Miracle-dz/UniFAR-FTUs huggingface dataset:
The conundrum of C-reactive protein as a risk marker for cardiovascular risk assessment: insight from EPIC-Norfolk and JUPITER.

This editorial refers to ‘Clinical implications of JUPITER in a contemporary European population: the EPIC-Norfolk prospective population study’[†][1], by B.M. Sondermeijer et al. , on page 1350 The challenge presented by the need to identify individuals with moderate cardiovascular risk who go on to undergo a clinical event remains a topic of intense debate. Subjects in this group present a SCORE of 1–5% at 10 years, and are typified by middle-aged men and women, an ever-expanding group as demographic patterns change worldwide. It is therefore of considerable relevance that criteria for risk assessment in this group in the recent Joint ESC/EAS Guideline recommendations for management of dyslipidaemia not only feature a lower target for LDL-cholesterol (LDL-C; 115 mg/dL), but also emphasize the critical need for estimation of the total cardiovascular risk profile.1 Such an approach to risk evaluation in primary prevention must now, however, integrate the concept of lifetime risk burden, which has the distinct advantage of integrating cumulative risk exposure as compared with a ‘point’ estimate at any given moment over a lifetime.2 A further dimension of risk assessment to enhance predictive power in this group concerns the potential use of circulating biomarkers of inflammation, either alone or in a multimarker panel. Use of high-sensitivity C-reactive protein, which, amongst other biomarkers, is associated with cardiovascular risk, has been prominent in such analyses.3 In this issue of the journal,4 and in continuity with their … [1]: #fn-2
Molecular regulation of endothelial nitric oxide synthase.

The three isoforms of nitric oxide synthase (NOS) are classified based on their mode of regulation by calmodulin (CaM). The "calcium-independent" inducible isoform (iNOS) contains tightly-bound CaM and is active at all levels of intracellular calcium. In contrast, the two calcium-dependent isoforms (neuronal, nNOS and endothelial eNOS) are activated by CaM-binding following stimulus-evoked increases in intracellular calcium. However, both the structural basis for these differences in regulation and the molecular basis for CaM-induced cNOS activation remained unclear. Given that the regulation of calmodulin regulated enzyme systems often involves the displacement of an intrinsic autoinhibitory domain, we attempted to identify regions of eNOS which may fulfill this autoinhibory function. Herein, I describe the identification of two autoinhibitory control elements (ACEs) in eNOS, one within the FMN binding domain (ACE-I) and one located at the C-terminus (ACE-2). Together with CaM, these form a tripartite system for the regulation of eNOS. ACE-lIACE-2 exerting negative effects to attenuate catalytic activity, which are overcome by the conformational changes induced by CaM-binding. The mechanism of ACE-lIACE-2-mediated inhibition and the alleviation of this inhibition were investigated.
Tele-Help Line for Caregivers (TLC)

Abstract This article presents a brief overview of the literature on the unique and diverse needs of rural caregivers and issues related to the design and implementation of caregiving interventions in rural areas. The Tele-Help Line for Caregivers (TLC), a clinical telehealth intervention currently underway for rural caregivers, is described. A case example is presented, demonstrating the benefits of a telehealth intervention for the rural caregiver. Each component of the intervention is described and preliminary outcome data are discussed. Issues related to the applicability of the intervention for a racially/ethnically diverse group of caregivers are also addressed.
Sympathetic overactivity due to sleep fragmentation is associated with elevated diurnal systolic blood pressure in healthy elderly subjects: the PROOF-SYNAPSE study.

AIMS Sleep fragmentation is a landmark of sleep disorders, because microarousals are systematically associated with sympathetic surges (i.e., sympathetic arousals). However, the impact of sympathetic sleep fragmentation on blood pressure (BP) remains understudied. We assessed the relationships between 24 h ambulatory BP monitoring, the autonomic arousal index (AAI) derived from pulse transit time, and heart rate variability indices. We hypothesized that repeated sympathetic arousals during sleep are associated with elevated BP in a large population of elderly volunteers. METHODS AND RESULTS Volunteer subjects (n = 780, 57.4% women) with a mean age of 68.7 years and free of known sleep-disordered breathing, coronary heart diseases, and neurological disorders underwent polygraphy, 24 h ECG Holter monitoring, and 24 h ambulatory BP monitoring. Multivariate regressions showed that sleep fragmentation, expressed by AAI, was associated with elevated diurnal (P = 0.008) and 24 h (P = 0.005) systolic BP and higher risk for 24 h [odds ratio (OR): 1.70 (1.04-2.80), P = 0.036] systolic hypertension, independently of confounders such as sleep-disordered breathing, body mass index, sex, diabetes, hypercholesterolaemia, and self-reported sleep duration and quality. Increased AAI was associated with higher nocturnal and diurnal low-frequency power (P < 0.001) and low-to-high-frequency ratio (P < 0.001), suggesting nocturnal and diurnal sympathetic overactivity. CONCLUSION In healthy elderly subjects, repetitive sympathetic arousals during sleep are associated with elevated systolic BP and higher risk of hypertension, after controlling for confounders. Sympathetic overactivity is the proposed underlying mechanism. CLINICAL TRIAL REGISTRATION NCT00766584 and NCT00759304.
Effective teaching of tertiary learners : strategies and faculty development implications

Opportunities for tertiary researchers to engage in professional growth episodes of a purely academic and curricular nature may be abundant and effective. Not so common, however, are opportunities through which university teachers may participate in long term, nonthreatening professional development initiatives to examine, compare, and improve their skills of instruction. The Teaching In Focus Project at The University of Lethbridge was a three-year project intended to facilitate an interfaculty educative dialogue specific to present and potential teaching effectiveness. This paper studies a variety of teaching characteristics contributing to optimum learning in a tertiary environment, and then examines the experiences of several University of Lethbridge professors as they attempt to parallel their own teaching habits with these characteristics of effectiveness. In addition, it links their experiences during the Teaching In Focus process with conditions highlighted in other effective professional development initiatives, and uses this comparison as a basis for the consideration of several facilitative conditions necessary for effective teaching-focused professional development at the tertiary level. Links are formed between research findings and reviewed literature in order to suggest conclusions regarding the question, "In what way is university teaching effectiveness impacted by participation in faculty development programs that promote professional self-examination, collaboration, and action research? "
GENERAL PRACTITIONERS' BELIEFS ABOUT OBESITY AND THEIR DECISION TO TREAT

The current study explored the relationships between GPs‟ beliefs about the cause of obesity and treatment choices. Participants (n = 81) responded to two sets of materials; vignettes featuring obese patients in which the grade and cause of obesity were manipulated, and a survey of beliefs about the causes of obesity. Participants were asked to rate how likely it would be for the patient to receive each of six treatments. Group comparisons, correlational analyses and logistic regression methods were employed. The results revealed that, as obesity increased, participants were more likely to refer patients on for all of the interventions rather than to 'watch and wait' and provide advice directly. The grade of obesity explained the most variance in ratings of treatment choice, suggesting that GPs' decisions are in line with current guidelines (NICE, 2006). Participants were more likely to agree with statements supporting an internal locus of control in the cause of obesity (LoCI) than an external locus of control (LoCE). Participants' beliefs that obesity is caused by LoCE factors were associated with them being more likely to refer for both medical interventions (pharmacological/surgical) and behavioural-based treatments (nurse/dietician/clinical psychology). Participants' beliefs that obesity is caused by LoCI factors were associated with GPs being more likely to 'watch and wait'. Previous research suggests that patients are more likely to believe obesity is out of their control (Ogden et al, 2001). The current study therefore suggests that GPs are more likely to work directly with patients who have different beliefs about the cause of obesity to their own. The implications of this finding for future research and practice are discussed.
The Nursing Presence in General Practice: Revealing Dimensions of Day-to-day Experience of Practice Nurses in New Zealand

This study makes visible and gives value to the day-to-day experience of practice nurses who work in New Zealand general practices. Nursing leaders internationally and locally have highlighted the importance of the Primary Health Care nurse to improving health outcomes, addressing inequalities and implementing new models of care. As one of the largest groups of Primary Health Care nurses, practice nurses have a significant part to play. There is however, no consensus and limited research related to the day-to-day experience of practice nurses. Therefore, the nature, extent, and contribution of nursing in general practice may be overlooked or misunderstood. Furthermore as an autonomous self-regulating profession, nursing has a responsibility to the public to provide understanding of nursing in the present and in the future, particularly when this relates to the care of families and the structure of health systems. Located within the qualitative research paradigm and utilising a narrative inquiry methodology, this study applies a 'supportive voice' to highlight the experience of five practice nurses, and in the process makes visible the dimensions of nursing work in New Zealand general practices. The five constructed narratives particularly draw attention to the complex nature of nursing work that practice nurses engage in daily, the importance of nurse-patient relationships and continuity of care and the significance of autonomous and specialty aspects of nursing practice. Ultimately, the value of the practice nurse in the day-to-day operation of general practice is brought to the fore.
Evaluation of Patients with Small, Subcentimeter Nodules

The prevalence of subcentimeter pulmonary nodules is on the rise due to widespread use of multidetector row computed tomography. These lesions have created a new set of challenges for patients and their physicians. Such nodules are poorly characterized by imaging tests and are difficult to biopsy. Fortunately, the available data suggest that the vast majority of such nodules are benign in etiology. However, this increases the challenge to provide a cost-effective evaluation that minimizes unnecessary radiation exposure and complications from invasive biopsies while promptly identifying malignancy when it is present. In this review, we summarize the current available literature regarding subcentimeter nodules, as well as the current recommendations regarding their investigation.
Calcium channel blockers improve exercise capacity and reduce N-terminal Pro-B-type natriuretic peptide levels compared with beta-blockers in patients with permanent atrial fibrillation.

AIMS Rate control of atrial fibrillation (AF) has become a main treatment modality, but we need more knowledge regarding the different drugs used for this purpose. In this study, we aimed to compare the effect of four common rate-reducing drugs on exercise capacity and levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with permanent AF. METHODS AND RESULTS We included 60 patients (mean age 71 ± 9 years, 18 women) with permanent AF and normal left ventricular function in a randomized, cross-over, investigator-blind study. Diltiazem 360 mg, verapamil 240 mg, metoprolol 100 mg, and carvedilol 25 mg were administered o.d. for 3 weeks. At baseline and on the last day of each treatment period, the patients underwent a maximal cardiopulmonary exercise test and blood samples were obtained at rest and at peak exercise. The exercise capacity (peak VO2) was significantly lower during treatment with metoprolol and carvedilol compared with baseline (no treatment) or treatment with diltiazem and verapamil (P < 0.001 for all). Compared with baseline, treatment with diltiazem and verapamil significantly reduced the NT-proBNP levels both at rest and at peak exercise, whereas treatment with metoprolol and carvedilol increased the levels (P < 0.05 for all). CONCLUSION Rate-reducing treatment with diltiazem or verapamil preserved exercise capacity and reduced levels of NT-proBNP compared with baseline, whereas treatment with metoprolol or carvedilol reduced the exercise capacity and increased levels of NT-proBNP.
Bronchoalveolar lavage-directed therapy in children with cystic fibrosis and Pseudomonas aeruginosa infection.

1 year after modern chemotherapy regimens is higher (more than 70% of patients) than that reported in the past (nearly 40%). However, this observation should not be a reason for disregarding the problem of ovarian toxicity of chemotherapy. Recent data showed that despite menses returning within 1 year in more than 90% of patients with breast cancer treated with chemotherapy, the probability of entering menopause before age 45 years was high, nearly 60%. We need to await the long-term follow-up of studies evaluating the role of GnRH analogues in preserving ovarian function, such as the PROMISE study, to answer the question about long-term maintenance of such function. Loibl and Gerber question the magnitude of the effect of the GnRH analogue in preserving ovarian function. The absolute difference in the occurrence of early menopause was 17%, the relative reduction of the risk of developing early menopause was 72%, and the number needed to treat was 6. Oncologists should take into account all the limitations of the PROMISE-GIM6 study, but they should also consider that GnRH analogue therapy to suppress ovarian function during chemotherapy is a treatment that can increase the probability of preserving ovarian function in young patients with breast cancer.
From Trauma to Healing: A Social Worker's Guide to Working with Survivors

Foreword AlexGitterman Introduction Part1: First Things First - Safety After Trauma 1. The Importance of Safety 2. Building Safe Relationships Part 2: Important Considerations 3. You Can be Affected Too - Secondary Trauma 4. Vulnerable Populations 5. Cultural Factors Part 3: Tools for Surviving Trauma 6. Crisis Management, Assessment, and Referral for Aid 7. Coping Skills and Self Care Part 4: The Survivor's Experience 8. Witnessing Trauma 9. Experiencing Trauma Directly Part 5: Potentially Traumatic Events 10. Life Threatening Illness 11. Intimate Partner Violence 12. Child Abuse and Neglect Part 6: Direct Interventions for Social Workers 13. Individual, Couples, and Family Therapy 14. Group Therapy 15. Other Trauma Interventions Part 7: Working in the Community 16. Program Development 17. Advocating for Survivors 18. Prevention and Community Organizing References Index
The role of the kallikrein-kinin system in prostate and breast tumourigenesis and tumour-associated angiogenesis..

III TABLE OF CONTENTS . VII LIST OF FIGURES . XIV LIST OF TABLES . XVI ABBREVIATIONS . XVII CHAPTER 1— INTRODUCTION. 2 1.1 Cancer, angiogenesis and the kallikrein-kinin system . 2 1.1.1 Cancer . 2 1.1.1.1 Historical background and definition of cancer . 2 1.1.1.2 Tumour initiation, progression and metastasis . 3 1.1.1.3 The role of the tumour microenvironment and inflammation in tumour progression and metastasis . 8 1.1.2 Angiogenesis . 10 1.1.2.1 The role of angiogenesis in tumour progression and metastasis . 10 1.1.2.2 Overview of the angiogenic cascade . 12 1.1.2.3 Regulators of angiogenesis . 13 1.1.2.3.1 VEGF . 13 1.1.2.3.2 COX . 17 1.1.2.3.3 Other regulators of angiogenesis . 17 1.1.2.4 Cells of the ECM . 17 viii 1.1.2.4. 1 Inflammation and angiogenesis . 17 1.1.2.4. 2 Inflammatory cells . 18 1.1.2.4. 2.1 Macrophages . 18 1.1.2.4. 2.2 Other leucocytes: T cells and granulocytes . 18 1.1.2.4. 3 Fibroblasts . 19 1.1.2.5 Non-cellular components of the ECM . 19 1.1.2.6 Cell adhesion . 21 1.1.2.6. 1 Cell adhesion and motility . 21 1.1.2.6. 2 Cell adhesion molecules . 21 1.1.3 Protease systems, cancer and angiogenesis . 23 1.1.3.1 Plasminogen activation system . 23 1.1.3.2 Matrix metalloproteinases (MMPs) . 24 1.1.3.3 The kallikrein-kinin system (KKS) . 25 1.1.3.3.1 Overview of the KKS components . 25 1.1.3.3.1.1 Kallikreins . 25 1.1.3.3.1.1.1 Location of TK . 27 1.1.3.3.1.1.2 Gene and protein structure of TK . 27 1.1.3.3.1.1.3 Regulation of TK . 28 1.1.3.3.1.1.3.1 Transcriptional regulation of kallikrein genes: steroid hormones . 28 1.1.3.3.1.1.3.2 Post-transcriptional regulation of TK activity . 28 1.1.3.3.1.2 Kininogen, kinins and kininases . 29 1.1.3.3.1.2.1 Location, structure and regulation . 30 1.1.3.3.1.3 Kinin receptors . 31 1.1.3.3.1.3.1 Gene and protein structure . 32 1.1.3.3.1.3.2 Regulation of receptor expression and activity . 33 ix 1.1.3.3.1.3.3 Receptor signalling pathways . 34 1.1.3.3.2 Physiology and pathophysiology of the KKS . 35 1.1.3.3.2.1 Biological effects of TK . 35 1.1.3.3.2.2 Biological effects of kinins, as mediated by B I R and B2R . 36 1.1.3.3.2.2.1 Vasoactivity 36 1.1.3.3.2.2.2 Promotion of growth . 36 1.1.3.3.2.2.2.1 NO and tyrosine kinases . 36 1.1.3.3.2.2.2.2 VEGF . 37 1.1.3.3.2.2.2.3 bFGF . 37 1.1.3.3.2.2.2.4 EGF . 38 1.1.3.3.2.2.2.5 TGF-13 . 38 1.1.3.3.2.2.2.6 Cytokine production . 38 1.1.3.3.2.2.2.7 Modulation of glucose metabolism . 38 1.1.3.3.2.2.3 Modulation of cell adhesion and motility . 39 1.1.3.3.2.2.4 Indirect proteolytic function . 39 1.1.3.3.2.3 The role of the KKS in inflammation . 39 1.1.3.3.2.4 The KKS and cancer . 41 1.1.3.3.2.5 The KKS and angiogenesis . 42 1.1.3.3.2.6 The KKS in prostate and breast cancer . 46 1.1.3.3.2.6.
Level of systolic blood pressure within the normal range and risk of recurrent stroke.

CONTEXT Recurrent stroke prevention guidelines suggest that larger reductions in systolic blood pressure (SBP) are positively associated with a greater reduction in the risk of recurrent stroke and define an SBP level of less than 120 mm Hg as normal. However, the association of SBP maintained at such levels with risk of vascular events after a recent ischemic stroke is unclear. OBJECTIVE To assess the association of maintaining low-normal vs high-normal SBP levels with risk of recurrent stroke. DESIGN, SETTING, AND PATIENTS Post hoc observational analysis of a multicenter trial involving 20,330 patients (age ≥50 years) with recent non-cardioembolic ischemic stroke; patients were recruited from 695 centers in 35 countries from September 2003 through July 2006 and followed up for 2.5 years (follow-up ended on February 8, 2008). Patients were categorized based on their mean SBP level: very low-normal (<120 mm Hg), low-normal (120-<130 mm Hg), high-normal (130-<140 mm Hg), high (140-<150 mm Hg), and very high (≥150 mm Hg). MAIN OUTCOME MEASURES The primary outcome was first recurrence of stroke of any type and the secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. RESULTS The recurrent stroke rates were 8.0% (95% CI, 6.8%-9.2%) for the very low-normal SBP level group, 7.2% (95% CI, 6.4%-8.0%) for the low-normal SBP group, 6.8% (95% CI, 6.1%-7.4%) for the high-normal SBP group, 8.7% (95% CI, 7.9%-9.5%) for the high SBP group, and 14.1% (95% CI, 13.0%-15.2%) for the very high SBP group. Compared with patients in the high-normal SBP group, the risk of the primary outcome was higher for patients in the very low-normal SBP group (adjusted hazard ratio [AHR], 1.29; 95% CI, 1.07-1.56), in the high SBP group (AHR, 1.23; 95% CI, 1.07-1.41), and in the very high SBP group (AHR, 2.08; 95% CI, 1.83-2.37). Compared with patients in the high-normal SBP group, the risk of secondary outcome was higher for patients in the very low-normal SBP group (AHR, 1.31; 95% CI, 1.13-1.52), in the low-normal SBP group (AHR, 1.16; 95% CI, 1.03-1.31), in the high SBP group (AHR, 1.24; 95% CI, 1.11-1.39), and in the very high SBP group (AHR, 1.94; 95% CI, 1.74-2.16). CONCLUSION Among patients with recent non-cardioembolic ischemic stroke, SBP levels during follow-up in the very low-normal (<120 mm Hg), high (140-<150 mm Hg), or very high (≥150 mm Hg) range were associated with increased risk of recurrent stroke. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00153062.
Exposure to parental smoking in childhood or adolescence is associated with increased carotid intima-media thickness in young adults: evidence from the Cardiovascular Risk in Young Finns study and the Childhood Determinants of Adult Health Study.

AIM Recent evidence suggests that the exposure of children to their parents' smoking adversely effects endothelial function in adulthood. We investigated whether the association was also present with carotid intima-media thickness (IMT) up to 25 years later. METHODS AND RESULTS The study comprised participants from the Cardiovascular Risk in Young Finns Study (YFS, n = 2401) and the Childhood Determinants of Adult Health (CDAH, n = 1375) study. Exposure to parental smoking (none, one, or both) was assessed at baseline by questionnaire. B-mode ultrasound of the carotid artery determined IMT in adulthood. Linear regression on a pooled dataset accounting for the hierarchical data and potential confounders including age, sex, parental education, participant smoking, education, and adult cardiovascular risk factors was conducted. Carotid IMT in adulthood was greater in those exposed to both parents smoking than in those whose parents did not smoke [adjusted marginal means: 0.647 mm ± 0.022 (mean ± SE) vs. 0.632 mm ± 0.021, P = 0.004]. Having both parents smoke was associated with vascular age 3.3 years greater at follow-up than having neither parent smoke. The effect was independent of participant smoking at baseline and follow-up and other confounders and was uniform across categories of age, sex, adult smoking status, and cohort. CONCLUSIONS These results show the pervasive effect of exposure to parental smoking on children's vascular health up to 25 years later. There must be continued efforts to reduce smoking among adults to protect young people and to reduce the burden of cardiovascular disease across the population.
Canned soup consumption and urinary bisphenol A: a randomized crossover trial.

lesterol-lowering foods given at 2 levels of intensity of dietary advice on serum lipids in hyperlipidemia: a randomized controlled trial. JAMA. 2011;306(8): 831-839. 2. Weingärtner O, Lütjohann D, Ji S, et al. Vascular effects of diet supplementation with plant sterols. J Am Coll Cardiol. 2008;51(16):1553-1561. 3. Patel MD, Thompson PD. Phytosterols and vascular disease. Atherosclerosis. 2006;186(1):12-19. 4. Teupser D, Baber R, Ceglarek U, et al. Genetic regulation of serum phytosterol levels and risk of coronary artery disease. Circ Cardiovasc Genet. 2010;3(4): 331-339. 5. Weingärtner O, Böhm M, Laufs U. Controversial role of plant sterol esters in the management of hypercholesterolaemia. Eur Heart J. 2009;30(4):404-409.