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Study Objectives: This study evaluated the differences in obesity-related outcomes across multiple adolescent sleep health domains, including circadian misalignment (CM), circadian timing, and sleep duration., Methods: 53 adolescents (aged 14-18; body mass index [BMI] percentile < 95%; 53.7% female) completed a cross-sectional study that included baseline assessment of height; weight; demographics; and 10 days assessment of sleep, physical activity, and dietary outcomes. Sleep duration, sleep timing, and physical activity data were collected from all participants using wrist-worn and waist-worn actigraphs. Dietary intake was measured using the Automated Self-Administered 24 Hours dietary recalls on 3 randomized days. Circadian timing was measured using dim-light melatonin onset (DLMO), and CM was calculated as the distance of time between DLMO and the average sleep onset time. Participants were categorized into groups (early vs late circadian timing, aligned vs misaligned circadian timing, and adequate sleep vs short sleep), and differences in dietary outcomes, physical activity, and BMI were analyzed using t- tests., Results: Adolescents with later DLMO ( M  = 21:30 ± 1:11) had 0.63 higher BMI and 0.47% less averaged daily percent fat consumption than adolescents with early DLMO. Adolescents with CM ( M  = 1:42 ± 1:06) consumed 451.77 more averaged daily kcal consumption compared with those with circadian alignment. No statistically significant differences were found in any obesity-related outcome between sleep duration groups., Conclusions: Our cross-sectional findings indicate that focusing on sleep timing and circadian alignment, beyond sleep duration, may promote better health outcomes for healthy adolescents. The findings of this study could enhance sleep education and inform clinical models for prevention efforts for pediatric obesity., Competing Interests: None. The authors report there are no competing interests to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.)

Competing Interests: Declaration of interests The authors declare no competing interests.

Study Objectives: This study examines the impact of sleep duration, bedtime, and sleep disturbance during early childhood on the risk of cardiometabolic disorder (CMD) in early adolescence., Methods: Within the Health Outcomes and Measures of Environment Study, we examined sleep patterns of 330 children from ages 2 to 8 years and the relationship of these sleep patterns with cardiometabolic risk measures at age 12 (N = 220). We used a group-based semi-parametric mixture model to identify distinct trajectories in sleep duration, bedtime timing, and sleep disturbance for the entire sample. We then examined the associations between sleep trajectories and CMD risk measures using general linear models using both an unadjusted model (no covariates) and an adjusted model (adjusting for child pubertal stage, child sex, duration of breastfeeding, household income, maternal education, and maternal serum cotinine)., Results: In the unadjusted and adjusted models, we found significant differences in CMD risk scores by trajectories of sleep disturbance. Children in the "high" disturbance trajectory had higher CMD risk scores than those in the 'low' disturbance trajectory (p's = 0.002 and 0.039, respectively). No significant differences in CMD risk were observed for bedtime timing or total sleep time trajectories in the unadjusted or adjusted models., Conclusions: In this cohort, caregiver-reported sleep disturbance in early childhood was associated with more adverse cardiometabolic profiles in early adolescence. Our findings suggest that trials to reduce CMD risk via sleep interventions-which have been conducted in adolescents and adults-may be implemented too late., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Rumen microbes break down complex dietary carbohydrates into energy sources for the host and are increasingly shown to be a key aspect of animal performance. Host genotypes can be combined with microbial DNA sequencing to predict performance traits or traits related to environmental impact, such as enteric methane emissions. Metagenome profiles were generated from 3139 rumen samples, collected from 1200 dual purpose ewes, using restriction enzyme-reduced representation sequencing (RE-RRS). Phenotypes were available for methane (CH4) and carbon dioxide (CO2) emissions, the ratio of CH4 to CH4 plus CO2 (CH4Ratio), feed efficiency (residual feed intake: RFI), liveweight at the time of methane collection (LW), liveweight at 8 months (LW8), fleece weight at 12 months (FW12) and parasite resistance measured by faecal egg count (FEC1). We estimated the proportion of phenotypic variance explained by host genetics and the rumen microbiome, as well as prediction accuracies for each of these traits., Results: Incorporating metagenome profiles increased the variance explained and prediction accuracy compared to fitting only genomics for all traits except for CO2 emissions when animals were on a grass diet. Combining the metagenome profile with host genotype from lambs explained more than 70% of the variation in methane emissions and residual feed intake. Predictions were generally more accurate when incorporating metagenome profiles compared to genetics alone, even when considering profiles collected at different ages (lamb vs adult), or on different feeds (grass vs lucerne pellet). A reference-free approach to metagenome profiling performed better than metagenome profiles that were restricted to capturing genera from a reference database. We hypothesise that our reference-free approach is likely to outperform other reference-based approaches such as 16S rRNA gene sequencing for use in prediction of individual animal performance., Conclusions: This paper shows the potential of using RE-RRS as a low-cost, high-throughput approach for generating metagenome profiles on thousands of animals for improved prediction of economically and environmentally important traits. A reference-free approach using a microbial relationship matrix from log 10 proportions of each tag normalized within cohort (i.e., the group of animals sampled at the same time) is recommended for future predictions using RE-RRS metagenome profiles., (© 2023. The Author(s).)

Physical traits that improve welfare and disease outcomes for sheep are becoming increasingly important due to both increased climate challenges and societal expectations. Such traits include tail length, the amount of skin (vs. wool) on the underside of the tail, and the area of no-wool (hair) on the belly and breech areas (surrounding the anus) of the animal. An industry dataset consisting of records from individual stud breeders and industry progeny tests was available to estimate the genetic parameters associated with these traits and to investigate the potential for within-breed genetic selection. The heritability estimate for tail length was 0.68 ± 0.01 when breed was not fitted, and 0.63 ± 0.01 when breed was fitted. Similar trends were observed for breech and belly bareness which had heritability estimates around 0.50 (± 0.01). The estimates for these bareness traits are both higher than previous reports from animals of the same age. There was, however, between breed variation in the starting point for these traits, with some breeds having significantly longer tails and a wooly breech and belly, and limited variability. Overall, the results of this study show that flocks exhibiting some variation will be able to make rapid genetic progress in selecting for bareness and tail length traits, and therefore have the potential to make progress towards a sheep that is easier to look after and suffers fewer welfare insults. For those breeds that showed limited within-breed variation, outcrossing may be required to introduce genotypes that exhibit shorter tail length and bareness of belly and breech to increase the rate of genetic gain. Whatever approach is taken by the industry, these results support that genetic improvement can be used to breed "ethically improved sheep"., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Objective/background: Adherence to positive airway pressure (PAP) treatment among children and adolescents is often suboptimal. Little is understood about modifiable determinants of PAP adherence. We evaluated whether patient and caregiver-perceived treatment barriers (across behavioral, environmental, emotional, and physical domains), as well as insomnia severity, were associated with PAP adherence among youth with sleep disordered breathing (SDB)., Patients/methods: We conducted a retrospective review of 188 patients prescribed PAP, ages 2-19 years. At the clinical visit, PAP adherence was assessed via objective download/smartcard and patients and their caregivers completed validated standardized questionnaires on barriers to PAP adherence and sleep onset and maintenance difficulties. We tested predictors of PAP adherence using linear regression., Results: On average, patients wore their PAP 2/3 of nights for 5.3 ± 3.4 h. Patients reported more barriers overall compared to caregivers, and specifically more behavioral and emotional barriers (e.g., over a third of patients reported they just want to forget about sleep apnea). After controlling for demographic/treatment characteristics, patient-reported barriers accounted for a significant proportion of the variance in percent nights used (51%) and average nightly use (42%). Greater difficulties with sleep maintenance predicted poorer PAP adherence (percent nights and nightly duration)., Conclusions: Study findings suggest that assessment of both patient and caregiver-perceived barriers to PAP adherence, as well as evaluating for sleep maintenance concerns, may provide important treatment targets for promoting PAP adherence among youth. Results also support the potential benefit of a multi-disciplinary team-based approach to managing SDB and promoting PAP adherence., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: This study explored the genetic variability in the New Zealand sheep population for economically important skin traits. Skins were collected at slaughter from two progeny test flocks, resulting in 725 skins evaluated for grain strain, flatness, crust leather strength and overall suitability for shoe leather. DNA profiles collected from skins post-slaughter were matched to individual animals using previously collected high-density genotypes., Results: Considerable phenotypic variation for skin traits was observed, with around 40% of the skins being identified as suitable for high-value shoe leather production. Several key traits associated with leather production, including flatness, tear strength, grain strength and grain strain were found to be moderate to highly heritable (h 2 = 0.28-0.82). There were no major significant genome-wide association study (GWAS) peaks associated with many of the traits examined, however, one single-nucleotide polymorphism (SNP) reached significance for the flatness of the skin over the hindquarters., Conclusion: This research confirms that suitable lamb skins can be bred for use as high-value shoe leather. While moderately to highly heritable, skin traits in New Zealand lambs appear to be polygenic with no genes of major effect underlaying the traits of interest. Given the complex nature of these traits, the identification and selection of animals with higher-value skins may be enabled by geomic selection. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Study Objectives: Children with overweight or obesity are more likely to experience sleep disorders, although the role of weight in pediatric insomnia treatment has not been examined. The current study examined the relationships of high body mass with pretreatment insomnia severity and global sleep problems and the potential moderating impact of weight on changes in insomnia severity following insomnia treatment., Methods: Participants included 1,133 youth ages 2-18 years clinically referred for insomnia treatment. The Pediatric Insomnia Severity Index was collected at the initial assessment and throughout treatment as part of routine clinical care. Treatment status was coded as no treatment, early termination, and completed treatment. Secondary measures of global sleep problems at the initial assessment included the Adolescent Sleep Wake Scale, Adolescent Sleep Hygiene Scale, and Children's Sleep Habits Questionnaire. Medical chart review of visits within ± 3 months of baseline was used to obtain age-adjusted and sex-adjusted body mass index Z-score., Results: Among adolescents, regression analyses found that higher body mass index Z-score modestly predicted baseline insomnia severity ( P = .021) and worse sleep hygiene ( P < .001). For children, higher body mass index Z-score was modestly associated with baseline total sleep problems ( P = .006) but not insomnia severity ( P = .792). Across ages, body mass index Z-score predicted neither treatment status nor insomnia improvement ( P > .05). Findings were similar in categorical analyses comparing patients with overweight/obesity to healthy weight., Conclusions: Although there is evidence that children of higher body mass present for insomnia treatment with greater sleep concerns, body mass does not predict treatment completion or insomnia improvement. Data suggest insomnia treatment is effective irrespective of weight status., Citation: Duraccio KM, Simmons DM, Beebe DW, Byars KC. Relationship of overweight and obesity to insomnia severity, sleep quality, and insomnia improvement in a clinically referred pediatric sample. J Clin Sleep Med . 2022;18(4):1083-1091., (© 2022 American Academy of Sleep Medicine.)

This study examined how short sleep impacts dietary consumption in adolescents by testing whether experimentally shortening sleep influences the amount, macronutrient content, food types, and timing of food consumed. Ninety-three adolescents completed a within-subjects crossover paradigm comparing five nights of short sleep (6.5-hour sleep opportunity) to five nights of Healthy Sleep (9.5-hour sleep opportunity). Within each condition, adolescents completed three multiple-pass dietary recalls that recorded the types, amount, and timing of food intake. The following outcomes were averaged across days of dietary recall within condition: kilocalories, grams of carbohydrates, fat, protein, and added sugars, glycemic load of foods, and servings of specific types of foods (low-calorie drinks, sweetened drinks, fruits/vegetables, meats/proteins, processed snacks, "fast food" entrees, grains, and sweets/desserts). Timing of consumption of kilocalorie and macronutrient outcomes were also examined across four noncumulative time bins: 06:00-10:59, 11:00-15:59, 16:00-20:59, and 21:00-01:00. Adolescents slept 2 h and 20 min longer in Healthy Sleep than in Short Sleep (p < .0001). While in Short Sleep, adolescents ate more grams of carbohydrates (p = .031) and added sugars (p = .047), foods higher in glycemic load (p = .013), and servings of sweet drinks (p = .023) and ate fewer servings of fruits/vegetables (p = .006) compared to Healthy Sleep. Differences in consumption of kilocalories, fat, and carbohydrates emerged after 9:00 pm (ps = .012, .043, .006, respectively). These experimental findings suggest that adolescents who have insufficient sleep exhibit dietary patterns that may increase the risk for negative weight and cardiometabolic outcomes. Future health promotion efforts should include promoting optimal sleep to increase healthy dietary habits., (© Sleep Research Society 2022. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Pulmonary endarterectomy (PEA) is the main treatment for chronic thromboembolic pulmonary hypertension (CTEPH). Postoperative unfractionated heparin dosing can be monitored by activated partial thromboplastin time (APTT) or by anti-factor Xa activity (anti-Xa). In pseudo heparin resistance, APTT response to heparin is blunted due to elevated Factor VIII (FVIII) which can underestimate anticoagulation. We examined possible pseudo heparin resistance after PEA and assessed the impact of FVIII. APTT response to heparin before and after operation was determined in 13 PEA patients anticoagulated with unfractionated heparin. APTT and anti-Xa concordance was analyzed from paired postoperative samples, and antithrombin, fibrinogen and FVIII levels were measured. Single-cell RNA sequencing was used to characterize FVIII gene expression in PEA specimens of 5 patients. APTT response to heparin was blunted after PEA. APTT and anti-Xa were discordant in 36% of postoperative samples and most common discordant patterns were subtherapeutic APTT with therapeutic (16%) or supratherapeutic (11%) anti-Xa. Overall, APTT underestimated anticoagulation relative to anti-Xa in one-third of the samples. FVIII levels were elevated before surgery, increased substantially 1 and 3 days (median 4.32 IU/mL) after PEA, and were higher in discordant than concordant samples. Single-cell RNA sequencing showed FVIII gene expression in PEA specimen endothelial cells. Pseudo heparin resistance is common after PEA likely due to highly elevated postoperative FVIII levels indicating that anti-Xa reflects postoperative heparinization better than APTT in these patients. FVIII production by the pulmonary artery endothelium may participate in local prothrombotic processes important for CTEPH pathogenesis., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Robust biomarkers of chronological age have been developed in humans and model mammalian species such as rats and mice using DNA methylation data. The concept of these so-called "epigenetic clocks" has emerged from a large body of literature describing the relationship between genome-wide methylation levels and age. Epigenetic clocks exploit this phenomenon and use small panels of differentially methylated cytosine (CpG) sites to make robust predictions of chronological age, independent of tissue type. Here, we present highly accurate livestock epigenetic clocks for which we have used the custom mammalian methylation array "HorvathMammalMethyl40" to construct the first epigenetic clock for domesticated goat ( Capra hircus ), cattle ( Bos taurus ), Red ( Cervus elaphus ) and Wapiti deer ( Cervus canadensis ) and composite-breed sheep ( Ovis aries ). Additionally, we have constructed a 'farm animal clock' for all species included in the study, which will allow for robust predictions to be extended to various breeds/strains. The farm animal clock shows similarly high accuracy to the individual species' clocks ( r > 0.97), utilizing only 217 CpG sites to estimate age (relative to the maximum lifespan of the species) with a single mathematical model. We hypothesise that the applications of this livestock clock could extend well beyond the scope of chronological age estimates. Many independent studies have demonstrated that a deviation between true age and clock derived molecular age is indicative of past and/or present health (including stress) status. There is, therefore, untapped potential to utilize livestock clocks in breeding programs as a predictor for age-related production traits.

Facial eczema (FE) is a significant metabolic disease that affects New Zealand ruminants. Ingestion of the mycotoxin sporidesmin leads to liver and bile duct damage, which can result in photosensitisation, reduced productivity and death. Strategies used to manage the incidence and severity of the disease include breeding. In sheep, there is considerable genetic variation in the response to FE. A commercial testing program is available for ram breeders who aim to increase tolerance, determined by the concentration of the serum enzyme, gamma-glutamyltransferase 21 days after a measured sporidesmin challenge (GGT21). Genome-wide association studies were carried out to determine regions of the genome associated with GGT21. Two regions on chromosomes 15 and 24 are reported, which explain 5% and 1% of the phenotypic variance in the response to FE, respectively. The region on chromosome 15 contains the β-globin locus. Of the significant SNPs in the region, one is a missense variant within the haemoglobin subunit β ( HBB ) gene. Mass spectrometry of haemoglobin from animals with differing genotypes at this locus indicated that genotypes are associated with different forms of adult β-globin. Haemoglobin haplotypes have previously been associated with variation in several health-related traits in sheep and warrant further investigation regarding their role in tolerance to FE in sheep. We show a strategic approach to the identification of regions of importance for commercial breeding programs with a combination of discovery, statistical and biological validation. This study highlights the power of using increased density genotyping for the identification of influential genomic regions, combined with subsequent inclusion on lower density genotyping platforms.

Pneumonia is an important issue for sheep production, leading to reduced growth rate and a predisposition to pleurisy. The objective of this study was to identify loci associated with pneumonic lesions and pleurisy in New Zealand progeny test lambs. The lungs from 3,572 progeny-test lambs were scored for presence and severity of pneumonic lesions and pleurisy at slaughter. Animals were genotyped using the Illumina Ovine Infinium HD SNP BeadChip (606,006 markers). The heritability of lung lesion score and pleurisy were calculated using the genomic relationship matrix, and genome-wide association analyses were conducted using EMMAX and haplotype trend regression. At slaughter, 35% of lambs had pneumonic lesions, with 9% showing lesions on more than half of any individual lobe. The number of lambs recorded as having pleurisy by the processing plants was 9%. Heritability estimates for pneumonic lesions and pleurisy scores adjusted for heteroscedasticity (CPSa and PLEURa) were 0.16 (± 0.03) and 0.05 (± 0.02), respectively. Five single-nucleotide polymorphisms (SNPs) were significantly associated with pneumonic lesions at the genome-wide level, and additional 37 SNPs were suggestively significant. Four SNPs were significantly associated with pleurisy, with an additional 11 SNPs reaching the suggestive level of significance. There were no regions that overlapped between the 2 traits. Multiple SNPs were in regions that contained genes involved in either the DNA damage response or the innate immune response, including several that had previously been reported to have associations with respiratory disease. Both EMMAX and HTR analyses of pleurisy data showed a significant peak on chromosome 2, located downstream from the transcription factor SP3. SP3 activates or suppresses the expression of numerous genes, including several genes with known functions in the immune system. This study identified several SNPs associated with genes involved in both the innate immune response and the response to DNA damage that are associated with pneumonic lesions and pleurisy in lambs at slaughter. Additionally, the identification in sheep of several SNPs within genes that have previously been associated with the respiratory system in cattle, pigs, rats, and mice indicates that there may be common pathways that underlie the response to invasion by respiratory pathogens in multiple species.

Gastrointestinal nematode infection is a constraint on sheep production worldwide. Selective breeding programmes to enhance resistance to nematode infection are currently being implemented in a number of countries. Identification of loci associated with resistance to infection or causative mutations for resistance would enable more effective selection. Loci associated with indicator traits for nematode resistance has been identified in previous studies. In this study, Scottish Blackface, Texel and Suffolk lambs were used to validate the effects at eight genomic regions previously associated with nematode resistance (OAR3, 4, 5, 7, 12, 13, 14, 21). No SNP was significantly associated with nematode resistance at the region-wide level but seven SNPs in three of the regions (OAR4, 12, 14) were nominally associated with trichostrongyle egg count in this study and six of these were also significant when fitted as single SNP effects. Nematodirus egg count was nominally associated with SNPs on OAR3, 4, 7 and 12., (© 2018 Stichting International Foundation for Animal Genetics.)

Gastrointestinal nematodes are a serious cause of morbidity and mortality in grazing ruminants. The major ovine defence mechanism is acquired immunity, with protective immunity developing over time in response to infection. Nematode resistance varies both within and between breeds and is moderately heritable. A detailed understanding of the genes and mechanisms involved in protective immunity, and the factors that regulate this response, is required to aid both future breeding strategies and the development of effective and sustainable nematode control methods. The aim of this study was to compare the abomasal lymph node transcriptome of resistant and susceptible lambs in order to determine biological processes differentially expressed between resistant and susceptible individuals. Scottish Blackface lambs, with divergent phenotypes for resistance, were challenged with 30,000 Teladorsagia circumcincta larvae (L3), and abomasal lymph nodes recovered at 7 and 14days post-infection (dpi). High-throughput sequencing of cDNA from the abomasal lymph node was used to quantitatively sample the transcriptome with an average of 32 million reads per sample. A total of 194 and 144 genes were differentially expressed between resistant and susceptible lambs at 7 and 14 dpi respectively. Differentially expressed networks and biological processes were identified using Ingenuity Pathway Analysis. Genes involved in the inflammatory response, attraction of T lymphocytes and binding of leukocytes were more highly expressed in resistant animals at 7 dpi and in susceptible animals at 14 dpi indicating that resistant animals respond to infection earlier than susceptible animals. Twenty-four Single Nucleotide Polymorphisms (SNP) within 11 differentially expressed genes, were tested for association with gastrointestinal nematode resistance in the Scottish Blackface lambs. Four SNP, in 2 genes (SLC30A2 and ALB), were suggestively associated with faecal egg count. In conclusion, a large number of genes were differentially expressed in the abomasal lymph node of resistant and susceptible lambs responding to gastrointestinal nematode challenge. Resistant Scottish Blackface lambs appear to generate an earlier immune response to T. circumcincta. In susceptible lambs this response appears to be delayed. SNP in 2 differentially expressed genes were suggestively associated with faecal egg count indicating that differentially expressed genes may be considered candidate loci for mediating nematode resistance., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Gastrointestinal nematode infection represents a major threat to the health, welfare and productivity of sheep populations worldwide. Infected lambs have a reduced ability to absorb nutrients from the gastrointestinal tract, resulting in morbidity and occasional mortality. The current chemo-dominant approach to nematode control is considered unsustainable due to the increasing incidence of anthelmintic resistance. In addition, there is growing consumer demand for food products from animals not subjected to chemical treatment. Future mechanisms of nematode control must rely on alternative, sustainable strategies such as vaccination or selective breeding of resistant animals. Such strategies take advantage of the host's natural immune response to nematodes. The ability to resist gastrointestinal nematode infection is considered to be dependent on the development of a protective acquired immune response, although the precise immune mechanisms involved in initiating this process remain to be fully elucidated. In this study, current knowledge on the innate and acquired host immune response to gastrointestinal nematode infection in sheep and the development of immunity is reviewed., (© 2015 John Wiley & Sons Ltd.)

The objective of this study was to identify Scottish Blackface lambs that were at the extremes of the spectrum of resistance to gastrointestinal nematodes and characterise their response to an experimental nematode challenge. Lambs (n = 90) were monitored for faecal egg count (FEC) (2 samples from each of 2 independent natural infections). The most resistant (n = 10) and susceptible (n = 10) individuals were selected and challenged with 30,000 Teladorsagia circumcincta larvae (L3) at 9 months of age. Response to infection was monitored by measuring FEC, plasma pepsinogen, serum antibodies against nematode larval antigens and haematology profile, until necropsy at 71 days post infection. Worm burden, worm fecundity and the level of anti-nematode antibodies in abomasal mucosa were determined at necropsy. FEC was consistently higher in susceptible animals (P < 0.05), validating the selection method. Worm fecundity was significantly reduced in resistant animals (P = 0.03). There was also a significant correlation (r = 0.88; P < 0.001) between the number of adult worms and FEC at slaughter. There was no effect of phenotype (resistance/susceptibility) on plasma pepsinogen or on haematology profile. Phenotype had a significant effect on the level of anti-nematode IgA antibodies in serum (P < 0.01), reflecting a higher peak in resistant animals at day 7 post infection. It is concluded that significant variation in the response to gastrointestinal nematode challenge exists within the Scottish Blackface population with resistant animals displaying significantly lower FEC, lower worm fecundity and higher concentration of anti-nematode IgA antibodies in serum., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Gastrointestinal nematodes are one of the most serious causes of disease in domestic ruminants worldwide. There is considerable variation in resistance to gastrointestinal nematodes within and between sheep breeds, which appears to be due to underlying genetic diversity. Through selection of resistant animals, rapid genetic progress has been demonstrated in both research and commercial flocks. Recent advances in genome sequencing and genomic technologies provide new opportunities to understand the ovine host response to gastrointestinal nematodes at the molecular level, and to identify polymorphisms conferring nematode resistance., Results: Divergent lines of Romney and Perendale sheep, selectively bred for high and low faecal nematode egg count, were genotyped using the Illumina® Ovine SNP50 BeadChip. The resulting genome-wide SNP data were analysed for selective sweeps on loci associated with resistance or susceptibility to gastrointestinal nematode infection. Population differentiation using FST and Peddrift revealed sixteen regions, which included candidate genes involved in chitinase activity and the cytokine response. Two of the sixteen regions identified were contained within previously identified QTLs associated with nematode resistance., Conclusions: In this study we identified fourteen novel regions associated with resistance or susceptibility to gastrointestinal nematodes. Results from this study support the hypothesis that host resistance to internal nematode parasites is likely to be controlled by a number of loci of moderate to small effects.

The aim of this study was to investigate the importance of Toll-like receptor 4 (TLR4) signaling on cardiac myocytes versus immune cells in lipopolysaccharide (LPS)-induced cardiac dysfunction. Cardiac myocytes isolated from LPS-treated C57Bl/6 mice showed reduced shortening and calcium transients as compared with myocytes from untreated mice. In addition, LPS-treated C57Bl/6 mice showed impaired cardiac mitochondrial function, including reduced respiration and reduced time of induction of permeability transition. All of the aforementioned cardiac dysfunction was dependent on TLR4, because LPS-treated TLR4-deficient mice did not have reduced myocyte shortening or mitochondrial dysfunction. To evaluate the role of cardiac myocyte versus leukocyte TLR4, LPS was injected into chimeric mice with TLR4-positive leukocytes and TLR4-deficient myocytes. These mice showed reduced myocyte shortening in response to LPS. Myocytes from chimeric mice with TLR4-deficient leukocytes and TLR4-positive myocytes had no response to LPS. In addition, isolated myocytes from C57Bl/6 mice subsequently treated with LPS and serum for various times did not have reduced shortening, despite the presence of TLR4 mRNA and protein, as determined by reverse-transcription polymerase chain reaction and fluorescent-activated cell sorting. In fact, cardiac myocytes had equivalent amounts of TLR4 as endothelium; however, only the latter is responsive to LPS. Furthermore, signaling pathways downstream of TLR4 were not activated during direct LPS treatment of myocytes. In conclusion, TLR4 on leukocytes, and not on cardiac myocytes, is important for cardiac myocyte impairment during endotoxemia.

Anesthetic technique for pulmonary transplantation varies with recipient's underlying lung disease, procedure performed and regional practice. The pulmonary allograft is vulnerable to mechanical and biochemical injury throughout the harvesting, preservation and engraftment procedures. Mechanisms of allograft injury are reviewed, with suggestions for incorporation of strategies to minimize injury into clinical practice. Particular emphasis is placed on the use of nitric oxide for treatment of reperfusion injury.

Background: Lung growth in children is associated with dramatic increases in the number and surface area of alveolated airways. Modelling studies have shown the slope of the alveolar plateau (phase III) is sensitive to the total cross-sectional area of these airways. Therefore, the influence of age and body size on the phase III slope of the volumetric capnogram was investigated., Methods: Phase III slope (alveolar dcCO2/dv) and airway deadspace (VDaw) were derived from repeated single-breath carbon dioxide expirograms collected on 44 healthy mechanically ventilated children (aged 5 months-18 yr) undergoing minor surgery. Ventilatory support was standardized (VT = 8.5 and 12.5 ml/kg, f = 8-15 breaths/min, inspiratory time = 1 s, end-tidal partial pressure of carbon dioxide = 30-45 mmHg), and measurements were recorded by computerized integration of output from a heated pneumotachometer and mainstream infrared carbon dioxide analyzer inserted between the endotracheal tube and anesthesia circuit. Experimental data were compared to simulated breath data generated from a numeric pediatric lung model., Results: An increased VDaw, a smaller VDaw/VT, and flatter phase III slope were found at the larger tidal volume (P < 0.01). Strong relationships were seen at VT = 12.5 ml/kg between airway deadspace and age (R2 = 0.77), weight (R2 = 0.93), height (R2 = 0.78), and body surface area (R2 = 0.89). The normalized phase III slopes of infants were markedly steeper than that of adolescents and were reduced at both tidal volumes with increasing age, weight, height, and body surface area. Phase III slopes and VDaw generated from modelled carbon dioxide washout simulations closely matched the experimental data collected in children., Conclusions: Morphometric increases in the alveolated airway cross-section with lung growth is associated with a decrease of the phase III slope. During adolescence, normalized phase III slopes approximate those of healthy adults. The change in slope with lung growth may reflect a decrease in diffusional resistance for carbon dioxide transport within the alveolated airway resulting in diminished acinar carbon dioxide gradients.

The authors followed 38 children with delayed speech development approximately two to four years after initial diagnosis, assessing and comparing their subsequent speech and language, and over-all development. Nearly all of the children had appropriate language levels for their general development. Just over half had less articulation competence than expected for their age, but this was not related to language achievement or age. It appears that the prognosis for future language development is favourable for these children. The results suggest that articulation might be a developmentally related process with a good prognosis, but further follow-up is necessary to determine ultimate competence of children in whom this is delayed.

Apnoeic oxygenation (AO) combined with extracorporeal CO2 removal (ECCO2R), using venovenous perfusion across a membrane area of 0.1 m2 has been shown to be feasible in six healthy anaesthetized rabbits. In a further twelve rabbits, ECCO2R has been randomly compared with conventional mechanical ventilation (CMV) following saline lavage to induce respiratory failure. Blood gases were maintained for up to 6 h within the same range (PaO2 = 8-20 kPa, PaCO2 = 4-6 kPa) in two groups of six by varying airway pressures and the oxygen fraction delivered either to the membrane lung (ECCO2R group) or to the ventilator (CMV group). The influence of single hourly sustained inflations (SI) on oxygenation was studied. ECCO2R subjects remained stable and survived. CMV subjects deteriorated and had 80% mortality. Hyaline membranes were absent from ECCO2R subjects and present in all CMV subjects. The response to SI suggests that a lung volume recruitment is maintained during AO for up to 1 h but is ineffective during CMV.

Haemolysis of human blood has been examined in vitro as a function of pH in the range 7.2-8.0. The hydrogen ion concentration of freshly donated blood from 11 donors was manipulated in 42 experiments, entirely by altering the carbon dioxide fraction of air with which the blood was equilibrated using a membrane lung. In contrast to the known alkalaemic haemolysis which occurs in canine blood, we observed no correlation between plasma haemoglobin concentrations and blood pH. We conclude that alkalaemic haemolysis is unlikely to complicate the clinical application of extracorporeal carbon dioxide removal in the management of acute respiratory failure.