bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discrimination and Mental Health–Related Service Use in a National Study of Asian Americans
Authors: Spencer Michael S. , Chen Juan , Gee Gilbert C. , Fabian Cathryn G. , Takeuchi David T. 
Published: March 2010

Objectives. We examined the association between perceived discrimination and use of mental health services among a national sample of Asian Americans. Methods. Our data came from the National Latino and Asian American Study, the first national survey of Asian Americans. Our sample included 600 Chinese, 508 Filipinos, 520 Vietnamese, and 467 other Asians (n=2095). We used logistic regression to examine the association between discrimination and formal and informal service use and the interactive effect of discrimination and English language proficiency. Results. Perceived discrimination was associated with more use of informal services, but not with less use of formal services. Additionally, higher levels of perceived discrimination combined with lower English proficiency were associated with more use of informal services. Conclusions. The effect of perceived discrimination and language proficiency on service use indicates a need for more bilingual services and more collaborations between formal service systems and community resources.
Comparison of Disability Rates Among Older Adults in Aggregated and Separate Asian American/Pacific Islander Subpopulations
Authors: Fuller-Thomson Esme , Brennenstuhl Sarah , Hurd Marion 
Published: March 2010

Objectives. We assessed the prevalence and adjusted odds of 4 types of disability among 7 groups of older Asian American/Pacific Islander (AAPI) subpopulations, both separately and aggregated, compared with non-Hispanic Whites. Methods. Data were from the nationally representative 2006 American Community Survey, which included institutionalized and community-dwelling Hawaiian/Pacific Islander (n = 524), Vietnamese (n = 2357), Korean (n = 2082), Japanese (n = 3230), Filipino (n = 5109), Asian Indian (n = 2942), Chinese (n = 6034), and non-Hispanic White (n = 641 177) individuals aged 55 years and older. The weighted prevalence, population estimates, and odds ratios of 4 types of disability (functional limitations, limitations in activities of daily living, cognitive problems, and blindness or deafness) were reported for each group. Results. Disability rates in older adults varied more among AAPI subpopulations than between non-Hispanic Whites and the aggregated Asian group. Asian older adults had, on average, better disability outcomes than did non-Hispanic Whites. Conclusions. This study provides the strongest evidence to date that exclusion of institutionalized older adults minimizes disparities in disabilities between Asians and Whites. The aggregation of Asians into one group obscures substantial subgroup variability and fails to identify the most vulnerable groups (e.g., Hawaiian/Pacific Islanders and Vietnamese).
Naturally Arising Human CD4 T-Cells That Recognize Islet Autoantigens and Secrete Interleukin-10 Regulate Proinflammatory T-Cell Responses via Linked Suppression
Authors: Tree Timothy I.M. , Lawson Jennifer , Edwards Hannah , Skowera Ania , Arif Sefina , Roep Bart O. , Peakman Mark 
Published: March 2010

OBJECTIVERegulatory T-cells (Tregs) recognizing islet autoantigens are proposed as a key mechanism in the maintenance of self-tolerance and protection from type 1 diabetes. To date, however, detailed information on such cells in humans, and insight into their mechanisms of action, has been lacking. We previously reported that a subset of CD4 T-cells secreting high levels of the immunosuppressive cytokine interleukin-10 (IL-10) is significantly associated with late onset of type 1 diabetes and is constitutively present in a majority of nondiabetic individuals. Here, we test the hypothesis that these T-cells represent a naturally generated population of Tregs capable of suppressing proinflammatory T-cell responses.RESEARCH DESIGN AND METHODSWe isolated and cloned islet-specific IL-10–secreting CD4+ T-cells from nondiabetic individuals after brief ex vivo exposure to islet autoantigens using cytokine capture technology and examined their phenotype and regulatory potential.RESULTSIslet-specific IL-10+ CD4 T-cells are potent suppressors of Th1 effector cells, operating through a linked suppression mechanism in which there is an absolute requirement for the cognate antigen of both the regulatory and effector T-cells to be presented by the same antigen-presenting cell (APC). The regulatory T-cells secrete perforin and granzymes, and suppression is associated with the specific killing of APCs presenting antigen to effector T-cells.CONCLUSIONSThis hitherto undescribed population of islet autoantigen–specific Tregs displays unique characteristics that offer exquisite specificity and control over the potential for pathological autoreactivity and may provide a suitable target with which to strengthen β-cell–specific tolerance.
Prevention of Diabetes by FTY720-Mediated Stabilization of Peri-Islet Tertiary Lymphoid Organs
Authors: Penaranda Cristina , Tang Qizhi , Ruddle Nancy H. , Bluestone Jeffrey A. 
Published: March 2010

OBJECTIVE
The nonobese diabetic (NOD) mouse is a well-established mouse model of spontaneous type 1 diabetes, which is characterized by an autoimmune destruction of the insulin-secreting pancreatic β-cells. In this study, we address the role of tertiary lymphoid organs (TLOs) that form in the pancreas of NOD mice during disease progression.

METHODS
We developed a model designed to “lock” lymphocytes in the pancreatic lymph node (PLN) and pancreas by the use of FTY720, which blocks the exit of lymphocytes from lymph nodes. A combination of flow cytometry, immunofluorescence, and analysis of clinical scores was used to study the effects of long-term FTY720 treatment on TLO development and development of diabetes.

RESULTS
Continuous treatment of NOD mice with FTY720 prevented diabetes development even at a time of significant insulitis. Treatment withdrawal led to accelerated disease independent of the PLN. Interestingly, naive T-cells trafficked to and proliferated in the TLOs. In addition, morphological changes were observed that occurred during the development of the disease. Remarkably, although the infiltrates are not organized into T/B-cell compartments in 8-week-old mice, by 20 weeks of age, and in age-matched mice undergoing FTY720 treatment, the infiltrates showed a high degree of organization. However, in naturally and FTY720-induced diabetic mice, T/B-cell compartmentalization was lost.

CONCLUSION
Our data show that TLOs are established during diabetes development and suggest that islet destruction is due to a loss of TLO integrity, which may be prevented by FTY720 treatment.
Alterations in Skeletal Muscle Fatty Acid Handling Predisposes Middle-Aged Mice to Diet-Induced Insulin Resistance
Authors: Koonen Debby P.Y. , Sung Miranda M.Y. , Kao Cindy K.C. , Dolinsky Vernon W. , Koves Timothy R. , Ilkayeva Olga , Jacobs René L. , Vance Dennis E. , Light Peter E. , Muoio Deborah M. , Febbraio Maria , Dyck Jason R.B. 
Published: March 2010

OBJECTIVE
Although advanced age is a risk factor for type 2 diabetes, a clear understanding of the changes that occur during middle age that contribute to the development of skeletal muscle insulin resistance is currently lacking. Therefore, we sought to investigate how middle age impacts skeletal muscle fatty acid handling and to determine how this contributes to the development of diet-induced insulin resistance.

RESEARCH DESIGN AND METHODS
Whole-body and skeletal muscle insulin resistance were studied in young and middle-aged wild-type and CD36 knockout (KO) mice fed either a standard or a high-fat diet for 12 weeks. Molecular signaling pathways, intramuscular triglycerides accumulation, and targeted metabolomics of in vivo mitochondrial substrate flux were also analyzed in the skeletal muscle of mice of all ages.

RESULTS
Middle-aged mice fed a standard diet demonstrated an increase in intramuscular triglycerides without a concomitant increase in insulin resistance. However, middle-aged mice fed a high-fat diet were more susceptible to the development of insulin resistance—a condition that could be prevented by limiting skeletal muscle fatty acid transport and excessive lipid accumulation in middle-aged CD36 KO mice.

CONCLUSION
Our data provide insight into the mechanisms by which aging becomes a risk factor for the development of insulin resistance. Our data also demonstrate that limiting skeletal muscle fatty acid transport is an effective approach for delaying the development of age-associated insulin resistance and metabolic disease during exposure to a high-fat diet.
Chronic Rapamycin Treatment Causes Glucose Intolerance and Hyperlipidemia by Upregulating Hepatic Gluconeogenesis and Impairing Lipid Deposition in Adipose Tissue
Authors: Houde Vanessa P. , Brûlé Sophie , Festuccia William T. , Blanchard Pierre-Gilles , Bellmann Kerstin , Deshaies Yves , Marette André 
Published: March 2010

OBJECTIVE
The mammalian target of rapamycin (mTOR)/p70 S6 kinase 1 (S6K1) pathway is a critical signaling component in the development of obesity-linked insulin resistance and operates a nutrient-sensing negative feedback loop toward the phosphatidylinositol 3-kinase (PI 3-kinase)/Akt pathway. Whereas acute treatment of insulin target cells with the mTOR complex 1 (mTORC1) inhibitor rapamycin prevents nutrient-induced insulin resistance, the chronic effect of rapamycin on insulin sensitivity and glucose metabolism in vivo remains elusive.

RESEARCH DESIGN AND METHODS
To assess the metabolic effects of chronic inhibition of the mTORC1/S6K1 pathway, rats were treated with rapamycin (2 mg/kg/day) or vehicle for 15 days before metabolic phenotyping.

RESULTS
Chronic rapamycin treatment reduced adiposity and fat cell number, which was associated with a coordinated downregulation of genes involved in both lipid uptake and output. Rapamycin treatment also promoted insulin resistance, severe glucose intolerance, and increased gluconeogenesis. The latter was associated with elevated expression of hepatic gluconeogenic master genes, PEPCK and G6Pase, and increased expression of the transcriptional coactivator peroxisome proliferator–activated receptor-γ coactivator-1α (PGC-1α) as well as enhanced nuclear recruitment of FoxO1, CRTC2, and CREB. These changes were observed despite normal activation of the insulin receptor substrate/PI 3-kinase/Akt axis in liver of rapamycin-treated rats, as expected from the blockade of the mTORC1/S6K1 negative feedback loop.

CONCLUSIONS
These findings unravel a novel mechanism by which mTORC1/S6K1 controls gluconeogenesis through modulation of several key transcriptional factors. The robust induction of the gluconeogenic program in liver of rapamycin-treated rats underlies the development of severe glucose intolerance even in the face of preserved hepatic insulin signaling to Akt and despite a modest reduction in adiposity.
Idd9.2andIdd9.3Protective Alleles Function in CD4+ T-Cells and Nonlymphoid Cells to Prevent Expansion of Pathogenic Islet-Specific CD8+ T-Cells
Authors: Hamilton-Williams Emma E. , Wong S.B. Justin , Martinez Xavier , Rainbow Daniel B. , Hunter Kara M. , Wicker Linda S. , Sherman Linda A. 
Published: March 2010

OBJECTIVEMultiple type 1 diabetes susceptibility genes have now been identified in both humans and mice, yet mechanistic understanding of how they impact disease pathogenesis is still minimal. We have sought to dissect the cellular basis for how the highly protective mouse Idd9 region limits the expansion of autoreactive CD8+ T-cells, a key cell type in destruction of the islets.RESEARCH DESIGN AND METHODSWe assess the endogenous CD8+ T-cell repertoire for reactivity to the islet antigen glucose-6-phosphatase–related protein (IGRP). Through the use of adoptively transferred T-cells, bone marrow chimeras, and reconstituted severe combined immunodeficient mice, we identify the protective cell types involved.RESULTSIGRP-specific CD8+ T-cells are present at low frequency in the insulitic lesions of Idd9 mice and could not be recalled in the periphery by viral expansion. We show that Idd9 genes act extrinsically to the CD8+ T-cell to prevent the massive expansion of pathogenic effectors near the time of disease onset that occurs in NOD mice. The subregions Idd9.2 and Idd9.3 mediated this effect. Interestingly, the Idd9.1 region, which provides significant protection from disease, did not prevent the expansion of autoreactive CD8+ T-cells. Expression of Idd9 genes was required by both CD4+ T-cells and a nonlymphoid cell to induce optimal tolerance.CONCLUSIONSIdd9 protective alleles are associated with reduced expansion of IGRP-specific CD8+ T-cells. Intrinsic expression of protective Idd9 alleles in CD4+ T-cells and nonlymphoid cells is required to achieve an optimal level of tolerance. Protective alleles in the Idd9.2 congenic subregion are required for the maximal reduction of islet-specific CD8+ T-cells.
Influence of Insulin in the Ventromedial Hypothalamus on Pancreatic Glucagon Secretion In Vivo
Authors: Paranjape Sachin A. , Chan Owen , Zhu Wanling , Horblitt Adam M. , McNay Ewan C. , Cresswell James A. , Bogan Jonathan S. , McCrimmon Rory J. , Sherwin Robert S. 
Published: March 2010

OBJECTIVE
Insulin released by the β-cell is thought to act locally to regulate glucagon secretion. The possibility that insulin might also act centrally to modulate islet glucagon secretion has received little attention.

RESEARCH DESIGN AND METHODS
Initially the counterregulatory response to identical hypoglycemia was compared during intravenous insulin and phloridzin infusion in awake chronically catheterized nondiabetic rats. To explore whether the disparate glucagon responses seen were in part due to changes in ventromedial hypothalamus (VMH) exposure to insulin, bilateral guide cannulas were inserted to the level of the VMH and 8 days later rats received a VMH microinjection of either 1) anti-insulin affibody, 2) control affibody, 3) artificial extracellular fluid, 4) insulin (50 μU), 5) insulin receptor antagonist (S961), or 6) anti-insulin affibody plus a γ-aminobutyric acid A (GABAA) receptor agonist muscimol, prior to a hypoglycemic clamp or under baseline conditions.

RESULTS
As expected, insulin-induced hypoglycemia produced a threefold increase in plasma glucagon. However, the glucagon response was fourfold to fivefold greater when circulating insulin did not increase, despite equivalent hypoglycemia and C-peptide suppression. In contrast, epinephrine responses were not altered. The phloridzin-hypoglycemia induced glucagon increase was attenuated (40%) by VMH insulin microinjection. Conversely, local VMH blockade of insulin amplified glucagon twofold to threefold during insulin-induced hypoglycemia. Furthermore, local blockade of basal insulin levels or insulin receptors within the VMH caused an immediate twofold increase in fasting glucagon levels that was prevented by coinjection to the VMH of a GABAA receptor agonist.

CONCLUSIONS
Together, these data suggest that insulin's inhibitory effect on α-cell glucagon release is in part mediated at the level of the VMH under both normoglycemic and hypoglycemic conditions.
Transcription Factor 7-Like 2 (TCF7L2) Polymorphism and Hyperglycemia in an Adult Italian Population-Based Cohort
Authors: Gambino Roberto , Bo Simona , Gentile Luigi , Musso Giovanni , Pagano Gianfranco , Cavallo-Perin Paolo , Cassader Maurizio 
Published: March 2010

OBJECTIVE
To assess whether TCF7L2 polymorphism has a role in the deterioration of glycemic control.

RESEARCH DESIGN AND METHODS
Metabolic variables were evaluated at baseline and after 6-year follow-up in 1,480 Caucasian subjects from a population-based cohort.

RESULTS
At baseline, T-allele carriers showed significantly lower BMI and homeostasis model assessment for β-cell function (HOMA-B) values and higher fasting glycemia and diabetes prevalence. At follow-up, fasting glucose and HOMA-B index were increased and reduced, respectively, in carriers of the T-allele. Incident impaired fasting glucose (IFG) and incident diabetes were 5.7, 10.7, 16.9% and 1.6, 1.7, 3.0% in the CC, CT, and TT genotypes, respectively. In a multiple logistic regression model, the association between incident IFG and the T-allele was significant (odds ratio [OR] 2.08 [95% CI 1.35–3.20] and 3.56 [2.11–5.98] in CT and TT genotypes, respectively).

CONCLUSIONS
The T-allele of TCF7L2 rs7903146 polymorphism was independently associated with increasing fasting glucose values toward hyperglycemia in the follow-up.
Long-Term Metformin Use Is Associated With Decreased Risk of Breast Cancer
Authors: Bodmer Michael , Meier Christian , Krähenbühl Stephan , Jick Susan S. , Meier Christoph R. 
Published: March 2010

OBJECTIVE
To evaluate whether use of oral hypoglycemic agents is associated with an altered breast cancer risk in women.

RESEARCH DESIGN AND METHODS
Using the U.K.-based General Practice Research Database, we conducted a nested case-control analysis among 22,621 female users of oral antidiabetes drugs with type 2 diabetes. We evaluated whether they had an altered risk of breast cancer in relation to use of various types of oral hypoglycemic agents. Case and control patients with a recorded diagnosis of type 2 diabetes were matched on age, calendar time, and general practice, and the multivariate conditional logistic regression analyses were further adjusted for use of oral antidiabetes drugs, insulin, estrogens, smoking BMI, diabetes duration, and HbA1c (A1C).

RESULTS
We identified 305 case patients with a recorded incident diagnosis of breast cancer. The mean ± SD age was 67.5 ± 10.5 years at the time of the cancer diagnosis. Long-term use of ≥40 prescriptions (&gt;5 years) of metformin, based on 17 exposed case patients and 120 exposed control patients, was associated with an adjusted odds ratio of 0.44 (95% CI 0.24–0.82) for developing breast cancer compared with no use of metformin. Neither short-term metformin use nor use of sulfonylureas or other antidiabetes drugs was associated with a materially altered risk for breast cancer.

CONCLUSIONS
A decreased risk of breast cancer was observed in female patients with type 2 diabetes using metformin on a long-term basis.
Skin-derived precursors differentiating into dopaminergic neuronal cells in the brains of Parkinson disease model rats
Authors: Higashida Tetsuhiro , Jitsuki Susumu , Kubo Atsuhiko , Mitsushima Dai , Kamiya Yoshinori , Kanno Hiroshi 
Published: March 2010

Object
In the authors' previous study, they observed that amino acids 157–171 of von Hippel-Lindau protein (VHL peptide) induced neuronal differentiation of skin-derived precursors. They also noted that transplantation of these differentiated cells into the striata of a Parkinson disease (PD) rat model reduced apomorphine-induced rotations. In the present study, they investigated if these cells produce dopamine in the striatum.

Methods
Skin-derived precursors were differentiated into neurons using VHL peptide and transplanted into the striata of a PD model of rats. Four weeks after transplantation, a probe was inserted into rat striata and extracellular dopamine was extracted by microdialysis. Dopamine levels were measured by high-pressure liquid chromatography. Brain sections were assessed by immunohistochemical analysis for the presence of tyrosine hydroxylase and dopamine transporter.

Results
Increased dopamine levels in the striata of the rats were observed after transplantation (p < 0.01), and these were correlated with a reduction in the number of apomorphine-induced rotations (p < 0.05). Skin-derived precursors observed along the tract of transplantation were positive for tyrosine hydroxylase and dopamine transporter.

Conclusions
This study suggests that transplantation of skin-derived precursors, differentiated into neuronal cells using VHL peptide, can improve PD-like symptoms by enabling production of dopamine in the striata in a PD model of rats.
Regional vascular relationships to the foramen ovale: an anatomical study with application to approaches to the external skull base with an emphasis on transcutaneous procedures for the treatment of trigeminal neuralgia
Authors: Tubbs R. Shane , Dixon Joshua , Loukas Marios , Cohen-Gadol Aaron A. 
Published: March 2010

Object
The foramen ovale and its neighboring vascular structures may be seen via external approaches to the skull base. More commonly, however, transcutaneous approaches to the foramen ovale are performed. Although complications with this latter technique are uncommon, studies of the distances to the surrounding extracranial vascular structures are lacking in the literature. The present study aimed to elucidate such anatomical relationships.

Methods
Twenty adult cadavers (40 sides) underwent dissection of the region surrounding the foramen ovale at the external skull base. Measurements between the external surface of the foramen ovale and surrounding vascular structures were made.

Results
From the nearest aspect of the undersurface of the foramen ovale, the authors found that the mean distances to the middle meningeal artery, maxillary artery, superior bulb of the internal jugular vein, and internal carotid artery at its entrance to and exit from the carotid canal were 3, 19, 20, 9, and 12 mm, respectively. Distances tended to be shorter in females, but this did not reach statistical significance. On the basis of these data, the authors also determined a safe zone while approaching the undersurface of the foramen ovale.

Conclusions
Additional knowledge of the neurovascular relationships surrounding the foramen ovale may be useful to the neurosurgeon and may help decrease the potential for complications.
A Clustering Approach to Segmenting Users of Internet-based Risk Calculators
Authors: Downs J. S. , Padman R. , Harle C. A. 
Published: March 2010

SummaryBackground: Risk calculators are widely available Internet applications that deliver quantitative health risk estimates to consumers. Although these tools are known to have varying effects on risk perceptions, little is known about who will be more likely to accept objective risk estimates.Objective: To identify clusters of online health consumers that help explain variation in individual improvement in risk perceptions from web-based quantitative disease risk information.Methods: A secondary analysis was performed on data collected in a field experiment that measured people’s pre-diabetes risk perceptions before and after visiting a realistic health promotion website that provided quantitative risk information. K-means clustering was performed on numerous candidate variable sets, and the different segmentations were evaluated based on between-cluster variation in risk perception improvement.Results: Variation in responses to risk information was best explained by clustering on pre-intervention absolute pre-diabetes risk perceptions and an objective estimate of personal risk. Members of a high-risk overesti-mater cluster showed large improvements in their risk perceptions, but clusters of both moderate-risk and high-risk underestimaters were much more muted in improving their optimistically biased perceptions.Conclusions: Cluster analysis provided a unique approach for segmenting health consumers and predicting their acceptance of quantitative disease risk information. These clusters suggest that health consumers were very responsive to good news, but tended not to incorporate bad news into their self-perceptions much. These findings help to quantify variation among online health consumers and may inform the targeted marketing of and improvements to risk communication tools on the Internet.
Motivational Interviewing (Patient-centered Counseling) to Address Childhood Obesity
Authors: Schwartz Robert P. 
Published: March 2010

CME EDUCATIONAL OBJECTIVES

1.
Discuss the utility and power of using open-ended questions and reflective listening in interactions with patients.

2.
Demonstrate the use of the elicit-provide-elicit tool.

3.
Outline the use of the importance and confidence scale in assessing motivation and readiness to change behavior.