Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. Methods: The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Gr...

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2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer.

XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the publication of the American Thyroid Association's guidelines for the management of these disorders was published in 2006, a large amount of new information has become available, prompting a revision of the guidelines. Methods: Relevant articles through December 2008 were reviewed by the task force and categorized by topic and level of evidence according to a modified schema used by the United States Preventative Services Task Force. Results: The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to optimal surgical management, radioiodine remnant ablation, a...

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Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer

Prospective Cohort Study

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes.

For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy.

Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

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Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Background Mesenchymal stem cells (MSCs), also known as multipotent progenitor cells, release several factors that support cell survival and enhance wound healing. We hypothesized that MSC-secreted molecules would induce a trophic effect in pancreatic islet culture conditions. Methods Pancreatic islets were co-cultured with MSCs, and ADP/ATP ratios, glucose stimulated insulin secretion (GSIS), and DNA fragmentation were evaluated to measure islet quality and viability in vitro. The induction of signal molecules related to the control of survival, function, and angiogenesis was also analyzed. Cell quality assays, DNA fragmentation assays, and islet transplantation into streptozotocin-induced diabetic mice were performed using MSC-conditioned medium (CM)-cultured islets. Furthermore, we identified soluble molecules within MSC-CM. Results Islets co-cultured with MSCs demonstrated lower ADP/ATP ratios, and higher GSIS indexes and viability. Furthermore, co-cultured islets revealed higher levels of anti-apoptotic signal molecules (X-linked inhibitor of apoptosis protein, Bcl-xL, Bcl-2, and heat shock protein-32) and demonstrated increased vascular endothelial growth factor receptor 2 and Tie-2 mRNA expression and increased levels of phosphorylated Tie-2 and focal adhesion kinase protein. Islets cultured in MSC-CM demonstrated lower ADP/ATP ratios, less apoptosis, and a higher GSIS indexes. Diabetic mice that received islet transplants (200 islet equivalent) cultured in MSC-CM for 48 hr demonstrated significantly lower blood glucose levels and enhanced blood vessel formation. In addition, interleukin-6, interleukin-8, vascular endothelial growth factor-A, hepatocyte growth factor, and transforming growth factor-beta were detected at significant levels in MSC-CM. Conclusions These results suggest that the trophic factors secreted by human MSCs enhance islet survival and function after transplantation.

Factors affecting graft and patient survival after live donor kidney transplantation in the UK.

Troglitazone is a new orally active hypoglycemic agent that has been shown to reduce insulin resistance and hyperinsulinemia in both diabetic animal models and non-insulin-dependent diabetes mellitus (NIDDM) subjects. To determine whether this drug could prevent the development of fructose-induced insulin resistance and related abnormalities, we studied the effects of troglitazone on the insulin resistance induced by fructose feeding in rats. Normal male Sprague-Dawley rats were fed a high-fructose diet for 3 weeks with and without troglitazone as a food admixture (0.2%) or were fed normal chow to serve as a control group. In vivo insulin resistnace was measured by the euglycemic hyperinsulinemic clamp technique at two different insulin infusion rates, 29 (submaximal stimulation) and 290 (maximal stimulation) pmol.kg-1.min-1. Fructose feeding markedly reduced submaximal glucose disposal rate (GDR) (113.8 +/- 8.3 vs. 176.0 +/- 5.6 mumol.kg-1.min-1, P < 0.05) and maximal GDR (255.9 +/- 5.6 vs. 313.6 +/- 10.5 mumol.kg-1.min-1, P < 0.05), reduced the suppressibility of submaximal hepatic glucose production (HGP; 45.5 +/- 5.0 vs. 11.7 +/- 5.0 mumol.kg-1.min-1, P < 0.05), and resulted in hypertriglyceridemia and hypertension. Troglitazone treatment completely restored the GDR (submaximal 158.2 +/- 5.6, maximal 305.3 +/- 6.1 mumol.kg-1.min-1) and submaximal HGP (9.4 +/- 2.8 mumol.kg-1.min-1) to control levels and also normalized the elevated plasma triglyceride concentration and systolic blood pressure levels in fructose-fed rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic effects of troglitazone on fructose-induced insulin resistance in the rat.

High-resolution ultrasonography (US) has made possible the detection of asymptomatic small thyroid nodules. Thyroid incidentalomas have created a clinical dilemma as to how to properly manage such incidental findings. We investigated the prevalence, the clinical and US characteristics, and optimal diagnostic approach to incidentally detected benign and malignant thyroid nodules < 1.5 cm. Retrospective review was done on 1475 patients who had visited Samsung Medical Center, Soul Korea from January 1999 to December 2000. The prevalence of thyroid incidentalomas was 13.4%. The malignancy rate within thyroid incidentalomas was 28.8%. There were no significant differences in age, nodule size and number, thyroid function test, and Tc99m thyroid scan between benign and malignant incidentalomas. US characteristics of solid echostructure, irregular margin, and calcification showed meaningful diagnostic value in detecting malignancy in thyroid incidentalomas (p < 0.05). Most malignant incidentalomas were low stage....

Prevalence, Clinical and Ultrasonographic Characteristics of Thyroid Incidentalomas

Background: Medullary thyroid carcinoma (MTC) is characterized by a high concentration of serum calcitonin. Routine measurement of serum calcitonin concentration has been advocated for detection of...

Routine measurement of serum calcitonin is useful for early detection of medullary thyroid carcinoma in patients with nodular thyroid diseases.

Although insulin resistance has been shown to be a primary defect causing type 2 (non insulin-dependent) diabetes mellitus in Pima Indians and Caucasians, insulin secretory defect has also been known to be an important factor in the development of type 2 diabetes. We undertook a study to investigate the initial abnormality of glucose intolerance in Koreans. A total of 370 Korean subjects were classified into 5 groups according to their degree of glucose intolerance (normal fasting glucose [NFG]/normal glucose tolerance [NGT], n = 95; impaired fasting glucose [IFG]/NGT, n = 29; NFG/impaired glucose tolerance [IGT], n = 60; IFG/IGT, n = 68; diabetes, n = 118). Insulinogenic index was used as an index of early-phase insulin secretion. Insulin resistance was assessed by the R value of the homeostasis model assessment [HOMA(R)]. Insulinogenic index significantly decreased in subjects with IFG/NGT and NFG/IGT compared with those with NFG/NGT. However, there was no significant difference in HOMA(R) between subjects with NFG/NGT and those with IFG/NGT or NFG/IGT. Insulinogenic index decreased significantly with the increase of plasma glucose 120-minute value at the earlier stage of glucose intolerance compared with HOMA(R). These results suggest that early-phase insulin secretory defect may be the initial abnormality in the development of type 2 diabetes in Korean subjects.

Moon-Kyu Lee

Papers

Factors affecting graft and patient survival after live donor kidney transplantation in the UK.

Metabolic effects of troglitazone on fructose-induced insulin resistance in the rat.

Prevalence, Clinical and Ultrasonographic Characteristics of Thyroid Incidentalomas

Routine measurement of serum calcitonin is useful for early detection of medullary thyroid carcinoma in patients with nodular thyroid diseases.

Insulin secretory dysfunction and insulin resistance in the pathogenesis of korean type 2 diabetes mellitus.