Quitters referring smokers: a quitline chain-referral pilot study

BACKGROUND: Telephone counseling Quitlines can support smoking cessation, but are under-utilized. We explored the use of smoker peer-referrals to increase use of a Quitline in Mississippi and Alabama. FINDINGS: Collaborating with the Alabama and Mississippi Quitline, we piloted peer-referrals to Quitlines. Successful \u27quitters\u27 who had used the Quitline were contacted at routine follow-up and recruited to participate as a peer-referrer and refer their friends and family who smoked to the Quitline. Peer-referrers completed a training session, received a manual and a set of Quitline brochures a peer-referral forms. These peer-referral forms were then returned to the Quitline telephone counselors who proactively called the referred smokers. Of the initial potential pool of 96 who quit using the Quitline, 24 peer-referrers (75% Women, 29% African-American, and high school graduates/GED 67%) were recruited and initially agreed to participate as peer-referrers. Eleven of the 24 who initially agreed were trained, and of these 11, 4 (4%) actively referred 23 friends and family over 2 months. From these 23 new referrals, three intakes (100% Women, 66% African-American) were completed. Of the initial pool of 96, 4 (4%) actively participated in referring friends and family. Quitline staff and peer-referrers noted several barriers including: time-point in which potential peer-referrers were asked to participate, an \u27overwhelming\u27 referral form to use and limited ways to refer. CONCLUSIONS: Though \u27quitters\u27 were willing to agree to peer-refer, we received a minority of referrals. However, we identified several areas to improve this new method for increasing awareness and access to support systems like the Quitline for smokers who want to quit

An Adjustable Gas-Mixing Device to Increase Feasibility of In Vitro Culture of Plasmodium falciparum Parasites in the Field

A challenge to conducting high-impact and reproducible studies of the mechanisms of P. falciparum drug resistance, invasion, virulence, and immunity is the lack of robust and sustainable in vitro culture in the field. While the technology exists and is routinely utilized in developed countries, various factors–from cost, to supply, to quality–make it hard to implement in malaria endemic countries. Here, we design and rigorously evaluate an adjustable gas-mixing device for the in vitro culture of P. falciparum parasites in the field to circumvent this challenge. The device accurately replicates the gas concentrations needed to culture laboratory isolates, short-term adapted field isolates, cryopreserved previously non-adapted isolates, as well as to adapt ex vivo isolates to in vitro culture in the field. We also show an advantage over existing alternatives both in cost and in supply. Furthermore, the adjustable nature of the device makes it an ideal tool for many applications in which varied gas concentrations could be critical to culture success. This adjustable gas-mixing device will dramatically improve the feasibility of in vitro culture of Plasmodium falciparum parasites in malaria endemic countries given its numerous advantages

What doesn't kill you makes you stranger: Dipeptidyl peptidase-4 (CD26) proteolysis differentially modulates the activity of many peptide hormones and cytokines generating novel cryptic bioactive ligands

Dipeptidyl peptidase 4 (DPP4) is an exopeptidase found either on cell surfaces where it is highly regulated in terms of its expression and surface availability (CD26) or in a free/circulating soluble constitutively available and intrinsically active form. It is responsible for proteolytic cleavage of many peptide substrates. In this review we discuss the idea that DPP4-cleaved peptides are not necessarily inactivated, but rather can possess either a modified receptor selectivity, modified bioactivity, new antagonistic activity, or even a novel activity relative to the intact parent ligand. We examine in detail five different major DPP4 substrates: glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), peptide tyrosine-tyrosine (PYY), and neuropeptide Y (NPY), and stromal derived factor 1 (SDF-1 aka CXCL12). We note that discussion of the cleaved forms of these five peptides are underrepresented in the research literature, and are both poorly investigated and poorly understood, representing a serious research literature gap. We believe they are understudied and misinterpreted as inactive due to several factors. This includes lack of accurate and specific quantification methods, sample collection techniques that are inherently inaccurate and inappropriate, and a general perception that DPP4 cleavage inactivates its ligand substrates. Increasing evidence points towards many DPP4-cleaved ligands having their own bioactivity. For example, GLP-1 can work through a different receptor than GLP-1R, DPP4-cleaved GIP can function as a GIP receptor antagonist at high doses, and DPP4-cleaved PYY, NPY, and CXCL12 can have different receptor selectivity, or can bind novel, previously unrecognized receptors to their intact ligands, resulting in altered signaling and functionality. We believe that more rigorous research in this area could lead to a better understanding of DPP4’s role and the biological importance of the generation of novel cryptic ligands. This will also significantly impact our understanding of the clinical effects and side effects of DPP4-inhibitors as a class of anti-diabetic drugs that potentially have an expanding clinical relevance. This will be specifically relevant in targeting DPP4 substrate ligands involved in a variety of other major clinical acute and chronic injury/disease areas including inflammation, immunology, cardiology, stroke, musculoskeletal disease and injury, as well as cancer biology and tissue maintenance in aging

Ambrein: a minor, but common constituent of mammalian faeces?

For nearly 200 years, the only natural source of the alcohol ambrein has been coproliths produced in about 1% of sperm whales and in related jetsam. However, the finding of ambrein in adipocere/faeces of human corpses, led us to hypothesise that ambrein might occur in the faeces of other mammals. Herein, we used a recently developed gas chromatography-mass spectrometry method, with suitable derivatisation of the hindered hydroxy group of ambrein, to screen a number of extracts of mammalian faeces. Minor proportions of ambrein were detected in digested human sewage sludge and in the dung of elephant, domestic cattle, giraffe and buffalo. Whether ambrein formation in the terrestrial species is associated with coprolith formation, is unknown, but solid deposits known as enteroliths and fecaliths occur in humans and some domestic animals

Genetic evidence that the Makira region in northeastern Madagascar is a hotspot of malaria transmission

Additional file 3: Figure S1. Contains the bootstrap re-sample statistics for comparing genetic relatedness

Cytokines and growth factors cross-link heparan sulfate

The glycosaminoglycan heparan sulfate (HS), present at the surface of most cells and ubiquitous in extracellular matrix, binds many soluble extracellular signalling molecules such as chemokines and growth factors, and regulates their transport and effector functions. It is, however, unknown whether upon binding HS these proteins can affect the long-range structure of HS. To test this idea, we interrogated a supramolecular model system, in which HS chains grafted to streptavidin-functionalized oligoethylene glycol monolayers or supported lipid bilayers mimic the HS-rich pericellular or extracellular matrix, with the biophysical techniques quartz crystal microbalance (QCM-D) and fluorescence recovery after photobleaching (FRAP). We were able to control and characterize the supramolecular presentation of HS chains—their local density, orientation, conformation and lateral mobility—and their interaction with proteins. The chemokine CXCL12α (or SDF-1α) rigidified the HS film, and this effect was due to protein-mediated cross-linking of HS chains. Complementary measurements with CXCL12α mutants and the CXCL12γ isoform provided insight into the molecular mechanism underlying cross-linking. Fibroblast growth factor 2 (FGF-2), which has three HS binding sites, was also found to cross-link HS, but FGF-9, which has just one binding site, did not. Based on these data, we propose that the ability to cross-link HS is a generic feature of many cytokines and growth factors, which depends on the architecture of their HS binding sites. The ability to change matrix organization and physico-chemical properties (e.g. permeability and rigidification) implies that the functions of cytokines and growth factors may not simply be confined to the activation of cognate cellular receptors

Simultaneous Effects of Light Intensity and Phosphorus Supply on the Sterol Content of Phytoplankton

Sterol profiles of microalgae and their change with environmental conditions are of great interest in ecological food web research and taxonomic studies alike. Here, we investigated effects of light intensity and phosphorus supply on the sterol content of phytoplankton and assessed potential interactive effects of these important environmental factors on the sterol composition of algae. We identified sterol contents of four common phytoplankton genera, Scenedesmus, Chlamydomonas, Cryptomonas and Cyclotella, and analysed the change in sterol content with varying light intensities in both a high-phosphorus and a low-phosphorus approach. Sterol contents increased significantly with increasing light in three out of four species. Phosphorus-limitation reversed the change of sterol content with light intensity, i.e., sterol content decreased with increasing light at low phosphorus supply. Generally sterol contents were lower in low-phosphorus cultures. In conclusion, both light and phosphorus conditions strongly affect the sterol composition of algae and hence should be considered in ecological and taxonomic studies investigating the biochemical composition of algae. Data suggest a possible sterol limitation of growth and reproduction of herbivorous crustacean zooplankton during summer when high light intensities and low phosphorus supply decrease sterol contents of algae

Enhanced cortical neural stem cell identity through short SMAD and WNT inhibition in human cerebral organoids facilitates emergence of outer radial glial cells

Cerebral organoids exhibit broad regional heterogeneity accompanied by limited cortical cellular diversity despite the tremendous upsurge in derivation methods, suggesting inadequate patterning of early neural stem cells (NSCs). Here we show that a short and early Dual SMAD and WNT inhibition course is necessary and sufficient to establish robust and lasting cortical organoid NSC identity, efficiently suppressing non-cortical NSC fates, while other widely used methods are inconsistent in their cortical NSC-specification capacity. Accordingly, this method selectively enriches for outer radial glia NSCs, which cyto-architecturally demarcate well-defined outer sub-ventricular-like regions propagating from superiorly radially organized, apical cortical rosette NSCs. Finally, this method culminates in the emergence of molecularly distinct deep and upper cortical layer neurons, and reliably uncovers cortex-specific microcephaly defects. Thus, a short SMAD and WNT inhibition is critical for establishing a rich cortical cell repertoire that enables mirroring of fundamental molecular and cyto-architectural features of cortical development and meaningful disease modelling

Polymorphism in dhfr/dhps genes, parasite density and ex vivo response to pyrimethamine in Plasmodium falciparum malaria parasites in Thies, Senegal☆

Resistance to sulfadoxine–pyrimethamine (SP) in Plasmodium falciparum malaria parasites is associated with mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes, and these mutations have spread resistance worldwide. SP, used for several years in Senegal, has been recommended for intermittent preventive treatment for malaria in pregnancy (IPTp) and has been widely implemented since 2003 in this country. There is currently limited data on SP resistance from molecular marker genotyping, and no data on pyrimethamine ex vivo sensitivity in Senegal. Molecular markers of SP resistance and pyrimethamine ex vivo sensitivity were investigated in 416 parasite samples collected from the general population, from the Thies region between 2003 and 2011. The prevalence of the N51I/C59R/S108N triple mutation in dhfr increased from 40% in 2003 to 93% in 2011. Furthermore, the prevalence of the dhfr N51I/C59R/S108N and dhps A437G quadruple mutation increased, from 20% to 66% over the same time frame, then down to 44% by 2011. There was a significant increase in the prevalence of the dhfr triple mutation, as well as an association between dhfr genotypes and pyrimethamine response. Conversely, dhps mutations in codons 436 and 437 did not show consistent variation between 2003 and 2011. These findings suggest that regular screening for molecular markers of antifolate resistance and ex vivo drug response monitoring should be incorporated with ongoing in vivo efficacy monitoring in areas where IPTp-SP is implemented and where pyrimethamine and sulfa drugs are still widely administered in the general population

Gender-dependent differences in plasma matrix metalloproteinase-8 elevated in pulmonary tuberculosis.

Tuberculosis (TB) remains a global health pandemic and greater understanding of underlying pathogenesis is required to develop novel therapeutic and diagnostic approaches. Matrix metalloproteinases (MMPs) are emerging as key effectors of tissue destruction in TB but have not been comprehensively studied in plasma, nor have gender differences been investigated. We measured the plasma concentrations of MMPs in a carefully characterised, prospectively recruited clinical cohort of 380 individuals. The collagenases, MMP-1 and MMP-8, were elevated in plasma of patients with pulmonary TB relative to healthy controls, and MMP-7 (matrilysin) and MMP-9 (gelatinase B) were also increased. MMP-8 was TB-specific (p<0.001), not being elevated in symptomatic controls (symptoms suspicious of TB but active disease excluded). Plasma MMP-8 concentrations inversely correlated with body mass index. Plasma MMP-8 concentration was 1.51-fold higher in males than females with TB (p<0.05) and this difference was not due to greater disease severity in men. Gender-specific analysis of MMPs demonstrated consistent increase in MMP-1 and -8 in TB, but MMP-8 was a better discriminator for TB in men. Plasma collagenases are elevated in pulmonary TB and differ between men and women. Gender must be considered in investigation of TB immunopathology and development of novel diagnostic markers