Striae gravidarum (SG), or stretch marks developing during pregnancy, affect up to 90% of women. While not medically dangerous, SG can be disfiguring, causing emotional and psychological distress. However, studies specifically addressing the prevention of SG, especially during pregnancy, are sparse. Furthermore, the molecular pathogenesis of SG is unclear and may differ from that of striae from other causes. Considering these factors, we review topical modalities that have been used specifically for preventing SG during pregnancy. We identify two major strategies (end points) addressed by these modalities, namely (i) preventing the de novo development of SG and (ii) reducing the severity of SG that have recently developed. We also identify risk factors for the development of SG and suggest that pregnant women with these risk factors are an appropriate target population for prevention. In reviewing the literature, we find that there is limited evidence that centella, and possibly massage with bitter almond oil, may prevent SG and/or reduce their severity. There is weak evidence that hyaluronic acid prevents SG. Tretinoin holds promise for reducing the severity of new-onset SG, but its use is limited by its pregnancy category. Finally, cocoa butter and olive oil are not effective for preventing SG or reducing the severity of lesions. We conclude that reliable methods for preventing SG are scarce. Furthermore, available topical modalities generally lack strong evidence from rigorous, well-designed, randomized controlled trials with ample numbers of subjects. Thus, further research is necessary to elucidate SG pathogenesis, which may lead to effective prevention modalities.

BACKGROUND Anti-TNF-α therapy has made a significant impact on the treatment of psoriasis. Despite being designed to neutralize TNF-α activity, the mechanism of action of these agents in the resolution of psoriasis remains unclear. OJECTIVES To better understand the mechanism of action of etanercept by examining very early changes in the lesional skin of psoriasis patients responding to etanercept. METHODS 20 chronic plaque psoriasis patients were enrolled and received 50mg etanercept twice weekly. Skin biopsies were obtained before treatment and on days 1, 3, 7 and 14 post-treatment. Skin mRNA expression was analysed by QRT-PCR and microarray; cytokine and phosphoprotein levels were assessed using multiplexed bead arrays. RESULTS In etanercept responders, we observed no significant changes in IL-17A, IL-22 and IFN-γ mRNA or protein in the first week of treatment; however, there was a 2.5-fold down-regulation of IL17RC mRNA (p<0.05) after day 1, accompanied by decreased ERK1/2 phosphorylation. Transcriptional analysis revealed genes suppressed by etanercept significantly overlapped with IL-17A-induced genes, and a marked overlap was also observed between the genes suppressed by etanercept and by the anti-IL17A therapy ixekizumab. Finally we show that TNF-α enhances the expression of IL-17RC and shRNA inhibition of IL-17R expression abrogates synergistic gene induction by TNF and IL17A. CONCLUSIONS These results suggest that the early responses of psoriasis plaques to etanercept may be due to decreased tissue responsiveness to IL-17A due to suppressed IL17RC expression in keratinocytes, blunting the strong synergy between TNF-α and IL-17, which contributes to the maintenance of psoriasis lesions.

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Early SG display marked separation of collagen bundles and emergence of disorganized collagen fibrils that fail to form bundles. These alterations may reflect ineffective repair of collagen bundles disrupted by intense skin stretching. Persistent disruption of the collagenous extracellular matrix likely promotes formation and atrophy of SG.

Poly(3,4-ethylenedioxythiophene) (PEDOT) and chitosan structures on Si, patterned by plasticizer-assisted imprint lithography (PAIL), are examined under a variety of imprinting conditions. The stabilities of pattern dimension and chemical functionality of these polymers are presented. Thermal annealing for 5min at 80°C is found to be an effective method to stabilize imprinted PEDOT patterns. Biofunctionality in chitosan as a function of imprint temperature and pressure is examined through fluorescence spectroscopy. The accessibility of the amine group of chitosan is observed to decrease for imprint temperatures above 80°C, whereas the chemical functionality is not affected by pressure up to 1MPa. Fluorescence spectra of the chitosan are observed to be strong functions of exposure time to O2 plasma.

25Toxoplasma gondii is a ubiquitous pathogen that can cause encephalitis, congenital 26 defects, and ocular disease. T. gondii has also been implicated as a risk factor for mental 27 illness in humans. The parasite persists in the brain as slow growing bradyzoites contained 28 within intracellular cysts. No treatments exist to eliminate this form of parasite. Although 29 proteolytic degradation within the parasite lysosomal-like vacuolar compartment (VAC) is 30 critical for bradyzoite viability, whether other aspects of the VAC are important for parasite 31 persistence remains unknown. An ortholog of Plasmodium falciparum CRT has previously 32 been identified in T. gondii (TgCRT). To interrogate the function of TgCRT in chronic stage 33 bradyzoites and its role in persistence, we knocked out TgCRT in a cystogenic strain and 34 assessed VAC size, VAC digestion of host-derived proteins and parasite 35 autophagosomes, and viability of in vitro and in vivo bradyzoites. We found that whereas 36 parasites deficient in TgCRT exhibit normal digestion within the VAC, they display a 37 markedly distended VAC and their viability is compromised both in vitro and in vivo. 38Interestingly, impairing VAC proteolysis in TgCRT deficient bradyzoites restored VAC size, 39 consistent with a role for TgCRT as a transporter of products of digestion from the VAC. In 40 conjunction with earlier studies, our current findings suggest a functional link between 41TgCRT and VAC proteolysis. This work provides further evidence of a crucial role for the 42 VAC in bradyzoite persistence and a new potential VAC target to abate chronic 43 Toxoplasma infection. 44 45 IMPORTANCE 46Individuals chronically infected with the intracellular parasite Toxoplasma gondii are at risk 47 of experiencing reactivated disease that can result in progressive loss of vision. No 48 3 effective treatments exist for chronic toxoplasmosis due in part to a poor understanding of 49 the biology underlying chronic infection and a lack of well validated potential targets. Here 50 we show that a T. gondii transporter is functionally linked to protein digestion within the 51 parasite lysosome-like organelle and that this transporter is necessary to sustain chronic 52 infection in culture and in experimentally infected mice. Ablating the transporter results in 53 severe bloating of the lysosome-like organelle. Together with earlier work, this study 54 suggests the parasite's lysosome-like organelle is vital for parasite survival, thus rendering 55 it a potential target for diminishing infection and reducing the risk of reactivated disease. 56 57 INTRODUCTION 58Toxoplasma gondii (T. gondii) is an opportunistic pathogen that causes encephalitis or 59 debilitating ocular and congenital diseases in humans (1-4). It has also been implicated as 60 a risk factor for schizophrenia and other major mental illnesses (5-8). The parasite 61 progresses through two major life stages during infection of its intermediate hosts: the 62 acute stage characterized by actively replicating tachyzoit...

is that the association signal we detected was due to the presence of regulatory rather than coding SNPs, as indeed is the case for many autoimmune diseases. 7 The data generated by the HapMap Consortium are consistent with this hypothesis, as they show that variants identified in our previous association study are in strong linkage disequilibrium with several SNPs mapping to the DSG3 promoter. The notion that alleles affecting DSG3 regulation may be pathogenic is also in agreement with results obtained in animal models, demonstrating that altered DSG3 expression can affect epidermal differentiation 8 and keratinocyte cohesion. 9 In this context, a functional and genetic characterization of DSG3 regulatory elements is now required and holds the promise to identify novel sequence variants affecting gene expression and disease susceptibility. AcknowledgmentsWe thank the PV network as well as all the patients who participated in this study.

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