The role of the ThyGeNEXT oncogene panel used in combination with the expanded miRNA panel ThyraMIRv2 in Indeterminate thyroid nodules: A large, blinded, real-world, observational study.

BACKGROUND: Molecular analysis of fine-needle aspiration biopsies (FNAB) improves the diagnostic accuracy of cytologically indeterminate thyroid nodules (ITNs). Recently, the use of MPTXv2 has been shown to further improve the accuracy of risk stratification of ITNs. METHODS: A total of 338 patient samples with atypia of undetermined significance (n = 260) or follicular neoplasm (n = 78) cytology diagnosis and corresponding surgical outcomes or clinical follow-up, collected between 2016 and 2020 were included. All samples underwent multiplatform testing (MPTXv1), which includes an oncogene panel (ThyGeNEXT®) plus a microRNA risk classifier (ThyraMIR®). A blinded, secondary analysis was performed to assess the added utility of MPTXv2 (ThyraMIR®v2). The average length of follow-up for the surveillance group (n = 248) was 30 months. RESULTS: Sensitivity at moderate threshold was 96% and specificity at positive threshold was 99% for MPTXv2. At 14% disease prevalence, the negative predictive value at the moderate threshold was 99% and the positive predictive value at the positive threshold was 89% for MPTXv2. MPTXv2 had fewer patients classified into the moderate-risk group than MPTXv1, which was statistically significant (p < .001). Using surgical resection, the gold standard for outcomes, MPTXv2 showed a statistically greater area under the curve (p = .028) than MPTXv1, demonstrating greater accuracy for MPTXv2. CONCLUSION: Both test versions demonstrated robust performance with low false-positive molecular results. Data suggest that incorporation of MPTXv1, and more recently MPTXv2, into clinical practice within our healthcare network resulted in improved accuracy of ITN risk stratification.

A Retrospective Evaluation of the Diagnostic Performance of an Interdependent Pairwise MicroRNA Expression Analysis with a Mutation Panel in Indeterminate Thyroid Nodules.

Background: The addition of genetic analysis to the evaluation of thyroid nodule fine-needle aspiration biopsy samples improves diagnostic accuracy of cytologically indeterminate thyroid nodules (ITNs) with Bethesda III or IV cytopathology. We previously reported the performance of a multiplatform molecular test, referred to in this study as MPTXv1, that includes a mutation panel (ThyGeNEXT®) plus an algorithmic microRNA (miRNA) risk classifier (ThyraMIR®). Complex interactions of growth-promoting and -suppressing miRNAs affect the phenotype. We previously demonstrated that accounting for these interactions with pairwise miRNA expression analysis improves the diagnosis of medullary thyroid carcinoma. In this study, we assess the impact of pairwise miRNA expression analysis on risk stratification of ITNs. Methods: Pairwise expression analysis of 11 miRNAs was performed on a training cohort of histopathology-proven benign nodules (n = 50) to define the mean and standard deviation of each pairwise analysis and create a Benign/Malignant Profiler (MPTXv2), deviations from which predicted the malignancy risk. Clinical validation of MPTXv2 was assessed using a cohort of 178 ITN (Bethesda III and IV) samples from a multicentered, blinded retrospective study, previously evaluated by MPTXv1. Results: Compared with MPTXv1, MPTXv2 significantly improved the test performance. The receiver operating characteristic (ROC) areas under the curve (AUC) increased from 0.85 to 0.97 (p < 0.001), and the diagnostic accuracy at the positive threshold increased significantly (p < 0.05) from 83% [95% confidence interval (CI) = 76-88] to 93% [CI = 89-96]. The significant improvement in the ROC AUC and the diagnostic accuracy was due to a strong statistical trend for improvement in specificity at the positive threshold. At the positive threshold, the specificity for MPTXv1 was 90% [CI = 84-95] and improved to 98% [CI = 94-99] for MPTXv2. Using the MPTXv2, the Moderate-Risk cohort decreased from 50 samples (28% of the cohort) to 24 samples (13% of the cohort). This 52% decrease is statistically significant (p < 0.001) and clinically meaningful. Conclusion: As compared with MPTXv1, pairwise miRNA expression analysis used in MPTXv2 significantly improved the diagnostic accuracy of ITN risk stratification and reduced the size of the Moderate-Risk group. Prospective trials are indicated to confirm these findings in a clinical practice setting.

Can cardiovascular MRI be used to more definitively characterize cardiac masses initially identified using echocardiography?

In diagnosing cardiac and paracardiac masses, cardiac MRI (CMR) has gained acceptance as the gold standard. CMR has been observed to be superior to echocardiography in characterizing soft-tissue structures and, specifically, in classifying cardiac masses. The aim of our study was to evaluate the association between mortality and cardiac or paracardiac masses initially identified by echocardiography (ECHO) and confirmed by CMR. Between January 2002 and August 2007, a total of 158 patients underwent both ECHO and CMR for the evaluation of cardiac masses that were equivocal or undefined by ECHO. The primary study endpoints were 5-year all-cause mortality and 5-year cardiac mortality. Causes of death as of April 1, 2015 were obtained from medical records or the National Death Index. Patients were analyzed according to mass type determined by CMR using the Kruskal-Wallis test, Kaplan-Meier curves, and the log-rank test. Over a mean duration of follow-up of 10.4 ± 2.9 years (range: 0.01-12 years) post-CMR, the overall all-cause mortality rate was 25.9% (41/158). Median age at death was 76 years and there were 21 females (51.2%). Mortality rates in the different classifications of cardiac masses by CMR were as follows: 20% (1/5) in patients with a Nondiagnostic CMR; 20% (1/5) in Other Diagnoses; 17.9% (7/39) in No Masses (includes Normal Anatomical Variants); 16.7% (3/18) in Benign Masses; 23.8% (15/63) in Fat; 50% (5/10) in Thrombus; and 61.5% (8/13) in Malignant Mass. The mean survival time in patients with No Mass (n = 39) was not significantly longer than patients with any type of cardiac mass (n = 114) (P = .16). No significant difference was found in age at death between patients when grouped by CMR classification (P = .40). However, among CMR-confirmed masses, there were some significant differences by mass classification type (P = .006). During the follow-up period, 26% (41/158) of patients died and 22% (9/41) of the deaths were cardiovascular related; there was no significant difference in mean survival times with respect to cause of mortality (P = .23). In patients with cardiac masses, dually confirmed by ECHO and CMR, significant differences in survival time were observed based upon CMR classified type of mass while CMR was instrumental in obviating invasive biopsy.

Ten-Year Mortality in the WISE Study (Women's Ischemia Syndrome Evaluation).

BACKGROUND: The WISE study (Women's Ischemia Syndrome Evaluation) was a prospective cohort study of 936 clinically stable symptomatic women who underwent coronary angiography to evaluate symptoms and signs of ischemia. Long-term mortality data for such women are limited. METHODS AND RESULTS: Obstructive coronary artery disease (CAD) was defined as ≥50% stenosis on angiography by core laboratory. We conducted a National Death Index search to assess the mortality of women who were alive at their final WISE contact date. Death certificates were obtained. All deaths were adjudicated as cardiovascular or noncardiovascular by a panel of WISE cardiologists masked to angiographic data. Multivariate Cox proportional hazards regression was used to identify significant independent predictors of mortality. At baseline, mean age was 58±12 years; 176 (19%) were non-white, primarily black; 25% had a history of diabetes mellitus, 59% hypertension, 55% dyslipidemia, and 59% had a body mass index ≥30. During a median follow-up of 9.5 years (range, 0.2-11.5 years), a total of 184 (20%) died. Of these, 115 (62%) were cardiovascular deaths; 31% of all cardiovascular deaths occurred in women without obstructive CAD (<50% stenosis). Independent predictors of mortality were obstructive CAD, age, baseline systolic blood pressure, history of diabetes mellitus, history of smoking, elevated triglycerides, and estimated glomerular filtration rate. CONCLUSIONS: Among women referred for coronary angiography for signs and symptoms of ischemia, 1 in 5 died from predominantly cardiac pathogeneses within 9 years of angiographic evaluation. A majority of the factors contributing to the risk of death seem to be modifiable by existing therapies. Of note, 1 in 3 of the deaths in this cohort occurred in women without obstructive CAD, a condition often considered benign and without guideline-recommended treatments. Clinical trials are needed to provide treatment guidance for the group without obstructive CAD.

Chemically Induced Degradation of the Oncogenic Transcription Factor BCL6.

The transcription factor BCL6 is a known driver of oncogenesis in lymphoid malignancies, including diffuse large B cell lymphoma (DLBCL). Disruption of its interaction with transcriptional repressors interferes with the oncogenic effects of BCL6. We used a structure-based drug design to develop highly potent compounds that block this interaction. A subset of these inhibitors also causes rapid ubiquitylation and degradation of BCL6 in cells. These compounds display significantly stronger induction of expression of BCL6-repressed genes and anti-proliferative effects than compounds that merely inhibit co-repressor interactions. This work establishes the BTB domain as a highly druggable structure, paving the way for the use of other members of this protein family as drug targets. The magnitude of effects elicited by this class of BCL6-degrading compounds exceeds that of our equipotent non-degrading inhibitors, suggesting opportunities for the development of BCL6-based lymphoma therapeutics.

Sudden Cardiac Death in Women With Suspected Ischemic Heart Disease, Preserved Ejection Fraction, and No Obstructive Coronary Artery Disease: A Report From the Women's Ischemia Syndrome Evaluation Study.

BACKGROUND: Sudden cardiac death (SCD) is often the first presentation of ischemic heart disease; however, there is limited information on SCD among women with and without obstructive coronary artery disease (CAD). We evaluated SCD incidence in the WISE (Women's Ischemia Syndrome Evaluation) study. METHODS AND RESULTS: Overall, 904 women with suspected ischemic heart disease with preserved ejection fraction and core laboratory coronary angiography were followed for outcomes. In case of death, a death certificate and/or a physician or family narrative of the circumstances of death was obtained. A clinical events committee rated all deaths as cardiovascular or noncardiovascular and as SCD or non-SCD. In total, 96 women (11%) died over a median of 6 years (maximum: 8 years). Among 65 cardiovascular deaths, 42% were SCD. Mortality per 1000 person-hours increased linearly with CAD severity (no CAD: 5.8; minimal: 15.9; obstructive: 38.6; P<0.0001). However, the proportion of SCD was similar across CAD severity: 40%, 58%, and 38% for no, minimal, and obstructive CAD subgroups, respectively (P value not significant). In addition to traditional risk factors (age, diabetes mellitus, smoking), a history of depression (P=0.018) and longer corrected QT interval (P=0.023) were independent SCD predictors in the entire cohort. Corrected QT interval was an independent predictor of SCD in women without obstructive CAD (P=0.033). CONCLUSIONS: SCD contributes substantially to mortality in women with and without obstructive CAD. Corrected QT interval is the single independent SCD risk factor in women without obstructive CAD. In addition to management of traditional risk factors, these data indicate that further investigation should address mechanistic understanding and interventions targeting depression and corrected QT interval in women.

Sensitivity and engineered resistance of myeloid leukemia cells to BRD9 inhibition.

Here we show that acute myeloid leukemia (AML) cells require the BRD9 subunit of the SWI-SNF chromatin-remodeling complex to sustain MYC transcription, rapid cell proliferation and a block in differentiation. Based on these observations, we derived small-molecule inhibitors of the BRD9 bromodomain that selectively suppress the proliferation of mouse and human AML cell lines. To establish these effects as on-target, we engineered a bromodomain-swap allele of BRD9 that retains functionality despite a radically altered bromodomain pocket. Expression of this allele in AML cells confers resistance to the antiproliferative effects of our compound series, thus establishing BRD9 as the relevant cellular target. Furthermore, we used an analogous domain-swap strategy to generate an inhibitor-resistant allele of EZH2. To our knowledge, our study provides the first evidence for a role of BRD9 in cancer and reveals a simple genetic strategy for constructing resistance alleles to demonstrate on-target activity of chemical probes in cells.

Cardiac magnetic resonance radiofrequency tissue tagging for diagnosis of constrictive pericarditis: A proof of concept study.

OBJECTIVE: Invasive cardiac catheterization is the venerable "gold standard" for diagnosing constrictive pericarditis. However, its sensitivity and specificity vary dramatically from center to center. Given the ability to unequivocally define segments of the pericardium with the heart via radiofrequency tissue tagging, we hypothesize that cardiac magnetic resonance has the capability to be the new gold standard. METHODS: All patients who were referred for cardiac magnetic resonance evaluation of constrictive pericarditis underwent cardiac magnetic resonance radiofrequency tissue tagging to define visceral-parietal pericardial adherence to determine constriction. This was then compared with intraoperative surgical findings. Likewise, all preoperative cardiac catheterization testing was reviewed in a blinded manner. RESULTS: A total of 120 patients were referred for clinical suspicion of constrictive pericarditis. Thirty-nine patients were defined as constrictive pericarditis positive solely via radiofrequency tissue-tagging cardiac magnetic resonance, of whom 21 were positive, 4 were negative, and 1 was equivocal for constrictive pericarditis, as defined by cardiac catheterization. Of these patients, 16 underwent pericardiectomy and were surgically confirmed. There was 100% agreement between cardiac magnetic resonance-defined constrictive pericarditis positivity and postsurgical findings. No patients were misclassified by cardiac magnetic resonance. In regard to the remaining constrictive pericarditis-positive patients defined by cardiac magnetic resonance, 10 were treated medically, declined, were ineligible for surgery, or were lost to follow-up. Long-term follow-up of those who were constrictive pericarditis negative by cardiac magnetic resonance showed no early or late crossover to the surgery arm. CONCLUSIONS: Cardiac magnetic resonance via radiofrequency tissue tagging offers a unique, efficient, and effective manner of defining clinically and surgically relevant constrictive pericarditis. Specifically, no patient who was identified with constriction via cardiac magnetic resonance underwent inappropriate sternotomy. However, catheterization had substantial and unacceptable false-positive and false-negative rates with important clinical ramifications.

Depression, dietary habits, and cardiovascular events among women with suspected myocardial ischemia.

BACKGROUND: Dietary habits and depression are associated with cardiovascular disease risk. Patients with depression often report poor eating habits, and dietary factors may help explain commonly observed associations between depression and cardiovascular disease. METHODS: From 1996 to 2000, 936 women were enrolled in the Women's Ischemia Syndrome Evaluation at 4 US academic medical centers at the time of clinically indicated coronary angiography and then assessed (median follow-up, 5.9 years) for adverse outcomes (cardiovascular disease death, heart failure, myocardial infarction, stroke). Participants completed a protocol including coronary angiography (coronary artery disease severity) and depression assessments (Beck Depression Inventory scores, antidepressant use, and depression treatment history). A subset of 201 women (mean age, 58.5 years; standard deviation, 11.4) further completed the Food Frequency Questionnaire for Adults (1998 Block). We extracted daily fiber intake and daily servings of fruit and vegetables as measures of dietary habits. RESULTS: In separate Cox regression models adjusted for age, smoking, and coronary artery disease severity, Beck Depression Inventory scores (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.01-1.10), antidepressant use (HR, 2.4; 95% CI, 1.01-5.9), and a history of treatment for depression (HR, 2.4; 95% CI, 1.1-5.3) were adversely associated with time to cardiovascular disease outcomes. Fiber intake (HR, 0.87; 95% CI, 0.78-0.97) and fruit and vegetable consumption (HR, 0.36; 95% CI, 0.19-0.70) were associated with a decreased time to cardiovascular disease event risk. In models including dietary habits and depression, fiber intake and fruit and vegetable consumption remained associated with time to cardiovascular disease outcomes, whereas depression relationships were reduced by 10% to 20% and nonsignificant. CONCLUSIONS: Among women with suspected myocardial ischemia, we observed consistent relationships among depression, dietary habits, and time to cardiovascular disease events. Dietary habits partly explained these relationships. These results suggest that dietary habits should be included in future efforts to identify mechanisms linking depression to cardiovascular disease.

Establishing magnetic resonance imaging as an accurate and reliable tool to diagnose and monitor esophageal cancer in a rat model.

OBJECTIVE: To assess the reliability of magnetic resonance imaging (MRI) for detection of esophageal cancer in the Levrat model of end-to-side esophagojejunostomy. BACKGROUND: The Levrat model has proven utility in terms of its ability to replicate Barrett's carcinogenesis by inducing gastroduodenoesophageal reflux (GDER). Due to lack of data on the utility of non-invasive methods for detection of esophageal cancer, treatment efficacy studies have been limited, as adenocarcinoma histology has only been validated post-mortem. It would therefore be of great value if the validity and reliability of MRI could be established in this setting. METHODS: Chronic GDER reflux was induced in 19 male Sprague-Dawley rats using the modified Levrat model. At 40 weeks post-surgery, all animals underwent endoscopy, MRI scanning, and post-mortem histological analysis of the esophagus and anastomosis. With post-mortem histology serving as the gold standard, assessment of presence of esophageal cancer was made by five esophageal specialists and five radiologists on endoscopy and MRI, respectively. RESULTS: The accuracy of MRI and endoscopic analysis to correctly identify cancer vs. no cancer was 85.3% and 50.5%, respectively. ROC curves demonstrated that MRI rating had an AUC of 0.966 (p<0.001) and endoscopy rating had an AUC of 0.534 (p = 0.804). The sensitivity and specificity of MRI for identifying cancer vs. no-cancer was 89.1% and 80% respectively, as compared to 45.5% and 57.5% for endoscopy. False positive rates of MRI and endoscopy were 20% and 42.5%, respectively. CONCLUSIONS: MRI is a more reliable diagnostic method than endoscopy in the Levrat model. The non-invasiveness of the tool and its potential to volumetrically quantify the size and number of tumors likely makes it even more useful in evaluating novel agents and their efficacy in treatment studies of esophageal cancer.

Clinical implications of the Women's Ischemia Syndrome Evaluation: inter-relationships between symptoms, psychosocial factors and cardiovascular outcomes.

Cardiovascular disease remains the leading cause of death in the USA and is associated with several modifiable (hypertension, diabetes, high cholesterol, tobacco use, physical inactivity, obesity and unhealthy diet) and nonmodifiable (age, gender and family history) risk factors. The role of psychosocial risk factors in the development of cardiovascular disease has a growing body of literature, and differences in men and women have been identified. The Women's Ischemia Syndrome Evaluation provides insight into psychosocial risk factors in a cohort of women presenting with chest pain who had a comprehensive battery of psychosocial assessments and long-term follow-up. This review focuses on symptom presentation for chest pain and its relationship to cardiovascular disease morbidity and mortality, quality of life, healthcare costs and psychosocial predictor variables, including anxiety, depression, hostility and social networks. In the Women's Ischemia Syndrome Evaluation, persistent chest pain was associated with an increased rate of adverse events and relatively high rates of depression and anxiety, with reduced functional capacity and impaired quality of life, over a median of 6 years of follow-up. More research is needed to better understand the relationships between symptoms and negative emotions and to determine whether psychological (pharmacologic and/or cognitive) interventions might impact both psychological and cardiovascular outcomes.

Mitral regurgitation recovery and atrial reverse remodeling following pulmonary vein isolation procedure in patients with atrial fibrillation: a clinical observation proof-of-concept cardiac MRI study.

BACKGROUND: Reverse remodeling of the left atrium (LA) following successful pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF) has been well documented. However, mitral regurgitation (MR) recovery after successful PVI has never been demonstrated systematically. The objective of our study was to retrospectively analyze the effectiveness of PVI in patients with AF on recovery of MR using cardiac magnetic resonance (CMR) imaging. METHODS: Prior to PVI, patients underwent a clinically indicated CMR imaging. Post-PVI (6 ± 2 months), patients underwent a follow-up MRI and were classified into two groups-responders (R) and non-responders (NR) to PVI-as assessed by cessation of AF at the end of the prespecified 6-month (14-day "P" sensitive event monitor defined) follow-up period. Furthermore, CMR was used to evaluate the severity of MR (0 to 4+) and to relate changes in MR to LA volumes as well as mitral apparatus geometry. Patients who had mild and higher MR (2+) on baseline CMR and had a post-PVI CMR were selected for final analysis. RESULTS: Out of the consecutive 122 patients with AF who underwent PVI, 74 patients that had mitral regurgitation on initial CMR were included in the study. Of these74 patients with AF with MR, 52 (70 %) were classified as R and 22 (30 %) were classified as NR. Baseline demographics were similar between the groups. In the subgroup with mild to severe MR, pre vs. post in the R group MR severity significantly improved (mean = 2.3, median = 2.0 vs. mean = 1.0, median = 1.0, p < 0.0001) and was matched by favorable reverse remodeling of the mitral apparatus geometry (annulus = 35 ± 4 vs. 33 ± 3 mm, p < 0.002; tenting area = 175 ± 56 vs.137 ± 37 mm(2), p < 0.003; tenting height = 8 ± 2 vs.7 ± 2 mm, p < 0.02; and tenting angle = 129 ± 10° vs. 131 ± 11°, p = 0.1). However, in the NR subgroup, MR failed to improve (mean = 2.2, median = 2.0 vs. mean = 1.5, median = 1.0, p = NS) and paralleled general failure of mitral geometry reverse remodeling (annulus = 35 ± 4 vs. 35 ± 4 mm, p = 0.2; tenting area = 153 ± 39 vs. 152 ± 34 mm(2), p = NS; tenting height = 7 ± 1 vs. 7.0 ± 2, p = 0.1; and tenting angle = 131 ± 11° vs. 133 ± 10°, p = NS). In those with lesser degrees of MR, favorable remodeling was predicated on responder status to PVI. Similarly, other cardiac dimensions pre- to post-PVI favorably improved in the R group, but not in the NR group. CONCLUSION: In those with durable maintenance of normal sinus rhythm (NSR), cardiac reverse remodeling demonstrated by 3D CMR occurs and is matched by marked improvements in MR and mitral apparatus, likely contributing to continued maintenance of NSR.

A prospective investigation of injury incidence and risk factors among army recruits in combat engineer training.

BACKGROUND: United States Army combat engineer (ENG) training is an intense 14-week course designed to introduce new recruits to basic soldiering activities, Army values and lifestyle, and engineering skills and knowledge. The present investigation examined injury rates and injury risk factors in ENG training. METHODS: At the start of their training, 1,633 male ENG recruits were administered a questionnaire containing items on date of birth, height, weight, tobacco use, prior physical activity, and injury history. Injuries during training were obtained from electronic medical records and the training units provided data on student graduation and attrition. Risk factors were identified using Cox regression. RESULTS: Ninety-two percent of the recruits successfully graduated from the course and 47% of the recruits experienced one or more injuries during training. Univariate Cox regression demonstrated that recruits were at higher injury risk if they reported that they were older, had a higher or lower body mass index, had smoked in the past, had performed less exercise (aerobic or muscle strength) or sports prior to ENG training, had experienced a previous time-loss lower limb injury (especially if they had not totally recovered from that injury), or had a lower educational level. CONCLUSIONS: The present investigation was the first to identify injury rates and identify specific factors increasing injury risk during ENG training. The identified risk factors provide a basis for recommending future prevention strategies.

A prospective investigation of injury incidence and injury risk factors among Army recruits in military police training.

BACKGROUND: United States Army military police (MP) training is a 19-week course designed to introduce new recruits to basic soldiering skills, Army values and lifestyle, and law enforcement skills and knowledge. The present investigation examined injury rates and injury risk factors in MP training. METHODS: At the start of training, 1,838 male and 553 female MP recruits were administered a questionnaire containing items on date of birth, height, weight, tobacco use, prior physical activity, injury history, and menstrual history. Injuries during training were obtained from electronic medical records and the training units provided data on student graduation and attrition. RESULTS: Successfully graduating from the course were 94.3% of the men and 83.7% of the women. Experiencing at least one injury during training were 34.2% of the men and 66.7% of the women (risk ratio (women/men) = 1.95, 95% confidence interval = 1.79-2.13). Recruits were at higher injury risk if they reported that they were older, had smoked in the past, or had performed less frequent exercise or sports prior to MP training. Men were at higher injury risk if they reported a prior injury and women were at higher risk if they reported missing at least six menstrual cycles in the last year or had previously been pregnant. CONCLUSION: The present investigation was the first to identify injury rates and identify specific factors increasing injury risk during MP training.

Fibromyalgia and the relevance of the whole-body vibration exercises in vibratory platforms: a short review

Among nonpharmacological strategy to manage fibromyalgia, exercise (aerobic) has shown efficacy. Whole-body vibration (WBV) exercise has been proposed as a potential clinical intervention. WBV would induce increase in growth hormone (GH). An impairment of the hypothalamic-pituitary-GH-Insulin Growth Factor-1(IGF-1) axis has been implicated in the pathophysiology of fibromyalgia. This article aims to review the studies on exploring the relationship between WBV and fibromyalgia. Literature searches were performed in the PubMed database on 04/03/2010 using terms related to "pain", "whole body vibration" and "fibromyalgia". An important number of publications were identified with the term "pain" and in comparison, only a small number of articles were found related to "fibromyalgia". Three publications found with "whole body vibration" and fibromyalgia were analyzed.There are reports describing increase in serum IGF-1 following exposure to WBV in elderly patients. However, one randomized fibromyalgia trial revealed no changes in serum IGF-1 levels in women undergoing WBV. Due to the paucity of available, effective therapies for fibromyalgia, further studies that explore the relationship between the neuroendocrine system, fibromyalgia and WBV are merited.

Family health narratives: midlife women's concepts of vulnerability to illness.

Perceptions of vulnerability to illness are strongly influenced by the salience given to personal experience of illness in the family. This article proposes that this salience is created through autobiographical narrative, both as individual life story and collectively shaped family history. The article focuses on responses related to health in the family drawn from semi-structured interviews with women in a qualitative study exploring midlife women's health. Uncertainty about the future was a major emergent theme. Most respondents were worried about a specified condition such as heart disease or breast cancer. Many women were uncertain about whether illness in the family was inherited. Some felt certain that illness in the family meant that they were more vulnerable to illness or that their relatives' ageing would be mirrored in their own inevitable decline, while a few expressed cautious optimism about the future. In order to elucidate these responses, we focused on narratives in which family members' appearance was discussed and compared to that of others in the family. The visualization of both kinship and the effects of illness led to strong similarities being seen as grounds for worry. This led to some women distancing themselves from the legacies of illness in their families. Women tended to look at the whole family as the context for their perceptions of vulnerability, developing complex patterns of resemblance or difference within their families.

Body mass index measurement in schools.

BACKGROUND: School-based body mass index (BMI) measurement has attracted much attention across the nation from researchers, school officials, legislators, and the media as a potential approach to address obesity among youth. METHODS: An expert panel, convened by the Centers for Disease Control and Prevention (CDC) in 2005, reviewed and provided expertise on an earlier version of this article. The panel comprised experts in public health, education, school counseling, school medical care, and a parent organization. This article describes the purposes of BMI measurement programs, examines current practices, reviews existing research, summarizes the recommendations of experts, identifies concerns, and provides guidance including a list of safeguards and ideas for future research. RESULTS: The implementation of school-based BMI measurement for surveillance purposes, that is, to identify the percentage of students in a population who are at risk for weight-related problems, is widely accepted; however, considerable controversy exists over BMI measurement for screening purposes, that is, to assess the weight status of individual students and provide this information to parents with guidance for action. Although some promising results have been reported, more evaluation is needed to determine whether BMI screening programs are a promising practice for addressing obesity. CONCLUSIONS: Based on the available information, BMI screening meets some but not all of the criteria established by the American Academy of Pediatrics for determining whether screening for specific health conditions should be implemented in schools. Schools that initiate BMI measurement programs should evaluate the effects of the program on BMI results and on weight-related knowledge, attitudes, and behaviors of youth and their families; they also should adhere to safeguards to reduce the risk of harming students, have in place a safe and supportive environment for students of all body sizes, and implement science-based strategies to promote physical activity and healthy eating.

Fibromyalgia: an overview.

In this article, the authors review current concepts in fibromyalgia. Findings regarding diagnosis, prevalence, comorbidities, and potential pathophysiologic links are discussed. Although fibromyalgia continues to be a complex disorder, there are specific criteria one must meet. Fibromyalgia questionnaires, along with commonalities of age, gender, menopause status, sleep disturbances, and mood symptoms, may aid in the diagnosis. Additionally, the close relationship between fibromyalgia and other chronic disorders should alert the physician to explore for comorbid illness. The relationship between fibromyalgia and irritable bowel syndrome, migraine headaches, and obesity are addressed. The roles of the hypothalamic-pituitary-axis, potential effects of neurotransmitters, and gender-specific hormones all substantiate this diagnosis and provide clues to causality, as well as venues for future treatment.

The Relationship Between Tamoxifen, Estrogen, and Depressive Symptoms.

Tamoxifen is widely used for the treatment of breast cancer. While it is generally well tolerated, clinically relevant depression may be a common side effect. This article reviews reports of depression associated with tamoxifen and considers the specific qualities of tamoxifen that may account for depressive symptomatology. A multitude of factors may be responsible for depression in the breast cancer patient such as adjuvant therapy, stage of treatment, and poor body image. Tamoxifen distinguishes itself due to its potential activity at the neuroendocrine level. Antagonist qualities of tamoxifen may block the neuroprotective effects of estrogen. This may result in down-regulation of neurotransmitters associated with mood regulation such as serotonin and norepinephrine. Additional research into the mechanism of tamoxifen-associated depression is needed. As the use of tamoxifen increases, it will be essential to consider the potential side effect of depression, which in itself may alter immune function and overall survival. The risk and benefits of tamoxifen must be carefully weighed and depressive symptoms should be monitored and treated in women receiving tamoxifen therapy.