Contact Hypersensitivity to Oxazolone Provokes Vulvar Mechanical Hyperalgesia in Mice

The interplay among pain, allergy and dysregulated inflammation promises to yield significant conceptual advances in immunology and chronic pain. Hapten-mediated contact hypersensitivity reactions are used to model skin allergies in rodents but have not been utilized to study associated changes in pain perception in the affected skin. Here we characterized changes in mechanical hyperalgesia in oxazolone-sensitized female mice challenged with single and repeated labiar skin exposure to oxazolone. Female mice were sensitized with topical oxazolone on their flanks and challenged 1-3 times on the labia. We then measured mechanical sensitivity of the vulvar region with an electronic pressure meter and evaluated expression of inflammatory genes, leukocyte influx and levels of innervation in the labiar tissue. Oxazolone-sensitized mice developed vulvar mechanical hyperalgesia after a single labiar oxazolone challenge. Hyperalgesia lasted up to 24 hours along with local influx of neutrophils, upregulation of inflammatory cytokine gene expression, and increased density of cutaneous labiar nerve fibers. Three daily oxazolone challenges produced vulvar mechanical hyperalgesic responses and increases in nerve density that were detectable up to 5 days post-challenge even after overt inflammation resolved. This persistent vulvar hyperalgesia is resonant with vulvodynia, an understudied chronic pain condition that is remarkably prevalent in 18-60 year-old women. An elevated risk for vulvodynia has been associated with a history of environmental allergies. Our pre-clinical model can be readily adapted to regimens of chronic exposures and long-term assessment of vulvar pain with and without concurrent inflammation to improve our understanding of mechanisms underlying subsets of vulvodynia and to develop new therapeutics for this condition.     

Gecko Adhesion on Wet and Dry Patterned Substrates

Perhaps one of the most astounding characteristics of the gecko adhesive system is its versatility. Geckos can locomote across complex substrates in a variety of conditions with apparent ease. In contrast, many of our synthetic pressure sensitive adhesives fail on substrates that are dirty, wet or rough. Although many studies have investigated the effect of environmental challenges on performance, the interaction of multiple, potentially compromising variables is studied less often. Here we focus on substrate structure and surface water, both of which are highly relevant to the biological system and to synthetic design. To do this we utilized a highly controlled, patterned substrate (Sharklet^®, by Sharklet^® Technologies Inc.). This allowed us to test independently and jointly the effects of reduced surface area substrates, with a defined pattern, on adhesion in both air and water. Our results show that adhesion is not significantly impaired in air, whereas surface area and pattern significantly affect adhesion in water. These findings highlight the need to study multiple parameters that are relevant to the gecko adhesive system to further improve our understanding of the biological system and to design better, more versatile synthetics.     

Use of single nucleotide polymorphisms identifies backcrossing and species misidentifications among three San Francisco estuary osmerids

Two threatened osmerid species native to the San Francisco Estuary (SFE)—Delta Smelt (Hypomesus transpacificus) and Longfin Smelt (Spirinchus thaleichthys)—are subject to broad human influence, including significant habitat alteration and the presence of the introduced osmerid, Wakasagi (Hypomesus nipponensis). The identification of these closely related species and their hybrids is difficult in field collected specimens which are subject to damage through handling and may be difficult to identify morphologically, especially when young. In addition, it is known that these three species hybridize, but the extent and effect of hybridization is difficult to quantify and monitor. We developed assays for 24 species-specific single nucleotide polymorphisms (SNPs) that identify whether a sample is a pure species (Delta Smelt, Longfin Smelt, or Wakasagi), a first generation (F₁) hybrid, or a backcross. We used this SNP panel to genetically identify wild osmerids collected in Yolo Bypass from 2010 to 2016 and detected nine Delta Smelt × Wakasagi F₁ hybrids and two Wakasagi × (Delta Smelt × Wakasagi) backcross hybrids; all assayed hybrids had Wakasagi as the maternal parent. The backcrossing into Wakasagi suggests that hybridization may only occur in one direction and thus preclude introgression to Delta Smelt. We also found substantial morphological field misidentifications (32.7%) in the Yolo Bypass samples resulting in more Wakasagi and fewer Delta Smelt than previously recorded when based on morphology. The SNP panel described in this study constitutes a valuable resource for monitoring hybridization in the SFE and assigning species identifications with accuracy and efficiency.     

Sprouted and Freeze‐Dried Wheat and Oat Seeds – Phytochemical Profile and in Vitro Biological Activities

This research was carried out to study phytochemical profile, in vitro antioxidant capacity, reducing power, anti‐hyperglycemic, anti‐inflammatory activities and simulated gastrointestinal digestion of 7‐day old cereal sprouts: spelt wheat ‘Nirvana’ (WSSpe), wheat ‘Simonida’ (WSSim), oat ‘Golozrni’ (OSG) and oat ‘Jadar’ (OSJ). OSG expressed significantly higher (P ≤ 0.05) total phenols (TPC) and flavonoids content (TFC), antioxidant capacities (DPPH and ABTS assays) and reducing power (EC₅₀^DPPH = 2.12 mg/ml; EC₅₀^ABTS = 0.87 mg/ml; EC_0.5^RP = 12.24 mg/ml) as well as anti‐hyperglycemic activity (EC₅₀^AHgA = 0.96 mg/ml). WSSpe had the highest content of chlorophyll (131.23 mg/100 g) and carotenoids (22.84 mg/100 g). WSSim possessed the most potent anti‐inflammatory activity (2.71 mg/ml), though not significantly different from OSG (2.77 mg/ml). The in vitro simulation of gastro‐intestinal digestion showed higher release of phenolic compounds in intestinal than in gastric fluid.     

Improved patient-reported outcomes in patients with psoriatic arthritis treated with abatacept: results from a phase 3 trial

Background

To explore the effect of abatacept treatment on patient-reported outcomes (PROs) in psoriatic arthritis (PsA).

Methods

Patients with PsA were randomised (1:1) to subcutaneous abatacept 125?mg weekly/placebo for 24?weeks with early escape (EE) to open-label abatacept (week 16). Adjusted mean changes from baseline to weeks 16 (all patients) and 24 (non-EE responders) in Health Assessment Questionnaire-Disability Index (HAQ-DI), Short Form-36 (SF-36; physical and mental component summary and domains), Dermatology Life Quality Index and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were evaluated. Subpopulations were analysed by baseline C-reactive protein (CRP) level (> vs?≤?upper limit of normal [ULN]) and prior tumour necrosis factor inhibitor (TNFi) exposure. Proportions of patients reporting improvements ≥ minimal clinically important differences (MCIDs) and?≥?normative values (NVs) in HAQ-DI, SF-36 and FACIT-F (week 16 before EE) were analysed.

Results

In total population, numerically higher improvements in most PROs were reported with abatacept (n?=?213) versus placebo (n?=?211) at both time points (P?>?0.05). Higher proportions of abatacept versus placebo patients reported PRO improvements ≥ MCID and?≥?NV at week 16. At week 16, all PRO improvements were numerically greater (P?>?0.05) in patients with baseline CRP?>?ULN versus CRP?≤?ULN (all significant [95% confidence interval] for abatacept vs placebo); improvements in SF-36 component summaries and FACIT-F were greater in TNFi-naïve versus TNFi-exposed patients (abatacept > placebo). Week 24 subgroup data were difficult to interpret due to low patient numbers.

Conclusions

Abatacept treatment improved PROs in patients with PsA versus placebo, with better results in elevated baseline CRP and TNFi-naïve subpopulations.

Trial registration

ClinicalTrials.gov number, NCT01860976 (funded by Bristol-Myers Squibb); date of registration: 23 May 2013.

     

Band‐like Charge Photogeneration at a Crystalline Organic Donor/Acceptor Interface

Organic photovoltaic cells possess desirable practical characteristics, such as the potential for low‐cost fabrication on flexible substrates, but they lag behind their inorganic counterparts in performance due in part to fundamental energy loss mechanisms, such as overcoming the charge transfer (CT) state binding energy when photogenerated charge is transferred across the donor/acceptor interface. However, recent work has suggested that crystalline interfaces can reduce this binding energy due to enhanced CT state delocalization. Solar cells based on rubrene and C₆₀ are investigated as an archetypal system because it allows the degree of crystallinity to be moldulated from a highly disordered to highly ordered system. Using a postdeposition annealing method to transform as‐deposited amorphous rubrene thin films into ones that are highly crystalline, it is shown that the CT state of a highly crystalline rubrene/C₆₀ heterojunction undergoes extreme delocalization parallel to the interface leading to a band‐like state that exhibits a linear Stark effect. This state parallels the direct charge formation of inorganic solar cells and reduces energetic losses by 220 meV compared with 12 other archetypal heterojunctions reported in the literature.