Gross Domestic Product (GDP) and productivity of schizophrenia trials: an ecological study

The 5000 randomised controlled trials (RCTs) in the Cochrane Schizophrenia Group's database affords an opportunity to research for variables related to the differences between nations of their output of schizophrenia trials. Ecological study – investigating the relationship between four economic/demographic variables and number of schizophrenia RCTs per country. The variable with closest correlation was used to predict the expected number of studies. GDP closely correlated with schizophrenia trial output, with 76% of the total variation about the Y explained by the regression line (r = 0.87, 95% CI 0.79 to 0.92, r2 = 0.76). Many countries have a strong tradition of schizophrenia trials, exceeding their predicted output. All nations with no identified trial output had GDPs that predicted zero trial activity. Several nations with relatively small GDPs are, nevertheless, highly productive of trials. Some wealthy countries seem either not to have produced the expected number of randomised trials or not to have disseminated them to the English-speaking world. This hypothesis-generating study could not investigate causal relationships, but suggests, that for those seeking all relevant studies, expending effort searching the scientific literature of Germany, Italy, France, Brazil and Japan may be a good investment

Molecular Analysis of Precursor Lesions in Familial Pancreatic Cancer

PMCID: PMC3553106This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Ethyl pyruvate reduces mortality in an endotoxin-induced severe acute lung injury mouse model

<p>Abstract</p> <p>Background</p> <p>Ethyl pyruvate (EP) was recently identified as an experimental therapeutic agent in a wide variety of model systems for inflammation-mediated tissue and cellular injury.</p> <p>Objective</p> <p>To evaluate the effect of ethyl EP on improving the survival in mice with LPS-induced acute lung injury (ALI).</p> <p>Methods</p> <p>ALI was induced by administering lipopolysaccharide (LPS) intratracheally. The mice were treated intraperitoneally (i.p.) with 100, 50 and 10 mg/kg EP immediately before intratracheal instillation of LPS, and 100 mg/kg EP was administered 0, 12, 24 and 48 hours after induction of ALI. The mortality rate was recorded and analyzed by the Kaplan-Meier method. Serum tumor necrosis factor (TNF)-α, interleukin (IL) -6 and IL-1 β were measured in bronchial alveolar lavage fluid using an enzyme-linked immunosorbent assay. High-mobility group box 1 levels were measured by Western immunoblotting.</p> <p>Results</p> <p>Treatment with EP significantly inhibited the release of HMGB1, TNF-α, IL-6 and IL-1β into bronchoalveolar lavage (BAL) fluids of ALI mice, and reduced the permeability index of the injured lung. High EP doses reduced the mortality from ALI and the permeability index (100 mg/kg and 50 mg/kg EP versus control; P < 0.0001). Early administration of high-dose EP significantly increased survival rate (0, 12 and 24 h versus control; P < 0.0001, P < 0.0001 and P = 0.01 respectively by log-rank test). There was no survival advantage when EP was initiated at 48 h.</p> <p>Conclusion</p> <p>Ethyl pyruvate improves survival and reduces the lung permeability index in mice with LPS-induced ALI.</p

The Role of Interleukin-1 and Interleukin-18 in Pro-Inflammatory and Anti-Viral Responses to Rhinovirus in Primary Bronchial Epithelial Cells

Human Rhinovirus (HRV) is associated with acute exacerbations of chronic respiratory disease. In healthy individuals, innate viral recognition pathways trigger release of molecules with direct anti-viral activities and pro-inflammatory mediators which recruit immune cells to support viral clearance. Interleukin-1alpha (IL-1α), interleukin-1beta (IL-1β) and interleukin-18 (IL-18) have critical roles in the establishment of neutrophilic inflammation, which is commonly seen in airways viral infection and thought to be detrimental in respiratory disease. We therefore investigated the roles of these molecules in HRV infection of primary human epithelial cells. We found that all three cytokines were released from infected epithelia. Release of these cytokines was not dependent on cell death, and only IL-1β and IL-18 release was dependent on caspase-1 catalytic activity. Blockade of IL-1 but not IL-18 signaling inhibited up-regulation of pro-inflammatory mediators and neutrophil chemoattractants but had no effect on virus induced production of interferons and interferon-inducible genes, measured at both mRNA and protein level. Similar level of virus mRNA was detected with and without IL-1RI blockade. Hence IL-1 signaling, potentially involving both IL-1β and IL-1α, downstream of viral recognition plays a key role in induction of pro-inflammatory signals and potentially in recruitment and activation of immune cells in response to viral infection instigated by the epithelial cells, whilst not participating in direct anti-viral responses

DNA Barcoding Reveals Cryptic Diversity in Lumbricus terrestris L., 1758 (Clitellata): Resurrection of L. herculeus (Savigny, 1826)

The widely studied and invasive earthworm, Lumbricus terrestris L., 1758 has been the subject of nomenclatural debate for many years. However these disputes were not based on suspicions of heterogeneity, but rather on the descriptions and nomenclatural acts associated with the species name. Large numbers of DNA barcode sequences of the cytochrome oxidase I obtained for nominal L. terrestris and six congeneric species reveal that there are two distinct lineages within nominal L. terrestris. One of those lineages contains the Swedish population from which the name-bearing specimen of L. terrestris was obtained. The other contains the population from which the syntype series of Enterion herculeum Savigny, 1826 was collected. In both cases modern and old representatives yielded barcode sequences allowing us to clearly establish that these are two distinct species, as different from one another as any other pair of congeners in our data set. The two are morphologically indistinguishable, except by overlapping size-related characters. We have designated a new neotype for L. terrestris. The newly designated neotype and a syntype of L. herculeus yielded DNA adequate for sequencing part of the cytochrome oxidase I gene (COI). The sequence data make possible the objective determination of the identities of earthworms morphologically identical to L. terrestris and L. herculeus, regardless of body size and segment number. Past work on nominal L. terrestris could have been on either or both species, although L. herculeus has yet to be found outside of Europe

Effect of Age on Variability in the Production of Text-Based Global Inferences

As we age, our differences in cognitive skills become more visible, an effect especially true for memory and problem solving skills (i.e., fluid intelligence). However, by contrast with fluid intelligence, few studies have examined variability in measures that rely on one’s world knowledge (i.e., crystallized intelligence). The current study investigated whether age increased the variability in text based global inference generation–a measure of crystallized intelligence. Global inference generation requires the integration of textual information and world knowledge and can be expressed as a gist or lesson. Variability in generating two global inferences for a single text was examined in young-old (62 to 69 years), middle-old (70 to 76 years) and old-old (77 to 94 years) adults. The older two groups showed greater variability, with the middle elderly group being most variable. These findings suggest that variability may be a characteristic of both fluid and crystallized intelligence in aging

Integrated monitoring of mola mola behaviour in space and time

Over the last decade, ocean sunfish movements have been monitored worldwide using various satellite tracking methods. This study reports the near-real time monitoring of finescale (< 10 m) behaviour of sunfish. The study was conducted in southern Portugal in May 2014 and involved satellite tags and underwater and surface robotic vehicles to measure both the movements and the contextual environment of the fish. A total of four individuals were tracked using custom-made GPS satellite tags providing geolocation estimates of fine-scale resolution. These accurate positions further informed sunfish areas of restricted search (ARS), which were directly correlated to steep thermal frontal zones. Simultaneously, and for two different occasions, an Autonomous Underwater Vehicle (AUV) videorecorded the path of the tracked fish and detected buoyant particles in the water column. Importantly, the densities of these particles were also directly correlated to steep thermal gradients. Thus, both sunfish foraging behaviour (ARS) and possibly prey densities, were found to be influenced by analogous environmental conditions. In addition, the dynamic structure of the water transited by the tracked individuals was described by a Lagrangian modelling approach. The model informed the distribution of zooplankton in the region, both horizontally and in the water column, and the resultant simulated densities positively correlated with sunfish ARS behaviour estimator (r(s) = 0.184, p < 0.001). The model also revealed that tracked fish opportunistically displace with respect to subsurface current flow. Thus, we show how physical forcing and current structure provide a rationale for a predator's finescale behaviour observed over a two weeks in May 2014

Human RNA Polymerase II-Association Factor 1 (hPaf1/PD2) Regulates Histone Methylation and Chromatin Remodeling in Pancreatic Cancer

Change in gene expression associated with pancreatic cancer could be attributed to the variation in histone posttranslational modifications leading to subsequent remodeling of the chromatin template during transcription. However, the interconnected network of molecules involved in regulating such processes remains elusive. hPaf1/PD2, a subunit of the human PAF-complex, involved in the regulation of transcriptional elongation has oncogenic potential. Our study explores the possibility that regulation of histone methylation by hPaf1 can contribute towards alteration in gene expression by nucleosomal rearrangement. Here, we show that knockdown of hPaf1/PD2 leads to decreased di- and tri-methylation at histone H3 lysine 4 residues in pancreatic cancer cells. Interestingly, hPaf1/PD2 colocalizes with MLL1 (Mixed Lineage Leukemia 1), a histone methyltransferase that methylates H3K4 residues. Also, a reduction in hPaf1 level resulted in reduced MLL1 expression and a corresponding decrease in the level of CHD1 (Chromohelicase DNA-binding protein 1), an ATPase dependent chromatin remodeling enzyme that specifically binds to H3K4 di and trimethyl marks. hPaf1/PD2 was also found to interact and colocalize with CHD1 in both cytoplasmic and nuclear extracts of pancreatic cancer cells. Further, reduced level of CHD1 localization in the nucleus in hPaf1/PD2 Knockdown cells could be rescued by ectopic expression of hPaf1/PD2. Micrococcal nuclease digestion showed an altered chromatin structure in hPaf1/PD2-KD cells. Overall, our results suggest that hPaf1/PD2 in association with MLL1 regulates methylation of H3K4 residues, as well as interacts and regulates nuclear shuttling of chromatin remodeling protein CHD1, facilitating its function in pancreatic cancer cells

A Randomized Trial of a Physical Conditioning Program to Enhance the Driving Performance of Older Persons

BACKGROUND: As the number of older drivers increases, concern has been raised about the potential safety implications. Flexibility, coordination, and speed of movement have been associated with older drivers’ on road performance. OBJECTIVE: To determine whether a multicomponent physical conditioning program targeted to axial and extremity flexibility, coordination, and speed of movement could improve driving performance among older drivers. DESIGN: Randomized controlled trial with blinded assignment and end point assessment. Participants randomized to intervention underwent graduated exercises; controls received home, environment safety modules. PARTICIPANTS: Drivers, 178, age ≥ 70 years with physical, but without substantial visual (acuity 20/40 or better) or cognitive (Mini Mental State Examination score ≥24) impairments were recruited from clinics and community sources. MEASUREMENTS: On-road driving performance assessed by experienced evaluators in dual-brake equipped vehicle in urban, residential, and highway traffic. Performance rated three ways: (1) 36-item scale evaluating driving maneuvers and traffic situations; (2) evaluator’s overall rating; and (3) critical errors committed. Driving performance reassessed at 3 months by evaluator blinded to treatment group. RESULTS: Least squares mean change in road test scores at 3 months compared to baseline was 2.43 points higher in intervention than control participants (P = .03). Intervention drivers committed 37% fewer critical errors (P = .08); there were no significant differences in evaluator’s overall ratings (P = .29). No injuries were reported, and complaints of pain were rare. CONCLUSIONS: This safe, well-tolerated intervention maintained driving performance, while controls declined during the study period. Having interventions that can maintain or enhance driving performance may allow clinician–patient discussions about driving to adopt a more positive tone, rather than focusing on driving limitation or cessation

Physiological roles of macrophages

Macrophages are present in mammals from midgestation, contributing to physiologic homeostasis throughout life. Macrophages arise from yolk sac and foetal liver progenitors during embryonic development in the mouse and persist in different organs as heterogeneous, self-renewing tissue-resident populations. Bone marrow-derived blood monocytes are recruited after birth to replenish tissue-resident populations and to meet further demands during inflammation, infection and metabolic perturbations. Macrophages of mixed origin and different locations vary in replication and turnover, but are all active in mRNA and protein synthesis, fulfilling organ-specific and systemic trophic functions, in addition to host defence. In this review we emphasise selected properties and non-immune functions of tissue macrophages which contribute to physiologic homeostasis