bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Use of Olaparib (AZD2281) Potentiates SN-38 Cytotoxicity in Colon Cancer Cells by Indirect Inhibition of Rad51-Mediated Repair of DNA Double-Strand Breaks
Authors: Tahara Makiko , Inoue Takeshi , Sato Futoshi , Miyakura Yasuyuki , Horie Hisanaga , Yasuda Yoshikazu , Fujii Hirofumi , Kotake Kenjiro , Sugano Kokichi 
Published: February 2014

Abstract
Potent application of topoisomerase I inhibitor plus PARP inhibitor has been suggested to be an effective strategy for cancer therapy. Reportedly, mismatch repair (MMR)–deficient colon cancer cells are sensitive to topoisomerase I inhibitor, presumably due to microsatellite instability (MSI) of the MRE11 locus. We examined the synergy of SN-38, an active metabolite of irinotecan, in combination with the PARP inhibitor olaparib in colon cancer cells showing different MMR status, such as MSI or microsatellite stable (MSS) phenotype. Treatment with SN-38 and olaparib in combination almost halved the IC50 of SN-38 for a broad spectrum of colon cancer cells independent of the MMR status. Furthermore, olaparib potentiated S-phase–specific double-strand DNA breaks (DSB) induced by SN-38, which is followed by Rad51 recruitment. siRNA-mediated knockdown of Rad51, but not Mre11 or Rad50, increased the sensitivity to olaparib and/or SN-38 treatment in colon cancer cells. In vivo study using mouse xenograft demonstrated that olaparib was effective to potentiate the antitumor effect of irinotecan. In conclusion, olaparib shows a synergistic effect in colon cancer cells in combination with SN-38 or irinotecan, potentiated by the Rad51-mediated HR pathway, irrespective of the Mre11-mediated failure of the MRN complex. These results may contribute to future clinical trials using PARP inhibitor plus topoisomerase I inhibitor in combination. Furthermore, the synergistic effect comprising topoisomerase I-mediated DNA breakage–reunion reaction, PARP and Rad51-mediated HR pathway suggests the triple synthetic lethal pathways contribute to this event and are applicable as a potential target for future chemotherapy. Mol Cancer Ther; 13(5); 1170–80. ©2014 AACR.
Noncalcified Coronary Plaque Volumes in Healthy People With a Family History of Early Onset Coronary Artery Disease
Authors: Kral Brian G. , Becker Lewis C. , Vaidya Dhananjay , Yanek Lisa R. , Qayyum Rehan , Zimmerman Stefan L. , Dey Damini , Berman Daniel S. , Moy Taryn F. , Fishman Elliot K. , Becker Diane M. 
Published: February 2014

Background—
Although age and sex distributions of calcified coronary plaque have been well described in the general population, noncalcified plaque (NCP) distributions remain unknown. This is important because NCP is a putative precursor for clinical coronary artery disease and could serve as a sentinel for aggressive primary prevention, especially in high-risk populations. We examined the distributions of NCP and calcified coronary plaque in healthy 30- to 74-year-old individuals from families with early onset coronary artery disease.

Methods and Results—

Participants in the GeneSTAR family study (N=805), mean age 51.1±10.8 years, 56% women, were screened for coronary artery disease risk factors and coronary plaque using dual-source computed tomographic angiography. Plaque volumes (mm
3
) were quantified using a validated automated method. The prevalence of coronary plaque was 57.8% in men and 35.8% in women (
P
<0.0001). NCP volume increased with age (
P
<0.001) and was higher in men than women (
P
<0.001). Although NCP, as a percentage of total plaque, was inversely related to age (
P
<0.01), NCP accounted for most of the total plaque volume at all ages, especially in men and women <55 years (>70% and >80%, respectively). Higher Framingham risk was associated with the number of affected vessels (
P
<0.01), but 44% of men and 20.8% of women considered intermediate risk had left main and 3-vessel disease involvement.

Conclusions—
The majority of coronary plaque was noncalcified, particularly in younger individuals. These findings support the importance of assessing family history and suggest that early primary prevention interventions may be warranted at younger ages in families with early onset coronary artery disease.
Right Ventricular Diastolic Performance in Children With Pulmonary Arterial Hypertension Associated With Congenital Heart Disease
Authors: Okumura Kenichi , Slorach Cameron , Mroczek Dariusz , Dragulescu Andreea , Mertens Luc , Redington Andrew N. , Friedberg Mark K. 
Published: February 2014

Background—
Right ventricular diastolic dysfunction influences outcomes in pulmonary arterial hypertension (PAH), but echocardiographic parameters have not been investigated in relation to invasive reference standards in pediatric PAH. We investigated echocardiographic parameters of right ventricular diastolic function in children with PAH in relation to simultaneously measured invasive reference measures.

Methods and Results—

We prospectively recruited children undergoing a clinically indicated cardiac catheterization for evaluation of PAH and pulmonary vasoreactivity testing. Echocardiography was performed simultaneously with invasive reference measurements by high-fidelity micromanometer catheter. For analysis, patients were divided into shunt and nonshunt groups. Sixteen children were studied. In the group as a whole, significant correlations were found among τ and tricuspid deceleration time,
E′
,
E/E′
, Time

E
–
E

′
, A wave velocity, and global early and late diastolic strain rate. d
p
/d
t
minimum correlated significantly with late diastolic tricuspid annular velocity (
A′
), tissue Doppler imaging–derived systolic:diastolic duration ratio, and global late diastolic strain rate. End-diastolic pressure correlated significantly with tissue Doppler imaging–derived systolic:diastolic duration ratio. On multivariate analysis, tricuspid deceleration time, Time

E
–
E

′
, and global early diastolic strain rate were independent predictors of τ, whereas tissue Doppler imaging–derived systolic:diastolic duration ratio was an independent predictor of d
p
/d
t
minimum. In general, correlations between echocardiographic and invasive parameters were better in the shunt group than in the nonshunt group.

Conclusions—
Echocardiography correlates with invasive reference measures of right ventricular diastolic function in children with PAH, although it does not differentiate between early versus late diastolic abnormalities. Newer echocardiographic techniques may have added value to assess right ventricular diastolic dysfunction in this population.
Low Socioeconomic Status Over 12 Years and Subclinical Cardiovascular Disease
Authors: Thurston Rebecca C. , El Khoudary Samar R. , Derby Carol A. , Barinas-Mitchell Emma , Lewis Tené T. , McClure Candace K. , Matthews Karen A. 
Published: February 2014

Background and Purpose—
The inverse relation between socioeconomic status and cardiovascular disease is well established. However, few studies have investigated socioeconomic status assessed repeatedly during adulthood in relation to subclinical atherosclerosis. We aimed to test whether consistently low socioeconomic status, as indexed by education, income, and financial strain, for 12 years of midlife was related to later carotid intima-media thickness and plaque among women.

Methods—
The Study of Women’s Health Across the Nation is a multisite longitudinal study of midlife women. Education was assessed at the study baseline, income and financial strain were obtained yearly for 12 years, and a carotid ultrasound was obtained at study year 12 among 1402 women. Associations were tested in linear and multinomial logistic regression models adjusted for demographic, biological, and behavioral risk factors.

Results—

A high school education or less (odds ratio [OR] [95% confidence interval {CI}], 1.72 [1.15–2.59];
P
<0.01), some college education (OR [95% CI], 1.65 [1.17–2.32];
P
<0.01), consistently low income (OR [95% CI], 1.83 [1.15–2.89];
P
<0.05), and consistent financial strain (OR [95% CI], 1.78 [1.21–2.61];
P
<0.01) for 12 years were associated with higher carotid plaque, and consistent financial strain was associated with elevated maximal intima-media thickness (β [SE]=0.02 [0.01];
P
<0.05) controlling for standard cardiovascular disease risk factors. When socioeconomic status indices were considered together, financial strain (β [SE]=0.02 [0.01];
P
<0.05) and low education (high school education or less: OR [95% CI], 1.55 [1.01–2.37];
P
<0.05; some college: OR [95% CI], 1.56 [1.09–2.21];
P
<0.05) were most consistently associated with intima-media thickness and plaque, respectively, controlling for risk factors.

Conclusions—
The findings indicate the importance of targeting economically disadvantaged women in efforts to prevent cardiovascular disease among women.
FIFA 11 for Health programme: Implementation in five countries in Sub-Saharan Africa
Authors: Fuller Colin W , Junge Astrid , Amaning Jacob , Kaijage Rogasian R , Kaputa John , Magwende George , Pambo Prince , Dvorak Jiri 
Published: February 2014

Objective: To assess the effectiveness of the FIFA 11 for Health programme in increasing children’s knowledge about communicable and non-communicable diseases in five countries of Sub-Saharan Africa. Method: A prospective five-cohort study was implemented in schools in Ghana (17), Malawi (12), Namibia (11), Tanzania (18) and Zambia (11). The programme consisted of eleven 90-minute sessions consisting of two 45-minute halves of Play Football (football skills) and Play Fair (health issues). Participants were boys and girls aged 10–14 years: Ghana (906), Malawi (1098), Namibia (439), Tanzania (720), Zambia (651). The main outcome measures recorded were children’s attendances at each session, their health knowledge (30-item questionnaire) before and after the interventions and the children’s evaluation of the programme itself by means of a six-item questionnaire. Results: Mean attendance by children during the programme ranged from 88% (Malawi) to 99% (Tanzania) of participants. Increases in the children’s overall level of health knowledge were recorded in all countries: range: 11% (Malawi) to 25% (Namibia). Children’s overall evaluation-rating of the programme was very positive in all countries, ranging from 93% (Zambia) to 98% (Namibia, Tanzania). Conclusions: The FIFA 11 for Health programme produced significant increases in children’s health knowledge and their awareness of disease prevention using an in-school, football-based health education programme. This success was most likely linked to the very high satisfaction rating given to the programme by the children involved. The success of the interventions also demonstrated the benefit of collaborating with the Ministries of Education in each country.
Intervention Effects of Knowledge and Skills of the Public to Respond to Public Health Emergencies in Sichuan Province, China
Authors: Li LI , Yu-bo LI , Yan NING , Yan CHAI , jun TANG Da , Jun-feng HU 
Published: February 2014

Background: Public health emergencies have a significant impact on the health of citizens, the local economy, and society as a whole. Currently, in many parts of China, there is a widespread lack of the knowledge and skills required for emergency preparedness and self-rescue. By carrying out targeted health education and intervention activities, and by popularizing the knowledge and skills in health emergencies, the abilities of citizens to respond to public health emergencies and protect themselves, reduce property damage, and eliminate unnecessary panic may be greatly improved. Objectives: The knowledge and skills of the public to respond to public health emergencies after an intervention in Sichuan province were surveyed. The conditions before and after the intervention were compared, and the effect of the intervention was evaluated. Methods: Four counties in Sichuan province were selected for baseline survey by means of a multistage random sampling method. Among the districts and counties, one of each was selected for baseline survey as an intervention group and another of each were selected as controls. After 1 year of intervention, respondents were selected from the intervention group by means of the method used for the baseline survey for effect evaluation. Results: After statistical analysis, it was shown that, after the intervention, the total awareness rate of knowledge to respond to public health emergencies increased from 42.6% to 58.4% among men and from 42.9% to 55.8% among women, both significant differences ( p < .001). It was also shown that the total awareness rates of the 18–35, 36–45, 46–60, and 60+ age-groups, respectively, increased from 44.5%, 43.7%, 42.2%, and 37.8% to 62.1%, 56.0%, 56.8%, and 51.9%, which were also significant differences ( p < .001). Intervention, educational level, occupation, discussion with the families, and disaster experience were the main influential factors for the knowledge and skills of sudden public health events. Conclusions: The study results show that, after the intervention in Sichuan province, the knowledge and skills of the public to respond to public health emergencies were significantly improved. It is also shown that health education interventions must be developed in accordance with geographical features, the educational level of the population, age characteristics, and other factors.
Biomechanical Consequences of a Complete Radial Tear Adjacent to the Medial Meniscus Posterior Root Attachment Site
Authors: Padalecki Jeffrey R. , Jansson Kyle S. , Smith Sean D. , Dornan Grant J. , Pierce Casey M. , Wijdicks Coen A. , LaPrade Robert F. 
Published: February 2014

Background: Complete radial tears near the medial meniscus posterior root attachment site disrupt the circumferential integrity of the meniscus (similar to a posterior root avulsion). These tears can compromise the circumferential integrity, and they have been reported in biomechanical studies to be comparable with the meniscectomized state. Purpose: To quantify the tibiofemoral contact pressure and contact area changes that occur in cadaveric knees from complete posterior horn radial tears and subsequent repairs of the medial meniscus adjacent to the posterior root attachment site. Study Design: Controlled laboratory study. Methods: Six nonpaired fresh-frozen human cadaveric knees each underwent 45 different testing conditions: 9 medial meniscus conditions (intact, root avulsion, root repair, serial radial tear at 3, 6, and 9 mm from the root attachment site, and in situ repair at the same 3 distances from the root attachment site) at 5 flexion angles (0°, 30°, 45°, 60°, and 90°), under a 1000-N axial load. Tekscan sensors were used to measure contact area and pressure in the medial and lateral compartments. Results: The medial meniscus root avulsion and all radial tear conditions resulted in significantly decreased contact area and increased mean contact pressure compared with the intact state for knee flexion angles beyond 0° ( P < .05). The root repair and in situ repairs restored contact area and pressure to levels statistically indistinguishable from those of the intact meniscus and increased contact area and decreased contact pressure compared with the corresponding tear conditions. Conclusion: Posterior horn radial tears adjacent to the medial meniscus root that extend to the meniscocapsular junction can lead to derangement of the loading profiles of the medial compartment that are similar to a root avulsion. Repair of these radial tears with an in situ pull-out technique restored joint mechanics to the intact state. Clinical Relevance: Complete radial tears of the posterior horn of the medial meniscus, which occur relatively frequently, are biomechanically equivalent to root avulsions and could potentially lead to medial compartment arthrosis. An in situ repair offers an alternative treatment to meniscectomy and can reestablish the posterior anchor point, thus improving load distribution in the medial compartment. Future clinical studies of these repairs are recommended.
The Lawton Instrumental Activities Daily Living/Activities Daily Living Scales
Authors: Koskas Pierre , Henry-Feugeas Marie Cécile , Feugeas Jean Paul , Poissonnet Aurore , Pons-Peyneau Cécile , Wolmark Yves , Drunat Olivier 
Published: February 2014

Objective: To examine the diagnostic ability of the Lawton Instrumental Activities Daily Living (IADLs) scale and the Activities Daily Living (ADLs) scale as a sensitive tool to Alzheimer’s disease (AD) in community-dwelling elderly people. Design: In an old age memory outpatient center, among patients with a clinical diagnosis of AD dementia or no dementia supported by at least 6 months of follow-up, we looked back at the baseline Lawton IADL scale (short version IADL-4 item), ADL scale, Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MOCA) values. Results: There were 109 patients with AD and 53 nondemented individuals (81.4 ± 4.6 years). The sensitivity of ADL scale or IADL-4 item or the MMSE was low (52%-57%). The most efficient AD classification used both the IADLs-4 item and the MOCA with a threshold score of 20. Besides age and memory scores, the main correlates of IADLs scale or ADLs scale were executive, neuropsychiatric, vascular, and extrapyramidal scores. Conclusion: Our results suggest that the Lawton IADLs-4 item scale and ADLs scale lack sensitivity to AD dementia in elderly people and support a better sensitivity of MOCA rather than MMSE and IADLs-4 item/ADLs at the expense of specificity.
Development and Validation of the Identification and Intervention for Dementia in Elderly Africans (IDEA) Study Dementia Screening Instrument
Authors: Gray William K. , Paddick Stella-Maria , Kisoli Aloyce , Dotchin Catherine L. , Longdon Anna R. , Chaote Paul , Samuel Maria , Jusabani Ahmed M. , Walker Richard W. 
Published: February 2014

Aim: The aim of this project was to develop a dementia screening instrument for use in the hospital or community in populations with low levels of formal education. Methods: A screening instrument was developed from retrospective data collected in a rural area of Tanzania in 2010. The community screening instrument for dementia was administered to over 95% of the population aged 70 years and older of 6 villages (n = 1198) in Hai district, Tanzania. Factor analysis, regression modeling, and Mokken scale analysis (MSA) were used to develop screening instruments from these data, which were then tested and refined during prospective fieldwork. Results: A 5-item screening instrument with an area under the receiver–operating characteristic (AUROC) curve of 0.871, sensitivity of 91.7%, and specificity of 61.7% was developed using a combination of factor analysis and logistic regression modeling and had a higher AUROC (0.786) than a 7-item screening instrument developed using MSA. During prospective testing and refinement (n = 60), the 5-item instrument performed well (AUROC 0.867) and took an average of less than 10 minutes to administer. Its performance was improved by including a matchstick design item added to measure praxis, AUROC 0.888. Conclusions: The 6-item brief dementia screening instrument has acceptable properties and will be further tested and validated during future fieldwork. Although developed for use in sub-Saharan Africa, it may be of use in other world regions where the use of other cognitive screening instruments may result in bias due to low levels of formal education.
Adverse Childhood and Recent Negative Life Events
Authors: Korten Nicole C. M. , Penninx Brenda W. J. H. , Pot Anne Margriet , Deeg Dorly J. H. , Comijs Hannie C. 
Published: February 2014

Objective: To examine whether persons who experienced adverse childhood events or recent negative life events have a worse cognitive performance and faster cognitive decline and the role of depression and apolipoprotein E-∊4 in this relationship. Methods: The community-based sample consisted of 10-year follow-up data of 1312 persons participating in the Longitudinal Aging Study Amsterdam (age range 65-85 years). Results: Persons who experienced adverse childhood events showed a faster 10-year decline in processing speed but only when depressive symptoms were experienced. Persons with more recent negative life events showed slower processing speed at baseline but no faster decline. Conclusions: Childhood adversity may cause biological or psychological vulnerability, which is associated with both depressive symptoms and cognitive decline in later life. The accumulation of recent negative life events did not affect cognitive functioning over a longer time period.
Long-Term Statin Use and Dementia Risk in Taiwan
Authors: Chen Ping-Yen , Liu Shi-Kai , Chen Chun-Lin , Wu Chi-Shin 
Published: February 2014

Background: The effect of statin use on dementia risk remains unclear. This study aims to examine the association between long-term statin use and dementia risk. Methods: A nest case–control study within a nationwide representative population-based cohort. Individuals aged 50 years and older participating in Taiwan’s National Health Insurance program between 1998 and 2009 were enrolled. A total of 9257 patients with at least 3 outpatient or 1 inpatient claims records for dementia were identified. Comparison patients were selected at a 1:2 ratio from age- and sex-matched participants without dementia. The cumulative period and average daily dosages of statins, fibrates, and other lipid-lowering agents were measured. Results: The authors found a duration–response relationship, as dementia risk decreased by 9% per year of treatment of statins (adjusted odds ratio = 0.91; 95% confidence interval, 0.85-0.97). Use of high average dose statins for more than 1 year was associated with a lower risk of dementia than use of low average dose. However, there was no significant difference in dementia risks between lipophilic and hydrophilic statins. Fibrates or other lipid-lowering agents had no significant association with dementia risk. Conclusion: Our results suggest that long-term use of statin is associated with a reduced dementia risk.
Multiple Cardiopulmonary Resuscitation Attempts in a Community Hospital
Authors: Barjaktarevic Igor , Bobe Lohaliz , Klapholz Ari , Dinan William 
Published: February 2014

Background: In hospital settings, inadequate recognition of futility of aggressive medical management in patients with terminal disease and lack of the timely transition to palliative care may lead to both excessive and potentially harmful treatment and unnecessary burden on hospital resources. In order to better understand the outcomes of futile medical management and recognize the need for more appropriate end-of-life care, we evaluated the survival of particularly vulnerable cohort of patients in a community hospital who had survived at least 1 cardiorespiratory arrest (CRA) but whose medical problems led to subsequent arrests. Methods: In this retrospective cohort study, we have reviewed the annual cardiopulmonary resuscitation (CPR) data in a community hospital in urban settings. Results: Analyzing the population of all patients who had CRA, 22.4% had more than 1 CRA episode and had multiple CPRs (42% of all inpatient CPR were performed on this group of patients). Overall survival at the discharge of patients who had single CRA is significantly better than survival at the discharge of patients who had more than 1 CRA episode (31% vs 4.5%). Only 18.5% of the patients who initially survived CPR after CRA were transitioned to “do not resuscitate” status subsequently, while vast majority had continued aggressive resuscitative efforts. Conclusion: Adjusting medical care based on futility assessment in patients with chronic illness who survive CRA is often neglected, but crucially relevant step in the optimization of health care system management.