Pathogen burden, inflammation, proliferation and apoptosis in human in-stent restenosis - Tissue characteristics compared to primary atherosclerosis

Pathogenic events leading to in-stent restenosis (ISR) are still incompletely understood. Among others, inflammation, immune reactions, deregulated cell death and growth have been suggested. Therefore, atherectomy probes from 21 patients with symptomatic ISR were analyzed by immunohistochemistry for pathogen burden and compared to primary target lesions from 20 stable angina patients. While cytomegalovirus, herpes simplex virus, Epstein-Barr virus and Helicobacter pylori were not found in ISR, acute and/or persistent chlamydial infection were present in 6/21 of these lesions (29%). Expression of human heat shock protein 60 was found in 8/21 of probes (38%). Indicated by distinct signals of CD68, CD40 and CRP, inflammation was present in 5/21 (24%), 3/21 (14%) and 2/21 (10%) of ISR cases. Cell density of ISR was significantly higher than that of primary lesions ( 977 +/- 315 vs. 431 +/- 148 cells/mm(2); p < 0.001). There was no replicating cell as shown by Ki67 or PCNA. TUNEL+ cells indicating apoptosis were seen in 6/21 of ISR specimens (29%). Quantitative analysis revealed lower expression levels for each intimal determinant in ISR compared to primary atheroma (all p < 0.05). In summary, human ISR at the time of clinical presentation is characterized by low frequency of pathogen burden and inflammation, but pronounced hypercellularity, low apoptosis and absence of proliferation. Copyright (C) 2004 S. Karger AG, Basel

A Structural Split in the Human Genome

Background: Promoter-associated CpG islands (PCIs) mediate methylation-dependent gene silencing, yet tend to co-locate to transcriptionally active genes. To address this paradox, we used data mining to assess the behavior of PCI-positive (PCI+) genes in the human genome. Results: PCI+ genes exhibit a bimodal distribution: (1) a 'housekeeping-like' subset characterized by higher GC content and lower intron length/number, and (2) a 'pseudogene paralog' subset characterized by lower GC content and higher intron length/number (p<0.001). These subsets are functionally distinguishable, with the former gene group characterized by higher expression levels and lower evolutionary rate (p<0.001). PCI-negative (PCI-) genes exhibit higher evolutionary rate and narrower expression breadth than PCI+ genes (p<0.001), consistent with more frequent tissue-specific inactivation. Conclusions: Adaptive evolution of the human genome appears driven in part by declining transcription of a subset of PCI+ genes, predisposing to both CpG→TpA mutation and intron insertion. We propose a model of evolving biological complexity in which environmentally-selected gains or losses of PCI methylation respectively favor positive or negative selection, thus polarizing PCI+ gene structures around a genomic core of ancestral PCI- genes. © 2007 Tang, Epstein.published_or_final_versio

Incidence of Lead System Malfunction Detected During Implantable Defibrillator Generator Replacement

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71565/1/j.1540-8159.1996.tb04183.x.pd

Prevalence and Determinants of Obesity among Primary School Children in Dar es Salaam, Tanzania.

Childhood obesity has increased dramatically and has become a public health concern worldwide. Childhood obesity is likely to persist through adulthood and may lead to early onset of NCDs. However, there is paucity of data on obesity among primary school children in Tanzania. This study assessed the prevalence and determinants of obesity among primary school children in Dar es Salaam. A cross sectional study was conducted among school age children in randomly selected schools in Dar es Salaam. Anthropometric and blood pressure measurements were taken using standard procedures. Body Mass Index (BMI) was calculated as weight in kilograms divided by the square of height in meters (kg/m2). Child obesity was defined as BMI at or above 95th percentile for age and sex. Socio-demographic characteristics of children were determined using a structured questionnaire. Logistic regression was used to determine association between independent variables with obesity among primary school children in Dar es Salaam. A total of 446 children were included in the analysis. The mean age of the participants was 11.1±2.0 years and 53.1% were girls. The mean BMI, SBP and DBP were 16.6±4.0 kg/m2, 103.9±10.3mmHg and 65.6±8.2mmHg respectively. The overall prevalence of child obesity was 5.2% and was higher among girls (6.3%) compared to boys (3.8%). Obese children had significantly higher mean values for age (p=0.042), systolic and diastolic blood pressures (all p<0.001). Most obese children were from households with fewer children (p=0.019) and residing in urban areas (p=0.002). Controlling for other variables, age above 10 years (AOR=3.3, 95% CI=1.5-7.2), female sex (AOR=2.6, 95% CI=1.4-4.9), urban residence (AOR=2.5, 95% CI=1.2-5.3) and having money to spend at school (AOR=2.6, 95% CI=1.4-4.8) were significantly associated with child obesity. The prevalence of childhood obesity in this population was found to be low. However, children from urban schools and girls were proportionately more obese compared to their counterparts. Primary preventive measures for childhood obesity should start early in childhood and address socioeconomic factors of parents contributing to childhood obesity

Outcome measurement in functional neurological disorder: a systematic review and recommendations.

OBJECTIVES: We aimed to identify existing outcome measures for functional neurological disorder (FND), to inform the development of recommendations and to guide future research on FND outcomes. METHODS: A systematic review was conducted to identify existing FND-specific outcome measures and the most common measurement domains and measures in previous treatment studies. Searches of Embase, MEDLINE and PsycINFO were conducted between January 1965 and June 2019. The findings were discussed during two international meetings of the FND-Core Outcome Measures group. RESULTS: Five FND-specific measures were identified-three clinician-rated and two patient-rated-but their measurement properties have not been rigorously evaluated. No single measure was identified for use across the range of FND symptoms in adults. Across randomised controlled trials (k=40) and observational treatment studies (k=40), outcome measures most often assessed core FND symptom change. Other domains measured commonly were additional physical and psychological symptoms, life impact (ie, quality of life, disability and general functioning) and health economics/cost-utility (eg, healthcare resource use and quality-adjusted life years). CONCLUSIONS: There are few well-validated FND-specific outcome measures. Thus, at present, we recommend that existing outcome measures, known to be reliable, valid and responsive in FND or closely related populations, are used to capture key outcome domains. Increased consistency in outcome measurement will facilitate comparison of treatment effects across FND symptom types and treatment modalities. Future work needs to more rigorously validate outcome measures used in this population

Improvements in 25 Years of Implantable Cardioverter Defibrillator Therapy

In 1980, Dr. Michel Mirowski and his team inserted the first implantable cardioverter defibrillator (ICD) in a patient. Initially, ICD therapy was not widely accepted, and many physicians actually considered this therapy unethical. Large secondary and primary prevention trials, demonstrating a beneficial effect of ICD therapy in selected patients not only on arrhythmic death but also on all-cause mortality, stimulated a rapid growth in the number of implants and increased patient’s and physician’s acceptance. Improvements in size and weight, arrhythmia discrimination capabilities, battery technology, shock waveform and output, monitoring capabilities and defibrillator electrode technology eventually resulted in the current large number of yearly implants. Today, almost 40 years after the conception of the ICD and 25 years after the first human implant, ICD therapy is the treatment of choice for patients at risk for life-threatening arrhythmias either as secondary or primary prevention. Furthermore, with the more recent addition of resynchronisation therapy to standard ICD therapy, it became possible to treat selected patients with advanced symptoms of heart failure and to lower the risk of sudden death

The geography of recent genetic ancestry across Europe

The recent genealogical history of human populations is a complex mosaic formed by individual migration, large-scale population movements, and other demographic events. Population genomics datasets can provide a window into this recent history, as rare traces of recent shared genetic ancestry are detectable due to long segments of shared genomic material. We make use of genomic data for 2,257 Europeans (the POPRES dataset) to conduct one of the first surveys of recent genealogical ancestry over the past three thousand years at a continental scale. We detected 1.9 million shared genomic segments, and used the lengths of these to infer the distribution of shared ancestors across time and geography. We find that a pair of modern Europeans living in neighboring populations share around 10-50 genetic common ancestors from the last 1500 years, and upwards of 500 genetic ancestors from the previous 1000 years. These numbers drop off exponentially with geographic distance, but since genetic ancestry is rare, individuals from opposite ends of Europe are still expected to share millions of common genealogical ancestors over the last 1000 years. There is substantial regional variation in the number of shared genetic ancestors: especially high numbers of common ancestors between many eastern populations likely date to the Slavic and/or Hunnic expansions, while much lower levels of common ancestry in the Italian and Iberian peninsulas may indicate weaker demographic effects of Germanic expansions into these areas and/or more stably structured populations. Recent shared ancestry in modern Europeans is ubiquitous, and clearly shows the impact of both small-scale migration and large historical events. Population genomic datasets have considerable power to uncover recent demographic history, and will allow a much fuller picture of the close genealogical kinship of individuals across the world.Comment: Full size figures available from http://www.eve.ucdavis.edu/~plralph/research.html; or html version at http://ralphlab.usc.edu/ibd/ibd-paper/ibd-writeup.xhtm

Effective cardiac resynchronization therapy for an adolescent patient with dilated cardiomyopathy seven years after mitral valve replacement and septal anterior ventricular exclusion

Cardiac resynchronization therapy (CRT) is a new treatment for refractory heart failure. However, most heart failure patients treated with CRT are middle-aged or old patients with idiopathic or ischemic dilated cardiomyopathy. We treated a 17 year 11 month old girl with dilated cardiomyopathy after mitral valve replacement (MVR) and septal anterior ventricular exclusion (SAVE). Seven years after the SAVE procedure, she presented complaining of palpitations and general fatigue with normal activity. Her echocardiogram showed reduced left ventricular function. Despite of optimal medical therapy, her left ventricular function continued to decline and she experienced regular arrhythmias such as premature ventricular contractions. We thus elected to perform cardiac resynchronization therapy with defibrillator (CRT-D). After CRT-D, her clinical symptoms improved dramatically and left ventricular ejection fraction (LVEF) improved from 31.2% to 51.3% as assessed by echocardiogram. Serum BNP levels decreased from 448.2 to 213.6 pg/ml. On ECG, arrhythmias were remarkably reduced and QRS duration was shortened from 174 to 152 msec. In conclusion, CRT-D is an effective therapeutic option for adolescent patients with refractory heart failure after left ventricular volume reduction surgery