Heavy metal characterisation in surface sediments off southeast coast of India: Implication on marine pollution

1810-1818The present study investigated heavy metals (Mn, Cr, Cu, Ni, Pb, and Zn) distribution in the surface sediments off Karaikal – Velankanni offshore along the east coast of Bay of Bengal as an indicator of marine pollution during 2004-2005. The sediments were analyzed for sand, silt, clay ratio, CaCO3, organic matter, and heavy metal (Mn, Cr, Cu, Ni, Pb, and Zn) contents. The contamination factor (CF) values for the heavy metals are found to be in the order: Mn >Cr >Ni >Zn >Cu >Pb during August 2004; and during January 2005 the CF values were found to be in the order: Zn >Mn >Cu >Ni >Pb >Cr. Zn contamination was found to be low to moderate. 10 samples were found with low and moderate Mn contamination. All the samples displayed moderate contamination with Cu, Ni, and Pb. Among the selected sediments, those which are collected from Karaikal and Velankanni shore were found to be highly contaminated by heavy elements due to the discharge of effluents from petrochemical, oil spills, port activity, and shipping activities. The occurrence of a wide range of elements in coastal sediments is mainly related to the textural variability of sediments during 2004 and 2005

Biomarkers of collagen synthesis predict progression in the PROFILE idiopathic pulmonary fibrosis cohort.

Idiopathic pulmonary fibrosis (IPF) is characterised by excessive extracellular matrix (ECM) deposition and remodelling. Measuring this activity provides an opportunity to develop tools capable of identifying individuals at-risk of progression. Longitudinal change in markers of ECM synthesis was assessed in 145 newly-diagnosed individuals with IPF. Serum levels of collagen synthesis neoepitopes, PRO-C3 and PRO-C6 (collagen type 3 and 6), were elevated in IPF compared with controls at baseline, and progressive disease versus stable disease during follow up, (PRO-C3 p  0 vs. LOW slope, slope < =0) demonstrated no relationship with mortality for these markers (PRO-C3 (HR 1.62, p = 0.080); PINP (HR 0.76, p = 0.309); PRO-C6 (HR 1.14, p = 0.628)). As previously reported, rising concentrations of collagen degradation markers C1M, C3M, C6M and CRPM were associated with an increased risk of overall mortality (HR = 1.84, CI 1.03–3.27, p = 0.038, HR = 2.44, CI 1.39–4.31, p = 0.002; HR = 2.19, CI 1.25–3.82, p = 0.006; HR = 2.13 CI 1.21–3.75, p = 0.009 respectively). Elevated levels of PRO-C3 and PRO-C6 associate with IPF disease progression. Collagen synthesis and degradation biomarkers have the potential to enhance clinical trials in IPF and may inform prognostic assessment and therapeutic decision making in the clinic

Effectiveness of prophylactic implantation of cardioverter-defibrillators without cardiac resynchronization therapy in patients with ischaemic or non-ischaemic heart disease: a systematic review and meta-analysis

Aims: Much controversy exists concerning the efficacy of primary prophylactic implantable cardioverter-defibrillators (ICDs) in patients with low ejection fraction due to coronary artery disease (CAD) or dilated cardiomyopathy (DCM). This is also related to the bias created by function improving interventions added to ICD therapy, e.g. resynchronization therapy. The aim was to investigate the efficacy of ICD-only therapy in primary prevention in patients with CAD or DCM.Methods and results: Public domain databases, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials, were searched from 1980 to 2009 for randomized clinical trials of ICD vs. conventional therapy. Two investigators independently abstracted the data. Pooled estimates were calculated using both fixed-effects and random-effects models. Eight trials were included in the final analysis (5343 patients). Implantable cardioverter-defibrillators significantly reduced the arrhythmic mortality [relative risk (RR): 0.40; 95 confidence interval (CI): 0.27-0.67] and all-cause mortality (RR: 0.73; 95 CI: 0.64-0.82). Regardless of aetiology of heart disease, ICD benefit was similar for CAD (RR: 0.67; 95 CI: 0.51-0.88) vs. DCM (RR: 0.74; 95 CI: 0.59-0.93).Conclusions: The results of this meta-analysis provide strong evidence for the beneficial effect of ICD-only therapy on the survival of patients with ischaemic or non-ischaemic heart disease, with a left ventricular ejection fraction ≤35, if they are 40 days from myocardial infarction and ≥3 months from a coronary revascularization procedure

Author Correction: The mTORC1/4E-BP1 axis represents a critical signaling node during fibrogenesis

Correction to: Nature Communications https://doi.org/10.1038/s41467-018-07858-8, published online 2 January 2019

Estimating process capability index Cpm using a bootstrap sequential sampling procedure

Construction of a confidence interval for process capability index CPM is often based on a normal approximation with fixed sample size. In this article, we describe a different approach in constructing a fixed-width confidence interval for process capability index CPM with a preassigned accuracy by using a combination of bootstrap and sequential sampling schemes. The optimal sample size required to achieve a preassigned confidence level is obtained using both two-stage and modified two-stage sequential procedures. The procedure developed is also validated using an extensive simulation study.<br /

ILK Induces Cardiomyogenesis in the Human Heart

Integrin-linked kinase (ILK) is a widely conserved serine/threonine kinase that regulates diverse signal transduction pathways implicated in cardiac hypertrophy and contractility. In this study we explored whether experimental overexpression of ILK would up-regulate morphogenesis in the human fetal heart.Primary cultures of human fetal myocardial cells (19-22 weeks gestation) yielded scattered aggregates of cardioblasts positive for the early cardiac lineage marker nk × 2.5 and containing nascent sarcomeres. Cardiac cells in colonies uniformly expressed the gap junction protein connexin 43 (C × 43) and displayed a spectrum of differentiation with only a subset of cells exhibiting the late cardiomyogenic marker troponin T (cTnT) and evidence of electrical excitability. Adenovirus-mediated overexpression of ILK potently increased the number of new aggregates of primitive cardioblasts (p<0.001). The number of cardioblast colonies was significantly decreased (p<0.05) when ILK expression was knocked down with ILK targeted siRNA. Interestingly, overexpression of the activation resistant ILK mutant (ILK(R211A)) resulted in much greater increase in the number of new cell aggregates as compared to overexpression of wild-type ILK (ILK(WT)). The cardiomyogenic effects of ILK(R211A) and ILK(WT) were accompanied by concurrent activation of β-catenin (p<0.001) and increase expression of progenitor cell marker islet-1, which was also observed in lysates of transgenic mice with cardiac-specific over-expression of ILK(R211A) and ILK(WT). Finally, endogenous ILK expression was shown to increase in concert with those of cardiomyogenic markers during directed cardiomyogenic differentiation in human embryonic stem cells (hESCs).In the human fetal heart ILK activation is instructive to the specification of mesodermal precursor cells towards a cardiomyogenic lineage. Induction of cardiomyogenesis by ILK overexpression bypasses the requirement of proximal PI3K activation for transduction of growth factor- and β1-integrin-mediated differentiation signals. Altogether, our data indicate that ILK represents a novel regulatory checkpoint during human cardiomyogenesis

The Level of Protein in Milk Formula Modifies Ileal Sensitivity to LPS Later in Life in a Piglet Model

Background: Milk formulas have higher protein contents than human milk. This high protein level could modify the development of intestinal microbiota, epithelial barrier and immune functions and have long-term consequences. Methodology/Principal findings: We investigated the effect of a high protein formula on ileal microbiota and physiology during the neonatal period and later in life. Piglets were fed from 2 to 28 days of age either a normoprotein (NP, equivalent to sow milk) or a high protein formula (HP, +40% protein). Then, they received the same solid diet until 160 days. During the formula feeding period ileal microbiota implantation was accelerated in HP piglets with greater concentrations of ileal bacteria at d7 in HP than NP piglets. Epithelial barrier function was altered with a higher permeability to small and large probes in Ussing chambers in HP compared to NP piglets without difference in bacterial translocation. Infiltration of T cells was increased in HP piglets at d28. IL-1b and NF-kappa B sub-units mRNA levels were reduced in HP piglets at d7 and d28 respectively; plasma haptoglobin also tended to be reduced at d7. Later in life, pro-inflammatory cytokines secretion in response to high doses of LPS in explants culture was reduced in HP compared to NP piglets. Levels of mRNA coding the NF-kappa B pathway sub-units were increased by the challenge with LPS in NP piglets, but not HP ones. Conclusions/Significance: A high protein level in formula affects the postnatal development of ileal microbiota, epithelial barrier and immune function in piglets and alters ileal response to inflammatory mediators later in life

Cyanobacterial lipopolysaccharides and human health – a review

Cyanobacterial lipopolysaccharide/s (LPS) are frequently cited in the cyanobacteria literature as toxins responsible for a variety of heath effects in humans, from skin rashes to gastrointestinal, respiratory and allergic reactions. The attribution of toxic properties to cyanobacterial LPS dates from the 1970s, when it was thought that lipid A, the toxic moiety of LPS, was structurally and functionally conserved across all Gram-negative bacteria. However, more recent research has shown that this is not the case, and lipid A structures are now known to be very different, expressing properties ranging from LPS agonists, through weak endotoxicity to LPS antagonists. Although cyanobacterial LPS is widely cited as a putative toxin, most of the small number of formal research reports describe cyanobacterial LPS as weakly toxic compared to LPS from the Enterobacteriaceae. We systematically reviewed the literature on cyanobacterial LPS, and also examined the much lager body of literature relating to heterotrophic bacterial LPS and the atypical lipid A structures of some photosynthetic bacteria. While the literature on the biological activity of heterotrophic bacterial LPS is overwhelmingly large and therefore difficult to review for the purposes of exclusion, we were unable to find a convincing body of evidence to suggest that heterotrophic bacterial LPS, in the absence of other virulence factors, is responsible for acute gastrointestinal, dermatological or allergic reactions via natural exposure routes in humans. There is a danger that initial speculation about cyanobacterial LPS may evolve into orthodoxy without basis in research findings. No cyanobacterial lipid A structures have been described and published to date, so a recommendation is made that cyanobacteriologists should not continue to attribute such a diverse range of clinical symptoms to cyanobacterial LPS without research confirmation