Increased Matrix Metalloproteinase (MMPs) Levels Do Not Predict Disease Severity or Progression in Emphysema

Rationale: Though matrix metalloproteinases (MMPs) are critical in the pathogenesis of COPD, their utility as a disease biomarker remains uncertain. This study aimed to determine whether bronchoalveolar lavage (BALF) or plasma MMP measurements correlated with disease severity or functional decline in emphysema. Methods: Enzyme-linked immunosorbent assay and luminex assays measured MMP-1, -9, -12 and tissue inhibitor of matrix metalloproteinase-1 in the BALF and plasma of non-smokers, smokers with normal lung function and moderate-to-severe emphysema subjects. In the cohort of 101 emphysema subjects correlative analyses were done to determine if MMP or TIMP-1 levels were associated with key disease parameters or change in lung function over an 18-month time period. Main Results: Compared to non-smoking controls, MMP and TIMP-1 BALF levels were significantly elevated in the emphysema cohort. Though MMP-1 was elevated in both the normal smoker and emphysema groups, collagenase activity was only increased in the emphysema subjects. In contrast to BALF, plasma MMP-9 and TIMP-1 levels were actually decreased in the emphysema cohort compared to the control groups. Both in the BALF and plasma, MMP and TIMP-1 measurements in the emphysema subjects did not correlate with important disease parameters and were not predictive of subsequent functional decline. Conclusions: MMPs are altered in the BALF and plasma of emphysema; however, the changes in MMPs correlate poorly with parameters of disease intensity or progression. Though MMPs are pivotal in the pathogenesis of COPD, these findings suggest that measuring MMPs will have limited utility as a prognostic marker in this disease. © 2013 D'Armiento et al

Place-of-residence errors on death certificates for two contiguous U. S. counties

BACKGROUND: Based on death certificate data, the Texas Department of Health Bureau of Vital Statistics calculates age adjusted all-cause mortality rates for each Texas county yearly. In 1998 the calculated rates for two adjacent Texas counties was disparate. These counties contain one city (Amarillo) and are identical in size. This study examined the accuracy of recorded county of residence for deaths in the two counties in 1998. In our jurisdiction, the county of residence is assigned by funeral homes. METHODS: A random sample of 20% of death certificates was selected. The accuracy of the county of residence was verified by using a large area map, Tax Appraisal District records, and U.S. Census Bureau databases. Inaccuracies in recording the county or zip code of residence was recorded. RESULTS: Eighteen of 354 (5.4%) death certificates recorded the incorrect county and 21 of 354 (5.9%) of death certificates recorded the zip code improperly. There was a 14.4% county recording error rate for one county compared to a 0.82% for the other county. The zip code error rate was similar for the two counties (5.9% vs. 5.8%). Of the county errors, 83% occurred for addresses within a zip code that contained addresses in both counties. CONCLUSION: This study demonstrated a large error rate (14%) in recording county of residence for deaths in one county. A similar rate was not seen in an adjacent county. This led to significant miscalculation of mortality rates for two counties. We believe that errors may have arisen in part from use of internet programs by funeral homes to assign the county of residence. With some of these programs, the county is determined by zip code, and when a zip code straddles two counties, the program automatically assigns the county whose name appears first in the alphabet. This type of error could be avoided if funeral homes determined the county of residence from Tax Appraisal District or Census Bureau records, both of which are available on the internet. This type of error could also be avoided if vital statistics offices verified the county and zip code of residence using official sources

Effects of non-steroidal anti-inflammatory drugs on cancer sites other than the colon and rectum: a meta-analysis

BACKGROUND: Observational studies have consistently shown that aspirin and non-steroidal anti-inflammatory drug (NSAID) use is associated with a close to 50% reduced risk of colorectal cancer. Studies assessing the effects of NSAIDs on other cancers have shown conflicting results. Therefore, we conducted a meta-analysis to evaluate the relationship between NSAID use and cancer other than colorectal. METHODS: We performed a search in Medline (from 1966 to 2002) and identified a total of 47 articles (13 cohort and 34 case-control studies). Overall estimates of the relative risk (RR) were calculated for each cancer site using random effects models. RESULTS: Aspirin use was associated with a reduced risk of cancer of the esophagus and the stomach (RR, 0.51; 95%CI (0.38–0.69), and 0.73; 95%CI (0.63–0.84)). Use of NSAIDs was similarly associated with a lower risk of esophageal and gastric cancers (RR,0.65; 95% CI(0.46–0.92) and RR,0.54; 95%CI (0.39–0.75)). Among other cancers, only the results obtained for breast cancer were fairly consistent in showing a slight reduced risk among NSAID and aspirin users (RR, 0.77; 95%CI (0.66–0.88), and RR, 0.77; 95%CI (0.69–0.86) respectively)). CONCLUSIONS: The results of this meta-analysis show that the potential chemopreventive role of NSAIDs in colorectal cancer might be extended to other gastrointestinal cancers such as esophagus and stomach. Further research is required to evaluate the role of NSAIDs at other cancers sites

Brane-World Gravity

The observable universe could be a 1+3-surface (the "brane") embedded in a 1+3+\textit{d}-dimensional spacetime (the "bulk"), with Standard Model particles and fields trapped on the brane while gravity is free to access the bulk. At least one of the \textit{d} extra spatial dimensions could be very large relative to the Planck scale, which lowers the fundamental gravity scale, possibly even down to the electroweak ($\sim$ TeV) level. This revolutionary picture arises in the framework of recent developments in M theory. The 1+10-dimensional M theory encompasses the known 1+9-dimensional superstring theories, and is widely considered to be a promising potential route to quantum gravity. At low energies, gravity is localized at the brane and general relativity is recovered, but at high energies gravity "leaks" into the bulk, behaving in a truly higher-dimensional way. This introduces significant changes to gravitational dynamics and perturbations, with interesting and potentially testable implications for high-energy astrophysics, black holes, and cosmology. Brane-world models offer a phenomenological way to test some of the novel predictions and corrections to general relativity that are implied by M theory. This review analyzes the geometry, dynamics and perturbations of simple brane-world models for cosmology and astrophysics, mainly focusing on warped 5-dimensional brane-worlds based on the Randall--Sundrum models. We also cover the simplest brane-world models in which 4-dimensional gravity on the brane is modified at \emph{low} energies -- the 5-dimensional Dvali--Gabadadze--Porrati models. Then we discuss co-dimension two branes in 6-dimensional models.Comment: A major update of Living Reviews in Relativity 7:7 (2004) "Brane-World Gravity", 119 pages, 28 figures, the update contains new material on RS perturbations, including full numerical solutions of gravitational waves and scalar perturbations, on DGP models, and also on 6D models. A published version in Living Reviews in Relativit

Childhood emotional problems and self-perceptions predict weight gain in a longitudinal regression model

<p>Abstract</p> <p>Background</p> <p>Obesity and weight gain are correlated with psychological ill health. We predicted that childhood emotional problems and self-perceptions predict weight gain into adulthood.</p> <p>Methods</p> <p>Data on around 6,500 individuals was taken from the 1970 Birth Cohort Study. This sample was a representative sample of individuals born in the UK in one week in 1970. Body mass index was measured by a trained nurse at the age of 10 years, and self-reported at age 30 years. Childhood emotional problems were indexed using the Rutter B scale and self-report. Self-esteem was measured using the LAWSEQ questionnaire, whilst the CARALOC scale was used to measure locus of control.</p> <p>Results</p> <p>Controlling for childhood body mass index, parental body mass index, and social class, childhood emotional problems as measured by the Rutter scale predicted weight gain in women only (least squares regression <it>N </it>= 3,359; coefficient 0.004; <it>P </it>= 0.032). Using the same methods, childhood self-esteem predicted weight gain in both men and women (<it>N </it>= 6,526; coefficient 0.023; <it>P </it>< 0.001), although the effect was stronger in women. An external locus of control predicted weight gain in both men and women (<it>N </it>= 6,522; coefficient 0.022; <it>P </it>< 0.001).</p> <p>Conclusion</p> <p>Emotional problems, low self-esteem and an external locus of control in childhood predict weight gain into adulthood. This has important clinical implications as it highlights a direction for early intervention strategies that may contribute to efforts to combat the current obesity epidemic.</p

Cannabidiol Reduces Aβ-Induced Neuroinflammation and Promotes Hippocampal Neurogenesis through PPARγ Involvement

Peroxisome proliferator-activated receptor-γ (PPARγ) has been reported to be involved in the etiology of pathological features of Alzheimer's disease (AD). Cannabidiol (CBD), a Cannabis derivative devoid of psychomimetic effects, has attracted much attention because of its promising neuroprotective properties in rat AD models, even though the mechanism responsible for such actions remains unknown. This study was aimed at exploring whether CBD effects could be subordinate to its activity at PPARγ, which has been recently indicated as its putative binding site. CBD actions on β-amyloid-induced neurotoxicity in rat AD models, either in presence or absence of PPAR antagonists were investigated. Results showed that the blockade of PPARγ was able to significantly blunt CBD effects on reactive gliosis and subsequently on neuronal damage. Moreover, due to its interaction at PPARγ, CBD was observed to stimulate hippocampal neurogenesis. All these findings report the inescapable role of this receptor in mediating CBD actions, here reported

Search for copy number variants in chromosomes 15q11-q13 and 22q11.2 in obsessive compulsive disorder

<p>Abstract</p> <p>Background</p> <p>Obsessive-compulsive disorder (OCD) is a clinically and etiologically heterogeneous syndrome. The high frequency of obsessive-compulsive symptoms reported in subjects with the 22q11.2 deletion syndrome (DiGeorge/velocardiofacial syndrome) or Prader-Willi syndrome (15q11-13 deletion of the paternally derived chromosome), suggests that gene dosage effects in these chromosomal regions could increase risk for OCD. Therefore, the aim of this study was to search for microrearrangements in these two regions in OCD patients.</p> <p>Methods</p> <p>We screened the 15q11-13 and 22q11.2 chromosomal regions for genomic imbalances in 236 patients with OCD using multiplex ligation-dependent probe amplification (MLPA).</p> <p>Results</p> <p>No deletions or duplications involving 15q11-13 or 22q11.2 were identified in our patients.</p> <p>Conclusions</p> <p>Our results suggest that deletions/duplications of chromosomes 15q11-13 and 22q11.2 are rare in OCD. Despite the negative findings in these two regions, the search for copy number variants in OCD using genome-wide array-based methods is a highly promising approach to identify genes of etiologic importance in the development of OCD.</p

TNFR1 inhibition with a nanobody protects against EAE development in mice

TNF has as detrimental role in multiple sclerosis (MS), however, anti-TNF medication is not working. Selective TNF/TNFR1 inhibition whilst sparing TNFR2 signaling reduces the pro-inflammatory effects of TNF but preserves the important neuroprotective signals via TNFR2. We previously reported the generation of a Nanobody-based selective inhibitor of human TNFR1, TROS that will be tested in experimental autoimmune encephalomyelitis (EAE). We specifically antagonized TNF/TNFR1 signaling using TROS in a murine model of MS, namely MOG(35-55)-induced EAE. Because TROS does not cross-react with mouse TNFR1, we generated mice expressing human TNFR1 in a mouse TNFR1-knockout background (hTNFR1 Tg), and we determined biodistribution of Tc-99m-TROS and effectiveness of TROS in EAE in those mice. Biodistribution analysis demonstrated that intraperitoneally injected TROS is retained more in organs of hTNFR1 Tg mice compared to wild type mice. TROS was also detected in the cerebrospinal fluid (CSF) of hTNFR1 Tg mice. Prophylactic TROS administration significantly delayed disease onset and ameliorated its symptoms. Moreover, treatment initiated early after disease onset prevented further disease development. TROS reduced spinal cord inflammation and neuroinflammation, and preserved myelin and neurons. Collectively, our data illustrate that TNFR1 is a promising therapeutic target in MS

Social Media and Depressive Symptoms in Childhood and Adolescence: A Systematic Review

Concerns are increasingly raised in academic and lay literature about the impact of the internet on young people’s well-being. This systematic review examined empirical research on the relationship between social media use and depressive symptoms in the child and adolescent population. A systematic search of Medline, PsycInfo and Embase databases yielded eleven eligible studies. Relevant results were extracted from each study, with a total sample of 12,646. Analysis revealed a small but statistically significant correlation between social media use and depressive symptoms in young people. However, studies varied widely in methods, sample size and results, making the clinical significance of these findings nuanced. Over half of the studies were cross-sectional, while those of longitudinal design were of limited duration. This review justifies further investigation of this phenomenon, with a need for consensus on variables and measurement