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Photobiomodulation, utilising non-ionising light in the visible and near-infrared (NIR) spectrum, has been suggested as a potential method for enhancing tissue repair, reducing inflammation and possibly mitigating cancer-therapy-associated side effects. NIR light is suggested to be absorbed intracellularly, mainly by chromophores within the mitochondria. This study examines the impact of 734 nm NIR light on cellular senescence. Cancer (MCF7 and A549) and non-cancer (MCF10A and IMR-90) cell populations were subjected to 63 mJ/cm 2 NIR-light exposure for 6 days. Senescence levels were quantified by measuring active senescence-associated beta-galactosidase. Exposure to NIR light significantly increases senescence levels in cancer (10.0%-203.2%) but not in non-cancer cells (p > 0.05). Changes in senescence were associated with significant modulation of mitochondrial homeostasis, including increased levels of reactive oxygen species (p < 0.05) and mitochondrial membrane potential (p < 0.05) post-NIR-light treatment. These results suggest that NIR light modulates cellular chemistry, arresting the proliferation of cancer cells via senescence induction while sparing non-cancer cells., (© 2024 The Author(s). Journal of Biophotonics published by Wiley‐VCH GmbH.)

Presented in this work is a thorough determination of the transition states between the different isomers of cyclic tetra-atomic silicon carbide, germanium carbide, and germanium silicide clusters. Through use of density functional theory (B3LYP-D3BJ, M06-2X, ωB97X-D4, and B2GP-PLYP) in conjunction with the aug-cc-pVTZ basis set, transition state structures and their barrier heights are determined for the interconversions between the various isomers for the family of tetra-atomic SiC, GeC, and GeSi compounds. SiC dust grains are known to be prevalent in interstellar dust, and among this group, so far only diamond-shaped (d-)SiC 3 has been detected in the interstellar medium (ISM). Determining which other structures might be detectable not only depends on their intrinsic spectroscopic features, but whether or not they are likely to exist as isomers in interstellar environments. By examining the energy barrier heights for transitions between isomers, we determined that many of these structures are unlikely to exhibit interconversion in the ISM, outside of hotter circumstellar environments. Although Boltzmann population ratios at approximate circumstellar temperatures suggest the presence of higher energy minima, it is likely that once interconversion happens, as molecules travel away from a star and cool, they will get kinetically trapped in the potential energy well they inhabit, making how the ratios freeze out dependent on the time and pathways the molecules take to cool down. As such, many of these higher energy minima may still be good candidates for detection including (rhomboidal) r-SiC 3 , r-GeC 3 , r-GeSi 3 , (trapezoidal) t-Si 2 C 2 , r-Ge 2 C 2 , and d-Si 3 C.

Background: Oversupply of dietary copper (Cu) is common among UK dairy herds, but studies on the long-term outcomes of this oversupply are scarce., Methods: A longitudinal study was undertaken to determine the long-term implications when 80 Holstein‒Friesian heifers with a mean (±standard error) age of 4.1 ± 0.1 months and a mean liveweight of 137 ± 2.4 kg were fed a recommended (R; 16 mg/kg dry matter [DM]) or high (H; 32 mg/kg DM) dietary Cu concentration until 6 weeks prior to calving., Results: Hepatic Cu concentrations in both treatment groups were elevated into the ranges used to diagnose chronic Cu toxicity in cattle at 6.9 months of age (798 ± 46.4 mg/kg DM for H vs. 643 ± 35.4 mg/kg DM for R), with associated evidence of liver damage. Hepatic Cu concentrations then returned to normality but remained higher (p < 0.001) for heifers fed H than for those fed R and were associated with a reduced (p = 0.044) conception rate to first and second services (73.7 ± 8.05% for H vs. 91.2 ± 7.68% for R)., Limitation: This retrospective analysis identified pre-study liver damage, which may have affected results., Conclusions: Supplying Cu in excess of requirements resulted in liver damage and reduced conception rates., (© 2024 The Author(s). Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

The apparent absorption of copper (Cu) in ruminants is low, with between 0.01 and 0.07 g/g absorbed from sources such as copper oxide (CuO) under typical feeding conditions, resulting in high levels of excretion. Improving the bioavailability of Cu could reduce the supplemental amount required to maintain Cu status and reduce excretion, particularly in the presence of dietary antagonists such as sulfur (S) and molybdenum (Mo). The objective of our study was to determine the Cu status of cows when fed nanoparticle CuO coated with Lys compared with conventional CuO when fed without or in combination with antagonists to Cu absorption (S and Mo) in the diet of dairy cows. Fifty-six multiparous Holstein-Friesian cows that were 48 d ± 17.4 (mean ± SD) post calving and yielding 40.6 ± 6.9 kg milk/d were used in a 2 × 2 factorial design. The 4 treatment groups were; CuO (O-), CuO with added antagonists (O+), nano CuO with a lysine coating (N-), and nano CuO with a Lys coating with added antagonists (N+), fed for 16 wks. We formulated the diets to contain approximately 17 mg Cu/kg dry matter (DM) and diets with antagonists contained an additional 1 g S/kg DM and 6 mg Mo/kg DM, with Lys added to O- and O+ to provide the same daily supply as N- and N+. Blood samples were collected at wk 0, 2, 4, 6, 10 and 16, and liver biopsy samples at wk 0 and 16. We found no effect of dietary treatment on DM intake, milk yield, live weight or body condition score, with mean values of 23.3 kg/d, 40.1 kg/d, 646 kg and 2.68, but milk SCC was higher in cows fed conventional compared with non CuO, or with added antagonist. We also found no effect of treatment on blood activity of gamma glutamyl transferase, superoxide dismutase or ceruloplasmin, hematology profile, or plasma Cu and iron concentration. We found that plasma Mo concentration was increased from 0.36 µmol/L in cows fed O- or N- to 0.80 µmol/L in those receiving O+ or N+. Additional dietary antagonists also decreased the concentration of Cu in the liver of cows fed conventional CuO (C+) over the study period by 1.3 mg/kg DM/d, but in cows fed dietary antagonists and nano CuO coated with Lys (N+), liver Cu concentration was increased by 1.1 mg/kg DM/d. Our study is the first to demonstrate that reducing the particle size of CuO into the nano scale with a lysine coating improves the bioavailability of CuO in the presence of dietary antagonists in dairy cattle, and we did not observe any negative effects on performance or health., (© 2024, The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

An extensive, high-level theoretical study on tetra-atomic germanium carbide/silicide clusters is presented. Accurate harmonic and anharmonic vibrational frequencies and rotational constants are calculated at the CCSD(T)-F12a(b)/cc-pVT(Q)Z-F12 levels of theory. With growing capabilities to discern more of the chemical composition of the interstellar medium (ISM), an accurate database of reference material is required. The presence of carbon is ubiquitous in the ISM, and silicon is known to be present in interstellar dust grains; however, germanium-containing molecules remain elusive. To begin understanding the presence and role of germanium in the ISM, we present this study of the vibrational and rotational spectroscopic properties of various germanium-containing molecules to aid in their potential identification in the ISM with modern observational tools such as the James Webb Space Telescope. Structures studied herein include rhomboidal (r-), diamond (d-), and trapezoidal (t-) tetra-atomic molecules of the form Ge x C 4- x and Ge x Si 4- x , where x = 0-4. The most promising structure for detection is r-Ge 2 C 2 via the ν 4 mode with a frequency of 802.7 cm -1 (12.5 μm) and an intensity of 307.2 km mol -1 . Other molecules that are potentially detectable, i.e., through vibrational modes or rotational transitions, include r-Ge 3 C, r-GeSi 3 , d-GeC 3 , r-GeC 3 , and t-Ge 2 C 2 .

Life may be expressed as the flow of electrons, protons, and other ions, resulting in large potential difference. It is also highly photo-sensitive, as a large proportion of the redox capable molecules it relies on are chromophoric. It is thus suggestive that a key organelle in eukaryotes, the mitochondrion, constantly adapt their morphology as part of the homeostatic process. Studying unstained in vivo nano-scale structure in live cells is technically very challenging. One option is to study a central electron carrier in metabolism, reduced nicotinamide adenine dinucleotide (NADH), which is fluorescent and mostly located within mitochondria. Using one and two-photon absorption (340-360 nm and 730 nm, respectively), fluorescence lifetime imaging and anisotropy spectroscopy of NADH in solution and in live cells, we show that mitochondria do indeed appear to be aligned and exhibit high anisotropy (asymmetric directionality). Aqueous solution of NADH showed an anisotropy of ~ 0.20 compared to fluorescein or coumarin of < 0.1 and 0.04 in water respectively and as expected for small organic molecules. The anisotropy of NADH also increased further to 0.30 in the presence of proteins and 0.42 in glycerol (restricted environment) following two-photon excitation, suggesting more ordered structures. Two-photon NADH fluorescence imaging of Michigan Cancer Foundation-7 (MCF7) also showed strong anisotropy of 0.25 to 0.45. NADH has a quantum yield of fluorescence of 2% compared to more than 40% for photoionisation (electron generation), when exposed to light at 360 nm and below. The consequence of such highly ordered and directional NADH patterns with respect to electron ejection upon ultra-violet (UV) excitation could be very informative-especially in relation to ascertaining the extent of quantum effects in biology, including electron and photonic cascade, communication and modulation of effects such as spin and tunnelling., (© 2024. The Author(s).)

Cells emit light at ultra-low intensities: photons which are produced as by-products of cellular metabolism, distinct from other light emission processes such as delayed luminescence, bioluminescence, and chemiluminescence. The phenomenon is known by a large range of names, including, but not limited to, biophotons, biological autoluminescence, metabolic photon emission and ultraweak photon emission (UPE), the latter of which shall be used for the purposes of this review. It is worth noting that the photons when produced are neither 'weak' nor specifically biological in characteristics. Research of UPE has a long yet tattered past, historically hamstrung by a lack of technology sensitive enough to detect it. Today, as technology progresses rapidly, it is becoming easier to detect and image these photons, as well as to describe their function. In this brief review we will examine the history of UPE research, their proposed mechanism, possible biological role, the detection of the phenomenon, and the potential medical applications., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mould, Mackenzie, Kalampouka, Nunn, Thomas, Bell and Botchway.)

We demonstrate that a Δ-density functional theory (Δ-DFT) approach based on atom-centered potentials (ACPs) represents a computationally inexpensive and accurate method for representing potential energy surfaces (PESs) for the HONO and HFCO molecules and vibrational frequencies derived therefrom. Using as few as 100 CCSD(T)-F12a reference energies, ACPs developed for use with B3LYP/def2-TZVPP are shown to produce PESs for HONO and HFCO with mean absolute errors of 27.7 and 5.8 cm -1 , respectively. Application of the multiconfigurational time-dependent Hartree (MCTDH) method with ACP-corrected B3LYP/def2-TZVPP PESs produces vibrational frequencies for cis - and trans -HONO with mean absolute percent errors (MAPEs) of 0.8 and 1.1, compared to 0.8 obtained for the two isomers with CCSD(T)-F12a/cc-pVTZ-F12/MCTDH. For HFCO, the vibrational frequencies obtained using the present (Δ-DFT)/MCTDH approach give a MAPE of 0.1, which is the error obtained with CCSD(T)-F12a/cc-pVTZ-F12/MCTDH. The ACP approach is therefore successful in representing a PES calculated at a high level of theory (CCSD(T)-F12a) and a promising method for the development of a general protocol for the representation of accurate molecular PESs and the calculation of molecular properties from them.

Background: Skin metastases are an important co-morbidity in melanoma. Despite broad adoption, electrochemotherapy implementation is hindered by a lack of treatment indications, uncertainty regarding procedural aspects, and the absence of quality indicators. An expert consensus may harmonize the approach among centres and facilitate comparison with other therapies., Methods: An interdisciplinary panel was recruited for a three-round e-Delphi survey. A literature-based 113-item questionnaire was proposed to 160 professionals from 53 European centres. Participants rated each item for relevance and degree of agreement on a five-point Likert scale, and received anonymous controlled feedback to allow revision. The items that reached concordant agreement in two successive iterations were included in the final consensus list. In the third round, quality indicator benchmarks were defined using a real-time Delphi method., Results: The initial working group included 122 respondents, of whom 100 (82 per cent) completed the first round, thus qualifying for inclusion in the expert panel (49 surgeons, 29 dermatologists, 15 medical oncologists, three radiotherapists, two nurse specialists, two clinician scientists). The completion rate was 97 per cent (97 of 100) and 93 per cent (90 of 97) in the second and third rounds respectively. The final consensus list included 54 statements with benchmarks (treatment indications, (37); procedural aspects, (1); quality indicators, (16))., Conclusion: An expert panel achieved consensus on the use of electrochemotherapy in melanoma, with a core set of statements providing general direction to electrochemotherapy users to refine indications, align clinical practices, and promote quality assurance programmes and local audits. The residual controversial topics set future research priorities to improve patient care., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Electrochemotherapy has been proven to be an efficient treatment for cutaneous metastases of various cancers. Data on breast cancer (BC) patients with cutaneous metastases were retrieved from the INSPECT database. Patients were divided by their receptor status: HER2+, HR+ (ER/PgR+), and TN (triple negative). Groups were similar for histological subtype and location of the nodules. Most patients were previously treated with surgery/systemic therapy/radiotherapy. We found no differences in the three groups in terms of response ratio (OR per patient 86% HER2+, 80% HR+, 76% TN, p = 0.8664). The only factor positively affecting the complete response rate in all groups was small tumor size (<3 cm, p = 0.0105, p = 0.0001, p = 0.0266, respectively). Local progression-free survival was positively impacted by the achievement of complete response in HER2+ ( p = 0.0297) and HR+ ( p = 0.0094), while overall survival was affected by time to local progression in all groups ( p = 0.0065 in HER2+, p < 0.0001 in HR+, p = 0.0363 in TN). ECT treatment is equally effective among groups, despite different receptor status. Response and local tumor control seem to be better in multiple small lesions than in big armor-like lesions, suggesting that treating smaller, even multiple, lesions at the time of occurrence is more effective than treating bigger long-lasting armor-like cutaneous lesions.

Given the lack of research regarding the effect of microalgal supplementation in dairy cows on milk mineral concentrations, this study investigated the effect of feeding different protein supplements in dairy cow diets on milk, feces, and blood plasma mineral concentrations, associated milk and blood plasma transfer efficiencies, and apparent digestibility. Lactating Finnish Ayrshire cows (n = 8) were allocated at the start of the trial to 4 diets used in a replicated 4 × 4 Latin square design experiment: (1) control diet (CON), (2) a pelleted rapeseed supplement (RSS; 2,550 g/d), (3) a mixture of rapeseed and Spirulina platensis (RSAL; 1,280 g of RSS + 570 g of S. platensis per day), and (4) S. platensis (ALG; 1,130 g of S. platensis per day). In each of the 4 experimental periods, a 2-wk adaptation to the experimental diets was followed by a 7-d sampling and measurement period. Feed samples were composited per measurement period, milk, and feed samples (4 consecutive days; d 17-20), and blood plasma samples (d 21) were composited for each cow period (n = 32). Data were statistically analyzed using a linear mixed effects model with diet, period within square, square and their interaction as fixed factors, and cow within square as a random factor. Cows fed ALG were not significantly different in their milk or blood plasma mineral concentrations compared with CON, although feeding ALG increased fecal concentrations of macrominerals (Ca and Mg) and trace elements (Co, Cu, Fe, I, Mn, and Zn), and reduced their apparent digestibility, compared with CON. When compared with CON and ALG, milk from cows fed RSAL and RSS had lower milk I concentrations (-69.6 and -102.7 μg/kg of milk, respectively), but total plasma I concentrations were not affected significantly. Feeding S. platensis to dairy cows did not affect mineral concentrations in cows' blood or milk, but care should be taken when rapeseed is fed to avoid reducing milk I concentrations which may in turn reduce consumers' I intake from milk and dairy products., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

The Australasian biogeographic realm is a major centre of diversity for orchids, with every subfamily of the Orchidaceae represented and high levels of endemism at the species rank. It is hypothesised that there is a commensurate diversity of viruses infecting this group of plants. In this study, we have utilised high-throughput sequencing to survey for viruses infecting greenhood orchids (Pterostylidinae) in New South Wales and the Australian Capital Territory. The main aim of this study was to characterise Pterostylis blotch virus (PtBV), a previously reported but uncharacterised virus that had been tentatively classified in the genus Orthotospovirus . This classification was confirmed by genome sequencing, and phylogenetic analyses suggested that PtBV is representative of a new species that is possibly indigenous to Australia as it does not belong to either the American or Eurasian clades of orthotospoviruses. Apart from PtBV, putative new viruses in the genera Alphaendornavirus , Amalgavirus , Polerovirus and Totivirus were discovered, and complete genome sequences were obtained for each virus. It is concluded that the polerovirus is likely an example of an introduced virus infecting a native plant species in its natural habitat, as this virus is probably vectored by an aphid, and Australia has a depauperate native aphid fauna that does not include any species that are host-adapted to orchids.

Hummingbirds (Trochilidae) are sensitive to environmental changes because of their extraordinary ecology, metabolism, and the highest red blood cell counts found in any vertebrate. These physiological attributes may render hummingbirds particularly susceptible to the effects of haemosporidian (blood parasite) infections. Much of the research on haemosporidians in hummingbirds has been conducted in South America; less is known about haemosporidian diversity and prevalence in North America. We sought to determine the prevalence and diversity of haemosporidians in a high-elevation species, the Broad-tailed Hummingbird (Selasphorus platycercus). Blood samples (N = 314) from 25 sites in Colorado and Wyoming were screened for haemosporidians using microscopy (n = 311) and PCR (n = 301). Both microscopy and sequencing diagnostic techniques detected haemosporidians in the same 5 hummingbirds, with an overall prevalence of 1.59%. Positive samples were sequenced at the cytochrome b gene and identified Haemoproteus archilochus and two Haemoproteus sp. not previously detected in North America. No parasites of the genera Plasmodium or Leucocytozoon were detected. Our study provides the first report of the prevalence and diversity of haemosporidians in Broad-tailed Hummingbirds in the Rocky Mountains., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

1. The amino acid composition of 10 different UK-grown field bean cultivar samples from the same harvest year were determined.2. Diets included each bean sample at a level of 200 g/kg feed compared against a control diet formulated with only soyabean sources, whereby the beans replaced the soyabean meal, and were used to compare ileal amino acid digestibility. The amino acid digestibility coefficients for the bean samples were obtained via substitution method.3. The data showed that one field bean sample, cultivar Sultan, had a lower amino acid digestibility (P < 0.05) than that of the other nine . This sample had a higher tannin content that may have affected amino acid digestibility.

A study was conducted to 1) investigate the influence of rapeseed cultivar on the range of variation in the chemical composition and feed value of rapeseed meals (RSM) for broilers and 2) to compare between single-cultivar RSM and a batch of UK-sourced proprietary rapeseed meal. Chemical composition was determined for a total of 10 single-cultivar RSM produced via prepressed solvent-extraction and a proprietary RSM. To investigate RSM digestibility a total of 360 birds were housed, six birds per pen, and between day 13 to 21 of age they received a diet containing per kg 250 g RSM and 750 g basal feed based on wheat and soybean meal. Titaniumdioxide (7 g/kg) was added as an inert marker. For the determination nitrogen-corrected metabolisable energy (AMEn) total excreta and feed intake were quantified over the last 4 d of the experiment. On the final day of the experiment ileal digesta were collected for determination of preceacal crude protein digestibility (pcCPD). With the exception of neutral detergent fibre (NDF), glucosinolates and soluble non-starch polysaccharides the coefficients of variation (CV%) for all major components were similar across all RSM (0.5 < CV% < 0.6). Glucosinolate contents were highest in the 10 single-cultivar RSM whereas NDF levels were greater in the proprietary RSM. Across the 10 single-cultivar RSM there was no significant effect of cultivar on AMEn or pcCPD. Pre-planned orthogonal contrasts indicated that the mean AMEn content and pcCPD of the proprietary RSM was significantly lower than the 10 single-cultivar RSM ( p < 0.001). In view of the above, processing rather than cultivar appears to be the main driver of nutritional value in RSM fed to broilers.

1. The chemical composition and physical characteristics of 10 different UK-grown field bean cultivar samples from the same harvest year were determined.2. Diets included each bean sample at a level of 200 g/kg, and were used to compare broiler growth performance and determine N-corrected apparent metabolisable energy (AMEn) and nutrient utilisation. The AMEn and nutrient retention coefficients for the bean samples were obtained via the slope-ratio method. The relationships were examined between variation in nutritive value for broilers and the laboratory analysis of the bean samples.3. The data showed significant differences (P < 0.05) among the bean cultivar samples for feed conversion ratio, AMEn and dry matter retention (DMR) coefficients. Further analysis showed that the feeding quality of different field bean cultivar samples, measured as AMEn, was highly correlated to crude protein (CP) (P < 0.05) and colour (P < 0.001) of the samples. Thus, beans with higher CP and pale colour had superior feeding value for broilers.

To test the hypothesis that Cu metabolism in dairy cows is affected by dietary starch concentration and additional sulfur S and Mo, 60 Holstein-Friesian dairy cows that were [mean ± standard error (SE)] 33 ± 2.5 days postcalving and yielding 41 ± 0.9 kg of milk/d were fed 1 of 4 diets in a 2 × 2 factorial design experiment over a 14-wk period. The 4 diets had a Cu concentration of approximately 15 mg/kg of dry matter (DM), a grass silage-to-corn silage ratio of 1:1, a dietary starch concentration of either 150 g/kg of DM (low starch, LS) or 220 g/kg of DM (high starch, HS), and were either unsupplemented (-) or supplemented (+) with an additional 0.8 g of S/kg of DM and 4.4 mg of Mo/kg of DM. We found an effect of dietary starch concentration on mean reticular pH, which was 0.15 pH units lower in cows fed the high starch diets. The addition of S and Mo decreased intake by 1.8 kg of DM/d, an effect that was evident beginning in wk 1 of the study. Mean milk and fat yields were 37.0 and 1.51 kg/d, respectively, and were not affected by dietary treatment. We found an effect of dietary starch concentration on milk protein concentration, protein yield, and urea nitrogen, which were increased by 2.8 g/kg, 0.09 kg/d, and 2.1 mg/dL, respectively, in cows fed the high starch diets. We found no effect of dietary treatment on either cow live weight or body condition. Mean plasma Cu, Fe, and Zn concentrations were 15.3, 42.1, and 14.4 µmol/L, respectively, and were not affected by dietary treatment. In contrast, we found an interaction between dietary starch concentration and Cu antagonists on plasma Mo, where feeding additional S and Mo increased plasma Mo to a greater extent when cows were offered the high versus low starch diet. We also found that increasing dietary starch concentration increased serum ceruloplasmin activity, but serum haptoglobin concentration was not affected by dietary treatment. The addition of S and Mo decreased hepatic Cu concentration, whereas in cows fed the higher dietary starch concentration, hepatic Cu concentration was increased over the period of our study. We concluded that increasing dietary starch concentration decreases rumen pH and increases milk protein yield and hepatic Cu concentration, whereas feeding additional S and Mo decreases intake and hepatic Cu concentration., (Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Historically, the field of tissue engineering has been adept at modulating the chemical and physical microenvironment. This approach has yielded significant progress, but it is imperative to further integrate our understanding of other fundamental cell signaling paradigms into tissue engineering methods. Bioelectric signaling has been demonstrated to be a vital part of tissue development, regeneration, and function across organ systems and the extracellular matrix is known to alter the bioelectric properties of cells. Thus, there is a need to bolster our understanding of how matrix and bioelectric signals interact to drive cell phenotype. We examine how cardiac progenitor cell differentiation is altered by simultaneous changes in both resting membrane potential and extracellular matrix composition. Pediatric c-kit + cardiac progenitor cells were differentiated on fetal or adult cardiac extracellular matrix while being treated with drugs that alter resting membrane potential. Smooth muscle gene expression was increased with depolarization and decreased with hyperpolarization while endothelial and cardiac expression were unchanged. Early smooth muscle protein expression is modified by matrix developmental age, with fetal ECM appearing to amplify the effects of resting membrane potential. Thus, combining matrix composition and bioelectric signaling represents a potential alternative for guiding cell behavior in tissue engineering and regenerative medicine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Neural crest cells (NCCs) comprise a transient progenitor cell population of neuroepithelial origin that contributes to a variety of cell types throughout vertebrate embryos including most mesenchymal cells of the cranial and facial structures. Consequently, abnormal NCC development underlies a variety of craniofacial defects including orofacial clefts, which constitute some of the most common birth defects. We previously reported the generation of manta ray ( mray ) mice that carry a loss-of-function allele of the gene encoding the preribosomal factor Pak1ip1. Here we describe cranioskeletal abnormalities in homozygous mray mutants that arise from a loss of NCCs after their specification. Our results show that the localized loss of cranial NCCs in the developing frontonasal prominences is caused by cell cycle arrest and cell death. In addition, and consistent with deficits in ribosome biosynthesis, homozygous mray mutants display decreased protein biosynthesis, further linking Pak1ip1 to a role in ribosome biogenesis., (Copyright © 2020 Panoutsopoulos, De Crescenzo, Lee, Lu, Ross, Borodinsky, Marcucio, Trainor and Zarbalis.)

Meiotic progression requires precise orchestration, such that one round of DNA replication is followed by two meiotic divisions. The order and timing of meiotic events is controlled through the modulation of the phosphorylation state of proteins. Key components of this phospho-regulatory system include cyclin-dependent kinase (CDK) and its cyclin regulatory subunits. Over the past two decades, studies in budding and fission yeast have greatly informed our understanding of the role of CDK in meiotic regulation. In this review, we provide an overview of how CDK controls meiotic events in both budding and fission yeast. We discuss mechanisms of CDK regulation through post-translational modifications and changes in the levels of cyclins. Finally, we highlight the similarities and differences in CDK regulation between the two yeast species. Since CDK and many meiotic regulators are highly conserved, the findings in budding and fission yeasts have revealed conserved mechanisms of meiotic regulation among eukaryotes., Competing Interests: The authors have no conflicts to report.

Accurate chromosome segregation depends on the proper attachment of kinetochores to spindle microtubules before anaphase onset. The Ipl1/Aurora B kinase corrects improper attachments by phosphorylating kinetochore components and so releasing aberrant kinetochore-microtubule interactions. The localization of Ipl1 to kinetochores in budding yeast depends upon multiple pathways, including the Bub1-Bub3 pathway. We show here that in meiosis, Bub3 is crucial for correction of attachment errors. Depletion of Bub3 results in reduced levels of kinetochore-localized Ipl1 and concomitant massive chromosome missegregation caused by incorrect chromosome-spindle attachments. Depletion of Bub3 also results in shorter metaphase I and metaphase II due to premature localization of protein phosphatase 1 (PP1) to kinetochores, which antagonizes Ipl1-mediated phosphorylation. We propose a new role for the Bub1-Bub3 pathway in maintaining the balance between kinetochore localization of Ipl1 and PP1, a balance that is essential for accurate meiotic chromosome segregation and timely anaphase onset., (© 2020 Cairo et al.)

The chemical characteristics of rapeseed meal (RSM) produced from two cultivars of UK-grown rapeseed, by both supercritical carbon dioxide extraction (ScCO 2 ) and cold-pressed hexane extraction (CpHe) were examined. Their nutritional value, with and without protease, was then assessed in a broiler digestibility trial. Basal feed was substituted with one of four RSM batches (200 g/kg) following adjustments for dry matter (DM) and ether extract (EE) content. Half of each diet was supplemented with a mono-component protease derived from Bacillus subtilis (Axtra®PRO, Danisco Animal Nutrition, Malborough, UK) giving a total of eight test diets. Two control diets, with and without protease were also fed. At 13 d age male Ross 308 broilers were randomly allocated to seven replicate pens (five birds per pen) and assigned to one of 10 diets. Total excreta were collected from 17 to 21 d age and feed intake was recorded. Pre-caecal protein digestibility (pcPd) was determined using TiO 2 as an indigestible marker. Colourimetrically CpHe RSM was substantially darker than ScCO 2 counterparts. The influence of oil recovery method (ORM) was also evident in DM, EE, ash free neutral detergent fibre (aNDFom), neutral detergent insoluble crude protein (NDICP) and glucosinolate content (GLS). The content of DM, EE and GLS was higher in ScCO 2 RSM whereas aNDFom and NDICP levels were greater in CpHe RSM. Protein solubility in KOH was greater in ScCO 2 RSM whilst levels of NDICP were lower. Collectively these results suggest that less heat damage was incurred to the RSM during ScCO 2 extraction. There was no significant main effect of cultivar nor were any significant interactions observed between treatment factors. Rapeseed meal ScCO 2 produced greater metabolisable energy, pcPd, nitrogen retention and energy metabolisability ( p < 0.05). Protease supplementation increased pcPd ( p < 0.05) irrespective of ORM and cultivar. The key implications of these findings are that by adopting oil recovery methods that minimise the exposure of RSM to thermal treatments and by adding a compatible protease there is scope to increase the nutritional value of RSM for broilers and increase its utilisation in modern poultry production.

Background: While physical (in) activity surveillance has grown and continues to grow globally, surveillance of sedentary behaviour is in its infancy. As surveillance evolves to meet the changing nature of these behaviours, there is a need for the development of national health survey questions to provide accurate and consistent measures over time. The development of national health survey content is a complex, detailed and often undocumented process. The objective of this paper is to outline the process that the Public Health Agency of Canada (PHAC) and Statistics Canada took in partnership with academic experts to develop a short, flexible, sedentary behaviour module for the Canadian Health Measures Survey (CHMS) and to provide an approach for the development of future survey content., Methods: Development of the module followed a multi-step process. The results of this paper describe this process and present a framework for content development., Results: Initially, PHAC and Statistics Canada analysts worked together to identify key content required for a potential survey module. Next, this work was formalized through a contract with academic experts, the scope included a: review of existing Canadian sedentary behaviour modules; literature review linking different sedentary behaviours to health outcomes; and, international scan of modules currently in use in large national health surveys and research. The key output from both review processes was recommendations for a short sedentary behaviour questionnaire module (International Sedentary Assessment Tool). These recommendations provided an evidence-informed basis for discussions about how to revise and update the CHMS sedentary behaviour questionnaire content. Qualitative testing was undertaken and a final module was developed using survey design best practices., Conclusions: Content volume in national surveys is limited due to demand to measure core content in addition to emerging health topics while keeping surveys as short as possible. Questions must therefore, be concise, valid/reliable, evidence-based, and developed using best practices. The paper describes the development process of a new survey module addressing the emerging area of sedentary behaviour for use in a national survey that may serve as a model for future population survey content development., Competing Interests: Competing interestsSAP has received an equipment competition award from PAL Technologies Inc. TJS has received additional research support from Stepscount Inc., and in-kind support from Stepscount Inc., Ergotron and Fitabase. TJS has also received honoraria for presentations on the health impact of sedentary behaviour. All other authors declare that they have no competing interests related to the work., (© The Author(s). 2019.)

Following wound damage to the skin, the scarring spectrum is wide-ranging, from a manageable normal scar through to pathological keloids. The question remains whether these fibrotic lesions represent simply a quantitative extreme, or alternatively, whether they are qualitatively distinct. A three-way comparison of the extracellular matrix (ECM) composition of normal skin, normal scar and keloids was performed using quantitative discovery-based proteomics. This approach identified 40 proteins that were significantly altered in keloids compared to normal scars, and strikingly, 23 keloid-unique proteins. The major alterations in keloids, when functionally grouped, showed many changes in proteins involved in ECM assembly and fibrillogenesis, but also a keloid-associated loss of proteases, and a unique cartilage-like composition, which was also evident histologically. The presence of Aggrecan and Collagen II in keloids suggest greater plasticity and mis-differentiation of the constituent cells. This study characterises the ECM of both scar types to a depth previously underappreciated. This thorough molecular description of keloid lesions relative to normal scars is an essential step towards our understanding of this debilitating clinical problem, and how best to treat it., Competing Interests: The authors have declared that no conflict of interest exists., (© 2019 The Authors.)

1. Four batches of wheat distillers dried grains with solubles (DDGS) produced by a single production plant were used to investigate variation in digestible energy (DE) and nutrient digestibility for laying hens. 2. A total of 144 Hy-Line Brown laying hens were allocated to eight treatment groups in replicates of six. Experimental diets were prepared by replacing the basal feed with either 150 g/kg or 300 g/kg of each batch of DDGS. 3. Chemical analysis of the DDGS showed variation between the different batches. Largest coefficients of variation were observed for starch (0.546) and total soluble non-starch polysaccharides (NSP; 0.276). 4. Digestible energy and the nutrient digestibility of each diet was measured using the ileal collection technique. Data were statistically analysed as a blocked 2 × 4 factorial design analysis of variance (ANOVA). 5. Variability between the different diets were observed for digestible energy and the digestibility of certain nutrients (P < 0.05). 6. The observed differences in energy utilisation and nutrient digestibility in laying hens suggested that the feeding quality of diets containing different wheat DDGS batches produced by a single production plant may still have large variation.

Despite the rapid increase in the use of wheat distillers dried grains with solubles (DDGS) within the poultry sector, little information is available on how the long-term feeding of this by-product will affect the performance of laying hens. This experiment examined the effect of wheat DDGS, with and without exogenous xylanase on dietary apparent metabolizable energy (AME), total tract dry matter retention (DMR), nitrogen retention (NR), fat digestibility (FD) coefficients, feed intake (FI), bodyweight gain (BWG), eggs laid, mean egg weight, egg mass output, and egg quality characteristics including albumin height (AH), Haugh units (HU), yolk color, eggshell strength, and thickness. A total of 320 Hy-Line brown laying hens were randomly allocated to 80 enriched layer colonies (groups of 4). A total of 2 control wheat-soybean meal-based diets were formulated to contain 11.60 MJ/kg. One of the diets contained 300 g/kg wheat DDGS, while the other was DDGS free, with a respective crude protein content of 171.1 g/kg and 166.5 g/kg. Both diets were divided by 2 and half of them were supplemented with 2,500 U/kg of xylanase, resulting in 4 diets in total. Data was analyzed as a 2 × 2 factorial arrangement of treatments with analysis of variance (ANOVA). Diets were fed ad libitum from 17 to 43 wk of age and data was collected from 23 to 43 wk. The inclusion of wheat DDGS reduced (P < 0.001) dry matter retention (DMR), FI, BWG, eggs laid, mean egg weight, and egg mass. However, xylanase supplementation improved AME and NR in diets containing wheat DDGS and FD in diets without DDGS (DDGS × xylanase, P < 0.05) and tended to improve (P < 0.10) BWG and egg mass output. For egg quality measurements, the inclusion of DDGS improved (P = 0.046) HU values, eggshell strength (P < 0.001), and increased (P < 0.001) yolk color intensity. This experiment showed xylanase can be used to improve the AME and NR of DDGS-based diets. However, the long-term feeding of 300 g/kg wheat DDGS negatively impacts the productive performance of hens., (© 2019 Poultry Science Association Inc.)

1. The aim of this study was to examine chemical composition, quality characteristics, apparent metabolisable energy (AME) and nutrient utilisation of wheat samples currently available to the UK poultry industry and their effect on broiler growth performance. 2. Seventeen current UK wheat samples were used to formulate 17 diets, all of which included 670 g/kg of each wheat sample and 330 g/kg of a balancer feed. Eight hundred 1-day-old male Ross 308 broilers were allocated randomly to 160 raised floor pens. Each diet was replicated eight times, fed ad libitum from 0 to 21d age in a randomised complete block design. Excreta were quantitatively collected during the last 3 days for AME determination. 3. The content of protein, ash and gross energy (GE) ranged from 97 to 143 g/kg DM, 12.8 to 19.6 g/kg DM and 17.81 to 18.24 MJ/kg DM, respectively. The amount of starch and total non-starch polysaccharides (NSP) ranged from 671 to 728 and 80.1 to 98.2 g/kg DM, respectively. The quality characteristics of wheat samples were in the expected range. 4. There were differences ( P < 0.05) in AME and N-corrected AME (AMEn) of wheat samples. The AME of the wheat had a maximum range of 1.13 MJ/kg DM between samples. Dry matter retention (DMR) and fat digestibility (FD) were significantly different ( P < 0.05) between wheat samples. 5. The daily feed intake (FI) and weight gain (WG) of broilers fed two wheat samples were significantly ( P < 0.05) lower as compared to other samples and their low FI and WG were not related to their chemical composition and quality characteristics. 6. The ash content of wheat samples was negatively associated with AMEn ( r = - 0.489, P < 0.05). The coefficient of FD was positively related to AMEn ( r = 0.552, P < 0.05). 7. Chemical composition and quality characteristics of the wheat did not relate ( P > 0.05) to FI and WG of broilers. There was no relationship between growth performance of broilers and AMEn of the wheat samples.

The aim of this study was to test the hypothesis of an improved growth, dietary nutrient availability and overall health of broiler chickens reared on recycled litter when fed a standardised combination of essential oils (EO; carvacrol, cinnamaldehyde and capsicum oleoresin). To assess the effect of dietary treatments, feed intake, weight gain, feed efficiency, availability of dietary nutrients and energy, villus morphometry, excreta sialic acid concentration, hepatic antioxidants and serum amyloid A (SAA) when fed to broiler chickens were evaluated. Counts of Eimeria spp. oocysts were also determined in excreta samples. Four experimental diets were offered, including two basal control diets based on either wheat or maize that contained 215 g CP/kg and 12.13 MJ/kg metabolisable energy and another two diets using the basal control diets supplemented with the EO combination at 100 mg/kg diet. Each diet was fed to eight floor pens, containing two birds each, following randomisation. Birds fed the EO-supplemented diets had an improved (P0.05) were observed in villus morphometry, sialic acid secretion, number of oocysts and SAA. Feeding the EO improved (P&lt;0.05) the retention of dietary Ca and Na. Compared with maize, feeding wheat-based diets improved the retention coefficients for Ca, P and Na (P&lt;0.05). Feeding dietary EO improved (P&lt;0.05) the concentrations of the hepatic antioxidants, including carotene, coenzyme Q10 and total vitamin E. The hepatic concentration of carotene of the maize-fed birds was 55.6% greater (P&lt;0.05) compared with the wheat-fed birds. These results demonstrated that the addition of a standardised combination of EO in wheat- and maize-based diets provided benefits in terms of feed efficiency, mineral retention and antioxidant status of the birds when reared on recycled litter.

Introduction: There is little evidence-based guidance on the use of prophylactic antibiotics in skin surgery; whilst antibiotics may protect against surgical site infections (SSI), they have associated side effects, increase the risk of adverse events, and can propagate antibiotic resistance. We present a protocol for a systematic review to establish whether the benefit of prophylactic antibiotics overrides the risk, for patients undergoing autograft surgery., Methods: The systematic review will be registered a priori on researchregistry.com and will be conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). A search strategy will be devised to investigate 'skin graft surgery and use of antibiotics'. The following electronic databases will be searched, 1979-2018: PubMed, MEDLINE®, EMBASE, SCOPUS, CINAHL, PsychINFO, SciELO, The Cochrane Library, including the Cochrane Central Register of Controlled Trials (CENTRAL), Database of Abstracts of Reviews of Effect (DARE), the Cochrane Methodology Register, Health Technology Assessment Database, the NHS Economic Evaluation Databases and Cochrane Groups, ClinicalTrials.gov, Current Controlled Trials Database, the World Health Organisation (WHO) International Clinical Trials Registry Platform, UpToDate.com, NHS Evidence and the York Centre for Reviews and Dissemination. Grey literature will be searched. All comparative study designs reporting on the use of antibiotics in skin graft surgery will be considered for inclusion, namely randomized controlled trials (RCTs). Two trained independent teams will screen all titles and abstracts, followed by relevant full texts, for eligibility. Data will be extracted under standardized extraction fields into a preformatted database. Note will be made of the indication for skin graft surgery (traumatic, congenital, malignant, benign), the graft site (head & neck, trunk, upper extremities, lower extremities), type of skin graft (split thickness, full-thickness). The primary outcome will be occurrence of SSI at the donor and/or recipient sites. Secondary outcomes, if reported, will include: length of hospital stay, revision surgery required, cost of medical care, time to wound healing and cosmetic outcome., Ethics and Dissemination: The systematic review will be published in a peer-reviewed journal and presented at national and international meetings within fields of plastic, reconstructive, and aesthetic surgery. The work will be disseminated electronically and in print. Brief reports of the review and findings will be disseminated to interested parties through email and direct communication. The review aims to guide healthcare practice and policy., (© 2019 The Authors.)

Objective: Conduct a meta-analysis to determine the impact of traumatic spinal cord injury (SCI) on echocardiographic measurements of left ventricular (LV) structure and function., Methods: MEDLINE and Embase were used for primary searches of studies reporting LV echocardiographic data in individuals with SCI. Of 378 unique citations, 36 relevant full-text articles were retrieved, and data from 27 studies were extracted for meta-analyses. Literature searches, article screening and data extraction were completed by two independent reviewers and compared for agreement. Primary analyses compared echocardiographic indices between individuals with SCI and able-bodied individuals, using a random effects model., Results: Data are reported as pooled effect estimates (95% CI). Data from 22 articles (474 participants) were included in the primary meta-analysis. Compared with able-bodied individuals, individuals with SCI had reductions to LV stroke volume of 11.8 mL (95% CI -17.8 to -5.9, p<0.001), end-diastolic volume of 19.6 mL (95% CI -27.2 to -11.9, p<0.001) and LV mass index of -7.7 g/m 2 (95% CI -11.6 to -3.8, p<0.001), but ejection fraction was not different between the groups (95% CI -2.6% to 0.6%, p=0.236). Individuals with SCI also had altered indices of diastolic function, specifically a lowered ratio of early-to-late filling velocities (p=0.039), and augmented ratio of early diastolic flow-to-tissue velocities (p=0.021)., Conclusions: Individuals with SCI have smaller LV volumes and mass, and altered systolic and diastolic function. While this meta-analysis demonstrates important alterations to echocardiographic measures of cardiac structure and function at rest, future work should consider the impacts of SCI on the heart's capacity or 'reserve' to respond to physiological challenges., Prospero Registration Number: CRD42017072333., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Several demographic and clinical factors have prognostic significance in idiopathic pulmonary arterial hypertension (IPAH). Studies in China and the USA have suggested an association between low socioeconomic status and reduced survival. The impact of social deprivation on IPAH survival in the UK is not known.280 patients with IPAH and hereditary PAH (HPAH) attending the Scottish Pulmonary Vascular Unit (Glasgow, UK) were assigned to social deprivation quintiles using the Scottish Index of Multiple Deprivation database. The association between survival and social deprivation quintile was assessed using Cox proportional hazards regression analysis.The distribution of IPAH/HPAH patients was more socially deprived than would be expected based on Scottish citizenry as a whole (Chi-squared 16.16, p=0.003), suggesting referral and access to care is not impeded by socioeconomic status. Univariate analysis demonstrated no significant association between social deprivation and survival (p=0.81), and this association failed to reach significance with inclusion of time, sex and age as covariates in the model (p=0.23). There were no statistically significant correlations between social deprivation and baseline clinical variables of prognostic importance except for age, sex and quality of life.Social deprivation is not a significant referral barrier or prognostic factor for IPAH and HPAH in Scotland., Competing Interests: Conflict of interest: None declared., (Copyright ©ERS 2018.)

To test the hypothesis that the metabolism of Cu in dairy cows is affected by basal forage and added S and Mo, 56 dairy cows that were 35 (standard error ± 2.2) days postcalving and yielding 38.9 kg of milk/d (standard error ± 0.91) were offered 1 of 4 diets in a 2 × 2 factorial design for a 14-wk period. The 4 diets contained approximately 20 mg of Cu/kg of dry matter (DM), and had a corn silage-to-grass silage ratio of 0.75:0.25 (C) or 0.25:0.75 (G) and were either unsupplemented (-) or supplemented (+) with an additional 2 g of S/kg of DM and 6.5 mg of Mo/kg of DM. We found an interaction between forage source and added S and Mo on DM intake, with cows offered G+ having a 2.1 kg of DM lower intake than those offered G-, but no effect on the corn silage-based diets. Mean milk yield was 38.9 kg/d and we observed an interaction between basal forage and added S and Mo, with yield being decreased in cows offered G+ but increased on C+. No effect of dietary treatment on milk composition or live weight was noted, but body condition was lower in cows fed added S and Mo irrespective of forage source. We found an interaction between forage source and added S and Mo on milk somatic cell count, which was higher in cows offered G+ compared with G-, but not in cows fed the corn silage-based diets, although all values were low (mean values of 1.72, 1.50, 1.39, and 1.67 log 10 /mL for C-, C+, G-, and G+, respectively). Mean plasma Cu, Fe, and Mn concentrations were 13.8, 41.3, and 0.25 µmol/L, respectively, and were not affected by dietary treatment, whereas plasma Mo was 0.2 µmol/L higher in cows receiving added S and Mo. The addition of dietary S and Mo decreased liver Cu balance over the study period in cows fed either basal forage, but the decrease was considerably greater in cows receiving the grass silage-based diet. Similarly, hepatic Fe decreased more in cows receiving G than C when S and Mo were included in the diet. We concluded that added S and Mo reduces hepatic Cu reserves irrespective of basal forage source, but this decrease is considerably more pronounced in cows receiving grass silage- than corn silage-based rations and is associated with a decrease in intake and milk performance and an increase in milk somatic cell count., (Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Effects of field beans with various tannin content and exogenous enzyme mixture containing tannase, pectinase and xylanase activities on N-corrected dietary apparent metabolisable energy (AMEn), coefficients of dry matter (DMR) and nitrogen retention (NR), fat digestibility, gastrointestinal tract (GIT) development, jejunal villus morphometry, ileal digesta viscosity and sialic acid were examined. Birds' growth performance and energy conversion ratio (ECR) were also measured. Birds were fed one of eight mash diets. The Control diet contained as major ingredients wheat (400 g/kg) and soybean meal (SBM) (127 g/kg and 221 g crude protein/kg and 12.83 MJ AMEn/kg. To reduce nutrient density, the Control diet also contained washed sand at 119 g/kg. Another three diets containing 300 g/kg of each of three experimental field bean cultivar samples in replacement for SBM and sand were also mixed. Each diet was fed to nine pens with two male Ross 308 broilers. Diets high in tannin had low AMEn, ECR, DMR and NR (p < 0.001). Feeding field beans increased (p < 0.001) the weights of the pancreas and the proventriculus and gizzard (PG) of the birds. Supplementing diets with the enzyme mixture improved (p < 0.001) feed conversion efficiency, AMEn and all nutrient utilisation coefficients despite the tannins in diets. The enzyme mixture reduced ileal digesta viscosity (p < 0.001) and the weight of pancreas, total GIT and PG (p < 0.05) of the birds. It can be concluded that the feeding value of field beans with different tannin contents may vary when fed to broilers. The supplementation of the enzyme mixture improved the feeding value of diets for broilers. The beneficial effect of the addition of the enzyme mixture seems to be mediated through reduced ileal digesta viscosity and improved nutrient availability.

An experiment examined the effects of two field bean cultivar samples with different tannin contents, the effect of heat treatment (micronising) and the effect of dietary supplementation of a proprietary enzyme preparation containing tannase, pectinase, and xylanase activities on metabolisable energy (ME), total tract dry matter digestibility (DMD) and ether extract digestibility (EED), nitrogen retention (NR), tannin degradability, gastrointestinal tract (GIT) development, and endogenous mucin losses excretion in broiler chickens. The Control diet contained per kg 221 g crude protein and 12.83 MJ ME. Four additional diets contained 300 g/kg of each of the two untreated or micronised experimental field bean cultivar samples. Each diet was then split into two batches and one of them was supplemented with 3400 units tannase per kg diet resulting in 10 diets in total. Each diet was fed to seven pens with two randomly selected male broilers each. Birds fed the high tannin bean sample had a lower weight gain (p < 0.001), and a lower determined apparent ME (p < 0.05), and DMD (p < 0.001) but a higher tannin degradability (p < 0.001). Compared to the Control diet, feeding field beans increased (p < 0.001) the weights of the proventriculus and gizzard of the birds, and also increased endogenous mucin losses (p < 0.05). Supplementing diets with the tannase-containing enzyme preparation improved dietary ME (p < 0.001), DMD (p < 0.001), NR (p < 0.001) and DEE (p < 0.05), but did not change tannin degradability. Heat treatment of the beans reduced the degradability of condensed tannins and increased endogenous mucin losses (p < 0.05). The differences in the feeding value of the different field bean samples were not improved by heat treatment, but enzyme supplementation improved the feeding value of all diets regardless of the bean samples or heat treatment. Further research is warranted to study the effectiveness of tannase supplementation in poultry diet formulations by dose response trials with purified tannase preparations.

A total of 72 male Ross 308 broilers were used in a study to investigate the effect of dietary tannase on apparent metabolisable energy (AME), coefficients of dry matter retention (DMR) and nitrogen retention (NR) and fat digestibility (FD) of a diet containing 300 g/kg field beans (Vicia faba). Growth performance variables and gastrointestinal tract development were also measured. Two treatments were used in this study: control (C) and C + 3400 tannase units (TU) per kg feed. Diets were formulated to be nutritionally adequate with the exception that the AME was lower than recommended (12.65 vs 12.97 MJ/kg, respectively). Inclusion of tannase increased AME by 0.4 MJ/kg DM. Tannase supplementation improved dietary DMR, NR and FD by 2.8%, 3.2% and 6.5%, respectively. Birds given tannase had 4.4% reduction in feed intake and 2.6% improvement in gain to feed ratio (P < 0.05). Compared to control diet, birds given tannase had reduced relative to body weight (%BW) proventriculus and gizzard and pancreas weights, 3.29% vs 3.09% and 0.47% vs 0.44%, respectively. The mechanisms of action of the studied enzyme require further elucidation.

Significant advances have been made in the management of pulmonary arterial hypertension (PAH) in the past decade. There is a greater understanding of the disease process, more robust markers of prognostication and a wider range of disease-targeted therapies, with three classes of drug therapy now established. This has resulted in improved prognosis and quality of life but has also increased the complexity in making treatment decisions. To utilise these pharmacotherapies to their best potential, several factors need to be considered. This article will discuss how best to initiate and escalate PAH therapy on an individual patient basis by discussing current pharmacotherapies available, specific patient factors and determining treatment response and prognosis at diagnosis and during follow-up.

Objective: To evaluate differences in presentation and outcomes in children with symptomatic congenital cytomegalovirus (cCMV) identified on newborn screening (screened group) and those identified based on clinical findings at birth (referred group)., Study Design: Data on 178 infants with symptomatic cCMV were analyzed. Demographic characteristics, clinical and laboratory findings documented in the nursery, and sequelae data were compared between the screened and the referred groups using χ(2) or Fisher exact test., Results: Two or more clinical findings were detected at birth in 91% of referred infants, and only 58% of screened infants (P < .001). Significantly more children in the referred group had hearing loss compared with screened infants (P = .009). Fifty-one percent of screened children were free of sequelae compared with only 28% of the referred group (P < .003)., Conclusions: Infants with symptomatic cCMV identified based on clinical suspicion have more severe disease at birth and more commonly have sequelae than those identified on newborn screening. Inclusion of referral infants in many previous reports may have overestimated the severity of disease because of selection bias. Defining the complete spectrum of symptomatic disease due to cCMV and providing precise estimates of disease burden can only be gathered from large newborn screening studies., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Background: Many people with asthma tolerate symptoms and lifestyle limitations unnecessarily by not utilizing proven therapies. Better support for self-management is known to improve asthma control, and increasingly the Internet and other digital media are being used to deliver that support., Objective: Our goal was to summarize current knowledge, evidenced through existing systematic reviews, of the effectiveness and implementation of digital self-management support for adults and children with asthma and to examine what features help or hinder the use of these programs., Methods: A comprehensive search strategy combined 3 facets of search terms: (1) online technology, (2) asthma, and (3) self-management/behavior change/patient experience. We undertook searches of 14 databases, and reference and citation searching. We included qualitative and quantitative systematic reviews about online or computerized interventions facilitating self-management. Title, abstract, full paper screening, and quality appraisal were performed by two researchers independently. Data extraction was undertaken using standardized forms., Results: A total of 3810 unique papers were identified. Twenty-nine systematic reviews met inclusion criteria: the majority were from the United States (n=12), the rest from United Kingdom (n=6), Canada (n=3), Portugal (n=2), and Australia, France, Spain, Norway, Taiwan, and Greece (1 each). Only 10 systematic reviews fulfilled pre-determined quality standards, describing 19 clinical trials. Interventions were heterogeneous: duration of interventions ranging from single use, to 24-hour access for 12 months, and incorporating varying degrees of health professional involvement. Dropout rates ranged from 5-23%. Four RCTs were aimed at adults (overall range 3-65 years). Participants were inadequately described: socioeconomic status 0/19, ethnicity 6/19, and gender 15/19. No qualitative systematic reviews were included. Meta-analysis was not attempted due to heterogeneity and inadequate information provision within reviews. There was no evidence of harm from digital interventions. All RCTs that examined knowledge (n=2) and activity limitation (n=2) showed improvement in the intervention group. Digital interventions improved markers of self care (5/6), quality of life (4/7), and medication use (2/3). Effects on symptoms (6/12) and school absences (2/4) were equivocal, with no evidence of overall benefits on lung function (2/6), or health service use (2/15). No specific data on economic analyses were provided. Intervention descriptions were generally brief making it impossible to identify which specific "ingredients" of interventions contribute most to improving outcomes., Conclusions: Digital self-management interventions show promise, with evidence of beneficial effects on some outcomes. There is no evidence about utility in those over 65 years and no information about socioeconomic status of participants, making understanding the "reach" of such interventions difficult. Digital interventions are poorly described within reviews, with insufficient information about barriers and facilitators to their uptake and utilization. To address these gaps, a detailed quantitative systematic review of digital asthma interventions and an examination of the primary qualitative literature are warranted, as well as greater emphasis on economic analysis within trials.

The effect of inorganic (INORG) or organic (ORG) Cu, fed without (-) or with (+) additional S and Mo on Cu status and performance was examined using 56 early lactation dairy cows in a 2×2 factorial study design. Supplementary Cu was added as either CuSO4 or BioplexCu (Alltech Inc., Nicholasville, KY) to provide an additional 10mg of Cu/kg of dry matter (DM), with S added at 1.5g/kg of DM and Mo at 6.8mg/kg of DM to reduce Cu bioavailability. The basal ration was composed of corn and grass silages (2:1 respectively, DM basis) and straight feeds. Cows commenced the study at wk 7 of lactation and remained on treatment for 16 wk. An interaction existed between Cu source and added S and Mo on DM intake, with cows offered INORG- Cu having an increased intake compared with those offered INORG+ or ORG- Cu. Milk yield averaged 35.4kg/d, and was 5% higher with milk fat content 6% lower in cows fed INORG compared with ORG Cu, but milk fat yield, energy-corrected milk yield, and milk protein content did not differ between treatments. A trend existed for cows to have a higher body weight gain when offered ORG compared with INORG Cu. Cows fed diets containing INORG Cu had a higher milk concentration of C17:0 and C18:3n-3 compared with those fed diets containing ORG Cu. Cows fed added S and Mo had a lower milk concentration of C17:0 and C18:0 compared with those that were not supplemented. No effect was observed of dietary treatment on plasma Cu concentration, which averaged 13.1 µmol/L, except during wk 12 when cows receiving added S and Mo had a lower concentration. No effect was observed of Cu source on mean plasma Mo concentrations, but during wk 16 cows offered INORG Cu had a higher concentration than those offered ORG Cu. Hepatic Cu levels decreased by approximately 0.9mg/kg of DM per day when fed additional S and Mo, but no effect of Cu source was observed. A trend existed for hepatic ATPase, Cu++ transporting, beta polypeptide (ATP7B) to be upregulated in cows when fed S and Mo along with ORG but not INORG Cu. In conclusion, the inclusion of an ORG compared with an INORG source of Cu reduced milk yield but increased milk fat concentration and body weight gain, with no effect on energy-corrected milk yield. Little effect was observed of dietary Cu supply on plasma mineral concentration, liver mRNA abundance, or milk fatty acid profile, whereas the addition of S and Mo reduced hepatic Cu concentrations., (Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Most of the genomic sequence of Chara australis virus (CAV), previously called Chara corallina virus, has been determined. It is a ssRNA molecule of 9065 nt with at least four ORFs. At its 5' end is an ORF encoding a protein of 227 kDa, distantly homologous to the multifunctional replicases of benyviruses and rubiviruses. Next is an ORF encoding a protein of 44 kDa, homologous to the helicases of pestiviruses. The third ORF encodes an unmatched protein of 38 kDa that is probably a movement protein. The fourth and 3'-terminal ORF encodes a protein of 17.7 kDa homologous to the coat proteins of tobamoviruses. The short methyltransferase region of the CAV replicase matches only the C-terminal motif of benyvirus methyltransferases. This and other clues indicate that approximately 11% and 2% of the 5' and 3' termini of the complete CAV genome, respectively, are missing from the sequence. The aligned amino acid sequences of the CAV proteins and their nearest homologues contain many gaps but relationships inferred from them were little affected by removal of these gaps. Sequence comparisons show that three of the CAV genes may have diverged from the most closely related genes of other viruses 250-450 million years ago, and the sister relationship between the genes of CAV and those of benyviruses and tobamoviruses, mirroring the ancient sister relationship between charophytes (i.e. the algal host of CAV) and embryophytes (i.e. the plant hosts of tobamoviruses and benyviruses), is congruent with this possibility.

The purpose of this study was to investigate the relationship that age has on factors affecting running economy (RE) in competitive distance runners. Fifty-one male and female subelite distance runners (Young [Y]: 18-39 years [n = 18]; Master [M]: 40-59 years [n = 22]; and Older [O]: 60-older [n = 11]) were measured for RE, step rate, lactate threshold (LT), VO2max, muscle strength and endurance, flexibility, power, and body composition. An RE test was conducted at 4 different velocities (161, 188, 215, and 241 m·min(-1)), with subjects running for 5 minutes at each velocity. The steady-state VO2max during the last minute of each stage was recorded and plotted vs. speed, and a regression equation was formulated. A 1 × 3 analysis of variance revealed no differences in the slopes of the RE regression lines among age groups (y = 0.1827x - 0.2974; R2 = 0.9511 [Y]; y = 0.1988x - 1.0416; R2 = 0.9697 [M]; y = 0.1727x + 3.0252; R2 = 0.9618 [O]). The VO2max was significantly lower in the O group compared to in the Y and M groups (Y = 64.1 ± 3.2; M = 56.8 ± 2.7; O = 44.4 ± 1.7 mlO2·kg(-1)·min(-1)). The maximal heart rate and velocity @ LT were significantly different among all age groups (Y = 197 ± 4; M = 183 ± 2; O = 170 ± 6 b·min(-1) and Y = 289.7 ± 27.0; M = 251.5 ± 32.9; O = 212.3 ± 24.6 m·min(-1), respectively). The VO2max @ LT was significantly lower in the O group compared to in the Y and M groups (Y = 50.3 ± 2.0; M = 48.8 ± 2.9; O = 34.9 ± 3.2 mlO2·kg(-1)·min(-1)). The O group was significantly lower than in the Y and M groups in flexibility, power, and upper body strength. Multiple regression analyses showed that strength and power were significantly related to running velocity. The results from this cross-sectional analysis suggest that age-related declines in running performance are associated with declines in maximal and submaximal cardiorespiratory variables and declines in strength and power, not because of declines in running economy.

1. The effect of three different levels of dietary trypsin inhibitor activity (achieved by varying the amount of non-toasted full fat soya bean in replacement for toasted full fat soya bean) on the incidence of spontaneously-occurring sub-clinical necrotic enteritis (NE) in broiler chickens was compared. A fourth dietary treatment compared the effect of a diet that used potato protein concentrate as the major protein source. The determined trypsin inhibitor activity increased with the increasing content of non-toasted soya bean: 1·90, 6·21, 8·46 and 3·72 mg/g for the three soya bean diets (0, 100 and 200 g of non-toasted soya bean/kg) and the potato protein diet respectively. 2. Although increasing amounts of the non-toasted full-fat soya bean increased the feed intakes of the birds, there was a marked reduction in protein digestibility, weight gain and feed conversion efficiency. 3. There was a linear increase in sub-clinical NE lesions in the duodenum, jejunum, mid small intestine and ileum with increasing non-toasted soya bean. Caecal Clostridium perfringens counts increased with the increasing dietary content of non-toasted soya bean. Serum α-toxin antibodies were higher in the birds fed the 200 g non-toasted soya bean/kg diet compared with the other diets. 4. The results demonstrated that variation in the amount of non-toasted dietary soya bean not only affects growth performance of broilers but also affects the incidence of sub-clinical necrotic enteritis in the flock. Ensuring the lowest possible trypsin-inhibitor activity in soya bean samples is a valuable tool to improve the health and welfare of birds and in reducing the financial losses from this disease.

1. An experiment was conducted to compare and explain the incidence of spontaneously occurring subclinical necrotic enteritis in broiler chickens that were fed on two practical broiler diets that differed in the major protein concentrates (soya bean meal or potato protein concentrates) and examine the relationships between the severity of the disease and the growth performance and physiological responses of the chickens. 2. A total of 840, 20-d-old birds were randomly allocated to 12 pens. Two maize-based nutritionally complete diets that either contained some potato protein or soya bean meal as the major protein supplement were fed for 16 d. Twelve birds were randomly sampled from each pen at the end of the feeding period and their blood sampled and intestinal tracts and livers dissected. 3. The birds fed on the potato protein diet had a significantly 7·7% lower feed intake and a significantly 7·8% lower growth rate compared with the birds fed on the soya-based diet. There were no significant differences in feed conversion efficiency or mortality. There were no differences in the determined apparent metabolisable energy concentrations, however, the apparent dry matter digestibility of the potato protein diet was significantly higher than that of the soya based diet and the apparent crude protein digestibility of the potato protein diet was significantly lower. 4. A significantly higher alpha toxin antibody titre was found in the birds fed on the potato protein diet compared with those fed on the soya protein diet. There was a significantly increased incidence of hepatic lesions in the birds fed on the potato protein diet compared with the birds fed on the soya diet. The mean incidence of intestinal necroses tended to be greater in the birds fed on the potato protein diet (23·6%) compared with the birds fed on the soya-based diet (15·3%). 5. There was a significant linear relationship between ileal digesta sialic acid concentration and serum alpha toxin antibodies, although there were a considerable number of outliers to this relationship. Measurement of sialic acid concentration may be a useful variable to indicate the severity of necrotic enteritis in broiler flocks.

The production of long-chain polyunsaturated fatty acids from precursor molecules linoleic acid (LA; 18:2omega6) and alpha-linolenic acid (ALA; 18:3omega3) is catalysed by sequential desaturase and elongase reactions. We report the isolation of a front-end Delta6-desaturase gene from the microalgae Ostreococcus lucimarinus and two elongase genes, a Delta6-elongase and a Delta5-elongase, from the microalga Pyramimonas cordata. These enzymes efficiently convert their respective substrates when transformed in yeast (39-75% conversion for omega3 substrate fatty acids), and the Delta5-elongase in particular displays higher elongation efficiency (75% for conversion of eicosapentaenoic acid (20:5omega3) to docosapentaenoic acid (22:5omega3)) than previously reported genes. In addition, the Delta6-desaturase is homologous with acyl-CoA desaturases and shows a strong preference for the omega3 substrate ALA.

An experiment was conducted to quantify the effects of 3 nutritionally complete (similar protein and energy) corn-based diets that contained different dietary protein concentrates (potato-CP 76%, fish-CP 66%, or a mixture of soy proteins, soybean meal-CP 48%, and full-fat soy-CP 36%) on the incidence of spontaneously occurring subclinical necrotic enteritis (NE) in broiler chickens. A total of 1,260 birds were placed into 18 solid floor pens (70 birds per pen) and fed 1 of the 3 experimental diets from 15 to 31 d of age. The weight gains and feed intakes of the birds fed the potato- and fish-based diets were lower (P < 0.001) than those of the birds fed the soy-based diets. Weight gain:feed intake ratio and mortality rate were not affected (P > 0.05) by dietary treatment The birds fed the potato-based diets had a higher incidence of necrotic lesions in the duodenum (P < 0.001) and proximal jejunum (P < 0.01) than those fed the soy-based diets. The chickens fed the potato-based diet had a higher (P < 0.001) proportion of moderate to severe duodenal and distal ileal hemorrhages and liver lesions than the birds fed the soy-based diet. There was also a higher (P < 0.05) level of serum antibodies for Clostridium perfringens alpha toxin in birds fed the potato-based diet compared with the other 2 diets. The birds fed the fish-based diet had a similar (P > 0.05) incidence of subclinical NE in comparison to the birds fed the soy-based diet, although there was a higher incidence of intestinal hemorrhagic lesions. The differences in incidence of subclinical NE were not consistent with the relatively small differences in amino acid content between the diets or in the contents of nonstarch polysaccharides. However, the potato protein-based diet had higher trypsin inhibitor activity and a lower lipid content that could have contributed to the increased incidence of subclinical NE.

A basal mixed ration supplying 36 mg of Zn/kg of dry matter (DM) was supplemented with 1 of 4 concentrates differing in level and form of dietary Zn. The concentrates were fed at 2 kg/cow per day and contained 300 mg of Zn/kg (to supply the total recommended level, according to NRC (2001); R) or 60 mg of Zn/kg (to supply 0.66 of the total recommended level; L), either supplemented as ZnO (I) or organically chelated Zn (O). Forty-four Holstein-Friesian dairy cows (12 primiparous and 32 multiparous), on average 31 d (SD +/- 11.4) into lactation, were allocated to 1 of the 4 treatments. All cows remained on the treatment for 14 wk. The data was analyzed by ANOVA as a 2 x 2 factorial design. Dry matter intake averaged 23.5 kg/d and did not differ between treatments. Cows supplemented with organically chelated Zn at the recommended level of inclusion (RO) had a higher milk yield (37.6 kg/d) than those fed inorganic Zn at the recommended level (RI; 35.2 kg/d) or organically chelated Zn at the low level (LO; 35.2 kg/d), but was not different from those fed inorganic Zn at the low level (LI; 36.0 kg/d). Milk composition was unaffected by dietary treatment. Animals that received the low level of Zn (LI and LO) had higher somatic cell counts [3.97 and 3.93 versus 4.35 and 4.55 (log(e)) for RI, RO, LI, and LO, respectively] and milk amyloid A levels than those receiving the recommended levels (RO and RI). There was no effect of treatment on body condition score, body weight, or locomotion score. Hoof hardness improved over the duration of the study but there were no differences between treatments. Similarly, blood plasma mineral levels for Zn, Cu, Mo, and Fe were not affected by treatment, whereas there was a trend for increased ceruloplasmin levels in cows receiving the recommended compared with the low level of Zn, but there was no effect of mineral form. There was also no effect of treatment on superoxide dismutase activity or blood hematology. It is concluded that supplementing Zn at the recommended level reduced somatic cell counts and milk amyloid A levels, whereas supplementation in an organic form at the recommended level also increased milk yield.

Shea nut meal is a by-product of the shea fat industry in West Africa. The objective was to determine the effect of shea nut meal fermentation using Aspergillus niger on growth performance of broiler chickens. An expeller shea nut meal was fermented in a closed plastic container for 8 d after the addition of 0.25 g of A. niger spores per kg of shea nut meal in 2 parts of water. Each of the 2 shea nut meal samples (the unfermented and fermented meals) replaced wheatfeed in a control diet at 100 g/kg and fed to 128 Ross 308 male broiler chickens (22 to 36 d). There were 8 replicates per diet (2 shea nut meal samples and the control wheatfeed diet) and 4 birds per replicate in cages (0.6 m x 0.6 m x 0.9 m). Analysis of variance of data was used to compare the treatment means. The fermentation method reduced the concentrations of total soluble phenolics (21.9%), bound plus soluble proanthocyanidins (34.5%), soluble proanthocyanidins (24.7%), and hydrolysable tannins (52.9%) in the shea nut meal. Broilers fed the fermented meal exhibited higher (P < 0.001) growth performance than those fed the unfermented meal. However, the growth performance of broilers fed each of the shea nut meal-based diets was lower (P < 0.001) than that of broilers fed the control diet. Mean live weight gain of broilers fed the fermented shea nut meal diet was 82% of that of broilers fed the control diet. The fermentation of shea nut meal using A. niger has the potential to improve the nutritive value of shea nut meal for poultry, but requires further development.