Expression of the NH(2)-terminal fragment of RasGAP in pancreatic beta-cells increases their resistance to stresses and protects mice from diabetes.

OBJECTIVE: Our laboratory has previously established in vitro that a caspase-generated RasGAP NH(2)-terminal moiety, called fragment N, potently protects cells, including insulinomas, from apoptotic stress. We aimed to determine whether fragment N can increase the resistance of pancreatic beta-cells in a physiological setting. RESEARCH DESIGN AND METHODS: A mouse line, called rat insulin promoter (RIP)-N, was generated that bears a transgene containing the rat insulin promoter followed by the cDNA-encoding fragment N. The histology, functionality, and resistance to stress of RIP-N islets were then assessed. RESULTS: Pancreatic beta-cells of RIP-N mice express fragment N, activate Akt, and block nuclear factor kappaB activity without affecting islet cell proliferation or the morphology and cellular composition of islets. Intraperitoneal glucose tolerance tests revealed that RIP-N mice control their glycemia similarly as wild-type mice throughout their lifespan. Moreover, islets isolated from RIP-N mice showed normal glucose-induced insulin secretory capacities. They, however, displayed increased resistance to apoptosis induced by a series of stresses including inflammatory cytokines, fatty acids, and hyperglycemia. RIP-N mice were also protected from multiple low-dose streptozotocin-induced diabetes, and this was associated with reduced in vivo beta-cell apoptosis. CONCLUSIONS: Fragment N efficiently increases the overall resistance of beta-cells to noxious stimuli without interfering with the physiological functions of the cells. Fragment N and the pathway it regulates represent, therefore, a potential target for the development of antidiabetes tools.

Le diabète de type 2 est-il uniquement une affaire d'hyperglycémie? Entre science, humanisme et economie [Type 2 diabetes, is it just a case of hyperglycemia? Confusion between the interests of science, humanity and the economy]

The recommendations for the treatment of type 2 diabetic patients are often centered on the glycemia. These clinical trials based on this approach show only a beneficial effects on the prevention of microangiopathy. The coronary artery disease which is the main cause of mortality among these patients, is not reduced. These data should be interpreted with a systemic prospect. The diabetes vascular complications have multifactorial causes and these clinical trials are motivated for the promotion of hypoglycemic agents. Fortunately, the STENO study offers another glance on the treatment of the diabetes, associating multirisk approach and patients' accompaniment. It obliges to have a critical glance on the research often moved by economic issues and gives to the center a humanistic approach based on the therapeutic relation.

Chirurgie du diabète: provocation ou réalité [Surgery for diabetes: challenge or reality?]

Bariatric surgery techniques can usually increase either sensitivity or insulin resistance, acting on three different levels: decrease of food intake, malabsorption and modifications of entero-insulaire axis activity. This latter is taken into account in order to develop a new protocol to obtain diabetes remission without important weight loss and nutritional deficiencies. Preliminary results are interesting but they come from very short time studies with few patients. Moreover, complications rate is at present very high. Knowing better gastrointestinal mechanisms of diabetes control and especially incretins role is absolutely necessary before identifying surgery as a true metabolic treatment.

2007 State of Iowa Juvenile Justice and Delinquency Prevention Act Formule Grand Update

This document is Iowa’s 2007 JJDP Act formula grant three year plan update. When specific items of this plan are unchanged from the previously submitted 2006 plan, we have reflected accordingly in the respective topic areas of this document. The bulk of this 2007 plan is an “update” of the program plan completed since submission of the original 2006 plan. The Division of Criminal and Juvenile Justice Planning (CJJP) wrote Iowa’s three year plan update. CJJP is the state agency responsible for administering the JJDP Act in Iowa. Federal officials refer to state administering agencies as the state planning agency (SPA). The Plan was developed and approved by Iowa’s Juvenile Justice Advisory Council. That Council assists with administration of the JJDP Act, and also provides guidance and direction to the SPA, the Governor and the legislature regarding juvenile justice issues in Iowa. Federal officials refer to such state level groups as state advisory groups (SAG’s).

Apports de la médecine nucléaire en cardiologie préventive: l'exemple du syndrome métabolique [Value of nuclear medicine in preventive cardiology: the metabolic syndrome example]

Metabolic syndrome represents a grouping of risk factors closely linked to cardiovascular diseases and diabetes. At first, nuclear medicine has no direct application in cardiology at the level of primary prevention, but positron emission tomography is a non invasive imaging technique that can assess myocardial perfusion as well as the endothelium-dependent coronary vasomotion--a surrogate marker of cardiovascular event rate--thus finding an application in studying coronary physiopathology. As the prevalence of the metabolic syndrome is still unknown in Switzerland, we will estimate it from data available in the frame of a health promotion program. Based on the deleterious effect on the endothelium already observed with two components, we will estimate the number of persons at risk in Switzerland.

Alcohol drinking, the metabolic syndrome and diabetes in a population with high mean alcohol consumption.

AIMS: To investigate the relationship of alcohol consumption with the metabolic syndrome and diabetes in a population-based study with high mean alcohol consumption. Few data exist on these conditions in high-risk drinkers. METHODS: In 6172 adults aged 35-75 years, alcohol consumption was categorized as 0, 1-6, 7-13, 14-20, 21-27, 28-34 and ≥ 35 drinks/week or as non-drinkers (0), low-risk (1-13), medium-to-high-risk (14-34) and very-high-risk (≥ 35) drinkers. Alcohol consumption was objectively confirmed by biochemical tests. In multivariate analysis, we assessed the relationship of alcohol consumption with adjusted prevalence of the metabolic syndrome, diabetes and insulin resistance, determined with the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Seventy-three per cent of participants consumed alcohol, 16% were medium-to-high-risk drinkers and 2% very-high-risk drinkers. In multivariate analysis, the prevalence of the metabolic syndrome, diabetes and mean HOMA-IR decreased with low-risk drinking and increased with high-risk drinking. Adjusted prevalence of the metabolic syndrome was 24% in non-drinkers, 19% in low-risk (P<0.001 vs. non-drinkers), 20% in medium-to-high-risk and 29% in very-high-risk drinkers (P=0.005 vs. low-risk). Adjusted prevalence of diabetes was 6.0% in non-drinkers, 3.6% in low-risk (P<0.001 vs. non-drinkers), 3.8% in medium-to-high-risk and 6.7% in very-high-risk drinkers (P=0.046 vs. low-risk). Adjusted HOMA-IR was 2.47 in non-drinkers, 2.14 in low-risk (P<0.001 vs. non-drinkers), 2.27 in medium-to-high-risk and 2.53 in very-high-risk drinkers (P=0.04 vs. low-risk). These relationships did not differ according to beverage types. CONCLUSIONS: Alcohol has a U-shaped relationship with the metabolic syndrome, diabetes and HOMA-IR, without differences between beverage types.

A two-week workshop to promote cardiovascular disease prevention programs in countries with limited resources.

Training is a crucial tool for building the capacity necessary for prevention and control of cardiovascular diseases (CVDs) in developing countries. This paper summarizes some features of a 2-week workshop aimed at enabling local health professionals to initiate a comprehensive CVD prevention and control program in a context of limited resources. The workshops have been organized in the regions where CVD prevention programs are being contemplated, in cooperation with health authorities of the concerned regions. The workshop's content includes a broad variety of issues related to CVD prevention and control, and to program development. Strong emphasis is placed on "learning by doing," and groups of 5-6 participants conduct a small-scale epidemiological study during the first week; during the second week, they draft a virtual program of CVD prevention and control adapted to the local situation. This practice-oriented workshop focuses on building expertise among anticipated key players, strengthening networks among relevant health professionals, and advocating the urgent need to tackle the emerging CVD epidemic in developing countries.

Vitamin d and stroke: promise for prevention and better outcome.

The role of vitamin D (VitD) has recently been expanded beyond bone homeostasis and regulation of calcium levels. VitD deficiency has been proposed as a new risk factor for cardiovascular disease, including stroke. Low 25(OH)VitD levels are very common among post-stroke patients, probably due to their limited mobility and decreased sunlight exposure along with a higher prevalence of malnutrition, and they have been associated with previous and incident cerebrovascular events. Contributing mechanisms have been linked to the association of VitD deficiency with the presence of hypertension, diabetes mellitus and atherosclerosis. Moreover, there is experimental evidence demonstrating that VitD exerts neuroprotective effects, such as stimulation of neurotrophic factors, quenching of oxidative hyperactivity and regulation of neuronal death, as well as antithrombotic properties. It is plausible that VitD supplementation could be a beneficial intervention for the prevention and/or treatment of cerebrovascular disease possibly by decreasing the aforementioned cerebrovascular risk factors and simultaneously by improving neurologic and cognitive functions, thereby reducing falls and fractures in post-stroke patients. However, study results are still conflicting and data from large, randomized clinical trials are needed to clarify these speculations.

Efficacy Of Canakinumab (Acz885), A Fully Human Anti-Interleukin (Il)-1beta Monoclonal Antibody, In The Prevention Of Flares In Gout Patients Initiating Allopurinol Therapy

Background: Gout patients initiating urate lowering therapy have an increased risk of flares. Inflammation in gouty arthritis is induced by IL-1b. Canakinumab targets and inhibits IL-1b effectively in clinical studies. This study compared different doses of canakinumab vs colchicine in preventing flares in gout patients initiating allopurinol therapy.Methods: In this 24 week double blind study, gout patients (20-79 years) initiating allopurinol were randomized (1:1:1:1:1:1:2) to canakinumab s.c. single doses of 25, 50, 100, 200, 300 mg, or 150 mg divided in doses every 4 weeks (50+50+25+25 mg [q4wk]) or colchicine 0.5 mg p.o. daily for 16 weeks. Primary outcome was to determine the canakinumab dose giving comparable efficacy to colchicine with respect to the number of gout flares occurring during first 16 weeks. Secondary outcomes included number of patients with gout flares and C-reactive protein (CRP) levels during the first 16 weeks.Results: 432 patients were randomized and 391 (91%) completed the study. All canakinumab doses were better than colchicine in preventing flares and therefore, a canakinumab dose comparable to colchicine could not be determined. Based on a negative binomial model, all canakinumab groups, except 25 mg, reduced the flare rate ratio per patient significantly compared to colchicine group (rate ratio estimates 25 mg 0.60, 50 mg 0.34, 100 mg 0.28, 200 mg 0.37, 300 mg 0.29, q4wk 0.38; p<=0.05). The percentage of patients with flares was lower for all canakinumab groups (25 mg 27.3%, 50 mg 16.7%, 100 mg 14.8%, 200 mg 18.5%, 300 mg 15.1%, q4wk 16.7%) compared to colchicine group (44.4%). All patients taking canakinumab were significantly less likely to experience at least one gout flare than patients taking colchicine (odds ratio range [0.22 - 0.47]; p<=0.05 for all). The median baseline CRP levels were 2.86 mg/L for 25 mg, 3.42 mg/L for 50 mg, 1.76 mg/L for 100 mg, 3.66 mg/L for 200 mg, 3.21 mg/L for 300 mg, 3.23 mg/L for q4wk canakinumab groups and 2.69 mg/L for colchicine group. In all canakinumab groups with median CRP levels above the normal range at baseline, median levels declined within 15 days of treatment and were maintained at normal levels (ULN=3 mg/L) throughout the 16 week period. Adverse events (AEs) occurred in 52.7% (25 mg), 55.6% (50 mg), 51.9% (100 mg), 51.9% (200 mg), 54.7% (300 mg), and 58.5% (q4wk) of patients on canakinumab vs 53.7% of patients on colchicine. Serious AEs (SAE) were reported in 2 (3.6%; 25 mg), 2 (3.7%, 50 mg), 3 (5.6%, 100 mg), 3 (5.6%, 200 mg), 3 (5.7%, 300 mg) and 1 (1.9%, q4wk) patients on canakinumab and in 5 (4.6%) patients on colchicine. One fatal SAE (myocardial infarction, not related to study drug) occurred in colchicine group.Conclusion: In this large randomized, double-blind active controlled study of flare prevention in gout patients initiating allopurinol therapy, treatment with canakinumab led to a statistically significant reduction in flares compared with colchicine (standard of care), and was well tolerated.

Diabetes care: opinions, needs and proposed solutions of Swiss patients and healthcare professionals: a qualitative study.

AIMS: To explore, both among patients with diabetes and healthcare professionals, opinions on current diabetes care and the development of the "Regional Diabetes Program". METHODS: We employed qualitative methods (focus groups - FG) and used purposive sampling strategy to recruit patients with diabetes and healthcare professionals. We conducted one diabetic and one professional FG in each of the four health regions of the canton of Vaud/Switzerland. The eight FGs were audio-taped and transcribed verbatim. Thematic analysis was then undertaken. RESULTS: Results showed variability in the perception of the quality of diabetes care, pointed to insufficient information regarding diabetes, and lack of collaboration. Participants also evoked patients' difficulties for self-management, as well as professionals' and patients' financial concerns. Proposed solutions included reinforcing existing structures, developing self-management education, and focusing on comprehensive and coordinated care, communication and teamwork. Patients and professionals were in favour of a "Regional Diabetes Program" tailored to the actors' needs, and viewed it as a means to reinforce existing care delivery. CONCLUSIONS: Patients and professionals pointed out similar problems and solutions but explored them differently. Combined with coming quantitative data, these results should help to further develop, adapt and implement the "Regional Diabetes Program".

Cytokines and hs-CRP levels in individuals treated with low-dose aspirin for cardiovascular prevention: a population-based study (CoLaus Study).

Pro-inflammatory cytokines and high-sensitive C-reactive protein (hs-CRP) are associated with increased risk for cardiovascular disease. Low-dose aspirin for CV prevention is reported to have anti-inflammatory effects. The aim of this study was to determine the association between pro-inflammatory cytokines and hs-CRP levels and low-dose aspirin use for cardiovascular prevention in a population-based cohort (CoLaus Study). We assessed blood samples in 6085 participants (3201 women) aged 35-75years. Medications' use and indications were recorded. Among aspirin users (n=1'034; 17%), overall low-dose users (351; 5.8%) and low-dose for cardiovascular prevention users (324; 5.3%) were selected for analysis. Pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α were assessed by a multiplex particle-based flow cytometric assay and hs-CRP by an immunometric assay. Cytokines and hs-CRP were presented in quartiles. Multivariate analysis adjusting for sex, age, smoking status, body mass index, diabetes mellitus and immunomodulatory drugs showed no association between cytokines and hs-CRP levels and low-dose aspirin use for cardiovascular prevention, either comparing the topmost vs. the three other quartiles (OR 95% CI, 0.84 (0.59-1.18), 1.03 (0.78-1.32), 1.10 (0.83-1.46), 1.00 (0.67-1.69) for IL-1β, IL-6, TNF-α and hs-CRP, respectively), or comparing the topmost quartile vs. the first one (OR 95% CI, 0.87 (0.60-1.26), 1.19 (0.79-1.79), 1.26 (0.86-1.84), 1.06 (0.67-1.69)). Low-dose aspirin use for cardiovascular prevention does not impact plasma pro-inflammatory cytokine and hs-CRP levels in a population-based cohort.

Iowa Tuberculosis Control Program 2014 Annual Report

This report provides a summary of Tuberculosis (TB) in Iowa and the activities and achievements of the TB Control Program and our partners during the 2014 calendar year. This report provides Iowa-specific TB rates, funding sources, and program-specific data, often in ten-year time lines to more accurately reflect trends. Previous reports included TB control efforts by the World Health Organization and the Centers for Disease Control and Prevention. Reports paid tribute to the role TB disease played in the history of man including historical TB treatments, myths, and bygone TB control practices. The 2014 Report does not include these overviews. Please refer to previous reports for this information. The annual report serves as an informational resource for stakeholders, local partners, policy makers and others interested in Iowa’s TB Control efforts.

Preemptive treatment approach to cytomegalovirus (CMV) infection in solid organ transplant patients: relationship between compliance with the guidelines and prevention of CMV morbidity.

Cytomegalovirus (CMV) remains a major cause of morbidity in solid organ transplant patients. In order to reduce CMV morbidity, we designed a program of routine virological monitoring that included throat and urine CMV shell vial culture, along with peripheral blood leukocyte (PBL) shell vial quantitative culture for 12 weeks post-transplantation, as well as 8 weeks after treatment for acute rejection. The program also included preemptive ganciclovir treatment for those patients with the highest risk of developing CMV disease, i.e., with either high-level viremia (>10 infectious units [IU]/106 PBL) or low-level viremia (<10 IU/106 PBL) and either D+/R- CMV serostatus or treatment for graft rejection. During 1995-96, 90 solid organ transplant recipients (39 kidneys, 28 livers, and 23 hearts) were followed up. A total of 60 CMV infection episodes occurred in 45 patients. Seventeen episodes were symptomatic. Of 26 episodes managed according to the program, only 4 presented with CMV disease and none died. No patient treated preemptively for asymptomatic infection developed disease. In contrast, among 21 episodes managed in non-compliance with the program (i.e., the monitoring was not performed or preemptive treatment was not initiated despite a high risk of developing CMV disease), 12 episodes turned into symptomatic infection (P=0.0048 compared to patients treated preemptively), and 2 deaths possibly related to CMV were recorded. This difference could not be explained by an increased proportion of D+/R- patients or an increased incidence of rejection among patients with episodes treated in non-compliance with the program. Our data identify compliance with guidelines as an important factor in effectively reducing CMV morbidity through preemptive treatment, and suggest that the complexity of the preemptive approach may represent an important obstacle to the successful prevention of CMV morbidity by this approach in the regular healthcare setting.

Iowa Immunization Program Annual Report 2010, March 31, 2011

The Bureau of Immunization is part of the Division of Acute Disease Prevention and Emergency Response (ADPER) at the Iowa Department of Public Health (IDPH). The ADPER division provides support, technical assistance and consultation to local hospitals, public health agencies, community health centers, emergency medical service programs and local health care providers regarding infectious diseases, disease prevention and control, injury prevention and public health and health care emergency preparedness and response. The division encompasses the Center for Acute Disease Epidemiology (CADE), the Bureau of Immunization and Tuberculosis (ITB), the Bureau of Emergency Medical Services (EMS), the Bureau of Communication and Planning (CAP), the Office of Health Information Technology (HIT), and the Center for Disaster Operations and Response (CDOR). The Bureau of Immunization and Tuberculosis includes the Immunization Program, the Tuberculosis Control Program, and the Refugee Health Program. The mission of the Immunization Program is to decrease vaccine‐preventable diseases through education, advocacy and partnership. While there has been major advancement in expanding immunizations to many parts of Iowa’s population, work must continue with public and private health care providers to promote the program’s vision of healthy Iowans living in communities free of vaccine‐preventable diseases. Accomplishing this goal will require achieving and maintaining high vaccination coverage levels, improving vaccination strategies among under‐vaccinated populations, prompt reporting and thorough investigation of suspected disease cases, and rapid institution of control measures. The Immunization Program is comprised of multiple programs that provide immunization services throughout the state: Adolescent Immunization Program, Adult Immunization Program, Immunization Registry Information System (IRIS), Vaccines for Children Program (VFC), Perinatal Hepatitis B Program, and Immunization Assessment Program.

Iowa Immunization Program Annual Report 2011, February 20, 2012

The Bureau of Immunization is part of the Division of Acute Disease Prevention and Emergency Response (ADPER) at the Iowa Department of Public Health (IDPH). The ADPER division provides support, technical assistance and consultation to local hospitals, public health agencies, community health centers, emergency medical service programs and local health care providers regarding infectious diseases, disease prevention and control, injury prevention and public health and health care emergency preparedness and response. The division encompasses the Center for Acute Disease Epidemiology (CADE), the Bureau of Immunization and Tuberculosis (ITB), the Bureau of Emergency Medical Services (EMS), the Bureau of Communication and Planning (CAP), the Office of Health Information Technology (HIT), and the Center for Disaster Operations and Response (CDOR). The Bureau of Immunization and Tuberculosis includes the Immunization Program, the Tuberculosis Control Program, and the Refugee Health Program. The mission of the Immunization Program is to decrease vaccine‐preventable diseases through education, advocacy and partnership. While there has been major advancement in expanding immunizations to many parts of Iowa’s population, work must continue with public and private health care providers to promote the program’s vision of healthy Iowans living in communities free of vaccine‐preventable diseases. Accomplishing this goal will require achieving and maintaining high vaccination coverage levels, improving vaccination strategies among under‐vaccinated populations, prompt reporting and thorough investigation of suspected disease cases, and rapid institution of control measures. The Immunization Program is comprised of multiple programs that provide immunization services throughout the state: Adolescent Immunization Program, Adult Immunization Program, Immunization Registry Information System (IRIS), Vaccines for Children Program (VFC), Perinatal Hepatitis B Program, and Immunization Assessment Program.