bluuebunny/crossref_metadata_2025 huggingface dataset:
First‐line non‐cytotoxic therapy in chemotherapy‐naive patients with metastatic castration‐resistant prostate cancer: a systematic review of 10 randomised clinical trials
Authors: Poorthuis Michiel H.F. , Vernooij Robin W.M. , van Moorselaar R. Jeroen A. , de Reijke Theo M.
Published: January 2017

The aim of this study is to systematically evaluate all available treatment options in chemotherapy‐naive patients with metastatic castration‐resistant prostate cancer (mCRPC). We systematically searched PubMed, EMBASE, and the Cochrane libraries up to 1 March 2016 for peer‐reviewed publications on randomised clinical trials (RCTs). RCTs were included if progression‐free survival (PFS), overall survival (OS), quality of life (QoL), or adverse events (AEs) were quantitatively evaluated. We assessed the risk of bias with the Cochrane Collaboration's tool and graded the evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group's approach. We included 25 articles, reporting on 10 unique RCTs describing seven different comparisons. In one RCT, a prolonged OS and PFS (high quality) were found with abiraterone and prednisone compared to placebo plus prednisone. In one RCT, a prolonged OS and PFS (high quality) were found with enzalutamide compared to placebo. In two RCTs, a prolonged OS (high and moderate quality) was found with 223radium compared to placebo, but its effect on PFS is unknown. In three RCTs, a prolonged OS (moderate quality) was found with sipuleucel‐T compared to placebo, but no prolonged PFS (low quality). In one RCT a prolonged PFS (high quality) was found with orteronel compared to placebo, but no prolonged OS (moderate quality). In one RCT, a prolonged OS (moderate quality) was found with bicalutamide compared to placebo, but its effect on PFS is unknown. In one RCT, a prolonged PFS (high quality) was found with enzalutamide compared to bicalutamide, but its effect on OS is unknown. The best evidence was found for abiraterone and enzalutamide for effective prolongation of OS and PFS to treat chemotherapy‐naive patients with mCRPC. However, taking both QoL and AEs into consideration, other treatment modalities could be considered for individual patients.
Salvage high‐intensity focused ultrasound (HIFU) for locally recurrent prostate cancer after failed radiation therapy: Multi‐institutional analysis of 418 patients
Authors: Crouzet Sebastien , Blana Andreas , Murat Francois J. , Pasticier Gilles , Brown Stephen C. W. , Conti Giario N. , Ganzer Roman , Chapet Olivier , Gelet Albert , Chaussy Christian G. , Robertson Cary N. , Thuroff Stefan , Ward John F.
Published: January 2017

Objective

To report the oncological outcome of salvage high‐intensity focused ultrasound (S‐HIFU) for locally recurrent prostate cancer after external beam radiotherapy (EBRT) from a multicentre database.

Patients and Methods

This retrospective study comprises patients from nine centres with local recurrent disease after EBRT treated with S‐HIFU from 1995 to 2009. The biochemical failure‐free survival (bFFS) rate was based on the ‘Phoenix’ definition (PSA nadir + 2 ng/mL). Secondary endpoints included progression to metastasis and cancer‐specific death. Kaplan–Meier analysis was performed examining overall (OS), cancer‐specific (CSS) and metastasis‐free survival (MFS). Adverse events and quality of life status are reported.

Results

In all, 418 patients with a mean (SD) follow‐up of 3.5 (2.5) years were included. The mean (SD) age was 68.6 (5.8) years and the PSA level before S‐HIFU was 6.8 (7.8) ng/mL. The median PSA nadir after S‐HIFU was 0.19 ng/mL. The OS, CSS and MFS rates at 7 years were 72%, 82% and 81%, respectively. At 5 years the bFFS rate was 58%, 51% and 36% for pre‐EBRT low‐, intermediate‐ and high‐risk patients, respectively. The 5‐year bFFS rate was 67%, 42% and 22% for pre‐S‐HIFU PSA level ≤4, 4–10 and ≥10 ng/mL, respectively. Complication rates decreased after the introduction of specific post‐RT parameters: incontinence (grade II or III) from 32% to 19% (P = 0.002); bladder outlet obstruction or stenosis from 30% to 15% (P = 0.003); recto‐urethral fistula decreased from 9% to 0.6% (P < 0.001). Study limitations include being a retrospective analysis from a registry with no control group.

Conclusion

S‐HIFU for locally recurrent prostate cancer after failed EBRT is associated with 7‐year CSS and MFS rates of >80% at a price of significant morbidity. S‐HIFU should be initiated early following EBRT failure
Novel approaches to the treatment of bacterial biofilm infections
Authors: Hughes Gareth , Webber Mark A
Published: January 2017

Bacterial infection remains a major challenge to healthcare and is responsible for significant morbidity and mortality. This situation is becoming complicated by an increasingly ageing and susceptible population and large numbers of bacterial isolates, which have developed resistance to antibiotics. Bacteria that form biofilms and colonize or infect medical devices or wounds are particularly hard to treat as biofilms are inherently highly antibiotic resistant. Most infections have a component where bacteria exist as a biofilm and as a result, prevention or treatment of biofilm‐associated infections is highly important. A number of novel strategies to kill biofilms have been in development; these include the use of weak organic acids, photo irradiation and the application of bacteriophage. All have promise and are able to effectively kill biofilms in model systems, but for each there are still unanswered questions. This review summarizes the main features of biofilm infections, each of these novel approaches and the evidence that is still lacking before these potential treatments can be incorporated into clinical usage.

Linked Articles

This article is part of a themed section on Drug Metabolism and Antibiotic Resistance in Micro‐organisms. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.14/issuetoc
Immediate versus modified release hydrocortisone in mitotane‐treated patients with adrenocortical cancer
Authors: Weigel Marianne , Hahner Stefanie , Sherlock Mark , Agha Amar , Behan Lucy Ann , Stewart Paul M. , Arlt Wiebke , Beier Daniela , Frey Kathrin , Zopf Kathrin , Quinkler Marcus
Published: January 2017

Objective

Mitotane induces hepatic CYP3A4 activity, resulting in accelerated cortisol inactivation, and also increases cortisol binding globulin (CBG). Therefore, higher hydrocortisone doses are required in patients with adrenocortical cancer (ACC) on mitotane treatment. Modified release hydrocortisone has not been used in mitotane‐treated ACC patients yet.

Aim

Case series to compare serum cortisol, calculated free serum cortisol and ACTH levels in ACC patients on mitotane treatment with immediate and modified release hydrocortisone.

Design

Pharmacokinetics of immediate and modified release hydrocortisone, each administered at a dose of 40‐20‐0 mg, in nine patients with ACC and adjuvant mitotane treatment. For comparison, ten patients with secondary adrenal insufficiency (SAI) on three different hydrocortisone regimens and ten healthy males were included.

Methods

Serum cortisol and plasma ACTH were measured by chemiluminescent enzyme immunoassay, and CBG by RIA, followed by calculation of free cortisol.

Results

Calculated free serum cortisol levels after 40 mg immediate release hydrocortisone in ACC patients (46 ± 14 nmol/l) were similar to those after 10 mg immediate release hydrocortisone intake in men with SAI (64 ± 16 nmol/l) or to the physiological morning free cortisol levels in healthy subjects (31 ± 5 nmol/l). Compared to immediate release hydrocortisone, free cortisol levels after 40 mg modified release hydrocortisone in ACC patients were significantly lower (12 ± 3 nmol/l; P = 0·03) resulting in a generally lower AUC (98 ± 21 vs 149 ± 37 nmol h/l; P = 0·02).

Conclusions

40‐20‐0 mg immediate release, but not modified release hydrocortisone, resulted in sufficient glucocorticoid coverage in patients with ACC receiving mitotane treatment. The use of equivalent doses of modified release hydrocortisone preparation should be avoided in patients on mitotane treatment.
Pharmacological indices and pulmonary distribution of rifampicin after repeated oral administration in healthy foals
Authors: Berlin S. , Kirschbaum A. , Spieckermann L. , Oswald S. , Keiser M. , Grube M. , Venner M. , Siegmund W.
Published: January 2017

Background

The treatment of equine lung infections by Rhodococcus equi with rifampicin is empirically based because pharmacokinetic/pharmacodynamic (PK/PD) indices and pivotal clinical outcome data are not available.

Objectives

To evaluate the pharmacokinetics and pulmonary distribution of rifampicin into epithelial lining fluid (ELF) and bronchoalveolar lavage cells (BALC) to predict antimicrobial activity in the lung using PK/PD indices.

Study design

Controlled, randomised, two‐period, crossover, repeated‐dose study with an initial arm to measure disposition after i.v. administration of rifampicin.

Methods

Pharmacokinetics and lung distribution were evaluated in six healthy foals treated with 10 mg/kg bwt rifampicin i.v. (initial arm) and with repeated oral doses of rifampicin at 10 mg/kg bwt and 20 mg/kg bwt once per day for 10 days (crossover arms). ELF and BALC were sampled by bronchoalveolar lavage 24 h after the last oral dosing. Rifampicin and 25‐O‐desacetyl rifampicin were quantified using liquid chromatography tandem‐mass spectrometry. Enzyme induction by rifampicin was confirmed by evaluation of plasma 4β‐OH‐cholesterol:cholesterol ratios.

Results

The distribution volume of rifampicin administered i.v. was ~0.85 L/kg. Terminal elimination half‐life was ~11 h. Orally given rifampicin was slowly absorbed (Tmax, range: 2.5–8.0 h) and eliminated with apparent half‐lives of ~6–8 h. Trough concentrations in ELF and BALC were 1.01 ± 0.20 μg/mL and 1.25 ± 0.29 μg/mL, respectively, after 10 mg/kg bwt rifampicin and 2.71 ± 1.25 μg/mL and 3.09 ± 1.63 μg/mL, respectively, after 20 mg/kg bwt rifampicin. The average ratios of area under the plasma concentration time curve during an administration interval of 24 h (AUC0−24 h) to minimum inhibitory concentration (MIC) were 145 and 322 h, respectively, for less susceptible strains of R. equi (MIC90: 0.5 μg/mL).

Main limitations

The clearance and bioavailability of rifampicin after repeated oral dosing were not evaluated.

Conclusions

Treatment with rifampicin at 10 mg/kg bwt administered once per day is suitable to generate drug concentrations above the MIC90 in the ELF and BALC of foals. Future clinical studies with rifampicin in combination with macrolide antibiotics with low drug interaction potential are required to translate the PK/PD indices into protocols for the treatment of R. equi lung infections.
Biologically agglutinated eukaryotic microfossil from Cryogenian cap carbonates
Authors: Moore K. R. , Bosak T. , Macdonald F. A. , Lahr D. J. G. , Newman S. , Settens C. , Pruss S. B.
Published: January 2017

Cryogenian cap carbonates that overlie Sturtian glacial deposits were formed during a post‐glacial transgression. Here, we describe microfossils from the Kakontwe Formation of Zambia and the Taishir Formation of Mongolia—both Cryogenian age, post‐Sturtian cap carbonates—and investigate processes involved in their formation and preservation. We compare microfossils from these two localities to an assemblage of well‐documented microfossils previously described in the post‐Sturtian Rasthof Formation of Namibia. Microfossils from both new localities have 10 ± 1 μm‐thick walls composed of carbonaceous matter and aluminosilicate minerals. Those found in the Kakontwe Formation are spherical or ovoid and 90 ± 5 μm to 200 ± 5 μm wide. Structures found in the Taishir Formation are mostly spherical, 50 ± 5 μm to 140 ± 5 μm wide, with distinct features such as blunt or concave edges. Chemical and mineralogical analyses show that the walled structures and the clay fraction extracted from the surrounding sediments are composed of clay minerals, especially muscovite and illite, as well as quartz, iron and titanium oxides, and some dolomite and feldspar. At each locality, the mineralogy of the microfossil walls matched that of the clay fractions of the surrounding sediment. The abundance of these minerals in the walled microfossils relative to the surrounding carbonate matrix and microbial laminae, and the presence of minerals that cannot precipitate from solution (titanium oxide and feldspar), suggests that the composition represents the original mineralogy of the structures. Furthermore, the consistency in mineralogy of both microfossils and sediments across the three basins, and the uniformity of size and shape among mineral grains in the fossil walls indicate that these organisms incorporated these minerals by primary biological agglutination. The discovery of new, mineral‐rich microfossil assemblages in microbially laminated and other fine‐grained facies of Cryogenian cap carbonates from multiple localities on different palaeocontinents demonstrates that agglutinating eukaryotes were widespread in carbonate‐dominated marine environments in the aftermath of the Sturtian glaciation.
Landscape genetics indicate recently increased habitat fragmentation in African forest‐associated chafers
Authors: Eberle Jonas , Rödder Dennis , Beckett Marc , Ahrens Dirk
Published: January 2017

Today, indigenous forests cover less than 0.6% of South Africa's land surface and are highly fragmented. Most forest relicts are very small and typically occur in fire‐protected gorges along the eastern Great Escarpment. Yet, they hold a unique and valuable fauna with high endemism and ancient phylogenetic lineages, fostered by long‐term climatic stability and complex microclimates. Despite numerous studies on southern African vegetation cover, the current state of knowledge about the natural extension of indigenous forests is rather fragmentary. We use an integrated approach of population‐level phylogeography and climatic niche modeling of forest‐associated chafer species to assess connectivity and extent of forest habitats since the last glacial maximum. Current and past species distribution models ascertained potential fluctuations of forest distribution and supported a much wider potential current extension of forests based on climatic data. Considerable genetic admixture of mitochondrial and nuclearDNAamong many populations and an increase in mean population mutation rate in Extended Bayesian Skyline Plots of all species indicated more extended or better connected forests in the recent past (<5 kya). Genetic isolation of certain populations, as revealed by population differentiation statistics (), as well as landscape connectivity statistics and habitat succession scenarios suggests considerable loss of habitat connectivity. As major anthropogenic influence is likely, conservational actions need to be considered.
The combined and separate impacts of climate extremes on the current and future US rainfed maize and soybean production under elevated CO2
Authors: Jin Zhenong , Zhuang Qianlai , Wang Jiali , Archontoulis Sotirios V. , Zobel Zachary , Kotamarthi Veerabhadra R.
Published: January 2017

Heat and drought are two emerging climatic threats to the US maize and soybean production, yet their impacts on yields are collectively determined by the magnitude of climate change and rising atmospheric CO2 concentrations. This study quantifies the combined and separate impacts of high temperature, heat and drought stresses on the current and future US rainfed maize and soybean production and for the first time characterizes spatial shifts in the relative importance of individual stress. Crop yields are simulated using the Agricultural Production Systems Simulator (APSIM), driven by high‐resolution (12 km) dynamically downscaled climate projections for 1995–2004 and 2085–2094. Results show that maize and soybean yield losses are prominent in the US Midwest by the late 21st century under both Representative Concentration Pathway (RCP) 4.5 and RCP8.5 scenarios, and the magnitude of loss highly depends on the current vulnerability and changes in climate extremes. Elevated atmospheric CO2 partially but not completely offsets the yield gaps caused by climate extremes, and the effect is greater in soybean than in maize. Our simulations suggest that drought will continue to be the largest threat to US rainfed maize production under RCP4.5 and soybean production under both RCP scenarios, whereas high temperature and heat stress take over the dominant stress of drought on maize under RCP8.5. We also reveal that shifts in the geographic distributions of dominant stresses are characterized by the increase in concurrent stresses, especially for the US Midwest. These findings imply the importance of considering heat and drought stresses simultaneously for future agronomic adaptation and mitigation strategies, particularly for breeding programs and crop management. The modeling framework of partitioning the total effects of climate change into individual stress impacts can be applied to the study of other crops and agriculture systems.
Pathogenetic determinants in Kawasaki disease: the haematological point of view
Authors: Del Principe Domenico , Pietraforte Donatella , Gambardella Lucrezia , Marchesi Alessandra , Tarissi de Jacobis Isabella , Villani Alberto , Malorni Walter , Straface Elisabetta
Published: January 2017

Kawasaki disease is a multisystemic vasculitis that can result in coronary artery lesions. It predominantly affects young children and is characterized by prolonged fever, diffuse mucosal inflammation, indurative oedema of the hands and feet, a polymorphous skin rash and non‐suppurative lymphadenopathy. Coronary artery involvement is the most important complication of Kawasaki disease and may cause significant coronary stenosis resulting in ischemic heart disease. The introduction of intravenous immunoglobulin decreases the incidence of coronary artery lesions to less than 5%. The etiopathogenesis of this disease remains unclear. Several lines of evidence suggest that an interplay between a microbial infection and a genetic predisposition could take place in the development of the disease. In this review, we summarize the state of the art of pathogenetic mechanisms of Kawasaki disease underscoring the relevance of haematological features as a novel field of investigation.
Volumetric assessment of alveolar clefts: a literature review
Authors: Blessmann Weber João Batista , de Macedo Menezes Luciane , Azeredo Fabiane , Lessa Filho Luciano Schwartz
Published: January 2017

Objective

To conduct a review of the literature on methods for volumetric assessment of alveolar clefts and ascertain which methods are most precise to guide future research.

Methods

The PubMed and MEDLINE databases were searched for English‐language reports of clinical and in vitro studies with detailed descriptions of imaging modality, sample characteristics, and method for measurement of alveolar cleft volume.

Results

The search strategy yielded 34 articles, of which 14 were selected for in‐depth analysis. According to the findings of computed tomography (CT)‐based studies, the CT modalities and software employed for assessment were deemed reliable and satisfactory.

Conclusions

Measurement of alveolar cleft volume by the proposed methods and using the equipment and software employed in the analyzed studies has high efficacy and efficiency and can be safely used for cleft lip and palate treatment planning.
Effects of different sources of protein on the growth performance, blood chemistry and polypeptide profiles in the gastrointestinal tract digesta of newly weaned piglets
Authors: Zhong R. Z. , Xia J. Q. , Sun H. , Qin G. X.
Published: January 2017

To determine the effects of different sources of protein on the growth performance of newly weaned piglets, 72 newly weaned piglets were randomly assigned to three groups fed different diets (soya bean, casein and dried distillers' grain with solubles (DDGS) feeds). Casein and DDGS feeds consisted of soya bean feed in which 5% of the CP was replaced with casein‐ or DDGS‐derived CP respectively. Blood and chyme samples were collected from each piglet 2 h post‐feeding on days 0 and 28 of the feeding period. The DDGS feed decreased DMI (p = 0.024) and increased FCR (p = 0.025) due to lower nitrogen utilization (p = 0.078) than those of other feeds. Total amino acid content in chyme demonstrated that casein feed digested rapidly in the duodenum (p = 0.005), whereas DDGS feed was digested primarily in the distal jejunum (p = 0.003) and ileocecum (p = 0.002). However, polypeptide profiles in chyme exhibited a pattern different from those of amino acids. There were no differences in the polypeptide profiles in the stomachs of piglets fed soya bean or casein feeds (p > 0.05), but soya bean group had greater amounts of small polypeptides (mass under m/z 3000 Da) in the duodenum (p = 0.052) than other groups. In contrast, the DDGS feed group had more large polypeptides (m/z 3000–4000 Da) in the stomach than the other groups (p < 0.001). In addition, 10 pairs of polypeptides with matching masses were identified in the plasma and digesta, indicating that polypeptides may have been transported across the intestinal epithelial cells and into the blood. Taken together, substitution of 5% of the CP in soya bean meal‐based feed with DDGS‐derived CP decreased the growth performance of newly weaned piglets due to poor digestibility and N utilization of DDGS feed, as well as untimely digestion of casein feed.
Estimates of Linkage Disequilibrium and Effective Population Size in Wild and Selected Populations of the Pacific Oyster Using Single‐nucleotide Polymorphism Markers
Authors: Zhong Xiaoxiao , Li Qi , Kong Lingfeng , Yu Hong
Published: January 2017

The level and extent of linkage disequilibrium (LD) and effective population size (Ne) were studied in three selected lines and a wild population of Pacific oyster, Crassostrea gigas, using 61 single‐nucleotide polymorphisms. Significant differences were detected in the average r2 between the selected lines and wild population for both syntenic and nonsyntenic loci with LD beyond population‐specific critical values (P<0.05). Moreover, the proportions of syntenic and nonsyntenic loci with the expected LD level in the wild population were lower than that in the selected lines. Taken together, the LD level of the selected lines was higher than that of the wild population. The extent of LD analysis showed that a short range of LD (0–0.23 cM) was detected in the four populations, and the decay distance was lower in the wild population than in the selected lines. Ne values ranged from 47.6 to 58.5 in the selected lines and ranged from 527.9 to 709.6 with infinite upper limits in the wild population. Further variance analysis of LD demonstrated that genetic drift and epistatic selection might account for the increased LD levels in selected lines. The LD information will be valuable for further association study and marker‐assisted selection in oysters.
Soft selective sweeps in fungicide resistance evolution: recurrent mutations without fitness costs in grapevine downy mildew
Authors: Delmas Chloé E. L. , Dussert Yann , Delière Laurent , Couture Carole , Mazet Isabelle D. , Richart Cervera Sylvie , Delmotte François
Published: January 2017

Adaptation produces hard or soft selective sweeps depending on the supply of adaptive genetic polymorphism. The evolution of pesticide resistance in parasites is a striking example of rapid adaptation that can shed light on selection processes. Plasmopara viticola, which causes grapevine downy mildew, forms large populations, in which resistance has rapidly evolved due to excessive fungicide use. We investigated the pathways by which fungicide resistance has evolved in this plant pathogen, to determine whether hard or soft selective sweeps were involved. An analysis of nucleotide polymorphism in 108 field isolates from the Bordeaux region revealed recurrent mutations of cytb and CesA3 conferring resistance to quinone outside inhibiting (QoI) and carboxylic acid amide (CAA) fungicides, respectively. Higher levels of genetic differentiation were observed for nucleotide positions involved in resistance than for neutral microsatellites, consistent with local adaptation of the pathogen to fungicide treatments. No hitchhiking was found between selected sites and neighbouring polymorphisms in cytb and CesA3, confirming multiple origins of resistance alleles. We assessed resistance costs, by evaluating the fitness of the 108 isolates through measurements of multiple quantitative pathogenicity traits under controlled conditions. No significant differences were found between sensitive and resistant isolates, suggesting that fitness costs may be absent or negligible. Our results indicate that the rapid evolution of fungicide resistance in P. viticola has involved a soft sweep.
Utility of urinary tubular markers for monitoring chronic tubulointerstitial injury after ischemia–reperfusion
Authors: Ichikawa Daisuke , Kamijo‐Ikemori Atsuko , Sugaya Takeshi , Ohata Keiichi , Hisamichi Mikako , Hoshino Seiko , Kimura Kenjiro , Shibagaki Yugo
Published: January 2017

Aim

The aim of this study was to elucidate whether urinary tubular markers during the chronic phase of acute kidney injury (AKI) are associated with chronic tubulointerstitial damage.

Methods

Male human L‐type fatty acid binding protein (L‐FABP) chromosomal transgenic (Tg) mice underwent ischaemic reperfusion (I/R) injury via renal pedicle clamping for either 10 min or 20 min. Contralateral nephrectomy was performed at the time of tissue reperfusion. The kidneys were analyzed 20 days after the last I/R.

Results

Serum creatinine levels 20 days post‐I/R were significantly higher in the 20 min I/R than in the 10 min I/R and control groups and were similar between the 10 min I/R and control groups. The degree of tubulointerstitial damage 20 days post‐I/R was significantly more severe in the 20 min I/R than in the 10 min I/R and control groups, as well as in the 10 min I/R than in the control group. Urinary levels of human L‐FABP, albumin, and kidney injury molecule‐1 (KIM‐1) 20 days post‐I/R were significantly higher in the 20 min I/R than in the control group, whereas urinary L‐FABP was significantly higher in the 10 min I/R than in the control group. Conversely, urinary neutrophil gelatinase‐associated lipocalin levels did not significantly differ between the three groups. Finally, the urinary levels of human L‐FABP, albumin, and KIM‐1 levels 20 days post‐I/R were significantly correlated with the degree of renal damage.

Conclusions

Urinary levels of human L‐FABP, albumin and, KIM‐1 may be useful for monitoring AKI‐to‐CKD transition in clinical practice.
Phytochemicals for the Prevention of Photocarcinogenesis
Authors: Montes de Oca Mary K. , Pearlman Ross L. , McClees Sarah F. , Strickland Rebecca , Afaq Farrukh
Published: January 2017

Ultraviolet (UV) exposure has an array of damaging effects and is the main cause of skin cancer in humans. Nonmelanoma skin cancer (NMSC), including basal cell carcinoma and squamous cell carcinoma, is the most common type of cancer. Incidence of NMSC has increased due to greater UV radiation, increased life expectancy and other changes in lifestyle; the annual cost of skin cancer treatment in the United States has increased concurrently to around eight billion dollars. Because of these trends, novel approaches to skin cancer prevention have become an important area of research to decrease skin cancer morbidity and defray the costs associated with treatment. Chemoprevention aims to prevent or delay the development of skin cancer through the use of phytochemicals. Use of phytochemicals as chemopreventive agents has gained attention due to their low toxicity and anticarcinogenic properties. Phytochemicals also exhibit antioxidant, anti‐inflammatory and antiproliferative effects which support their use as chemopreventive agents, particularly for skin cancer. Preclinical and human studies have shown that phytochemicals decrease UV‐induced skin damage and photocarcinogenesis. In this review article, we discuss the selected phytochemicals that may prevent or delay UV‐induced carcinogenesis and highlight their potential use for skin protection.
Mutants of Ca2+‐regulated Photoprotein Obelin for Site‐specific Conjugation
Authors: Krasitskaya Vasilisa V. , Burakova Ludmila P. , Komarova Anastasia A. , Bashmakova Eugenia E. , Frank Ludmila A.
Published: January 2017

Color variants of Ca2+‐regulated photoprotein obelin were shown to be an important tool for dual‐analyte binding assay. To provide site‐directed conjugation with biospecific molecules, several obelin color mutants carrying unique cysteine residues were obtained and characterized for their novel properties. A pair of obelins Y138F,A5C and W92F,H22E,D12C was found to be most suitable (in terms of high bioluminescent activity and stability) as reporters in simultaneous assay of two targets in a sample. Availability of SH‐groups, accessible for chemical modification, essentially simplifies the synthesis of biospecific conjugates, increases their yield and conserves obelins' bioluminescence activity. Conjugates with immunoglobulin and oligonucleotide were produced and successfully applied in single nucleotide polymorphism genotyping.
Serum‐mediated Haemonchus contortus larval aggregation differs by larval stage and is enhanced by complement
Authors: Garza J. J. , Greiner S. P. , Bowdridge S. A.
Published: January 2017

The objectives of this study were to measure Haemonchus contortus larval aggregation by complement/antibody complexes, determine effect of breed resistance and infection status and determine the effect of larval maturation on larval aggregation in vitro. Larval binding assays were performed on H. contortus L3, exsheathed L3 and L4 incubated with serum from either parasite naïve or H. contortus primed St. Croix (resistant) and Suffolk (susceptible) lambs. No differences in L3 aggregation were observed between serum from either breed or infection status. Exsheathed L3 (60%) and L4 (42%) aggregation by primed Suffolk serum was significantly reduced compared with L3 (80%, P<.001). Removal of either complement or antibody effectively eliminated L3 aggregation (P<.001). Combination of antibody‐depleted and complement‐inactivated serum restored L3 aggregation to levels consistent with unprocessed serum, supporting a role for antibody and complement in aggregation (P<.001). Use of fluorescence‐labelled anti‐sheep IgG antibody allowed documentation of IgG bound to serum complexes within L3 masses and was present only in larvae incubated with normal serum, and complement‐ and antibody‐depleted serum combination. These data indicate that complement/antibody complexes inhibit larval motility through larval aggregation which may be critical in early larval clearance of H. contortus.
Morphological and histochemical investigation of the response of Olea europaea leaves to fungal attack by Spilocaea oleagina
Authors: Lanza B. , Ragnelli A. M. , Priore M. , Aimola P.
Published: January 2017

This study investigated the response of Olea europaea (cv. Conservolea) leaves to attack by the fungal pathogen Spilocaea oleagina. Cryostat and semithin sections of healthy and S. oleagina‐infected olive leaves were analysed histochemically for polyphenol oxidase (PPO) activity and tested for programmed cell death (PCD) induction by means of terminal deoxynucleotidyl transferase‐mediated dUTP nick end labelling (TUNEL). At all stages of infection, the fungus remained localized between the external and internal layers of cuticle without crossing the pectocellulosic layer. No PCD phenomena could be detected in plant cells at any stage of the disease. However, extensive degeneration of palisade parenchyma cells was observed in advanced infections, with massive loss of cytoplasmic contents and disappearance of cell compartments. Polyphenol oxidases are enzymes that, in olive, oxidize o‐diphenols (principally oleuropein and rutin) to produce o‐diquinones and melanins, substances that are toxic to many pathogens. No significant increase in overall PPO activity was found in infected leaves; on the contrary, enzyme activity was gradually lost as infection progressed, most probably due to degradation of plastids within mesophyll cells, in which such enzymes are normally confined. Only a limited local PPO activation occurred in a few upper epidermal cells of the leaf, indicating a feeble induction of a plant response.
HAYNES NS-163 Alloy: A Novel Nitride Dispersion-Strengthened CO-Base Alloy
Authors: Fahrmann Michael G. , Deodeshmukh Vinay P. , Krishna Srivastava S.
Published: January 2017

HAYNES® NS-163® alloy was developed by Haynes International Inc., Kokomo, IN, for high-temperature structural applications by pursuing a dual manufacturing approach: the fabrication of components in the readily weldable and formable mill-annealed condition, and their subsequent strengthening by means of a gas nitriding process. The latter process results in dispersion-strengthening by virtue of formation of internal nitrides. Since this process is diffusion-controlled, component section thicknesses are limited to approximately 2.0 mm (0.080 in.). Microstructures and mechanical properties of nitrided sheet samples are presented. Oxidation resistance and the need for coatings at temperatures exceeding 980 °C (1800 °F) are addressed as well.
Influence of Freestream Turbulence Intensity on Bypass Transition Parameters in a Boundary Layer
Authors: Grzelak Joanna , Wierciński Zygmunt
Published: January 2017

An experimental investigation was carried out to study the turbulent flow behind passive grids in a subsonic wind tunnel. The enhanced level of turbulence was generated by five wicker metal grids with square meshes and different parameters (diameter of the grid rod d = 0.3 to 3 mm and the grid mesh size M = 1 to 30 mm). The velocity of the flow was measured by means of a one-dimensional hot-wire probe. For this purpose, skewness, kurtosis, and transverse variation of the velocity fluctuations were determined, obtaining knowledge of the degree of turbulence isotropy and homogeneity in the flow behind grids of variable geometry, for different incoming velocities U = 4, 6, 10, 15, 20 m/s. Approximately, the isotropic and homogeneous turbulence was obtained for x/M > 30. Next, several correlations for turbulence degeneration law were tested. Finally, as the main goal of the study, impact of turbulence intensity on bypass laminar–turbulent transition parameters (transition inception, shape parameter, and the length of the transition region) on a flat plate was investigated. Parameter ITum was created as an integral taken from the leading edge of the plate to the transition inception, divided by the distance from the leading edge to the transition inception, expressing in this way the averaged value of turbulence intensity.
Self-Similarity Analysis of Turbulent Wake Flows
Authors: Wei Tie
Published: January 2017

This paper investigates the self-similarity properties in the far downstream of high Reynolds number turbulent wake flows. The growth rate of the wake layer width, dδ/dx; the decaying rate of the maximum velocity defect, dUs/dx; and the scaling for the maximum mean transverse (across the stream) velocity, Vmax, are derived directly from the self-similarity of the continuity equation and the mean momentum equation. The analytical predictions are validated with the experimental data. Using an approximation function for the mean axial flow, the self-similarity analysis yields approximate solutions for the mean transverse velocity, V, and the Reynolds shear stress, T=−〈uv〉. Close relations among the shapes of U, V, and T are revealed.
Experimental Characterization and Simulation of a Piezo-Actuated Micro Dispensing Valve
Authors: Bonhoeffer Bastian , Boldrini Marlon , Boiger Gernot , Kwade Arno , Juhnke Michael
Published: January 2017

The dispensing behavior of a piezo-actuated micro-valve that closes the gap between the nanoliter range (e.g., inkjet technology) and the microliter range (e.g., standard displacement technology) has been investigated by experimental and numerical means. Water and different Newtonian model fluids with defined fluid properties were utilized for experimental characterization. The dispensed amount per single dispensing event could be freely adjusted from a few nanoliters to several hundred microliters showing the large working range and flexibility of the micro-valve, while maintaining a high accuracy with a low relative standard deviation. A correlation between fluid properties, dispensing parameters, and the resulting steady-state mass flow was established, showing good consistency of the experimental data. Furthermore, a three-dimensional numerical model for the quantitative simulation of the micro-valve's dispensing behavior regarding fluid mass flow was developed and validated, showing a high degree of correspondence between the experiments and simulations. Investigations of the transient behavior after the opening of the micro-valve revealed a nonlinear relationship between the valve opening time and dispensed mass for short opening times. This behavior was dependent on the working pressure but independent of the type of fluid.
Experimental and Numerical Flow Analysis of Low-Speed Fans at Highly Loaded Windmilling Conditions
Authors: Ortolan Aurélie , Courty-Audren Suk-Kee , Binder Nicolas , Carbonneau Xavier , Rosa Nicolás García , Challas Florent
Published: January 2017

This paper aims for the analysis of experimental and numerical results of windmilling flow topologies far from freewheeling condition. Two major cooling fans were investigated: a baseline design and an innovative one meant to reach good performance in both compressor and turbine modes. Experiments are conducted with global and local characterizations to determine energy recovery potential and local loss mechanisms. Also, tests were performed on a turbofan engine to confirm some trends observed on the cooling fans. The numerical study is carried out with mixing plane steady simulations, the results of which are in fair agreement with experimental data. The difference of local topology between freewheeling and highly loaded windmill demonstrates that classical deviation rules such as Carter's are not well-suited to highly loaded windmilling flows. Finally, under certain conditions, the minor influence of the stator on the rotor topology indicates that nonrotating elements can be considered as loss generators.
Interlayer couplings, Moiré patterns, and 2D electronic superlattices in MoS
2
/WSe
2
hetero-bilayers
Authors: Zhang Chendong , Chuu Chih-Piao , Ren Xibiao , Li Ming-Yang , Li Lain-Jong , Jin Chuanhong , Chou Mei-Yin , Shih Chih-Kang
Published: January 2017

A periodic modulation of the local bandgap in the rotationally aligned MoS
2
/WSe
2
bilayer creates a 2D electronic superlattice.
Dynamics of influenza-induced lung-resident memory T cells underlie waning heterosubtypic immunity
Authors: Slütter Bram , Van Braeckel-Budimir Natalija , Abboud Georges , Varga Steven M. , Salek-Ardakani Shahram , Harty John T.
Published: January 2017

Lung-resident memory T cell memory depends on reseeding from the circulating effector memory pool. See the Focus by
Borges da Silva and Jameson
.
Retrieving short-term memories of flu
Authors: Borges da Silva Henrique , Jameson Stephen C.
Published: January 2017

Circulating T
EM
constantly seed the lung T
RM
pool after influenza infection. See the related Research Article by

Slütter
et al.
Hyperosmotic Agents and Antibiotics Affect Dissolved Oxygen and pH Concentration Gradients in Staphylococcus aureus Biofilms
Authors: Kiamco Mia Mae , Atci Erhan , Mohamed Abdelrhman , Call Douglas R. , Beyenal Haluk
Published: January 2017

Biofilms on wound surfaces are treated topically with hyperosmotic agents, such as medical-grade honey and cadexomer iodine; in some cases, these treatments are combined with antibiotics. Tissue repair requires oxygen, and a low pH is conducive to oxygen release from red blood cells and epithelialization. We investigated the variation of dissolved oxygen concentration and pH with biofilm depth and the variation in oxygen consumption rates when biofilms are challenged with medical-grade honey or cadexomer iodine combined with vancomycin or ciprofloxacin. Dissolved oxygen and pH depth profiles in
Staphylococcus aureus
biofilms were measured using microelectrodes. The presence of cadexomer iodine with vancomycin or ciprofloxacin on the surface of the biofilm permitted a measurable concentration of oxygen at greater biofilm depths (101.6 ± 27.3 μm,
P
= 0.02; and 155.5 ± 27.9 μm,
P
= 0.016, respectively) than in untreated controls (30.1 μm). Decreases in pH of ∼0.6 and ∼0.4 units were observed in biofilms challenged with medical-grade honey alone and combined with ciprofloxacin, respectively (
P
< 0.001 and 0.01, respectively); the number of bacteria recovered from biofilms was significantly reduced (1.26 log) by treatment with cadexomer iodine and ciprofloxacin (
P
= 0.002) compared to the untreated control. Combining cadexomer iodine and ciprofloxacin improved dissolved oxygen concentration and penetration depth into the biofilm, while medical-grade honey was associated with a lower pH; not all treatments established a bactericidal effect in the time frame used in the experiments.

IMPORTANCE
Reports about using hyperosmotic agents and antibiotics against wound biofilms focus mostly on killing bacteria, but the results of these treatments should additionally be considered in the context of how they affect physiologically important parameters, such as oxygen concentration and pH. We confirmed that the combination of a hyperosmotic agent and an antibiotic results in greater dissolved oxygen and reduced pH within an
S. aureus
biofilm.
Extraintestinal Pathogenic and Antimicrobial-Resistant Escherichia coli, Including Sequence Type 131 (ST131), from Retail Chicken Breasts in the United States in 2013
Authors: Johnson James R. , Porter Stephen B. , Johnston Brian , Thuras Paul , Clock Sarah , Crupain Michael , Rangan Urvashi
Published: January 2017

Chicken meat products are hypothesized to be vehicles for transmitting antimicrobial-resistant and extraintestinal pathogenic
Escherichia coli
(ExPEC) to consumers. To reassess this hypothesis in the current era of heightened concerns about antimicrobial use in food animals, we analyzed 175 chicken-source
E. coli
isolates from a 2013 Consumer Reports national survey. Isolates were screened by PCR for ExPEC-defining virulence genes. The 25 ExPEC isolates (12% of 175) and a 2:1 randomly selected set of 50 non-ExPEC isolates were assessed for their phylogenetic/clonal backgrounds and virulence genotypes for comparison with their resistance profiles and the claims on the retail packaging label (“organic,” “no antibiotics,” and “natural”). Compared with the findings for non-ExPEC isolates, the group of ExPEC isolates had a higher prevalence of phylogroup B2 isolates (44% versus 4%;
P
< 0.001) and a lower prevalence of phylogroup A isolates (4% versus 30%;
P
= 0.001), a higher prevalence of multiple individual virulence genes, higher virulence scores (median, 11 [range, 4 to 16] versus 8 [range, 1 to 14];
P
= 0.001), and higher resistance scores (median, 4 [range, 0 to 8] versus 3 [range, 0 to 10];
P
< 0.001). All five isolates of sequence type 131 (ST131) were ExPEC (
P
= 0.003), were as extensively resistant as the other isolates tested, and had higher virulence scores than the other isolates tested (median, 12 [range, 11 to 13] versus 8 [range, 1 to 16];
P
= 0.005). Organic labeling predicted lower resistance scores (median, 2 [range, 0 to 3] versus 4 [range, 0 to 10];
P
= 0.008) but no difference in ExPEC status or virulence scores. These findings document a persisting reservoir of extensively antimicrobial-resistant ExPEC isolates, including isolates from ST131, in retail chicken products in the United States, suggesting a potential public health threat.

IMPORTANCE
We found that among
Escherichia coli
isolates from retail chicken meat products purchased across the United States in 2013 (many of these isolates being extensively antibiotic resistant), a minority had genetic profiles suggesting an ability to cause extraintestinal infections in humans, such as urinary tract infection, implying a risk of foodborne disease. Although isolates from products labeled “organic” were less extensively antibiotic resistant than other isolates, they did not appear to be less virulent. These findings suggest that retail chicken products in the United States, even if they are labeled “organic,” pose a potential health threat to consumers because they are contaminated with extensively antibiotic-resistant and, presumably, virulent
E. coli
isolates.
Effectiveness of an improvement programme to prevent interruptions during medication administration in a paediatric hospital: a preintervention–postintervention study
Authors: Dall'Oglio Immacolata , Fiori Martina , Di Ciommo Vincenzo , Tiozzo Emanuela , Mascolo Rachele , Bianchi Natalia , Ciofi Degli Atti Marta Luisa , Ferracci Antonella , Gawronski Orsola , Pomponi Manuel , Raponi Massimiliano
Published: January 2017

Objective

To assess the effectiveness of an improvement programme to reduce the number of interruptions during the medication administration process in a paediatric hospital.

Design and methods

A prestudy–post study design was used to monitor nursing interruptions during medication cycles in a paediatric hospital. Interruptions were reported on an observation sheet (MADOS-P) adapted to the paediatric context.

Setting

A 600-bed tertiary paediatric research hospital in Italy.

Intervention

The interventions included a yellow sash worn by nurses during medication cycles, a yellow-taped floor area indicating the ‘No interruption area’, visual notices in the medication areas, education sessions for healthcare providers and families, patient and parent information material.

Results

225 medication cycles were observed before the intervention (T0) and 261 after the intervention (T1). The median of interruptions occurring in each cycle decreased significantly from baseline to postintervention (8.0 vs 2.0, p=0.002), as the rate ratios (interruptions/patient post–pre ratio: 0.34; interruptions/medication post–pre ratio: 0.37; interruptions/hour of medication cycle post–pre ratio: 0.53, p<0.001). During preintervention, the main causes of interruptions were ‘other patients’ (19.9%), ‘other nurses’ (17.2%) and ‘conversation’ (15.7%); during postintervention, they were ‘other nurses’ (26.1%), ‘conversation’ (18.2%) and ‘other patients’ (17.4%).

Conclusions

This bundle of interventions proved to be an effective improvement programme to prevent interruptions during medication administration in a paediatric context.