A nonsense variant in the KRT14 gene in a domestic shorthair cat with epidermolysis bullosa simplex.

Epidermolysis bullosa simplex (EBS) is a hereditary blistering disease affecting the skin and mucous membranes. It has been reported in humans, cattle, buffaloes and dogs, but so far not in cats. In humans, EBS is most frequently caused by variants in the KRT5 or KRT14 genes. Here, we report a case of feline epidermolysis bullosa simplex and describe the causative genetic variant. An 11-month-old male domestic shorthair cat presented with a history of sloughed paw pads and ulcerations in the oral cavity and inner aspect of the pinnae, starting a few weeks after birth. Clinical and histopathological findings suggested a congenital blistering disease with a split formation within the basal cell layer of the epidermis and oral mucous epithelium. The genetic investigation revealed a homozygous nonsense variant in the KRT14 gene (c.979C>T, p.Gln327*). Immunohistochemistry showed a complete absence of keratin 14 staining in all epithelia present in the biopsy. To the best of our knowledge, this is the first report of feline EBS, and the first report of a spontaneous pathogenic KRT14 variant in a non-human species. The homozygous genotype in the affected cat suggests an autosomal recessive mode of inheritance.

Silencing of Apis mellifera dorsal genes reveals their role in expression of the antimicrobial peptide defensin-1.

Like all other insects, two key signalling pathways [Toll and immune deficiency (Imd)] regulate the induction of honey bee immune effectors that target microbial pathogens. Amongst these effectors are antimicrobial peptides (AMPs) that are presumed to be produced by the nuclear factors kappa B (NF-κB) Dorsal and Relish from the Toll and Imd pathways, respectively. Using in silico analysis, we previously proposed that the honey bee AMP defensin-1 was regulated by the Toll pathway, whereas hymenoptaecin was regulated by Imd and abaecin by both the Toll and Imd pathways. Here we use an RNA interference (RNAi) assay to determine the role of Dorsal in regulating abaecin and defensin-1. Honey bees have two dorsal genes (dorsal-1 and dorsal-2) and two splicing isoforms of dorsal-1 (dorsal-1A and dorsal-1B). Accordingly, we used both single and multiple (double or triple) isoform knockdown strategies to clarify the roles of dorsal proteins and their isoforms. Down-regulation of defensin-1 was observed for dorsal-1A and dorsal-2 knockdowns, but abaecin expression was not affected by dorsal RNAi. We conclude that defensin-1 is regulated by Dorsal (Toll pathway).

Lower airway flow influences peak nasal inspiratory flow in school-aged children.

BACKGROUND: Rhinitis and asthma frequently coexist. Peak nasal inspiratory flow (PNIF) objectively evaluates nasal obstruction. Lower airway flow's impact on PNIF has seldom been analysed in children. We aimed to study the associations between PNIF and: 1)forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF) in children with allergic rhinitis and asthma and healthy controls; 2)allergic rhinitis and asthma control subjective evaluation. METHODS: Sequential assessments of PNIF before and after nasal decongestion and spirometry with bronchodilation test were performed in 65 children (6-12 years) with allergic rhinitis and asthma, and 24 gender, age-matched healthy controls. The Control of Allergic Rhinitis and Asthma Test in children (CARATkids) was used for control assessment. Associations were investigated by multiple linear regression models. RESULTS: Baseline and decongested PNIF correlated with baseline and post-bronchodilation FEV1 and PEF, observed independently of rhinitis and asthma diagnosis. The best model for PNIF included PEF, age and gender. No association was found between PNIF and CARATkids scores, except for nasal obstruction self-report. CONCLUSION: In school-aged children, besides age and gender, PEF values should ideally be known to interpret PNIF values. PNIF can be complementary to subjective control assessment in children with allergic rhinitis and asthma.

Effects of animal type (wild vs. domestic) and diet alfalfa level on intake and digestibility of European adult rabbits (Oryctolagus cuniculus).

The aim of this study was to evaluate the effect of the level of alfalfa in the diet on feed intake and digestibility of two types of rabbits, wild (Oryctolagus cuniculus algirus) vs. domestic (O. cuniculus cuniculus). Ten wild (W; mean LW = 927 g) and 10 domestic (D; mean LW = 4,645 g) adult rabbit does were fed ad libitum two pelleted diets: a control diet (C) with 15% of dehydrated alfalfa hay (as feed basis) and a test diet (A) with 36% of dehydrated alfalfa hay (as feed basis), according to a change-over design. Wild does dry matter (DM) intake per kg live weight (BW) was 55% higher (p < .001) than the intake of the D ones (58 g vs. 37 g DM per kg BW respectively). However, no difference (p > .05) was found when intake was expressed per kg0.75 BW (ca. 56 g DM) and tended to be higher (p = .07) in D does when expressed per kg0.67 BW (62 g vs. 55 g DM). Domestic does showed a higher (p < .05) DM, organic matter, crude energy and neutral detergent fibre digestibility (3; 2; 3; 3 percentage points respectively) than W does. The amount of nutrients and energy digested by D does was lower per kg BW (p < .001), similar per kg0.75 BW (p > .05) and tended to be higher per kg0.67 BW (p < .1) than in W does. The diet content of alfalfa did not affect (p > .05) the feed intake nor the diet digestibility. This study suggests that W rabbits exhibit a higher intake per kg BW and a lower digestibility than their D counterparts, which results in similar digestible nutrient and energy intake per kg BW powered to 0.75. The nutritive value of dehydrated alfalfa for rabbits, evaluated through intake and digestibility, seems to be equivalent to their base diets (forage plus concentrate).

Bioaccumulation of mercury, cadmium, zinc, chromium, and lead in muscle, liver, and spleen tissues of a large commercially valuable catfish species from Brazil.

The increasing amounts of heavy metals entering aquatic environments can result in high accumulation levels of these contaminants in fish and their consumers, which pose a serious risk to ecosystems and human health. We investigated the concentrations of mercury (Hg), cadmium (Cd), zinc (Zn), chromium (Cr), and lead (Pb) in muscle, liver, and spleen tissues of Pseudoplatystoma corruscans specimens collected from two sites on the Paraopeba River, Brazil. The level of heavy metals concentrations in the tissues was often higher in viscera (i.e. liver and spleen) than in muscle, and thus, the viscera should not be considered for human consumption. Correlations between metal concentrations and fish size were not significant. Although the levels of muscle bioaccumulation of Hg, Cd, Zn, Cr, and Pb, generally do not exceed the safe levels for human consumption, the constant presence of heavy metals in concentrations near those limits considered safe for human consumption, is a reason for concern, and populations who constantly consume fish from polluted rivers should be warned. Our findings also indicate that in a river network where certain areas are connected to other areas with high rates of environmental pollutants, people should be cautious about the regular consumption of fish, even when the fish consumed are caught in stretches of the basin where contamination levels are considered low, since many of the freshwater fish with high commercial value, such as the catfish surubim, are migratory.

Animal models of heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) constitutes a clinical syndrome in which the diagnostic criteria of heart failure are not accompanied by gross disturbances of systolic function, as assessed by ejection fraction. In turn, under most circumstances, diastolic function is impaired. Although it now represents over 50 % of all patients with heart failure, the mechanisms of HFpEF remain understood, precluding effective therapy. Understanding the pathophysiology of HFpEF has been restricted by both limited access to human myocardial biopsies and by the lack of animal models that fully mimic human pathology. Animal models are valuable research tools to clarify subcellular and molecular mechanisms under conditions where the comorbidities and other confounding factors can be precisely controlled. Although most of the heart failure animal models currently available represent heart failure with reduced ejection fraction, several HFpEF animal models have been proposed. However, few of these fulfil all the features present in human disease. In this review we will provide an overview of the currently available models to study HFpEF from rodents to large animals as well as present advantages and disadvantages of these models.

Comparative digestibility of low-quality grass hay by two breeds of cattle differing in mature live weight.

The digestive capacity of the Portuguese native breed of Barrosão cattle and the Holstein-Friesian breed was measured when fed meadow hay (72-74 g CP and 641-671 g NDF/kg dry matter), offered either alone or supplemented with soya bean meal (150 g/kg dry matter), at maintenance level. Four mature cows of each breed were used. Average initial live weight (LW) was 457 and 635 kg for the Barrosão and the Holstein-Friesian cows respectively. The organic matter digestibility (OMD) of the meadow hay was higher in Holstein-Friesian than in Barrosão cows (p < 0.08) whether supplemented or not. The neutral detergent fibre digestibility of the hay was also higher in Holstein-Frisian when the hay was fed alone (p < 0.08). The soya bean meal supplementation increased the OMD and the NDFD digestibility of the total diet (p < 0.05), but not the OMD digestibility of the hay (p > 0.05). The results obtained in this study suggest a higher ability to digest fibre in the large dairy breed than in the small native breed. This suggestion is also supported by previous findings with sheep breeds largely differing in mature live weight.

Evaluation of monte carlo to support commissioning of the treatment planning system of new pencil beam scanning proton therapy facilities.

Objective. To demonstrate the potential of Monte Carlo (MC) to support the resource-intensive measurements that comprise the commissioning of the treatment planning system (TPS) of new proton therapy facilities.Approach. Beam models of a pencil beam scanning system (Varian ProBeam) were developed in GATE (v8.2), Eclipse proton convolution superposition algorithm (v16.1, Varian Medical Systems) and RayStation MC (v12.0.100.0, RaySearch Laboratories), using the beam commissioning data. All models were first benchmarked against the same commissioning data and validated on seven spread-out Bragg peak (SOBP) plans. Then, we explored the use of MC to optimise dose calculation parameters, fully understand the performance and limitations of TPS in homogeneous fields and support the development of patient-specific quality assurance (PSQA) processes. We compared the dose calculations of the TPSs against measurements (DDTPSvs.Meas.) or GATE (DDTPSvs.GATE) for an extensive set of plans of varying complexity. This included homogeneous plans with varying field-size, range, width, and range-shifters (RSs) (n= 46) and PSQA plans for different anatomical sites (n= 11).Main results. The three beam models showed good agreement against the commissioning data, and dose differences of 3.5% and 5% were found for SOBP plans without and with RSs, respectively. DDTPSvs.Meas.and DDTPSvs.GATEwere correlated in most scenarios. In homogeneous fields the Pearson's correlation coefficient was 0.92 and 0.68 for Eclipse and RayStation, respectively. The standard deviation of the differences between GATE and measurements (±0.5% for homogeneous and ±0.8% for PSQA plans) was applied as tolerance when comparing TPSs with GATE. 72% and 60% of the plans were within the GATE predicted dose difference for both TPSs, for homogeneous and PSQA cases, respectively.Significance. Developing and validating a MC beam model early on into the commissioning of new proton therapy facilities can support the validation of the TPS and facilitate comprehensive investigation of its capabilities and limitations.

Optimising the hygiene of a liquid feeding system to improve the quality of liquid feed for pigs.

Poor feeding system hygiene may contribute to uncontrolled spontaneous fermentation in liquid pig feed and its associated undesirable effects. This study aimed to determine the effects of an intensive sanitisation programme in a grow-finisher liquid feeding system by monitoring microbiological and physico-chemical parameters of liquid feed and microbial colonisation of the feeding system surfaces. The sanitisation programme involved a combination of physical and chemical cleaning between batches of grow-finisher pigs, combined with nightly rinsing of the system with an organic acid blend. Improved hygiene of the internal surfaces of the mixing tank and feed pipeline, particularly until week 5 post-cleaning, was evidenced by reduced counts of lactic acid bacteria, total aerobes, Enterobacteriaceae, yeasts and moulds and decreased adenosine triphosphate concentrations. Enterobacteriaceae and moulds remained undetectable on pipeline surfaces for 10 weeks. Scanning electron microscopy of the feed pipelines confirmed these findings. Conversely, the impact on liquid feed microbiology was minimal and short-lived. However, acetic acid, ethanol and biogenic amine concentrations decreased in the feed post-cleaning and no gross energy losses were observed. Therefore, by controlling surface microbial communities on liquid feeding systems via implementation of the sanitisation programme developed in the current study, on-farm liquid feed quality should be improved.

Development of optimised tissue-equivalent materials for proton therapy.

Objective. In proton therapy there is a need for proton optimised tissue-equivalent materials as existing phantom materials can produce large uncertainties in the determination of absorbed dose and range measurements. The aim of this work is to develop and characterise optimised tissue-equivalent materials for proton therapy.Approach. A mathematical model was developed to enable the formulation of epoxy-resin based tissue-equivalent materials that are optimised for all relevant interactions of protons with matter, as well as photon interactions, which play a role in the acquisition of CT numbers. This model developed formulations for vertebra bone- and skeletal muscle-equivalent plastic materials. The tissue equivalence of these new materials and commercial bone- and muscle-equivalent plastic materials were theoretical compared against biological tissue compositions. The new materials were manufactured and characterised by their mass density, relative stopping power (RSP) measurements, and CT scans to evaluate their tissue-equivalence.Main results. Results showed that existing tissue-equivalent materials can produce large uncertainties in proton therapy dosimetry. In particular commercial bone materials showed to have a relative difference up to 8% for range. On the contrary, the best optimised formulations were shown to mimic their target human tissues within 1%-2% for the mass density and RSP. Furthermore, their CT-predicted RSP agreed within 1%-2% of the experimental RSP, confirming their suitability as clinical phantom materials.Significance. We have developed a tool for the formulation of tissue-equivalent materials optimised for proton dosimetry. Our model has enabled the development of proton optimised tissue-equivalent materials which perform better than existing tissue-equivalent materials. These new materials will enable the advancement of clinical proton phantoms for accurate proton dosimetry.

A portable primary-standard level graphite calorimeter for absolute dosimetry in clinical pencil beam scanning proton beams.

Objective. To report the use of a portable primary standard level graphite calorimeter for direct dose determination in clinical pencil beam scanning proton beams, which forms part of the recommendations of the proposed Institute of Physics and Engineering in Medicine (IPEM) Code of Practice (CoP) for proton therapy dosimetry.Approach. The primary standard proton calorimeter (PSPC) was developed at the National Physical Laboratory (NPL) and measurements were performed at four clinical proton therapy facilities that use pencil beam scanning for beam delivery. Correction factors for the presence of impurities and vacuum gaps were calculated and applied, as well as dose conversion factors to obtain dose to water. Measurements were performed in the middle of 10 × 10 × 10 cm3homogeneous dose volumes, centred at 10.0, 15.0 and 25.0 g·cm-2depth in water. The absorbed dose to water determined with the calorimeter was compared to the dose obtained using PTW Roos-type ionisation chambers calibrated in terms of absorbed dose to water in60Co applying the recommendations in the IAEA TRS-398 CoP.Main results.The relative dose difference between the two protocols varied between 0.4% and 2.1% depending on the facility. The reported overall uncertainty in the determination of absorbed dose to water using the calorimeter is 0.9% (k= 1), which corresponds to a significant reduction of uncertainty in comparison with the TRS-398 CoP (currently with an uncertainty equal or larger than 2.0% (k= 1) for proton beams).Significance. The establishment of a purpose-built primary standard and associated CoP will considerably reduce the uncertainty of the absorbed dose to water determination and ensure improved accuracy and consistency in the dose delivered to patients treated with proton therapy and bring proton reference dosimetry uncertainty in line with megavoltage photon radiotherapy.

Development of a heterogeneous phantom to measure range in clinical proton therapy beams.

PURPOSE: In particle therapy, determination of range by measurement or calculation can be a significant source of uncertainty. This work investigates the development of a bespoke Range Length Phantom (RaLPh) to allow independent determination of proton range in tissue. This phantom is intended to be used as an audit device. METHOD: RaLPh was designed to be compact and allows different configurations of tissue substitute slabs, to facilitate measurement of range using radiochromic film. Fourteen RaLPh configurations were tested, using two types of proton fluence optimised water substitutes, two types of bone substitute, and one lung substitute slabs. These were designed to mimic different complex tissue interfaces. Experiments were performed using a 115 MeV mono-energetic scanning proton beam to investigate the proton range for each configuration. Validation of the measured film ranges was performed via Monte Carlo simulations and ionisation chamber measurements. The phantom was then assessed as an audit device, by comparing film measurements with Treatment Planning System (TPS) predicted ranges. RESULTS: Varying the phantom slab configurations allowed for measurable range differences, and the best combinations of heterogeneous material gave agreement between film and Monte Carlo on average within 0.2% and on average within 0.3% of ionisation chamber measurements. Results against the TPS suggest a material density override is currently required to enable the phantom to be an audit device. CONCLUSION: This study found that a heterogeneous phantom with radiochromic film can provide range verification as part of a dedicated audit for clinical proton therapy beams.

Application of a portable primary standard level graphite calorimeter for absolute dosimetry in a clinical low-energy passively scattered proton beam.

Objective. A calibration service based on a primary standard calorimeter for the direct determination of absorbed dose for proton beams does not exist. A new Code of Practice (CoP) for reference dosimetry of proton beams is being developed by a working party of the UK Institute of Physics and Engineering in Medicine (IPEM), which will recommend that ionisation chambers are calibrated directly in their clinical beams against the proposed Primary Standard Proton Calorimeter (PSPC) developed at the National Physical Laboratory (NPL). The aim of this work is to report on the use of the NPL PSPC to directly calibrate ionisation chambers in a low-energy passively scattered proton beam following recommendations of the upcoming IPEM CoP.Approach. A comparison between the dose derived using the proposed IPEM CoP and the IAEA TRS-398 protocol was performed, andkQvalues were determined experimentally for three types of chambers. In total, 9 plane-parallel and 3 cylindrical chambers were calibrated using the two protocols for two separate visits.Main results. The ratio of absorbed dose to water obtained with the PSPC and with ionisation chambers applying TRS-398 varied between 0.98 and 1.00, depending on the chamber type. The new procedure based on the PSPC provides a significant improvement in uncertainty where absorbed dose to water measured with a user chamber is reported with an uncertainty of 0.9% (1σ), whereas the TRS-398 protocol reports an uncertainty of 2.0% and 2.3% (1σ) for cylindrical and plane-parallel chambers, respectively. ThekQvalues found agree within uncertainties with those from TRS-398 and Monte Carlo calculations.Significance. The establishment of a primary standard calorimeter for the determination of absorbed dose in proton beams combined with the introduction of the associated calibration service following the IPEM recommendations will reduce the uncertainty and improve consistency in the dose delivered to patients.

[Gynecology/Obstetrics. Magnesium sulfate for fetal neuroprotection in preterm delivery. Latest advances in contraception.]. / Gynécologie - obstétrique.

Morbidity of neonates born before 32 weeks remains significant. Cerebral palsy is found in up to 8 to 10% of survivors. Three randomized controlled trials evaluated the effectiveness of magnesium sulphate given to mothers with a risk of imminent very preterm delivery to prevent perinatal death or cerebral palsy in children. These studies suggest a reduction of the risk of cerebral palsy by magnesium sulphate from 6.5% to 4.8% (relative risk 0.71, 95% CI 0.55-0.91). These results remain controversial, but warrant information to the parents and the implementation of treatments protocols for selected cases.

Structural and optical characterization of ZnO nanowires grown on alumina by thermal evaporation method.

Zinc oxide nanowires have been grown on alumina substrate by thermal evaporation of zinc nanopowder in the presence of oxygen flow. The growth was performed under ambient pressure and without the use of foreign catalyst. Scanning electron microscopy (SEM) observation showed that the as-grown sample consists of bulk ZnO crystal on the substrate surface with nanowires growing from this base. Growth mechanism of the observed morphology is suggested to be governed by the change of zinc vapour supersaturation during the growth process. X-ray diffraction (XRD) measurement was used to identify the crystalline phase of the nanowires. Optical properties of the nanowires were investigated using Raman scattering and photoluminescence (PL). The appearance of dominant, Raman active E2 (high) phonon mode in the Raman spectrum has confirmed the wurtzite hexagonal phase of the nanowires. With above bandgap excitation the low temperature PL recombination is dominated by donor bound exciton luminescence at -3.37 eV with a narrow full width at half maximum. Free exciton emission is also seen at low temperature and can be observed up to room temperature. The optical data indicates that the grown nanowires have high optical quality.

Effects of ambient temperature and soybean meal supplementation on intake and digestion of two sheep breeds differing in mature size.

The aim of this study was to compare the intake and digestive physiology of mature ewes of two breeds--Ile-de-France (mature weight: 75-80 kg) and Churra-da-Terra-Quente (CTQ; mature weight: 45-50 kg)--and evaluate the effects of ambient temperature and protein supplementation in the comparison. The temperature (25 °C vs. 11 °C) and soybean meal supplementation (150 g/kg of ingested hay on dry matter basis vs. unsupplemented control) were evaluated in 48 adult ewes of two breeds fed hay ad libitum and at a restricted level of intake. The intake, digestibility, rumen pH and NH(3)-N, rumen outflow rates, faeces particle size and thyroid hormones levels were measured. These hormones can be related with gastrointestinal motility, thus explaining rumen outflow rate patterns. Dry matter intake per kg of body weight was higher in CTQ ewes (p < 0.05). This breed also exhibited lower organic matter and neutral detergent fibre digestibility (p < 0.001) and higher solid (p < 0.001) and liquid (p < 0.01) rumen outflow rates irrespective of intake level, supplementation or temperature. Rumen pH remained above 6.6 in all treatments. NH(3)-N rumen content was similar (p > 0.05) when breeds were fed only hay. There was no breed effect (p > 0.05) on faeces particle size. Triiodothyronine was not affected (p > 0.05) by breed and thyroxine was higher (p < 0.10) in the CTQ breed but only at the lower temperatures (breed × temperature, p < 0.05). Ile-de-France sheep showed a lack of adaptation to lower temperatures. This study suggests that the native CTQ breed fulfils its metabolic needs by having a higher intake and inherits faster flow through the gastrointestinal tract, as a result, its digestive ability is diminished.

Tuning rheology and aggregation behaviour of TEMPO-oxidised cellulose nanofibrils aqueous suspensions by addition of different acids.

The present work intends to study the variations in the rheological properties and aggregation behaviour of TEMPO-oxidised cellulose nanofibrils (CNF) aqueous suspensions, as a function of changes in concentration and systematic changes in the pH, by addition of acids with different anions. It was found that CNF suspensions form strong gels at mass fractions higher than 0.35 % and the gel point is ca. 0.18 %. On the other hand, aggregation is enhanced at acidic pH conditions due to lower charge repulsion among fibrils, leading to an increase of the suspension viscosity. However, distinct rheological behaviours were presented by CNF suspensions as different acids were applied. It was found that phosphate ions resulted in significant aggregation leading to formation of particles of large size and very strong gels, at pH 2.3; distinctly, the presence of acetate ions resulted in lower aggregation, lower particle size and weaker gels, at the same pH value.

Influence of initial chemical composition and characteristics of pulps on the production and properties of lignocellulosic nanofibers.

This work aimed to study the influence of the initial chemical composition (glucans, lignin, xylan, and mannans), intrinsic viscosity, and carboxylate groups of pulps on the production process and final properties of lignocellulosic nanofibers (LCNF). Pulps of pine sawdust, eucalyptus sawdust, and sugarcane bagasse subjected to conventional pulping and highly oxidized processes were the starting materials. The LCNF were obtained by TEMPO mediated oxidation and mechanical fibrillation with a colloidal grinder. The nanofibrillation degree, chemical charge content, rheology, laser profilometry, cristallinity and atomic force microscopy were used to characterize the LCNF. The carboxylate groups, hemicelluloses and lignin of the initial pulps were important factors that affected the production process of LCNF. The results revealed that intrinsic viscosity and carboxylate groups of the initial pulps affected LCNF production process, whereas lignin and hemicelluloses influenced the viscosity of LCNF aqueous suspensions, the roughness of LCNF films, and the carboxylate groups content of LCNF.