Pericytes: A newly recognized player in wound healing

Pericytes have generally been considered in the context of stabilizing vessels, ensuring the blood barriers, and regulating the flow through capillaries. However, new reports suggest that pericytes may function at critical times to either drive healing with minimal scarring or, perversely, contribute to fibrosis and ongoing scar formation. Beneficially, pericytes probably drive much of the vascular involution that occurs during the transition from the regenerative to the resolution phases of healing. Pathologically, pericytes can assume a fibrotic phenotype and promote scarring. This perspective will discuss pericyte involvement in wound repair and the relationship pericytes form with the parenchymal cells of the skin. We will further evaluate the role pericytes may have in disease progression in relation to chronic wounds and fibrosis.     

Personalized mailed feedback for college drinking prevention: a randomized clinical trial

The current study was designed to evaluate the efficacy of a mailed feedback and tips intervention as a universal prevention strategy for college drinking. Participants (N = 1,488) were randomly assigned to feedback or assessment-only control conditions. Results indicated that the mailed feedback intervention had a preventive effect on drinking rates overall, with participants in the feedback condition consuming less alcohol at follow-up in comparison with controls. In addition, abstainers in the feedback condition were twice as likely to remain abstinent from alcohol at follow-up in comparison with control participants (odds ratio = 2.02), and feedback participants were significantly more likely to refrain from heavy episodic drinking (odds ratio = 1.43). Neither gender nor severity of baseline drinking moderated the efficacy of the intervention in these analyses, but more conservative analyses utilizing last-observation carryforward suggested women and abstainers benefited more from this prevention approach. Protective behaviors mediated intervention efficacy, with participants who received the intervention being more likely to use strategies such as setting limits and alternating alcohol with nonalcoholic beverages. Implications of these findings for universal prevention of college drinking are discussed.     

Identification of protein complexes in detergent-resistant membranes of Plasmodium falciparum schizonts

Merozoite surface proteins of the human malaria parasite Plasmodium falciparum are involved in initial contact with target erythrocytes, a process that begins a cascade of events required for successful invasion of these cells. In order to identify complexes that may play a role in invasion we purified detergent-resistant membranes (DRMs), known to be enriched in merozoite surface proteins, and used blue native-polyacrylamide gel electrophoresis (BN-PAGE) to isolate high molecular weight complexes for identification by mass spectrometry. Sixty-two proteins were detected and these mostly belonged to expected DRM proteins classes including GPI-anchored, multi-membrane spanning and rhoptry proteins. Proteins from seven known complexes were identified including MSP-1/7, the low (RAP1/2 and RAP1/3), and high (RhopH1/H2/H3) molecular weight rhoptry complexes, and the invasion motor complex (GAP45/GAP50/myosinA). Remarkably, a large proportion of identified spectra were derived from only 4 proteins: the GPI-anchored proteins MSP-1 and Pf92, the putative GPI-anchored protein Pf113 and RAP-1, the core component of the two RAP complexes. Each of these proteins predominated in high molecular weight species suggesting their aggregation in much larger complexes than anticipated. To demonstrate that the procedure had isolated novel complexes we focussed on MSP-1, which predominated as a distinct species at approximately 500 kDa by BN-PAGE, approximately twice its expected size. Chemical cross-linking supports the existence of a stable MSP-1 oligomer of approximately 500 kDa, probably comprising a highly stable homodimeric species. Our observations also suggests that oligomerization of MSP-1 is likely to occur outside the C-terminal epidermal growth factor (EGF)-like domains. Confirmation of MSP-1 oligomerization, together with the isolation of a number of known complexes by BN-PAGE, makes it highly likely that novel interactions occur amongst members of this proteome.     

The subcellular localisation of trypanosome RRP6 and its association with the exosome

The exosome, a complex of 3'-exoribonucleases and associated proteins, is involved in the degradation of eukaryotic mRNAs in the cytoplasm, and has RNA processing and quality control functions in the nucleus. In yeast, the nuclear exosome differs from the cytoplasmic one in that it contains an additional non-essential component, Rrp6p. In contrast, a small proportion of human RRP6 has been shown to localise to the cytoplasm as well. When we purified the Trypanosoma brucei exosome from cytosolic extracts we found RRP6, apparently in stoichiometric amounts. We here confirm that RRP6 is in the trypanosome cytoplasm and nucleus. The level of RRP6 was unaffected by depletion of core exosome subunits by RNA interference and over-expression of tagged RRP6 was possible, indicating that RRP6 can be present independent of exosome association.     

Occupational sensitization to lupin in the workplace: occupational asthma, rhinitis, and work-aggravated asthma

BACKGROUND: Lupin is a legume. Its seed can be ground into flour and incorporated into food as a protein source. Cases of rhinitis, urticaria, and anaphylaxis from ingestion of lupin have been reported as well as asthma. OBJECTIVE: To present a cross-sectional study of workers in a food processing company who were exposed to lupin and developed occupational allergy secondary to inhaling lupin products. METHODS: Subjects were interviewed using a standardized questionnaire, including demographics and current and past symptoms. They underwent skin prick tests (SPTs) to common aeroallergens and lupin products, spirometry, and off-line exhaled nitric oxide measurement. Symptomatic subjects, sensitized to lupin on SPT, underwent methacholine bronchial provocation challenge. Those with bronchial hyperresponsiveness had specific bronchial provocation challenge to lupin. RESULTS: A total of 53/54 subjects completed testing (98%). Overall, 21% (11/53) had positive SPT results to lupin. The lupin-sensitive group had a trend toward atopy (P = .06). Seven of 11 (64%) subjects in this group were symptomatic; all had rhinitis, and 2 had wheeze. Two subjects had positive methacholine challenges, and 1 had a positive specific bronchial provocation challenge to lupin with both an early-phase and a late-phase response. CONCLUSION: Allergy to inhaled lupin occurs in the workplace. A high sensitization rate on SPT was found, which correlated with symptoms. The clinical significance of cross-reactivity between legumes on SPT is unclear. CLINICAL IMPLICATIONS: Sensitization to the legume, lupin, can occur from exposure at work and carries a high prevalence of clinical symptoms, which in some cases leads to occupational rhinitis and asthma.     

Delayed and deficient dermal maturation in mice lacking the CXCR3 ELR-negative CXC chemokine receptor

Replacement of wounded skin requires the initially florid cellular response to abate and even regress as the dermal layer returns to a relatively paucicellular state. The signals that direct this "stop and return" process have yet to be deciphered. CXCR3 chemokine receptor and its ligand CXCL11/IP-9/I-TAC are expressed by basal keratinocytes and CXCL10/IP-10 by keratinocytes and endothelial cells during wound healing in mice and humans. In vitro, these ligands limit motility in dermal fibroblasts and endothelial cells. To examine whether this signaling pathway contributes to wound healing in vivo, full-thickness excisional wounds were created on CXCR3 wild-type (+/+) or knockout (-/-) mice. Even at 90 days, long after wound closure, wounds in the CXCR3(-/-) mice remained hypercellular and presented immature matrix components. The CXCR3(-/-) mice also presented poor remodeling and reorganization of collagen, which resulted in a weakened healed dermis. This in vivo model substantiates our in vitro findings that CXCR3 signaling is necessary for inhibition of fibroblast and endothelial cell migration and subsequent redifferentiation of the fibroblasts to a contractile state. These studies establish a pathophysiologic role for CXCR3 and its ligand during wound repair.     

Evidence for Electrical Coupling in the SubCoeruleus (SubC) Nucleus

SubCoeruleus (SubC) neurons, which are thought to modulate rapid-eye-movement (REM) sleep, were recorded in brain stem slices from 7- to 20-day rats and found to manifest spikelets, indicative of electrical coupling. Spikelets occurred spontaneously or could be induced by superfusion of the cholinergic agonist carbachol. Whole cell recordings revealed that carbachol induced membrane oscillations and spikelets in the theta frequency range in SubC neurons in the presence of fast synaptic blockers. Electrical coupling in neurons is mediated by the gap junction protein connexin 36 (Cx 36). We found that Cx 36 gene expression and protein in the mesopontine tegmentum decreased during development. Cx 36 protein levels specifically in the SubC decreased in concert with the developmental decrease in REM sleep. The presence of electrical coupling in the SubC introduces a novel potential mechanism of action for the regulation of sleep-wake states.     

Impulse oscillometry measurement of distal airways obstruction in depleted uranium‐exposed Gulf War veterans

Introduction

A cohort of Gulf War I veterans who sustained exposure to depleted uranium undergoes biennial surveillance for potential uranium‐related health effects. We performed impulse oscillometry and hypothesized that veterans with higher uranium body burdens would have more obstructive abnormalities than those with lower burdens.

Methods

We compared pulmonary function of veterans in high versus low urine uranium groups by evaluating spirometry and oscillometry values.

Results

Overall mean spirometry and oscillometry resistance values fell within the normal ranges. There were no significant differences between the high and low uranium groups for any parameters. However, more veterans were classified as having obstruction by oscillometry (42%) than spirometry (8%).

Conclusions

While oscillometry identified more veterans as obstructed, obstruction was not uranium‐related. However, the added sensitivity of this method implies a benefit in wider surveillance of exposed cohorts and holds promise in identifying abnormalities in areas of the lung historically described as silent.

     

Evaluating the readability and suitability of construction occupational safety and health materials designed for workers

Introduction

Printed materials for training and hazard communication are an essential part of occupational safety and health programs, but must be understood by their intended audience.

Methods

Researchers collected 103 safety training handouts, brochures, and Safety Data Sheets and scored them for readability and suitability using four standard health communication instruments: the SMOG test, the Flesch‐Kincaid Reading Ease Assessment, the SAM (Suitability Assessment of Materials), and CCI (the CDC Clear Communication Index).

Results

Some of the materials used unfamiliar and technical terms. The SAM and CCI checklists revealed several elements of design and layout known to facilitate communication and comprehension, but missing from most of the materials scored.

Conclusion

Occupational safety and health professionals preparing curricula and handouts for distribution to workers should incorporate some form of readability and suitability assessment to help ensure their written materials are clear and comprehensible to all segments of their audience.