Whanau Maori and Pacific peoples' knowledge, perceptions, expectations and solutions regarding antibiotic treatment of upper respiratory tract infections: a qualitative study.

INTRODUCTION: The rate of community antibiotic use is high in Aotearoa New Zealand (NZ) when compared to other nations, and in NZ, as in most other nations, antibiotics are very commonly prescribed for self-limiting upper respiratory tract infections (URTIs). Resources that build knowledge, perceptions and understanding can potentially reduce unnecessary antibiotic consumption. METHODS: To inform the content of educational resources, we conducted an in-depth qualitative study with 47 participants via 6 focus groups of the knowledge, attitudes, and expectations of whanau Maori and Pacific peoples about antibiotics and URTIs. RESULTS: Focus groups with 47 participants identified four themes: Knowledge that might influence expectations to receive antibiotics for URTIs; Perceptions - the factors that influence when and why to seek medical care for URTI; Expectations - the features of successful medical care for URTI; Solutions - how to build community knowledge about URTI and their treatment and prevention. Knowledge that might reduce expectations to receive antibiotics for URTI included confidence in the use of alternative remedies, knowledge that URTI are usually caused by viruses, and concerns about antibiotic adverse effects. Participants commonly reported that they would confidently accept their doctor's recommendation that an antibiotic was not necessary for an URTI, provided that a thorough assessment had been performed and that treatment decisions were clearly communicated. CONCLUSION: These findings suggest that building patients' knowledge and skills about when antibiotics are necessary, and increasing doctors' confidence and willingness not to prescribe an antibiotic for patients with an URTI, could significantly reduce inappropriate antibiotic prescribing in NZ.

Factors associated with advanced colorectal cancer differ between young and older adults in England: a population-based cohort study.

AIM: Advanced stage presentation of colorectal cancer is associated with poorer survival outcomes, particularly among young adults. This study aimed to determine whether demographic risk factors for advanced stage presentation differed between young and older adults. METHOD: Individual-level data on all incident colorectal cancers in people aged 20 years and above were extracted from the National Cancer Registration and Analysis Service database for the years 2012 to 2015. Patients were divided into two cohorts: young-onset colorectal cancer (YOCC) if aged 20-49 years and older-onset colorectal cancer (OOCC) if aged 50 years and above. Logistic regression was used to identify risk factors for advanced stage presentation, defined as TNM Stage III or IV, in each cohort. RESULTS: There were 7075 (5.2%) patients in the YOCC cohort and 128 345 (94.8%) patients in the OOCC cohort. Tumours in the YOCC cohort were more likely to be at an advanced stage (67.2% vs 55.3%, P < 0.001) and located distally (63.7% vs 55.4%, P < 0.001). No demographic factor was consistently associated with advanced stage presentation in the YOCC cohort. Among the OOCC cohort, increased social deprivation [OR (Index of Multiple Deprivation quintile 5 vs 1) = 1.11 (95% CI 1.07-1.16), P < 0.001], Black/Black British ethnicity [OR (baseline White) = 1.25 (95% CI 1.11-1.40), P < 0.001] and residence in the East Midlands [OR (baseline London) = 1.11 (95% CI 1.04-1.17), P = 0.001] were associated with advanced stage presentation. CONCLUSION: Demographic factors associated with advanced disease were influenced by age. The effects of social deprivation and ethnicity were only observed in older adults and mirror trends in screening uptake. Targeted interventions for high-risk groups are warranted.

Demographic trends in the incidence of young-onset colorectal cancer: a population-based study.

BACKGROUND: Evidence is emerging that the incidence of colorectal cancer is increasing in young adults, but the descriptive epidemiology required to better understand these trends is currently lacking. METHODS: A population-based cohort study was carried out including all adults aged 20-49 years diagnosed with colorectal cancer in England between 1974 and 2015. Data were extracted from the National Cancer Registration and Analysis Service database using ICD-9/10 codes for colorectal cancer. Temporal trends in age-specific incidence rates according to sex, anatomical subsite, index of multiple deprivation quintile and geographical region were analysed using Joinpoint regression. RESULTS: A total of 56 134 new diagnoses of colorectal cancer were analysed. The most sustained increase in incidence rate was in the group aged 20-29 years, which was mainly driven by a rise in distal tumours. The magnitude of incident rate increases was similar in both sexes and across Index of Multiple Deprivation quintiles, although the most pronounced increases in incidence occurred in the southern regions of England. CONCLUSION: Colorectal cancer should no longer be considered a disease of older people. Changes in incidence rates should be used to inform future screening policy, preventative strategies and research agendas, as well as increasing public understanding that younger people need to be aware of the symptoms of colorectal cancer.

ANTECEDENTES: Están apareciendo evidencias de que la incidencia del cáncer colorrectal (colorectal cancer, CRC) está aumentando en adultos jóvenes, pero se carece de la epidemiología descriptiva necesaria para comprender mejor estas tendencias. MÉTODOS: Se realizó un estudio de cohortes de base poblacional de todos los adultos de 20 a 49 años diagnosticados de CRC en Inglaterra entre 1974 y 2015. Los datos se extrajeron de la base de datos NCRAS utilizando los códigos ICD9/10 para el CRC. Las tendencias temporales en las tasas de incidencia específicas por edad (incidence rates, IR) según el sexo, la localización anatómica, el quintil del índice de privación múltiple (index of multiple deprivation, IMD) y la región geográfica se analizaron mediante un modelo de regresión joinpoint. RESULTADOS: Se analizaron un total de 56.134 nuevos diagnósticos de CRC. El aumento más sostenido en la IR se produjo en el grupo de edad de 20 a 29 años, principalmente a expensas de un incremento de los tumores distales. La magnitud de los aumentos de IR fue similar en ambos sexos y en los quintiles del IMD, aunque los aumentos más pronunciados en la incidencia se registraron en las regiones del sur de Inglaterra. CONCLUSIÓN: El CRC ya no debe ser considerado una enfermedad de las personas mayores: los cambios en las tasas de incidencia deberán tenerse en cuenta en las futuras políticas de cribado, en las estrategias preventivas y en los proyectos de investigación, así como para aumentar la toma de conciencia de la población de que las personas más jóvenes deben estar al corriente de los síntomas del CRC.

Dynamics of genomic architecture during composite breed development in cattle.

Some livestock breeds face the challenge of reduced genetic variation, increased inbreeding depression owing to genetic drift and selection. Hybridization can reverse these processes and increase levels of productivity and adaptation to various environmental stressors. Samples from American Brangus were used to evaluate the indicine/taurine composition through nine generations (~45 years) after the hybridization process was completed. The purpose was to determine how hybridization alters allelic combinations of a breed over time when genetic factors such as selection and drift are operating. Furthermore, we explored genomic regions with deviations from the expected composition from the progenitor breeds and related these regions to traits under selection. The Brangus composition deviated from the theoretical expectation, defined by the breed association, of 62.5% taurine, showing taurine composition to be 70.4 ± 0.6%. Taurine and indicine proportion were not consistent across chromosomes. Furthermore, these non-uniform areas were found to be associated with traits that were probably under selection such as intermuscular fat and average daily gain. Interestingly, the sex chromosomes were predominantly taurine, which could be due to the composite being formed particularly in the final cross that resulted in progeny designated as purebred Brangus. This work demonstrated the process of new breed formation on a genomic level. It suggests that factors like genetic drift, selection and complementarity shift the genetic architecture into a uniquely different population. These findings are important to better understand how hybridization and crossbreeding systems shape the genetic architecture of composite populations.

A Systematic Review and Meta-Analysis of Prognostic Biomarkers in Anal Squamous Cell Carcinoma Treated With Primary Chemoradiotherapy.

Recent studies suggest that the treatment response and survival from head and neck tumours can be stratified according to biomarker status, particularly human papillomavirus (HPV) status and p16 expression, but the evidence for predictive biomarkers in anal squamous cell carcinoma (ASCC) remains limited. The aim of this study was to determine which biomarkers were associated with locoregional recurrence (LRR), overall survival and disease-free survival (DFS) in ASCC. A systematic search was undertaken of the MEDLINE, Embase, Cochrane Library, CINAHL and Web of Science databases using validated terms for ASCC, biomarkers and prognosis. Biomarkers were included in the meta-analysis if they were reported by at least four studies and provided sufficient data to permit the calculation of survival effect estimates. HPV status, p16, p53 and epidermal growth factor receptor (EGFR) met the inclusion criteria for meta-analysis and were reported by 17 retrospective cohort studies describing 1635 patients. When compared with HPV-negative tumours, HPV-positive tumours were associated with reduced LRR (pooled hazard ratio = 0.27 [95% confidence interval 0.16-0.48]; P < 0.001), improved overall survival (hazard ratio =0.26 [0.12-0.59]; P = 0.001) and DFS (hazard ratio = 0.33 [0.16-0.70]; P = 0.003). Likewise, p16-positive tumours were associated with reduced LRR (hazard ratio = 0.26 [0.13-0.52]; P < 0.001), improved overall survival (hazard ratio = 0.44 [0.24-0.81]; P = 0.009) and DFS (hazard ratio = 0.44 [0.23-0.83]; P = 0.012) when compared with p16-negative tumours. HPV-positive/p16-positive tumours had improved overall survival when compared with HPV-negative/p16-negative tumours (hazard ratio = 0.27 [0.15-0.48], P < 0.001), but not HPV-negative/p16-positive tumours (hazard ratio = 0.64 [0.21-1.90]; P = 0.421). p53 mutation was associated with worse DFS (hazard ratio = 1.63 [1.33-2.01]; P = 0.003). There was no association between EGFR status and any survival outcome. HPV status, p16 and p53 expression are of prognostic utility in ASCC. Future studies should prospectively validate these findings with a view to conducting subsequent randomised controlled trials where patients are stratified according to biomarker status and randomised to different treatment regimens.

Pre- and post-puberty expression of genes and proteins in the uterus of Bos indicus heifers: the luteal phase effect post-puberty.

Progesterone signaling and uterine function are crucial in terms of pregnancy establishment. To investigate how the uterine tissue and its secretion changes in relation to puberty, we sampled tissue and uterine fluid from six pre- and six post-pubertal Brahman heifers. Post-pubertal heifers were sampled in the luteal phase. Gene expression of the uterine tissue was investigated with RNA-sequencing, whereas the uterine fluid was used for protein profiling with mass spectrometry. A total of 4034 genes were differentially expressed (DE) at a nominal P-value of 0.05, and 26 genes were significantly DE after Bonferroni correction (P < 3.1 × 10-6 ). We also identified 79 proteins (out of 230 proteins) that were DE (P < 1 × 10-5 ) in the uterine fluid. When we compared proteomics and transcriptome results, four DE proteins were identified as being encoded by DE genes: OVGP1, GRP, CAP1 and HBA. Except for CAP1, the other three had lower expression post-puberty. The function of these four genes hypothetically related to preparation of the uterus for a potential pregnancy is discussed in the context of puberty. All DE genes and proteins were also used in pathway and ontology enrichment analyses to investigate overall function. The DE genes were enriched for terms related to ribosomal activity. Transcription factors that were deemed key regulators of DE genes are also reported. Transcription factors ZNF567, ZNF775, RELA, PIAS2, LHX4, SOX2, MEF2C, ZNF354C, HMG20A, TCF7L2, ZNF420, HIC1, GTF3A and two novel genes had the highest regulatory impact factor scores. These data can help to understand how puberty influences uterine function.

A systematic review of local excision followed by adjuvant therapy in early rectal cancer: are pT1 tumours the limit?

AIM: Total mesorectal excision remains the cornerstone of treatment for rectal cancer. Significant morbidity means local excision may be more appropriate in selected patients. Adjuvant therapy reduces local recurrence and improves survival; however, there is a paucity of data on its impact following local excision, which this systematic review aims to address. METHODS: A systematic search of the MEDLINE, Embase and Cochrane databases using validated terms for rectal cancer, adjuvant therapy and local excision was performed. Included studies focused on local excision with adjuvant therapy for adenocarcinoma of the rectum. Primary outcome measures were local recurrence, survival and morbidity. Studies providing neoadjuvant therapy or local excision alone were excluded. RESULTS: Twenty-two studies described 804 patients. Indications for local excision included favourable histology, patient choice and comorbidities. T1, T2 and T3 tumours accounted for 35.1%, 58.0% and 6.9% of cases, respectively. The most frequent local excision technique was transanal excision (77.7%). Adjuvant therapy included long-course chemoradiation or radiotherapy. Median follow-up was 51 months (range 1-165). The pooled local recurrence was 5.8% (95% CI 3.0-9.5) for pT1, 13.8% (95% CI 10.1-17.9) for pT2 and 33.7% (95% CI 19.2-50.1) for pT3 tumours. The overall median disease-free survival was 88% (range 50%-100%) with a pooled overall morbidity of 15.1% (95% CI 11.0-18.7). CONCLUSIONS: This area remains highly relevant to modern clinical practice. The data suggest that local excision followed by adjuvant therapy can achieve acceptable long-term outcomes in high-risk pT1 tumours, but not in T2 tumours and above in whom radical surgery should be offered.

Genome-wide association study of Stayability and Heifer Pregnancy in Red Angus cattle.

Reproductive performance is the most important component of cattle production from the standpoint of economic sustainability of commercial beef enterprises. Heifer Pregnancy (HPG) and Stayability (STAY) genetic predictions are 2 selection tools published by the Red Angus Association of America (RAAA) to assist with improvements in reproductive performance. Given the importance of HPG and STAY to the profitability of commercial beef enterprises, the objective of this study was to identify QTL associated with both HPG and STAY in Red Angus cattle. A genome-wide association study (GWAS) was performed using deregressed HPG and STAY EBV, calculated using a single-trait animal model and a 3-generation pedigree with data from the Spring 2015 RAAA National Cattle Evaluation. Each individual animal possessed 74,659 SNP genotypes. Individual animals with a deregressed EBV reliability > 0.05 were merged with the genotype file and marker quality control was performed. Criteria for sifting genotypes consisted of removing those markers where any of the following were found: average call rate less than 0.85, minor allele frequency < 0.01, lack of Hardy-Weinberg equilibrium (P < 0.0001), or extreme linkage disequilibrium (r2 > 0.99). These criteria resulted in 2,664 animals with 62,807 SNP available for GWAS. Association studies were performed using a Bayes Cπ model in the BOLT software package. Marker significance was calculated as the posterior probability of inclusion (PPI), or the number of instances a specific marker was sampled divided by the total number of samples retained from the Markov chain Monte Carlo chains. Nine markers, with a PPI ≥ 3% were identified as QTL associated with HPG on BTA 1, 11, 13, 23, and 29. Twelve markers, with a PPI ≥ 75% were identified as QTL associated with STAY on BTA 6, 8, 9, 12, 15, 18, 22, and 23.

Antibacterials dispensed in the community comprise 85%-95% of total human antibacterial consumption.

WHAT IS KNOWN AND OBJECTIVE: Interventions intended to slow the emergence and spread of antibacterial resistance through enhanced antimicrobial stewardship will be more effective if informed by an accurate knowledge of current patterns of antibacterial consumption. For example, knowledge of the relative magnitude of community antibacterial consumption in relation to hospital antibacterial consumption within each nation or region should help guide decisions about the relative importance of community and hospital antimicrobial stewardship programmes. It is commonly stated that community antibacterial consumption comprises approximately 80% of total national antibacterial consumption. We aimed to determine this proportion across a large range of nations. METHODS: We measured community and hospital antibacterial consumption in New Zealand during 2015, from both reimbursement and purchase data, and compared the New Zealand data with those reported from a large range of other nations during similar time periods. RESULTS AND DISCUSSION: Community antibacterial consumption comprised approximately 85%-95% of total antibacterial consumption in all nations for which data were available, and in New Zealand comprised a higher proportion than in any other nation. The proportion of total antibacterial consumption comprised by community consumption was significantly higher in countries with relatively high levels of total antibacterial consumption than in countries with relatively low levels of total antibacterial consumption. WHAT IS NEW AND CONCLUSION: The high proportion of total antibacterial consumption comprised by community antibacterial consumption suggests devoting particular attention to improved community antimicrobial stewardship. These results suggest that improving antimicrobial stewardship in the community may provide greater overall benefits in combating antibacterial resistance than improving antimicrobial stewardship in hospitals.

Potentiating the effects of radiotherapy in rectal cancer: the role of aspirin, statins and metformin as adjuncts to therapy.

BACKGROUND: Complete tumour response (pCR) to neo-adjuvant chemo-radiotherapy for rectal cancer is associated with a reduction in local recurrence and improved disease-free and overall survival, but is achieved in only 20-30% of patients. Drug repurposing for anti-cancer treatments is gaining momentum, but the potential of such drugs as adjuncts, to increase tumour response to chemo-radiotherapy in rectal cancer, is only just beginning to be recognised. METHODS: A systematic literature search was conducted and all studies investigating the use of drugs to enhance response to neo-adjuvant radiation in rectal cancer were included. 2137 studies were identified and following review 12 studies were extracted for full text review, 9 studies were included in the final analysis. RESULTS: The use of statins or aspirin during neo-adjuvant therapy was associated with a significantly higher rate of tumour downstaging. Statins were identified as a significant predictor of pCR and aspirin users had a greater 5-year progression-free survival and overall survival. Metformin use was associated with a significantly higher overall and disease-free survival, in a subset of diabetic patients. CONCLUSIONS: Aspirin, metformin and statins are associated with increased downstaging of rectal tumours and thus may have a role as adjuncts to neoadjuvant treatment, highlighting a clear need for prospective randomised controlled trials to determine their true impact on tumour response and overall survival.

SNP detection using RNA-sequences of candidate genes associated with puberty in cattle.

Fertility traits, such as heifer pregnancy, are economically important in cattle production systems, and are therefore, used in genetic selection programs. The aim of this study was to identify single nucleotide polymorphisms (SNPs) using RNA-sequencing (RNA-Seq) data from ovary, uterus, endometrium, pituitary gland, hypothalamus, liver, longissimus dorsi muscle, and adipose tissue in 62 candidate genes associated with heifer puberty in cattle. RNA-Seq reads were assembled to the bovine reference genome (UMD 3.1.1) and analyzed in five cattle breeds; Brangus, Brahman, Nellore, Angus, and Holstein. Two approaches used the Brangus data for SNP discovery 1) pooling all samples, and 2) within each individual sample. These approaches revealed 1157 SNPs. These were compared with those identified in the pooled samples of the other breeds. Overall, 172 SNPs within 13 genes (CPNE5, FAM19A4, FOXN4, KLF1, LOC777593, MGC157266, NEBL, NRXN3, PEPT-1, PPP3CA, SCG5, TSG101, and TSHR) were concordant in the five breeds. Using Ensembl's Variant Effector Predictor, we determined that 12% of SNPs were in exons (71% synonymous, 29% nonsynonymous), 1% were in untranslated regions (UTRs), 86% were in introns, and 1% were in intergenic regions. Since these SNPs were discovered in RNA, the variants were predicted to be within exons or UTRs. Overall, 160 novel transcripts in 42 candidate genes and five novel genes overlapping five candidate genes were observed. In conclusion, 1157 SNPs were identified in 62 candidate genes associated with puberty in Brangus cattle, of which, 172 were concordant in the five cattle breeds. Novel transcripts and genes were also identified.

Diagnostic accuracy of faecal biomarkers in detecting colorectal cancer and adenoma in symptomatic patients.

BACKGROUND: The diagnosis of colorectal cancer (CRC) can be difficult as symptoms are variable with poor specificity. Thus, there is a quest for simple, non-invasive testing that can help streamline those with significant colonic pathology. AIM: To assess using faecal immunochemical test for haemoglobin (FIT) or faecal calprotectin (FCP) to detect CRC and adenoma in symptomatic patients referred from primary care. METHODS: A total of 799 referred for urgent lower gastrointestinal investigations were prospectively recruited. Of these, 430 completed colonic investigations and returned stool samples, and were included in the final statistical analysis. Faecal immunochemical test for haemoglobin was performed on HM-JACKarc analyser (Kyowa Medex, Tokyo, Japan), and FCP by the EliA Calprotectin immunoassay (Thermo Fisher Scientific, Waltham, United States). RESULTS: The negative predictive value (NPV) using FIT alone or both markers (FIT and FCP) in combination was similar at 99% for CRC, with a sensitivity and specificity of 84% and 93%, respectively. FIT measurements were significantly higher in left-sided colonic lesions compared with the right side; 713 vs. 94; P = 0.0203). For adenoma, the NPV using FIT alone, or both markers (FIT and FCP) in combination, was similar at 94% with a sensitivity and specificity of 69% and 56%, respectively. CONCLUSIONS: Undetectable faecal immunochemical test for haemoglobin is sufficiently sensitive to exclude colorectal cancer, with higher values in left-sided lesions. FCP in combination does not appear to provide additional diagnostic information. Further studies to determine the health economic benefits of implementing faecal immunochemical test for haemoglobin in primary care are required.

Static and dynamic components of right ventricular afterload are negatively associated with calf survival at high altitude.

The purposes of this study were to evaluate mean, systolic, and diastolic pulmonary arterial pressures; pulmonary arterial pulse pressures; and systemic oxygen extraction fraction as risk factors for the survival of suckling calves on one ranch located at an altitude of ≥ 2,730 m in Colorado, USA. A prospective cohort study of 58 calves was performed. Pulmonary arterial pressures and systemic oxygen extraction were measured when calves were approximately 3 mo (86 ± 7 d) and 7 mo (197 ± 6 d) of age. Seven of the 58 calves (12%), 4 steers and 3 heifers, were unaccounted for and presumed dead between 3 and 7 mo of age. Calves presumed to have died between 3 and 7 mo of age had significantly greater mean ( = 0.005) and systolic ( = 0.001) pulmonary arterial pressures and greater pulse pressures ( = 0.03) at 3 mo of age than calves that survived to 7 mo. Calves presumed to have died tended to have greater systemic oxygen extraction fractions at 3 mo of age than calves that survived ( = 0.13). Diastolic pressure was not associated with survival ( = 0.27). Mean pulmonary arterial pressure is predominantly determined by static resistance attributable to distal pulmonary arterial remodeling. Pulse pressure and systolic pulmonary arterial pressure represents the dynamic or oscillatory resistance and is determined by the characteristics of ventricular ejection and proximal arterial stiffness. These findings indicate that it may be beneficial to include pressure measurements indicative of both static and dynamic pulmonary arterial resistance in the selection of breeding stock at high altitude.

Angus calves born and raised at high altitude adapt to hypobaric hypoxia by increasing alveolar ventilation rate but not hematocrit.

The objective of this study was to evaluate the effect of altitude on arterial blood-gases and hematocrit in Angus-based calves. It was hypothesized that alveolar ventilation rate, as indicated by arterial pCO, would increase with altitude but hematocrit would not. Five Angus-based herds ( = 30 to 80 per cohort) located at 105 m, 1,470 m, 2,010 m, 2,170 m, and 2,730 m above sea level were enrolled in this prospective cohort study. A portable analyzer measured blood-gas tensions in coccygeal arterial blood. Calves at 1,470 m, 2,170 m, and 2,730 m were sampled twice, at approximately 4 mo and 7 mo of age. Calves at 105 m and 2,010 m were sampled once, at 7 or 4 mo of age, respectively. Linear regression analyses were used to determine the fixed effect of herd (a proxy for altitude) on the 4 outcome variables pCO, pO, pH, and hematocrit, while controlling for age and sex. As hypothesized, alveolar ventilation rate increased with altitude ( < 0.001). Hematocrit, however, did not show a clear association with altitude except for an increase from 105 m to ≥ 1,470 m ( < 0.001). Arterial pO decreased significantly with increasing altitude in calves at 4 mo and 7 mo of age ( < 0.001). The adjusted mean values of the 4 variables studied were similar at 4 and 7 mo of age for all of the herds studied. This indicates that suckling calves show minimal respiratory or erythrocytic adaptation to hypoxemia and hypocapnia with increasing age, regardless of altitude. We propose that the lack of an erythrocytic response in hypoxemic calves born and raised at high altitude prevents a deleterious increase in viscous resistance and, consequently, pulmonary arterial pressure. This physiological response, or lack thereof, may be a survival adaptation in a species predisposed to hypoxia-induced pulmonary hypertension.

Transcriptome analyses identify five transcription factors differentially expressed in the hypothalamus of post- versus prepubertal Brahman heifers.

Puberty onset is a developmental process influenced by genetic determinants, environment, and nutrition. Mutations and regulatory gene networks constitute the molecular basis for the genetic determinants of puberty onset. The emerging knowledge of these genetic determinants presents opportunities for innovation in the breeding of early pubertal cattle. This paper presents new data on hypothalamic gene expression related to puberty in (Brahman) in age- and weight-matched heifers. Six postpubertal heifers were compared with 6 prepubertal heifers using whole-genome RNA sequencing methodology for quantification of global gene expression in the hypothalamus. Five transcription factors (TF) with potential regulatory roles in the hypothalamus were identified in this experiment: , , , , and . These TF genes were significantly differentially expressed in the hypothalamus of postpubertal versus prepubertal heifers and were also identified as significant according to the applied regulatory impact factor metric ( < 0.05). Two of these 5 TF, and , were zinc fingers, belonging to a gene family previously reported to have a central regulatory role in mammalian puberty. The gene belongs to the family of homologues of Drosophila sine oculis () genes implicated in transcriptional regulation of gonadotrope gene expression. Tumor-related genes such as and are known to affect basic cellular processes that are relevant in both cancer and developmental processes. Mutations in were associated with puberty in humans. Mutations in these TF, together with other genetic determinants previously discovered, could be used in genomic selection to predict the genetic merit of cattle (i.e., the likelihood of the offspring presenting earlier than average puberty for Brahman). Knowledge of key mutations involved in genetic traits is an advantage for genomic prediction because it can increase its accuracy.

Heritabilities and genetic correlations of pulmonary arterial pressure and performance traits in Angus cattle at high altitude.

Pulmonary arterial pressure (PAP) is an indicator trait for pulmonary hypertension and for the risk of developing high-altitude disease (HAD) in cattle. Pulmonary arterial pressures provide a tool for selection of breeding cattle for tolerance to high altitude in mountainous regions of the United States. The objective of this study was to evaluate relationships between growth performance traits and yearling PAP (42.4 ± 9.9 mmHg; = 5,776; elevation 2,150 m) using data from 1993 to 2014 in the John E. Rouse Colorado State University Beef Improvement Center (CSU-BIC) Angus herd. The breeding program used sires ( = 299) from both low- and high-elevation environments. We hypothesized that little to no genetic relationship exists between PAP and birth weight (BWT; direct and maternal), weaning weight (WW; direct and maternal), yearling weight (YW; direct and maternal), and postweaning gain (PWG). Historic selection of natural service sires from within the herd required a PAP of ≤ 42 mmHg. Outside AI sires ( = 156) used in this breeding program were not PAP tested and therefore were used with little knowledge of these sires' high-altitude adaptability. Performance traits (± SD) routinely recorded included BWT (36.2 ± 5.1 kg; = 8,695), WW (213.5 ± 31.8 kg; = 8,010), YW (345.6 ± 83.8 kg; = 5,580), and PWG (122.0 ± 63.7 kg; = 5,449), where PWG represented the total weight gained from weaning to yearling age. Four-trait analyses using REML were conducted with an animal model. The heritability estimates (± SE) for PAP (0.26 ± 0.03), BWT direct (0.42 ± 0.04) and maternal (0.14 ± 0.02), WW direct (0.29 ± 0.04) and maternal (0.19 ± 0.03), YW direct (0.45 ± 0.04) and maternal (0.23 ± 0.03), and PWG (0.14 ± 0.02) were in the range of those reported in previous literature. Estimates of genetic correlations (± SE) revealed weak relationships between PAP and direct and maternal BWT, direct and maternal WW, direct and maternal YW, and PWG of 0.15 ± 0.09, 0.14 ± 0.10, 0.23 ± 0.09, -0.01 ± 0.10, 0.12 ± 0.08, 0.00 ± 0.09, and -0.10 ± 0.10, respectively. The results of this study suggest that selection for lower PAP measures should have minimal influence on the growth performance of yearling Angus bulls and heifers at the CSU-BIC, supporting our hypothesis.

Genetic parameters estimated at receiving for circulating cortisol, immunoglobulin G, interleukin 8, and incidence of bovine respiratory disease in feedlot beef steers.

Bovine respiratory disease complex (i.e., shipping fever and bacterial bronchopneumonia) is a multifaceted respiratory illness influenced by numerous environmental factors and microorganisms. Bovine respiratory disease (BRD) is just one component of BRD complex. Because BRD is moderately heritable, it may be possible to reduce the incidence of BRD through genetic selection. The objectives of this study were to determine the heritability and associative genetic relationships among immune system traits (i.e., cortisol, total IgG, IgG isotypes, and IL-8) in cattle monitored for BRD incidence. At an average of 83 d after weaning (219 d age and mean = 221.7 kg [SD 4.34]), crossbred steer calves ( = 2,869) were received at a commercial feedlot in southeastern Colorado over a 2-yr period. At receiving, jugular blood samples were collected at 212 (yr 1) and 226 d (yr 2) of age for immune trait analyses. The BRD phenotype was defined as a binomial variable (0 = no and 1 = yes) and compared with immune system traits measured at receiving (prior to illness onset). An animal identified as BRD positive exhibited ≥ 2 clinical signs (i.e., eye or nasal discharge, cough, lethargy, rapid breathing, acute interstitial pneumonia, or acute upper respiratory syndrome and/or a rectal temperature > 39.7°C). Heritability and genetic correlation estimates for categorical variable BRD, cortisol, IgG, IgG1, IgG2, and IL-8 were estimated from a sire model using ASREML. Heritability estimates were low to moderate for BRD (0.17 ± 0.08), cortisol (0.13 ± 0.05), IgG (0.15 ± 0.05), IgG1 (0.11 ± 0.05), IgG2 (0.24 ± 0.06), and IL-8 (0.30 ± 0.06). A moderate negative genetic correlation was determined between BRD and cortisol ( = -0.19 ± 0.32). Moderate positive correlations were found between BRD with IgG (0.42 ± 0.28), IgG1 (0.36 ± 0.32), and IL-8 ( = 0.26 ± 0.26). Variation in the BRD phenotype and immune system traits suggested herd health improvement may be achieved through genetic selection.

The turnover of strains in intermittent and persistent nasal carriers of Staphylococcus aureus.

OBJECTIVES: We aimed to examine the dynamics of Staphylococcus aureus nasal carriage in healthy adults. METHOD: Selected S. aureus strains isolated from weekly nasal swabs obtained from 122 healthy young adults over a 13 week period were spa typed. RESULTS: The median duration of intermittent carriage was 4 weeks (IQR 2-6) and the median interval between episodes of carriage of different spa types was 3.5 weeks (IQR 2.25-4). 6/19 (32%) Persistent carriers were colonised with more than one spa type during the study, and in two persistent carriers a brief period of mixed colonisation with two spa types was observed. Even when the carriage strain changed, it was very rare for persistent carriers to have a period during which they were culture-negative (only 6/188 (3%) swabs submitted by persistent carriers failed to culture S. aureus). CONCLUSIONS: Our results imply that at least every eight weeks a healthy young adult is exposed to S. aureus sufficient to cause a new episode of carriage among intermittent carriers. Persistent carriers are almost always colonised with S. aureus and over the course of a year there will be at least one replacement of the dominant strain.

The altitude at which a calf is born and raised influences the rate at which mean pulmonary arterial pressure increases with age.

Right heart failure secondary to pulmonary hypertension is a leading cause of mortality among suckling beef calves in the Rocky Mountain region. The objective of this study was to track changes in pulmonary arterial pressures (PAP) in healthy calves born and raised at altitudes ranging from 1,470 to 2,730 m. It was hypothesized that calves located at higher altitudes would show a greater increase in mean PAP (mPAP) with age than would be experienced by calves located at lower altitudes. The rationale is that high altitude hypobaric hypoxia causes a greater rate of vascular remodeling and, consequently, greater resistance to blood flow than calves located at lower altitudes. A prospective study was conducted on 5 cohorts of suckling calves from 4 herds located at altitudes of 1,470, 2,010, 2,170, and 2,730 m. In total, 470 PAP measurements were obtained from 258 calves. As hypothesized, calves located at altitudes ≥2,170 m showed a significant increase in mPAP with age ( ≤ 0.002) whereas calves at 1,470 m did not ( = 0.16). Except for calves at 2,170 m ( < 0.001), systolic PAP did not increase with age ( ≥ 0.16). Diastolic PAP increased with age at altitudes ≥ 2,170 m ( ≤ 0.09) but did not change in calves at 1,470 m ( = 0.20). In summary, mPAP and the rate at which mPAP increases with age are positively associated with the altitude at which calves are born and raised.