bluuebunny/crossref_metadata_2025 huggingface dataset:
Advocacy for injury control strategies on way to safe communities in Jaipur city, India
Authors: Mathur SC
Published: October 2012

Background

Visit to various ‘Safe Community’ on a travel fellowship to two Scandinavian countries gave an opportunity to author to conceptualise and replicate the intervention in a developing country where coordination between stakeholders is challenging.

Purpose

This paper underscores the problem of accidents in a fast developing urban agglomeration; identifying the opportunities to introduce the interventions to reduce the occurrence of injury in variety of settings, and steps to involve the multiple partners in injury prevention programme.

Methods

Author participated in the 4th Travelling Seminar at Karolinska University in 1994. Since then he seized every available opportunity to introduce the ‘Safe Community’ practices in Jaipur city.

Outcome

NGO's working in the field of road traffic accidents was oriented to adopt a logical approach. Traffic Police and Urban Development authorities were persuaded to incorporate the safety prevention measures in launch of new projects. Priority to helmet use by two-wheelers; seat belts in cars; traffic education in schools yielded positive results in reduction of morbidity and mortality. Advocacy measures have paved the way for launch of ‘safe community’.

Contribution to the Field

In a city where population and area is expanding rapidly, there is an urgent need to introduce the strategies in city planning and management to reduce roadside, schools, and domestic accidents. Capacity gained through participation in a travel fellowship programme was fully exploited over one-and-half decade, the results of which needs to be measured.

1. Independent public health specialist
Life-course experience of hospitalised injuries in a rural Greek town during the last century: the Velestino study
Authors: Kanavidis P , Kousoulis AA , Michelakos T , Katsiardanis K , Anastasiou A , Katsiardani KP , Stefanadis C , Petridou E Th
Published: October 2012

Background

Lessons from the past regarding the impact of social and technological changes on injury profiles provide inexpensive and meaningful reflections in assessing policies and projects delivered for injury prevention.

Objective

To depict the nearly one-century long, life-course injury experience of seniors residing in Velestino, a Greek agricultural town, and comment on the transitional patterns following historical and socio-cultural events.

Methods

Given the lack of individualised electronic/paper records during the study period, the life-course experience of 124 injuries, sustained by 116 study subjects and hospital treated, has been reported to two treating physicians by all (N=643) eligible residents of Velestino, aged 65–102 years, who participated in a health and safety of seniors study.

Results

The proportion of injuries by gender was >24% among males and 13% among females, with eight residents reporting hospitalisation for more than one events. The overrepresentation of males is no surprise since the given time-span includes periods of war (dominant cause during the 1940s) and manual labor accidents, thereafter (increases related to familiarisation with introduction of tractors in agriculture during the 1960s and steep decline in the past 15 years). Traffic accidents emerge as leading injury cause in the second half of the century (50%) following construction of driveways, whereas home injuries are a significant cause only over the past decade.

Significance

In retrospect, patterns of injuries seem predictable and mostly preventable within their historical context, were effective prevention programmes to have been implemented. This study offers a plausible framework for injury research in resource-limited settings.
Safe children community: does it work? A comparison of child injury data in the district of Deutschlandsberg documents evidence
Authors: Peter Spitzer , Gudula Brandmayr , Sabine Distl
Published: October 2012

Background

In 2007 Grosse schuetzen Kleine/Safe Kids Austria introduced a broad Safe Children Community Programme in the district of Deutschlandsberg (comprises 39 communities with 60.000 inhabitants, 9.500 children aged 14 and under). At this time 2.219 child injuries occurred annually in this region. This number corresponds with an injury rate of 248 per 1.000 children per year.

Aims/Objectives/Purpose

The aim was to find a framework to evaluate the effect of a safe community work focused on child safety and to implement the key factors in a systematically work process.

Methods

Children who sustain an injury in the district of Deutschlandsberg are mostly treated in the local hospital or by the general practitioner. Severe cases are referred to the Children's Trauma centre in the capital city of Graz. By collecting and analysing all data available from these sources 95% of all injuries which required medical treatment could be covered in the study. The same data analysis has been done in a control district of the same size and distribution of population in order to show evidence after the intervention period.

Results/Outcome

After 5 years of intervention the preventative work shows substantial effects that relate to a multi-level prevention programme. The number of injuries to children dropped by 16% related to absolute cases. The injury rate declined by 7%.

Significance/Contribution to the Field

With the Safe Children Community project Grosse schuetzen Kleine/Safe Kids Austria wanted to supply evidence that the Indicators for Safe Children Communities make a difference when followed accordingly. Accompanying the programme with a comprehensive data surveillance in the intervention and the non-intervention district helped to bring this evidence forward.

It is very important to involve a hospital in safe community work for evaluating and documenting the success of such a project.
Occupational ATV-related injuries in Washington State's agricultural industry, 2004–2008
Authors: Jim Helmkamp , Dave Bonauto , Cody Spann , Mary Aitken
Published: October 2012

Background

All-terrain vehicles (ATV) are used in many work applications and are associated with work-related injury and deaths.

Objective

To describe injuries and WC costs among agriculture workers hurt using ATVs at work.

Methods

Washington (WA) State Workers’ Compensation (WC) State Fund data (2004–2008) were used to identify suspected ATV injury claims; medical records were reviewed for work-related ATV injury. Emphasis was on Crop Production-CP, Animal Production-AP, and Support Activities for Agriculture and Forestry-SA workers.

Results

251 claims were identified with 55% from workers in CP (109), AP (18) or SA (13). Total indemnity ($675 782) and medical ($651 496) costs represented 70% of total compensable costs incurred. Fractures were the most common (49%) injury (median medical cost ∼$5700). Nearly 37% (18) of claims identified overturn/rollover, followed by caught in/struck by ATV at 27% (13). Highest median indemnity costs were for workers who slipped/fell ($11 217) from the ATV. Highest median medical costs were to workers caught in/struck by the ATV ($10 081); this injury had the highest median number of loss days (217). The 5-year injury rate among CP/ AP workers was 57/ 100 000 FTEs.

Conclusions

This study is the first to describe injuries to agriculture workers using ATVs at work. Types of injuries events were similar to patterns for ATV recreational use.
Suicide ideation among medical students: a cross sectional study from South India
Authors: Jain A , Jain R , Menezes RG , Subba SH , Kotian MS , Nagesh KR
Published: October 2012

Background

Suicide ideation is a neglected issue in our society. Information on suicidal ideation is lacking in India.

Objectives

This study was conducted to study the prevalence of suicide ideation and its associated risk factors among medical students at Mangalore, India.

Methods

This pilot study was conducted on medical students by using a self-administered questionnaire. Data was collected from second year students on baseline characteristics, habits, thought of suicide ideation, and thought of life as burden. The collected data was analysed using SPSS V.11.5. χ2test was used to determine the risk factors and their significance was reported at p<0.05.

Results

Out of 305 students who filled questionnaire completely (response rate 87%), 119 (39%) were males and 186 (61%) were females. Around 8.3% (n=25) admitted alcohol consumption, 4.3% (n=13) were smokers, 3% (n=9) admitted to having tried/done substance abuse. More than half (172; 56.39%) were dissatisfied with academic performance (p=0.002), 34 (55.7%) students had broken up with their close friends (p=0.009), and 20 (6.56%) felt neglected by the parents/family. One fifth of respondents (61; 20%) had reported suicide ideation, 24 (7.9%) have given serious thought to committing suicide, 28 students (9.5%) consider their life as a burden.

Significance

Dissatisfaction in academics, neglect by the family, and break up with close friends had significant association with suicide ideation. These issues can be tackled by counselling. The awareness generated could be helpful in avoiding suicide. Also, quantification of the problem is the first step in prevention.
Attitudes towards and practice of helmet use among commercial motorcyclists in Dar Es Salaam region, Tanzania
Authors: Mwakapasa E , Outwater A
Published: October 2012

Background

The non-use of helmets is a specific factor leading to head injuries resulting from motorcycle crashes.

Purpose

The study's purpose was to explore the commercial motorcyclists' attitude and their practices of helmet wearing.

Methods

A cross-sectional survey was conducted in urban and peri-urban areas of Dar es Salaam region in May, 2011 at 40 randomly selected commercial motorcycle parking points. A total of 273 commercial motorcyclists participated. Face-to-face interviews were performed using a standard questionnaire while observations were conducted using adapted WHO checklist. Data was analysed using SPSS V.16.0.

Results

The majority of respondents (81.3%) reported that they wear helmets; few of them (32.4%) wearing a helmet consistently. Predictors of helmet use were having a positive attitude, towards helmet use for passengers (p=0.005), protective ability of helmets against head injury (p=0.003), wearing of helmets during the night (p=0.001) and the necessity of wearing helmets even by experienced riders (p=0.000).Commercial motorcyclists who had primary education were more likely to wear helmets than those who had no formal education (AOR 6.146; 95% CI 1.345 to 28.097). No significant difference in helmet wearing between urban and peri-urban areas (p=0.109). Observations showed that 52.7% were observed wearing helmets and 91.8% of them had no passenger's helmet.

Significance

Despite a generally positive attitude towards helmet use, most commercial motorcyclists do not wear helmet consistently. This highlights the need for exploring the factors behind inconsistent helmet use.
CHIRAL TWISTED "H" MOLECULE IN SIMPLE SHEAR FLOW
Authors: ZHANG QI-YI , SUN BAO-GUANG , XIANG XUN
Published: October 2012

For rigid chiral objects in the low Reynolds number of shear flows, both experimental and theoretical results show that the chiral objects and their enantiomers will migrate in the positive or negative vorticity directions. This phenomenon is widely explored for the possibility of separation of chiral objects in shear flow. Within the simplest twisted "H" molecule model of hydrodynamic interactions of particles, we have calculated the hydrodynamic forces exerted on chiral twisted "H" molecules by shear flows. The chiral parameters that determine their different migration forces in shear flows are identified. The analysis may also be extended to study other complex motions of chiral objects in natural situations and microfluidic cells as well as important chiral-flow interactions, such as the interparticle interactions mediated by fluid flows.
Downregulation of nuclear receptor FXR is associated with multiple malignant clinicopathological characteristics in human hepatocellular carcinoma
Authors: Su Hongying , Ma Chuang , Liu Jingfeng , Li Ningbo , Gao Meiqin , Huang Aimin , Wang Xichun , Huang Wendong , Huang Xiongfei
Published: October 2012

The nuclear receptor farnesoid X receptor (FXR) acts as a liver protector by regulating normal liver homeostasis. Spontaneously developed liver tumors have been found in FXR-null mice. However, the role of FXR in the tumorigenesis of human hepatocellular carcinoma (HCC) is still poorly understood. In this study, we measured the expression of FXR and its primary target gene, small heterodimer partner, and analyzed the clinical significance of FXR expression in HCC patients. A lentiviral vector that selectively overexpresses FXR was used to investigate the function of FXR in HCC cell proliferation both in vitro and in vivo . Our data showed that in human HCC, FXR expression was significantly reduced and was positively correlated with multiple malignant clinicopathological characteristics. Lentivirus-mediated exogenous FXR expression resulted in a marked increase of small heterodimer partner expression, significant repression of liver cancer cell proliferation, and tumor growth in nude mice. These results suggest that FXR may be of clinical and pharmacological importance as a promising biomarker of HCC.
Inhibition of IκB phosphorylation prevents load-induced cardiac dysfunction in mice
Authors: Tanaka Tetsu , Ogawa Masahito , Suzuki Jun-ichi , Sekinishi Asuka , Itai Akiko , Hirata Yasunobu , Nagai Ryozo , Isobe Mitsuaki
Published: October 2012

Pressure overload is known to be a cause of cardiac hypertrophy that often transits to heart failure. Although nuclear factor (NF)-κB is a key factor in the progression of cardiac hypertrophy, its pathophysiology is yet to be elucidated. Thus, we aimed to show that inhibition of NF-κB activation improves pressure overload-induced cardiac dysfunction. To assess the effect of inhibition on NF-κB activation in pressure overload cardiac hypertrophy, we used IMD-1041 in a murine thoracic aortic constriction (TAC) model. IMD-1041 inhibits the phosphorylation of IκB via inhibition of IκB kinase-β. IMD-1041 (100 mg·kg−1·day−1) or vehicle was administered orally into mice once a day, and mice were euthanized on day 42 after TAC. TAC resulted in left ventricular wall thickening, cardiac dysfunction, and increases of heart and lung weight, whereas IMD-1041 significantly suppressed the development of cardiac hypertropy 6 wk after TAC. Histologically, developed cardiac fibrosis and cardiomyocyte hypertrophy occurred in the vehicle-treated group, whereas IMD-1041 significantly attenuated these changes. IMD-1041 suppressed the expression of p65-positive cells and nuclear translocation of p65 induced by TAC compared with vehicle. Matrix metalloproteinase-2 activity increased in the vehicle + TAC-treated group; however, it was suppressed in the IMD-1041 + TAC-treated group. IMD-1041 treatment from day 28 to day 42 after TAC significantly attenuated the decrease in the percentage of fractional shortening and cardiac fibrosis without an antihypertrophic effect. In conclusion, IMD-1041 may be useful for preventing pressure overload-induced cardiac dysfunction and the transition of cardiac hypertrophy to contraction failure via suppression of NF-κB activation.
Mast cell engraftment of the peripheral lung enhances airway hyperresponsiveness in a mouse asthma model
Authors: Fuchs Barbara , Sjöberg Lisa , Westerberg Christine Möller , Ekoff Maria , Swedin Linda , Dahlén Sven-Erik , Adner Mikael , Nilsson Gunnar P.
Published: October 2012

Allergic asthma is a chronic inflammatory disease, characterized by airway hyperresponsiveness (AHR), inflammation, and tissue remodeling, in which mast cells play a central role. In the present study, we analyzed how mast cell numbers and localization influence the AHR in a chronic murine model of asthma. C57BL/6 (wild-type) and mast cell-deficient B6.Cg- KitW−shmice without (Wsh) and with (Wsh+MC) mast cell engraftment were sensitized to and subsequently challenged with ovalbumin for a 91-day period. In wild-type mice, pulmonary mast cells were localized in the submucosa of the central airways, whereas the more abundant mast cells in Wsh+MC mice were found mainly in the alveolar parenchyma. In Wsh+MC, ovalbumin challenge induced a relocation of mast cells from the perivascular space and central airways to the parenchyma. Allergen challenge caused a similar AHR in wild-type and Wsh mice in the resistance of the airways and the pulmonary tissue. In Wsh+MC mice the AHR was more pronounced. The elevated functional responses were partly related to the numbers and localization of connective tissue-type mast cells in the peripheral pulmonary compartments. A mast cell-dependent increase in IgE and IL-33 together with impairment of the IL-23/IL-17 axis was evoked in Wsh and Wsh+MC mice by allergen challenge. This study shows that within the same chronic murine asthma model the development of AHR can be both dependent and independent of mast cells. Moreover, the spatial distribution and number of pulmonary mast cells determine severity and localization of the AHR.
Endurance exercise training normalizes repolarization and calcium-handling abnormalities, preventing ventricular fibrillation in a model of sudden cardiac death
Authors: Bonilla Ingrid M. , Belevych Andriy E. , Sridhar Arun , Nishijima Yoshinori , Ho Hsiang-Ting , He Quanhua , Kukielka Monica , Terentyev Dmitry , Terentyeva Radmila , Liu Bin , Long Victor P. , Györke Sandor , Carnes Cynthia A. , Billman George E.
Published: October 2012

The risk of sudden cardiac death is increased following myocardial infarction. Exercise training reduces arrhythmia susceptibility, but the mechanism is unknown. We used a canine model of sudden cardiac death (healed infarction, with ventricular tachyarrhythmias induced by an exercise plus ischemia test, VF+); we previously reported that endurance exercise training was antiarrhythmic in this model (Billman GE. Am J Physiol Heart Circ Physiol 297: H1171–H1193, 2009). A total of 41 VF+ animals were studied, after random assignment to 10 wk of endurance exercise training (EET; n = 21) or a matched sedentary period ( n = 20). Following (>1 wk) the final attempted arrhythmia induction, isolated myocytes were used to test the hypotheses that the endurance exercise-induced antiarrhythmic effects resulted from normalization of cellular electrophysiology and/or normalization of calcium handling. EET prevented VF and shortened in vivo repolarization ( P < 0.05). EET normalized action potential duration and variability compared with the sedentary group. EET resulted in a further decrement in transient outward current compared with the sedentary VF+ group ( P < 0.05). Sedentary VF+ dogs had a significant reduction in repolarizing K+ current, which was restored by exercise training ( P < 0.05). Compared with controls, myocytes from the sedentary VF+ group displayed calcium alternans, increased calcium spark frequency, and increased phosphorylation of S2814 on ryanodine receptor 2. These abnormalities in intracellular calcium handling were attenuated by exercise training ( P < 0.05). Exercise training prevented ischemically induced VF, in association with a combination of beneficial effects on cellular electrophysiology and calcium handling.
Exercise alters mRNA expression of telomere-repeat binding factor 1 in skeletal muscle via p38 MAPK
Authors: Ludlow Andrew T. , Lima Laila C. J. , Wang Jenny , Hanson Erik D. , Guth Lisa M. , Spangenburg Espen E. , Roth Stephen M.
Published: October 2012

Telomeres protect chromosome ends and shorten with age in most tissues. Integral to the maintenance of telomeres is the protein complex shelterin. The gene expression regulation of shelterin proteins to physiological stressors is not understood in vivo. We have recently reported increased telomere-repeat binding factor 1 (TRF1) protein expression and longer telomere length in skeletal muscle of sedentary compared with chronically active mice. These provocative observations led us to examine the effects of acute physiological stress on shelterin expression in vivo in mice and to further define potential mechanisms associated with gene regulation of shelterin. Three groups of female C57Bl/6 mice were studied: one control group and two groups that underwent a 30-min treadmill running bout and were killed either immediately following or 1-h after the exercise. Following the exercise bout, mRNA expression of Trf1 was significantly reduced in the plantaris muscle, and this reduction was paralleled by significant increases in p38 MAPK phosphorylation. To determine if p38 mediated the decreases in Trf1 mRNA expression, C2C12 myotubes were treated with the calcium ionophore, A23187. In response to the A23187, Trf1 gene expression was significantly reduced, coupled with significant increases in p38 phosphorylation, similar to in vivo data. C2C12 myotubes pretreated with a p38 inhibitor (SB-202190) prevented the A23187-induced decrease in Trf1 mRNA expression, indicating a link between Trf1 gene expression and p38 MAPK activation. While it is too early to definitively report the effect of exercise on telomere biology in rodents or humans, these data provide important mechanistic insights into the paradoxical telomere shortening that occurs in skeletal muscle in response to chronic exercise in mice.
Age-related differences in Achilles tendon properties and triceps surae muscle architecture in vivo
Authors: Stenroth Lauri , Peltonen Jussi , Cronin Neil J. , Sipilä Sarianna , Finni Taija
Published: October 2012

This study examined the concurrent age-related differences in muscle and tendon structure and properties. Achilles tendon morphology and mechanical properties and triceps surae muscle architecture were measured from 100 subjects [33 young (24 ± 2 yr) and 67 old (75 ± 3 yr)]. Motion analysis-assisted ultrasonography was used to determine tendon stiffness, Young's modulus, and hysteresis during isometric ramp contractions. Ultrasonography was used to measure muscle architectural features and size and tendon cross-sectional area. Older participants had 17% lower ( P < 0.01) Achilles tendon stiffness and 32% lower ( P < 0.001) Young's modulus than young participants. Tendon cross-sectional area was also 16% larger ( P < 0.001) in older participants. Triceps surae muscle size was smaller ( P < 0.05) and gastrocnemius medialis muscle fascicle length shorter ( P < 0.05) in old compared with young. Maximal plantarflexion force was associated with tendon stiffness and Young's modulus ( r = 0.580, P < 0.001 and r = 0.561, P < 0.001, respectively). Comparison between old and young subjects with similar strengths did not reveal a difference in tendon stiffness. The results suggest that regardless of age, Achilles tendon mechanical properties adapt to match the level of muscle performance. Old people may compensate for lower tendon material properties by increasing tendon cross-sectional area. Lower tendon stiffness in older subjects might be beneficial for movement economy in low-intensity locomotion and thus optimized for their daily activities.
Effects of Surface Charges on Dental Implants: Past, Present, and Future
Authors: Guo Cecilia Yan , Matinlinna Jukka Pekka , Tang Alexander Tin Hong
Published: October 2012

Osseointegration is a major factor influencing the success of dental implantation. To achieve rapid and strong, durable osseointegration, biomaterial researchers have investigated various surface treatment methods for dental subgingival titanium (Ti) implants. This paper focuses on surface-charge modification on the surface of titanium dental implants, which is a relatively new and very promising methodology for improving the implants’ osseointegration properties. We give an overview on both theoretical explanations on how surface-charge affects the implants' osseointegration, as well as a potential surface charge modification method using sandblasting. Additionally, we discuss insights on the important factors affecting effectiveness of surface-charge modification methods and point out several interesting directions for future investigations on this topic.
Augmentation of Therapeutic Responses in Melanoma by Inhibition of IRAK-1,-4
Authors: Srivastava Ratika , Geng Degui , Liu Yingjia , Zheng Liqin , Li Zhaoyang , Joseph Mary Ann , McKenna Colleen , Bansal Navneeta , Ochoa Augusto , Davila Eduardo
Published: October 2012

Toll-like receptors (TLR) are expressed by a variety of cancers, including melanoma, but their functional contributions in cancer cells are uncertain. To approach this question, we evaluated the effects of stimulating or inhibiting the TLR/IL-1 receptor-associated kinases IRAK-1 and IRAK-4 in melanoma cells where their functions are largely unexplored. TLRs and TLR-related proteins were variably expressed in melanoma cell lines, with 42% expressing activated phospho-IRAK-1 constitutively and 85% expressing high levels of phospho-IRAK-4 in the absence of TLR stimulation. Immunohistochemical evaluation of melanoma tumor biopsies (n = 242) revealed two distinct patient populations, one that expressed p-IRAK-4 levels similar to normal skin (55%) and one with significantly higher levels than normal skin (45%). Levels of p-IRAK-4 levels did not correlate with clinical stage, gender, or age, but attenuated IRAK-1,-4 signaling with pharmacologic inhibitors or siRNA-enhanced cell death in vitro in combination with vinblastine. Moreover, in a xenograft mouse model of melanoma, the combined pharmacologic treatment delayed tumor growth and prolonged survival compared with subjects receiving single agent therapy. We propose p-IRAK-4 as a novel inflammation and prosurvival marker in melanoma with the potential to serve as a therapeutic target to enhance chemotherapeutic responses. Cancer Res; 72(23); 6209–16. ©2012 AACR.
Carbon Source and Myc Expression Influence the Antiproliferative Actions of Metformin
Authors: Javeshghani Shiva , Zakikhani Mahvash , Austin Shane , Bazile Miguel , Blouin Marie-José , Topisirovic Ivan , St-Pierre Julie , Pollak Michael N.
Published: October 2012

Epidemiologic and experimental data have led to increased interest in possible roles of biguanides in cancer prevention and/or treatment. Prior studies suggest that the primary action of metformin is inhibition of oxidative phosphorylation, resulting in reduced mitochondrial ATP production and activation of AMPK. In vitro, this may lead to AMPK-dependent growth inhibition if AMPK and its effector pathways are intact or to an energetic crisis if these are defective. We now show that the effect of exposure of several transformed cell lines to metformin varies with carbon source: in the presence of glutamine and absence of glucose, a 75% decrease in cellular ATP and an 80% decrease in cell number is typical; in contrast, when glucose is present, metformin exposure leads to increased glycolysis, with only a modest reduction in ATP level and cell number. Overexpression of myc was associated with sensitization to the antiproliferative effects of metformin, consistent with myc involvement in “glutamine addiction”. Our results reveal previously unrecognized factors that influence metformin sensitivity and suggest that metformin-induced increase in glycolysis attenuates the antiproliferative effects of the compound. Cancer Res; 72(23); 6257–67. ©2012 AACR.
Patient Navigation Significantly Reduces Delays in Breast Cancer Diagnosis in the District of Columbia
Authors: Hoffman Heather J. , LaVerda Nancy L. , Young Heather A. , Levine Paul H. , Alexander Lisa M. , Brem Rachel , Caicedo Larisa , Eng-Wong Jennifer , Frederick Wayne , Funderburk William , Huerta Elmer , Swain Sandra , Patierno Steven R.
Published: October 2012

Background: Patient Navigation (PN) originated in Harlem as an intervention to help poor women overcome access barriers to timely breast cancer treatment. Despite rapid, nationally widespread adoption of PN, empirical evidence on its effectiveness is lacking. In 2005, National Cancer Institute initiated a multicenter PN Research Program (PNRP) to measure PN effectiveness for several cancers. The George Washington Cancer Institute, a project participant, established District of Columbia (DC)-PNRP to determine PN's ability to reduce breast cancer diagnostic time (number of days from abnormal screening to definitive diagnosis).

Methods: A total of 2,601 women (1,047 navigated; 1,554 concurrent records-based nonnavigated) were examined for breast cancer from 2006 to 2010 at 9 hospitals/clinics in DC. Analyses included only women who reached complete diagnostic resolution. Differences in diagnostic time between navigation groups were tested with ANOVA models including categorical demographic and treatment variables. Log transformations normalized diagnostic time. Geometric means were estimated and compared using Tukey–Kramer P value adjustments.

Results: Average—geometric mean [95% confidence interval (CI)]—diagnostic time (days) was significantly shorter for navigated, 25.1 (21.7, 29.0), than nonnavigated women, 42.1 (35.8, 49.6). Subanalyses revealed significantly shorter average diagnostic time for biopsied navigated women, 26.6 (21.8, 32.5) than biopsied nonnavigated women, 57.5 (46.3, 71.5). Among nonbiopsied women, diagnostic time was shorter for navigated, 27.2 (22.8, 32.4), than nonnavigated women, 34.9 (29.2, 41.7), but not statistically significant.

Conclusions: Navigated women, especially those requiring biopsy, reached their diagnostic resolution significantly faster than nonnavigated women.

Impact: Results support previous findings of PN's positive influence on health care. PN should be a reimbursable expense to assure continuation of PN programs. Cancer Epidemiol Biomarkers Prev; 21(10); 1655–63. ©2012 AACR.
Follow-Up and Timeliness After an Abnormal Cancer Screening Among Underserved, Urban Women in a Patient Navigation Program
Authors: Markossian Talar W. , Darnell Julie S. , Calhoun Elizabeth A.
Published: October 2012

Background: We evaluated the efficacy of a Chicago-based cancer patient navigation program developed to increase the proportion of patients reaching diagnostic resolution and reduce the time from abnormal screening test to definitive diagnostic resolution.

Methods: Women with an abnormal breast (n = 352) or cervical (n = 545) cancer screening test were recruited for the quasi-experimental study. Navigation subjects originated from five federally qualified health center sites and one safety net hospital. Records-based concurrent control subjects were selected from 20 sites. Control sites had similar characteristics to the navigated sites in terms of patient volume, racial/ethnic composition, and payor mix. Mixed-effects logistic regression and Cox proportional hazard regression analyses were conducted to compare navigation and control patients reaching diagnostic resolution by 60 days and time to resolution, adjusting for demographic covariates and site.

Results: Compared with controls, the breast navigation group had shorter time to diagnostic resolution (aHR = 1.65, CI = 1.20–2.28) and the cervical navigation group had shorter time to diagnostic resolution for those who resolved after 30 days (aHR = 2.31, CI = 1.75–3.06), with no difference before 30 days (aHR = 1.42, CI = 0.83–2.43). Variables significantly associated with longer time to resolution for breast cancer screening abnormalities were being older, never partnered, abnormal mammogram and BI-RADS 3, and being younger and Black for cervical abnormalities.

Conclusions: Patient navigation reduces time from abnormal cancer finding to definitive diagnosis in underserved women.

Impact: Results support efforts to use patient navigation as a strategy to reduce cancer disparities among socioeconomically disadvantaged women. Cancer Epidemiol Biomarkers Prev; 21(10); 1691–700. ©2012 AACR.
Examining the Association Between Socioeconomic Status and Invasive Colorectal Cancer Incidence and Mortality in California
Authors: Steinbrecher Astrid , Fish Kari , Clarke Christina A. , West Dee W. , Gomez Scarlett L. , Cheng Iona
Published: October 2012

Background: Colorectal cancer (CRC) incidence and mortality rates vary across race/ethnicity. Socioeconomic status (SES) also influences CRC rates; however, these associations might be inconsistent across racial/ethnic groups and tumor subsite. We examined associations between area-level SES and CRC incidence and mortality in a population-based registry study of non-Hispanic Whites, African Americans, Hispanics, and Asians/Pacific Islanders from California.

Methods: Data on 52,608 incident CRC cases (1998–2002) and 14,515 CRC deaths (1999–2001) aged ≥50 years were obtained from the California Cancer Registry. Based on 2000 U.S. Census data, each cancer case and death was assigned a multidimensional census tract-level SES index. SES-specific quintiles of CRC incidence and mortality rates, incidence rate ratios (IRR) and mortality rate ratios, and 95% confidence intervals (CI) were estimated. Analyses were stratified by anatomical site, including left- versus right-sided tumors, race/ethnicity, and stage of disease.

Results: Overall CRC incidence and SES did not show a clear association, yet patterns of associations varied across tumor subsite and race/ethnicity. Positive associations between SES and CRC incidence were found in Hispanics [SES Q5 v. Q1: IRR = 1.54, CI = 1.39–1.69], irrespective of the subsite. For Whites [SES Q5 v. Q1: IRR = 0.80, CI = 0.77–0.83], and African Americans [SES Q5 v. Q1: IRR = 0.83, CI = 0.70–0.97] inverse associations were observed, predominantly for left-sided tumors. Mortality rates declined with increasing SES in Whites, whereas in Hispanics mortality rates significantly increased with SES.

Conclusions: Our findings show that SES differences in CRC incidence and mortality vary considerably across anatomical subsite and race/ethnicity.

Impact: Studies combining area- and individual-level SES information are warranted. Cancer Epidemiol Biomarkers Prev; 21(10); 1814–22. ©2012 AACR.
Insulin Therapy and Colorectal Adenomas in Patients with Diabetes Mellitus
Authors: Wong Patricia , Weiner Mark G. , Hwang Wei-Ting , Yang Yu-Xiao
Published: October 2012

Background: Patients with type 2 diabetes mellitus (DM) are at increased risk for colorectal adenomas and cancer because of endogenous hyperinsulinemia. Exogenous insulin therapy has been associated with higher colorectal cancer incidence. The aim of this study was to evaluate the association between exogenous insulin therapy and adenoma formation, accounting for duration of therapy and location and stage of the adenoma.

Methods: We conducted a cross-sectional study of patients with type 2 diabetes between the ages of 50 and 80 years who completed full colonoscopies. Cases were patients with any adenoma on index colonoscopy. Patients without any adenoma composed the control group. Multivariable logistic regression was used to calculate odds ratios (OR) and associated confidence intervals (CI).

Results: Compared with the controls, case patients (n = 196) did not have a significantly increased odds of insulin exposure, when exposure was defined as 12 months or more of insulin use compared with no insulin. However, the odds of insulin exposure among the cases was significantly increased when exposure was defined as 18 months or more (OR 1.6, 95% CI 1.1–2.5), 24 months or more (OR 1.7, CI 1.1–2.6), and 36 months or more (OR 2.0, 95% CI 1.2–3.4) of insulin use (test for trend P = 0.05). A similar trend in insulin exposure was seen among type 2 diabetics with advanced adenomas. Adenoma location was not significantly affected by insulin therapy.

Conclusions: Chronic insulin therapy is associated with increased risk of colorectal adenomas in patients with type 2 diabetes.

Impact: Diabetes patients receiving insulin may need more stringent colon cancer screening. Cancer Epidemiol Biomarkers Prev; 21(10); 1833–40. ©2012 AACR.
The Communications Revolution and Health Inequalities in the 21st Century: Implications for Cancer Control
Authors: Viswanath K. , Nagler Rebekah H. , Bigman-Galimore Cabral A. , McCauley Michael P. , Jung Minsoo , Ramanadhan Shoba
Published: October 2012

The radical and transformative developments in information and communication technologies (ICT) offer unprecedented opportunities to promote cancer control and enhance population and individual health. However, the current context in which these technologies are being deployed—where cancer incidence and mortality and communication are characterized by inequalities among different racial/ethnic and socioeconomic status groups—raises important questions for cancer communication research, policy, and practice. Drawing on illustrative data, this essay characterizes the communications revolution and elucidates its implications for cancer control, with a particular focus on communication inequalities and cancer disparities. Cancer Epidemiol Biomarkers Prev; 21(10); 1701–8. ©2012 AACR.
Dopamine Agonists Upregulate IL-6 and IL-8 Production in Human Keratinocytes
Authors: Parrado Andrea Cecilia , Canellada Andrea , Gentile Teresa , Rey-Roldán Estela Beatriz
Published: October 2012

Aim: Catecholamines regulate functions of the nervous, neuroendocrine and immune systems. Dopamine may modulate the activity of keratinocytes, which play a role in secreting cytokines and chemokines. The aim of this study was to evaluate the effect of dopaminergic agonists on the production of IL-6 and IL-8 by a non-tumoral human keratinocyte cell line (HaCaT). Methods: Cells were stimulated with dopamine and the D2 dopamine receptor agonist cabergoline. Levels of IL-6 and IL-8 in culture supernatants were then determined. Cell proliferation was also assessed. Assays were carried out in the presence or absence of the dopaminergic and β-adrenergic receptor antagonists (sulpiride and propranolol, respectively) and ascorbic acid. Results: Dopamine stimulated the production of IL-6 and IL-8 in a concentration-dependent manner. The effects observed on the secretion of IL-6 were more potent than those corresponding to IL-8 and were reduced by ascorbic acid. The dopamine-induced IL-6 secretion was partially reduced by sulpiride and abrogated by propranolol. The latter drug was able to block the effect of dopamine on the secretion of IL-8. The cabergoline-induced IL-6 release was reduced by sulpiride. Cell viability was not affected by any of the drugs. Conclusions: Dopaminergic agonists can stimulate keratinocytes to produce IL-6 and IL-8 which are related to inflammatory cutaneous processes. These effects are mediated by dopaminergic and β-adrenergic receptors and by receptor-independent oxidative mechanisms.
Novel Mechanism of Aortic Aneurysm Development in Mice Associated With Smoking and Leukocytes
Authors: Jin Jianping , Arif Batool , Garcia-Fernandez Francisca , Ennis Terri L. , Davis Elaine C. , Thompson Robert W. , Curci John A.
Published: October 2012

Objective—

The purpose of this study was to evaluate potential mechanisms promoting abdominal aortic aneurysm development with tobacco smoke (TS) exposure.

Methods and Results—

Experiments used the elastase perfusion model of abdominal aortic aneurysms with smoke-free controls. The effect of TS exposure was evaluated in C57/Bl6 mice, after broad-spectrum matrix metalloproteinase inhibition with doxycycline and in mice deficient in matrix metalloproteinase-9, matrix metalloproteinase-12, Cathepsin-S, and Neutrophil Elastase. Preparations of washed marrow, spleen, and peripheral blood leukocytes were transferred to smoke-free mice from 6-week TS-exposed mice or smoke-free mice. All mice were euthanized 14 days after elastase perfusion, and the percentage of change in aortic diameter (%Δ aortic diameter) was calculated. Electron microscopy of aortic tissue from animals exposed to TS without elastase exposure did not demonstrate any ultrastructural changes. Neither doxycycline nor any specific elastase deficiency was effective at preventing an increase in %Δ aortic diameter in TS-exposed animals. Smoke exposure for 6 weeks increased the %Δ aortic diameter after a smoke-free interval of up to 6 weeks before elastase perfusion. Leukocyte preparations from TS-exposed mice localized to abdominal aortic aneurysms and increased the %Δ aortic diameter in smoke-free mice.

Conclusion—

The effect of TS on the development of abdominal aortic aneurysms is not dependent on the activity of elastolytic enzymes and persists for long periods despite cessation of TS. Alterations in leukocyte response to aortic injury appear to mediate this effect.
Loss of Id3 Increases VCAM-1 Expression, Macrophage Accumulation, and Atherogenesis in
Ldlr
–/–
Mice
Authors: Lipinski Michael J. , Campbell Kirsti A. , Duong Son Q. , Welch Thomas J. , Garmey James C. , Doran Amanda C. , Skaflen Marcus D. , Oldham Stephanie N. , Kelly Kimberly A. , McNamara Coleen A.
Published: October 2012

Objective—

Inhibitor of differention-3 (Id3) promotes B cells homing to the aorta and atheroprotection in Apoe
−/−
mice. We sought to determine the impact of loss of Id3 in the
Ldlr
−/−
mouse model of diet-induced atherosclerosis and identify novel Id3 targets in the vessel wall.

Methods and Results—

Ex vivo optical imaging confirmed that
Id3
−/−
Ldlr
−/−
mice have significantly fewer aortic B cells than
Id3
+/+
Ldlr
−/−
mice. After 8 and 16 weeks of Western diet,
Id3
−/−
Ldlr
−/−
mice developed significantly more atherosclerosis than
Id3
+/+
Ldlr
−/−
mice, with
Id3
+/−
Ldlr
−/−
mice demonstrating an intermediate phenotype. There were no differences in serum lipid levels between genotypes. Immunostaining demonstrated that aortas from
Id3
−/−
Ldlr
−/−
mice had greater intimal macrophage density and C-C chemokine ligand 20 and vascular cell adhesion molecule 1 (VCAM-1) expression compared with
Id3
+/+
Ldlr
−/−
mice. Real-time polymerase chain reaction demonstrated increased VCAM-1 mRNA levels in the aortas of
Id3
−/−
Ldlr
−/−
mice. Primary vascular smooth muscle cells from
Id3
−/−
mice expressed greater amounts of VCAM-1 protein compared with control. Gain and loss of function studies in primary vascular smooth muscle cells identified a role for Id3 in repressing VCAM-1 promoter activation. Chromatin immunoprecipitation demonstrated interaction of E12 with the VCAM-1 promoter, which is inhibited by Id3.

Conclusion—

Id3 is an atheroprotective transcription regulator with targets in both B cells and vessel wall cells leading to reduced macrophage accumulation and reduced atherosclerosis formation.
Eplerenone in Patients With Systolic Heart Failure and Mild Symptoms
Authors: Rogers Jennifer K. , McMurray John J.V. , Pocock Stuart J. , Zannad Faiez , Krum Henry , van Veldhuisen Dirk J. , Swedberg Karl , Shi Harry , Vincent John , Pitt Bertram
Published: October 2012

Background—

Eplerenone is known to reduce time to first hospitalization for heart failure or cardiovascular death in patients with heart failure and mild symptoms. In chronic diseases such as heart failure, characterized by repeat hospitalizations, analyzing all heart failure hospitalizations, not just the first, should give a more complete picture of treatment benefits.

Methods and Results—

The Eplerenone in Mild Patients Hospitalization and SurvIval Study in Heart Failure (EMPHASIS-HF) trial compared eplerenone with placebo in 2737 patients with mild heart failure, followed for a median 2.08 years (interquartile range, 1.08–3.10 years). Data were collected on all hospitalizations, with a focus on those due to heart failure. Heart failure hospitalization rates in the eplerenone and placebo groups were 10.70 and 16.99 per 100 patient-years, respectively. Allowing for skewness in the frequency of hospitalizations by using the negative binomial generalized linear model, the rate ratio (eplerenone versus placebo) was 0.53 (95% confidence interval, 0.42–0.66;
P
<0.0001). A plot of cumulative hospitalization rates over time revealed that most of the reduced risk on eplerenone occurred in the first year of follow-up. Several baseline variables strongly predicted the risk of hospitalization. More complex statistical methods, adjusting for mortality (as informative censoring), made a negligible difference in these findings.

Conclusions—

Eplerenone markedly reduces the risk of heart failure hospitalizations in patients with heart failure and mild symptoms to a greater extent than is captured by only studying the time to first hospitalization. Future clinical trials in heart failure would gain from incorporating repeat hospitalizations into their primary evaluation of treatment effects.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00232180.
Genetic Heritability of Ischemic Stroke and the Contribution of Previously Reported Candidate Gene and Genomewide Associations
Authors: Bevan Steve , Traylor Matthew , Adib-Samii Poneh , Malik Rainer , Paul Nicola L. M. , Jackson Caroline , Farrall Martin , Rothwell Peter M. , Sudlow Cathie , Dichgans Martin , Markus Hugh S.
Published: October 2012

Background and Purpose—

The contribution of genetics to stroke risk, and whether this differs for different stroke subtypes, remainsuncertain. Genomewide complex trait analysis allows heritability to be assessed from genomewide association study (GWAS) data. Previous candidate gene studies have identified many associations with stoke but whether these are important requires replication in large independent data sets. GWAS data sets provide a powerful resource to perform replication studies.

Methods—

We applied genomewide complex trait analysis to a GWAS data set of 3752 ischemic strokes and 5972 controls and determined heritability for all ischemic stroke and the most common subtypes: large-vessel disease, small-vessel disease, and cardioembolic stroke. By systematic review we identified previous candidate gene and GWAS associations with stroke and previous GWAS associations with related cardiovascular phenotypes (myocardial infarction, atrial fibrillation, and carotid intima-media thickness). Fifty associations were identified.

Results—

For all ischemic stroke, heritability was 37.9%. Heritability varied markedly by stroke subtype being 40.3% for large-vessel disease and 32.6% for cardioembolic but lower for small-vessel disease (16.1%). No previously reported candidate gene was significant after rigorous correction for multiple testing. In contrast, 3 loci from related cardiovascular GWAS studies were significant:
PHACTR1
in large-vessel disease (
P
=2.63e
−6
),
PITX2
in cardioembolic stroke (
P
=4.78e
−8
), and
ZFHX3
in cardioembolic stroke (
P
=5.50e
−7
).

Conclusions—

There is substantial heritability for ischemic stroke, but this varies for different stroke subtypes. Previous candidate gene associations contribute little to this heritability, but GWAS studies in related cardiovascular phenotypes are identifying robust associations. The heritability data, and data from GWAS, suggest detecting additional associations will depend on careful stroke subtyping.