34587 Efficacy of ruxolitinib cream for the treatment of atopic dermatitis by anatomic region: Pooled analysis from two randomized phase 3 studies

Atopic dermatitis (AD) is a highly pruritic inflammatory skin disease. Two phase 3 studies (TRuE-AD1/TRuE-AD2) enrolled patients aged ≥12 years with AD for ≥2 years, an Investigator’s Global Assessment (IGA) score of 2/3, and 3%–20% affected body surface area. Patients (total N = 1249; median age, 32 years) were randomized (2:2:1) to twice-daily 0.75% ruxolitinib (Janus kinase [JAK] 1/JAK2 inhibitor) cream, 1.5% ruxolitinib cream, or vehicle cream for 8 weeks of double-blind treatment, and thereafter continued in a long-term, 44-week period of the studies. In this pooled analysis, mean percentage change from baseline in Eczema Area and Severity Index (EASI) anatomic region subscores is reported up to Week 8 (n = 1208). For the head and neck region, patients applying 0.75%/1.5% ruxolitinib cream (vs vehicle) achieved mean improvements of 59.3%/55.8% (vs 13.4%), 70.4%/71.3% (vs 22.4%), and 70.0%/78.7% (vs 45.0%) at Weeks 2, 4, and 8, respectively (all P \u3c.0001). Results were similar for the upper limbs region (48.5%/54.7% [vs 13.3%], 66.6%/70.3% [vs 25.0%], and 73.5%/74.9% [vs 35.1%] all P \u3c.0001). For the trunk region, patients achieved mean improvements of 49.8%/60.0% (vs 12.1%), 67.3%/73.8% (vs 15.0%), and 72.7%/81.0% (vs 15.6%) at Weeks 2, 4, and 8, respectively (all P \u3c.0001). Similar results were observed for the lower limbs region (46.0%/48.2% [vs 16.3%], 65.9%/66.2% [vs 13.9%], and 76.3%/74.9% [vs 39.8%]; all P \u3c.0001). Ruxolitinib cream was well tolerated, with an adverse event profile similar to vehicle. In summary, ruxolitinib cream demonstrated significant improvements vs vehicle in patients with AD across anatomic regions as early as Week 2

Crisaborole Ointment Improves Quality of Life of Patients with Mild to Moderate Atopic Dermatitis and Their Families.

IntroductionThe impact of crisaborole ointment, a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild to moderate atopic dermatitis (AD), on quality of life (QoL) was assessed in two identically designed phase 3 studies (AD-301: NCT02118766; AD-302: NCT02118792, both at http://www.clinicaltrials.gov ).MethodsIn both studies, patients aged ≥ 2 years with mild to moderate AD per the Investigator's Static Global Assessment were randomly assigned 2:1 to receive crisaborole or vehicle twice daily for 28 days. QoL was assessed using the Children's Dermatology Life Quality Index (CDLQI) (2-15 years), the Dermatology Life Quality Index (DLQI) (≥ 16 years), and the Dermatitis Family Impact Questionnaire (DFI) (parents/caregivers/family of patients aged 2-17 years). Established QoL score severity bands provided clinical context.ResultsGreater mean improvement in QoL was observed in crisaborole-treated patients than in vehicle-treated patients at day 29 [mean change from baseline (∆BL), CDLQI: - 4.6 vs. - 3.0; P < 0.001; DLQI: - 5.2 vs. - 3.5; P = 0.015]. At baseline, more than half the patients had a "moderate effect" or higher of AD on QoL. At day 29, there was a trend toward more crisaborole- than vehicle-treated patients having "small effect" to "no effect", The QoL of parents/caregivers/family improved more for crisaborole-treated than for vehicle-treated patients (∆BL, DFI: - 3.7 vs. - 2.7; P = 0.003).ConclusionCrisaborole treatment results in clinically meaningful improvement in QoL for patients and their parents/caregivers/families.Trial registrationAD-301: http://www.clinicaltrials.gov , NCT02118766; AD-302: http://www.clinicaltrials.gov , NCT02118792.FundingAnacor Pharmaceuticals, Inc., a wholly owned subsidiary of Pfizer Inc., New York, NY

A Presentation of the Religious Content on the Most Visited Croatian Internet Portals

Kompleksan međuodnos religije i medija predmet je zanimanja brojnih teoretičara. Stavivši u središte svoga interesa religiju u medijima (u smislu pojavljivanja i prezentacije institucionalnih religija u medijima), nastojalo se dobiti uvid u način na koji je ona predstavljana na trima najposjećenijim hrvatskim mrežnim portalima (24sata.hr, Index.hr i Net.hr) prema podacima koje je Gemius iznio za Hrvatsku. Istraživanja su pokazala da hrvatski građani imaju najviše povjerenja u informacije objavljene na mreži, a ako se tomu pridoda da je 63% građana Hrvatske starije od 15 godina 2011. rabilo mrežu (podaci istraživanja GfK centra), jasno je da su hrvatski mrežni portali važan čimbenik u oblikovanju javne sfere i hrvatske društvene stvarnosti. S druge strane, činjenica je i da zbog pritiska radi povećanja posjećenosti, što u konačnici rezultira povećanjem profita, mrežni portali pribjegavaju tabloidizaciji sadržaja, negativizmu, banalnim i šokantnim vijestima. Svrha je ovoga rada utvrditi na koji se način na najposjećenijim hrvatskim portalima predstavlja religijski sadržaj. Cilj je bio analizirati priloge o religiji koji su objavljivani na naslovnoj stranici triju najposjećenijih hrvatskih mrežnih portala. Analizom sadržaja njihovih naslovnica u razdoblju od 20. studenoga do 20. prosinca 2012. godine nastojalo se utvrditi koliko se tabloidni pristup novinarstvu odnosi na religijske sadržaje, odnosno koja su osnovna obilježja priloga s religijskom tematikom.The complex interplay between religion and the media is the subject of interest of many theorists. Thus, by focusing on the topic of religion in the media (in terms of appearance and presentation of institutional religion in the media), we have tried to gain insight into the way in which religion is presented on the three most visited Croatian Internet portals (24sata.hr, Index.hr and Net.hr, according to the GemiusAudience data for Croatia). Studies have shown that Croatian citizens place most of their confidence in the information available on the Internet. Also, 63% of Croatian citizens above the age of 15 availed themselves of the Internet in 2011 according to GfK research. It is clear therefore that Croatian Internet portals are an important factor in shaping the public sphere as well as Croatian social reality. On the other hand, due to the pressure for increased usage, ultimately resulting in increased profits, the fact remains that Internet portals have resorted to the tabloidization of content, negativism and reporting of banal and shocking news. The purpose of this article was to determine the way in which religious content is presented on the three most visited Croatian Internet portals. The aim was to analyze religious articles published on the front page of these portals with regard to the period between November 20 to December 20, 2012, and in so doing to try to determine in how far the tabloid approach to journalism applies to religious content, that is, to determine the main features of articles with religious themes

Natural Training Hydration Status, Sweat Rates, and Perception of Sweat Losses During Crossfit Training

International Journal of Exercise Science 9(5): 576-586, 2016. This study assessed 30 male and 20 female well-trained CrossFit (XF) athletes’ natural hydration statuses, fluid intake, and absolute and estimated sweat losses during training sessions lasting 30-47 min. Participants provided a pre-workout urine sample for assessment of hydration by urine specific gravity (USG). Nude pre- and post-workout body mass and fluid intakes were measured to determine sweat losses. To evaluate perception of total sweat loss, participants were asked to estimate their total sweat loss to compare against actual sweat loss. Mean sweat losses did not exceed 1% body mass for men (range = 0.31-1.58% body mass) or women (range = 0.53-1.34% body mass), but sweat rates were nearly double for men (1.663 ± 0.478 L/h) vs. women (0.886 ± 0.274 L/h). Pre-exercise USG indicated euhydration for the majority of participants (32/50 samples = USG \u3c 1.020). Only one participant had a USG \u3e1.030. Mean sweat loss (0.746 ± 0.305 L) and mean sweat loss prediction (0.655 ± 0.404 L) were not significantly different (p = 0.12), and accuracy did not differ (p = 0.44) between men (-9.5 ± 53.7%) and women (+4.3 ± 70.9). No relationship (r = 0.095) was found between sweat loss prediction and fluid intake. Despite high sweat rates, no athletes lost greater than 2% body mass during a strenuous workout. This data combined with consistently normal pre-exercise USG and high fluid intake during exercise suggests ad libitum fluid intake is sufficient to ensure euhydration in the majority of XF participants

Medical students\u27 knowledge of HPV, HPV vaccine, and HPV-associated head and neck cancer

On the basis of their training, medical students are considered the best case scenario among university students in knowledge of the human papillomavirus (HPV). We evaluated differences in knowledge of HPV, HPV vaccine, and head and neck cancer (HNC) among medical students. A previously validated questionnaire was completed by 247 medical students at a Midwestern university. Outcomes of interest were knowledge score for HPV and HPV vaccine, and HNC, derived from combining questionnaire items to form HPV knowledge and HNC scores, and analyzed using multivariate linear regression. Mean scores for HPV knowledge were 19.4 out of 26, and 7.2 out of 12 for HNC knowledge. In the final multivariate linear regression model, sex, race, and year of study were independently associated with HPV and HPV vaccine knowledge. Males had significantly lower HPV vaccine knowledge than females (β = -1.53; 95% CI: -2.53, -0.52), as did nonwhite students (β = -1.05; 95% CI: -2.07, -0.03). There was a gradient in HPV vaccine knowledge based on the year of study, highest among fourth year students (β = 6.75; 95% CI: 5.17, 8.33). Results were similar for factors associated with HNC knowledge, except for sex. HNC knowledge similarly increased based on year of study, highest for fourth year students (β = 2.50; 95% CI: 1.72, 3.29). Among medical students, gaps remain in knowledge of HPV, HPV vaccine, and HPV-linked HNC. Male medical students have significantly lower knowledge of HPV. This highlights the need to increase medical student knowledge of HPV and HPV-linked HNC

The Multiwavelength Survey by Yale-Chile (MUSYC): Deep Near-Infrared Imaging and the Selection of Distant Galaxies

We present deep near-infrared JHK imaging of four 10'x10' fields. The observations were carried out as part of the Multiwavelength Survey by Yale-Chile (MUSYC) with ISPI on the CTIO 4m telescope. The typical point source limiting depths are J~22.5, H~21.5, and K~21 (5sigma; Vega). The effective seeing in the final images is ~1.0". We combine these data with MUSYC UBVRIz imaging to create K-selected catalogs that are unique for their uniform size, depth, filter coverage, and image quality. We investigate the rest-frame optical colors and photometric redshifts of galaxies that are selected using common color selection techniques, including distant red galaxies (DRGs), star-forming and passive BzKs, and the rest-frame UV-selected BM, BX, and Lyman break galaxies (LBGs). These techniques are effective at isolating large samples of high redshift galaxies, but none provide complete or uniform samples across the targeted redshift ranges. The DRG and BM/BX/LBG criteria identify populations of red and blue galaxies, respectively, as they were designed to do. The star-forming BzKs have a very wide redshift distribution, a wide range of colors, and may include galaxies with very low specific star formation rates. In comparison, the passive BzKs are fewer in number, have a different distribution of K magnitudes, and have a somewhat different redshift distribution. By combining these color selection criteria, it appears possible to define a reasonably complete sample of galaxies to our flux limit over specific redshift ranges. However, the redshift dependence of both the completeness and sampled range of rest-frame colors poses an ultimate limit to the usefulness of these techniques.Comment: 17 pages in emulateapj style, 13 figures. Submitted to the Astronomical Journal. Data will be made available upon publicatio

Luteolin Decreases EGFR-Mediated Cell Proliferation and Induces Apoptosis in Glioblastoma Cell Lines.

Glioblastomas are a subtype of gliomas, which are the most aggressive and deadly form of brain tumours. The epidermal growth factor receptor (EGFR) is over-expressed and amplified in glioblastomas. Luteolin is a common bioflavonoid found in a variety of fruits and vegetables. The aim of the present study was to explore the molecular and biological effects of luteolin on EGF-induced cell proliferation and the potential of luteolin to induce apoptosis in glioblastoma cells. In vitro cell viability assays demonstrated that luteolin decreased cell proliferation in the presence or absence of EGF. Immunoblots revealed that luteolin decreased the protein expression levels of phosphorylated Akt, mTOR, p70S6K, and MAPK in the presence of EGF. Furthermore, our results revealed the ability of luteolin to induce caspase and PARP cleavages in glioblastoma cells in addition to promoting cell cycle arrest. Our results demonstrated that luteolin has an inhibitory effect on downstream signalling molecules activated by EGFR, particularly the Akt and MAPK signalling pathways, and provided a rationale for further clinical investigation into the use of luteolin as a therapeutic molecule in the management of glioblastoma. This article is protected by copyright. All rights reserved

Engineering bacteria to solve the Burnt Pancake Problem

<p>Abstract</p> <p>Background</p> <p>We investigated the possibility of executing DNA-based computation in living cells by engineering <it>Escherichia coli </it>to address a classic mathematical puzzle called the Burnt Pancake Problem (BPP). The BPP is solved by sorting a stack of distinct objects (pancakes) into proper order and orientation using the minimum number of manipulations. Each manipulation reverses the order and orientation of one or more adjacent objects in the stack. We have designed a system that uses site-specific DNA recombination to mediate inversions of genetic elements that represent pancakes within plasmid DNA.</p> <p>Results</p> <p>Inversions (or "flips") of the DNA fragment pancakes are driven by the <it>Salmonella typhimurium </it>Hin/<it>hix </it>DNA recombinase system that we reconstituted as a collection of modular genetic elements for use in <it>E. coli</it>. Our system sorts DNA segments by inversions to produce different permutations of a promoter and a tetracycline resistance coding region; <it>E. coli </it>cells become antibiotic resistant when the segments are properly sorted. Hin recombinase can mediate all possible inversion operations on adjacent flippable DNA fragments. Mathematical modeling predicts that the system reaches equilibrium after very few flips, where equal numbers of permutations are randomly sorted and unsorted. Semiquantitative PCR analysis of <it>in vivo </it>flipping suggests that inversion products accumulate on a time scale of hours or days rather than minutes.</p> <p>Conclusion</p> <p>The Hin/<it>hix </it>system is a proof-of-concept demonstration of <it>in vivo </it>computation with the potential to be scaled up to accommodate larger and more challenging problems. Hin/<it>hix </it>may provide a flexible new tool for manipulating transgenic DNA <it>in vivo</it>.</p