸F]FMA had relatively high uptake in liver and kidney. Tumor uptake was fast, reaching a maximum within 30 min. The tumor-to-muscle, tumor-to-blood and tumor-to-brain ratios at 60 min post injection were 2.2, 1.9 and 3.0, respectively. In PET imaging studies, tumors were visualized with L-[¹⁸F]FMA in both 9L rat and transgenic mouse.ConclusionL-[¹⁸F]FMA showed promising properties as a PET imaging agent for up-regulated ASC transporter associated with tumor proliferation.     

Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence-informed consensus workshop

Background

Injuries represent a significant and growing public health concern in China. This Review was conducted to document the characteristics of injured patients presenting to the emergency department of Chinese hospitals and to assess of the nature of information collected and reported in published surveillance studies.

Methods

A systematic search of MEDLINE and China Academic Journals supplemented with a hand search of journals was performed. Studies published in the period 1997 to 2007 were included and research published in Chinese was the focus. Search terms included emergency, injury, medical care.

Results

Of the 268 studies identified, 13 were injury surveillance studies set in the emergency department. Nine were collaborative studies of which eight were prospective studies. Of the five single centre studies only one was of a prospective design. Transport, falls and industrial injuries were common mechanisms of injury. Study strengths were large patient sample sizes and for the collaborative studies a large number of participating hospitals. There was however limited use of internationally recognised injury classification and severity coding indices.

Conclusion

Despite the limited number of studies identified, the scope of each highlights the willingness and the capacity to conduct surveillance studies in the emergency department. This Review highlights the need for the adoption of standardized injury coding indices in the collection and reporting of patient health data. While high level injury surveillance systems focus on population-based priority setting, this Review demonstrates the need to establish an internationally comparable trauma registry that would permit monitoring of the trauma system and would by extension facilitate the optimal care of the injured patient through the development of informed quality assurance programs and the implementation of evidence-based health policy.     

Systemic inflammatory response following acute myocardial infarction

Acute cardiomyocyte necrosis in the infarcted heart generates damage-associated molecular patterns, activating complement and toll-like receptor/interleukin-1 signaling, and triggering an intense inflammatory response. Inflammasomes also recognize danger signals and mediate sterile inflammatory response following acute myocardial infarction (AMI). Inflammatory response serves to repair the heart, but excessive inflammation leads to adverse left ventricular remodeling and heart failure. In addition to local inflammation, profound systemic inflammation response has been documented in patients with AMI, which includes elevation of circulating inflammatory cytokines, chemokines and cell adhesion molecules, and activation of peripheral leukocytes and platelets. The excessive inflammatory response could be caused by a deregulated immune system. AMI is also associated with bone marrow activation and spleen monocytopoiesis, which sustains a continuous supply of monocytes at the site of inflammation. Accumulating evidence has shown that systemic inflammation aggravates atherosclerosis and markers for systemic inflammation are predictors of adverse clinical outcomes (such as death, recurrent myocardial infarction, and heart failure) in patients with AMI.