Differential regulation of insulin-like growth factor binding protein-1 and -2 by insulin in the baboon (Papio anubis) endometrium

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to examine the effect of insulin on expression and synthesis of IGFBP-1 and IGFBP-2 in the baboon endometrium in vitro.</p> <p>Methods</p> <p>Baboon endometrial explants collected from cycling, ovariectomized, steroid-treated, simulated-pregnant and pregnant animals were cultured for 48 h in the presence or absence of insulin, with or without estradiol, progesterone and hCG.</p> <p>Results</p> <p>Insulin clearly inhibited IGFBP-1 production and mRNA expression in a time- and dose-dependent manner, whereas IGFBP-2 synthesis was not significantly affected. The inhibitory effects of insulin on IGFBP-1 were more evident in explants of non-pregnant tissue or tissue away from the implantation site. In the absence of insulin, synthesis of IGFBP-1 was induced in explants with low levels of de novo synthesis whereas IGFBP-2 synthesis was inhibited. This effect was potentiated by steroids and hCG in the explant cultures.</p> <p>Conclusion</p> <p>Insulin differentially regulates endometrial IGFBP-1 and IGFBP-2 secretion in the baboon.</p

Diabetes management before and after cancer diagnosis: missed opportunity

Background Few studies have examined the management of comorbidities in cancer patients. This study used population-based data to estimate the guideline concordance rates for diabetes management before and after cancer diagnosis and examined if diabetes management services among cancer patients was associated with characteristics of the hospital where the patient was treated. Methods We linked 2005-2009 Medicare claims data to information on 2,707 breast and colorectal cancers patients in state cancer registry files. Multivariate logistic regression models examined hospital characteristics associated with receipt of diabetes management care after cancer diagnosis. Results The rates of HbAlc testing, LDL-C testing, and retinal eye exam decreased from 72.7%, 79.6%, and 57.9% before cancer diagnosis to 58.3%, 69.5%, and 55.8% after diagnosis. The pre- and post-diagnosis diabetes management care was not significantly different by hospital characteristics in the bivariate analysis except for that the distance between residence and hospital was negatively related to retinal eye exam after diagnosis (P Conclusions Cancer patients received fewer diabetes management care after diagnosis than prior to diagnosis, even for those who were treated in large comprehensive centers. This may reflect a missed opportunity to connect diabetic cancer patients to diabetes care. This study provides benchmarks to measure improvements in comorbidity management among cancer patients

Alcohol Sale Status and Homicide Victimization in Kentucky, 2005-2012: Is There a Spatial Association?

To date, the association between the alcohol sale status of decedents’ residence and alcohol-related homicide victimization have not been studied as far as we know. The current study aims to: i) determine whether homicide victims who were residents of wet counties had higher odds of testing positive for alcohol than their counterparts in moist or dry counties after adjusting for confounders; ii) determine whether homicides and alcohol-related homicides tend to cluster spatially; iii) determine whether the aforementioned associations exist only in highly-populated counties. A multilevel logistic regression analysis was used to analyze the data on homicide victims in the Kentucky Violent Death Reporting System from 2005 to 2012. Spatial statistics were used to determine the spatial autocorrelation in rates of homicides and alcohol-related homicides. Overall, 944 homicide victims were included. The male to female ratio was 3:1. About 32.8% of homicide victims tested positive for alcohol. About 33.0% of homicide decedents who were residents in wet counties tested positive for alcohol compared to 32.5% of their counterparts in moist/dry counties. Residence in wet counties was associated with a statistically insignificant increase in the unadjusted odds ratio (OR) of alcohol-related homicide victimization (OR=1.20, 95% CI=0.81-1.77) as well as the adjusted odds (aOR=1.33, 95% CI=0.83-2.12). There was no association between population size and alcohol-related homicide rate

Does comorbidity explain the ethnic inequalities in cervical cancer survival in New Zealand? A retrospective cohort study

BACKGROUND: There are large ethnic differences in cervical cancer survival in New Zealand that are only partly explained by stage at diagnosis. We investigated the association of comorbidity with cervical cancer survival, and whether comorbidity accounted for the previously observed ethnic differences in survival. METHODS: The study involved 1,594 cervical cancer cases registered during 1994-2005. Comorbidity was measured using hospital events data and was classified using the Elixhauser instrument; effects on survival of individual comorbid conditions from the Elixhauser instrument were also assessed. Cox regression was used to estimate adjusted cervical cancer mortality hazard ratios (HRs). RESULTS: Comorbidity during the year before diagnosis was associated with cervical cancer-specific survival: those with an Elixhauser count of ≥3 (compared with a count of zero) had a HR of 2.17 (1.32-3.56). The HR per unit of Elixhauser count was 1.25 (1.11-1.40). However, adjustment for the Elixhauser instrument made no difference to the mortality HRs for Māori and Asian women (compared to 'Other' women), and made only a trivial difference to that for Pacific women. In contrast, concurrent adjustment for 12 individual comorbid conditions from the Elixhauser instrument reduced the Māori HR from 1.56 (1.19-2.05) to 1.44 (1.09-1.89), i.e. a reduction in the excess risk of 21%; and reduced the Pacific HR from 1.95 (1.21-3.13) to 1.62 (0.98-2.68), i.e. a reduction in the excess risk of 35%. CONCLUSIONS: Comorbidity is associated with cervical cancer-specific survival in New Zealand, but accounts for only a moderate proportion of the ethnic differences in survival

Racial and Socioeconomic Disparities Are More Pronounced in Inflammatory Breast Cancer Than Other Breast Cancers

Inflammatory breast cancer (IBC) is a rare yet aggressive form of breast cancer. We examined differences in patient demographics and outcomes in IBC compared to locally advanced breast cancer (LABC) and all other breast cancer patients from the Breast and Prostate Cancer Data Quality and Patterns of Care Study (POC-BP), containing information from cancer registries in seven states. Out of 7,624 cases of invasive carcinoma, IBC and LABC accounted for 2.2% (N = 170) and 4.9% (N = 375), respectively. IBC patients were more likely to have a higher number (P = 0.03) and severity (P = 0.01) of comorbidities than other breast cancer patients. Among IBC patients, a higher percentage of patients with metastatic disease versus nonmetastatic disease were black, on Medicaid, and from areas of higher poverty and more urban areas. Black and Hispanic IBC patients had worse overall and breast cancer-specific survival than white patients; moreover, IBC patients with Medicaid, patients from urban areas, and patients from areas of higher poverty and lower education had worse outcomes. These data highlight the effects of disparities in race and socioeconomic status on the incidence of IBC as well as IBC outcomes. Further work is needed to reveal the causes behind these disparities and methods to improve IBC outcomes

Update and Next Steps for Real-World Translation of Interventions for Type 2 Diabetes Prevention: Reflections From a Diabetes Care Editors’ Expert Forum

The International Diabetes Federation estimates that 415 million adults worldwide now have diabetes and 318 million have impaired glucose tolerance. These numbers are expected to increase to 642 million and 482 million, respectively, by 2040. This burgeoning pandemic places an enormous burden on countries worldwide, particularly resource-poor regions. Numerous landmark trials evaluating both intensive lifestyle modification and pharmacological interventions have persuasively demonstrated that type 2 diabetes can be prevented or its onset can be delayed in high-risk individuals with impaired glucose tolerance. However, key challenges remain, including how to scale up such approaches for widespread translation and implementation, how to select appropriately from various interventions and tailor them for different populations and settings, and how to ensure that preventive interventions yield clinically meaningful, cost-effective outcomes. In June 2015, a Diabetes Care Editors’ Expert Forum convened to discuss these issues. This article, an outgrowth of the forum, begins with a summary of seminal prevention trials, followed by a discussion of considerations for selecting appropriate populations for intervention and the clinical implications of the various diagnostic criteria for prediabetes. The authors outline knowledge gaps in need of elucidation and explore a possible new avenue for securing regulatory approval of a prevention-related indication for metformin, as well as specific considerations for future pharmacological interventions to delay the onset of type 2 diabetes. They conclude with descriptions of some innovative, pragmatic translational initiatives already under way around the world

Identification of sVSG117 as an immunodiagnostic antigen and evaluation of a dual-antigen lateral flow test for the diagnosis of human african trypanosomiasis

The diagnosis of human African trypanosomiasis (HAT) caused by Trypanosoma brucei gambiense relies mainly on the Card Agglutination Test for Trypanosomiasis (CATT). There is no immunodiagnostic for HAT caused by T. b. rhodesiense. Our principle aim was to develop a prototype lateral flow test that might be an improvement on CATT.Pools of infection and control sera were screened against four different soluble form variant surface glycoproteins (sVSGs) by ELISA and one, sVSG117, showed particularly strong immunoreactivity to pooled infection sera. Using individual sera, sVSG117 was shown to be able to discriminate between T. b. gambiense infection and control sera by both ELISA and lateral flow test. The sVSG117 antigen was subsequently used with a previously described recombinant diagnostic antigen, rISG65, to create a dual-antigen lateral flow test prototype. The latter was used blind in a virtual field trial of 431 randomized infection and control sera from the WHO HAT Specimen Biobank.In the virtual field trial, using two positive antigen bands as the criterion for infection, the sVSG117 and rISG65 dual-antigen lateral flow test prototype showed a sensitivity of 97.3% (95% CI: 93.3 to 99.2) and a specificity of 83.3% (95% CI: 76.4 to 88.9) for the detection of T. b. gambiense infections. The device was not as good for detecting T. b. rhodesiense infections using two positive antigen bands as the criterion for infection, with a sensitivity of 58.9% (95% CI: 44.9 to 71.9) and specificity of 97.3% (95% CI: 90.7 to 99.7). However, using one or both positive antigen band(s) as the criterion for T. b. rhodesiense infection improved the sensitivity to 83.9% (95% CI: 71.7 to 92.4) with a specificity of 85.3% (95% CI: 75.3 to 92.4). These results encourage further development of the dual-antigen device for clinical use

Proteomic identification of immunodiagnostic antigens for <i>Trypanosoma vivax </i>infections in cattle and generation of a proof-of-concept lateral flow test diagnostic device

Trypanosoma vivax is one of the causative agents of Animal African Trypanosomosis in cattle, which is endemic in sub-Saharan Africa and transmitted primarily by the bite of the tsetse fly vector. The parasite can also be mechanically transmitted, and this has allowed its spread to South America. Diagnostics are limited for this parasite and in farm settings diagnosis is mainly symptom-based. We set out to identify, using a proteomic approach, candidate diagnostic antigens to develop into an easy to use pen-side lateral flow test device. Two related members the invariant surface glycoprotein family, TvY486_0045500 and TvY486_0019690, were selected. Segments of these antigens, lacking N-terminal signal peptides and C-terminal transmembrane domains, were expressed in E. coli. Both were developed into ELISA tests and one of them, TvY486_0045500, was developed into a lateral flow test prototype. The tests were all evaluated blind with 113 randomised serum samples, taken from 37 calves before and after infection with T. vivax or T. congolense. The TvY486_0045500 and TvY486_0019690 ELISA tests gave identical sensitivity and specificity values for T. vivax infection of 94.5% (95% CI, 86.5% to 98.5%) and 88.0% (95% CI, 75.7% to 95.5%), respectively, and the TvY486_0045500 lateral flow test prototype a sensitivity and specificity of 92.0% (95% CI, 83.4% to 97.0%) and 89.8% (95% CI, 77.8% to 96.6%), respectively. These data suggest that recombinant TvY486_0045500 shows promise for the development of a pen-side lateral flow test for the diagnosis of T. vivax animal African trypanosomosis