Loci associated with conception rate in crossbred beef heifers.

The inability of beef cattle to maintain full term pregnancies has become an economic concern for the beef industry. Herd management and nutritional improvements have alleviated environmental impacts on embryonic and fetal loss, yet additional gains can be made through genomic selection. The objectives of this study were to identify loci and gene-sets in crossbred beef heifers associated with the number of services required to become pregnant (TBRD) and heifer conception rate at first service (HCR1). Heifers (n = 709) from a commercial beef operation underwent one round of artificial insemination, before exposure to bulls for natural service for 50 days. Pregnancy and time of conception was determined by ultrasound 35 days after the breeding season. Heifers were genotyped using the GeneSeek (Lincoln, NE) Bovine GGP50K BeadChip prior to genome-wide association analyses (GWAA) conducted using an EIGENSTRAT-like model to identify loci associated (P < 1 × 10-5) with TBRD and HCR1. One locus was associated (P = 8.97 × 10-6) with TBRD on BTA19 and included the positional candidate gene ASIC2, which is differentially expressed in the endometrium of fertility classified heifers, and the positional candidate gene, SPACA3. Gene-set enrichment analyses using SNP (GSEA-SNP) data, was performed and identified one gene-set, oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen as enriched (NES = 3.15) with TBRD and contained nine leading edge genes that contributed to the enrichment of the gene set. The enriched gene-set is involved in catalyzing oxidation-reduction reactions, which have been associated with oxidative stressors impacting pregnancy success. No loci were associated nor gene-sets enriched with HCR1. Identification of loci, positional candidate genes, gene-sets and leading edge genes enriched for fertility facilitate genomic selection that allows producers to select for reproductively superior cattle, reduce costs associated with infertility, and increase percent calf crop.

Validating loci associated with bovine respiratory disease complex in pre-weaned Holstein calves.

Bovine respiratory disease (BRD) is considered one of the most economically important diseases in the cattle industry. Ultimately, the selection of cattle that are less susceptible to disease will allow producers to reduce the prevalence of BRD and lessen its economic impact. The objective of this study was to validate previously identified loci associated with susceptibility to BRD in an independent population of 140 pre-weaned Holstein calves from Wisconsin (WI). Using the McGuirk health scoring system, calves were classified as either clinically affected with BRD (n = 35) or healthy (n = 105). Additive genotypic tests were performed for genomic regions previously associated with susceptibility to BRD in calves from California (CA) and New Mexico (NM). Using this method, 4 loci (P < 0.01) consisting of 10 SNP were validated in the WI population, including 2 loci from CA, 1 locus from NM, and 1 locus from a combined CA + NM population. Most of the positional candidate genes and transcription factor binding site motifs associated with these loci have functions related to innate and adaptive immune responses. The validation of loci associated with susceptibility to BRD in independent populations allows producers to more reliably select cattle that are less susceptible to BRD, improving animal welfare, decreasing the annual revenue losses, and lowering the prevalence of the disease.

Genome-wide association analysis and gene set enrichment analysis with SNP data identify genes associated with 305-day milk yield in Holstein dairy cows.

Milk production traits, such as 305-day milk yield (305MY), have been under direct selection to improve production in dairy cows. Over the past 50 years, the average milk yield has nearly doubled, and over 56% of the increase is attributable to genetic improvement. As such, additional improvements in milk yield are still possible as new loci are identified. The objectives of this study were to detect SNPs and gene sets associated with 305MY in order to identify new candidate genes contributing to variation in milk production. A population of 781 primiparous Holstein cows from six central Washington dairies with records of 305MY and energy corrected milk were used to perform a genome-wide association analysis (GWAA) using the Illumina BovineHD BeadChip (777 962 SNPs) to identify QTL associated with 305MY (P < 1.0 × 10-5 ). A gene set enrichment analysis with SNP data (GSEA-SNP) was performed to identify gene sets (normalized enrichment score > 3.0) and leading edge genes (LEGs) influencing 305MY. The GWAA identified three QTL comprising 34 SNPs and 30 positional candidate genes. In the GSEA-SNP, five gene sets with 58 unique and 24 shared LEGs contributed to 305MY. Identification of QTL and LEGs associated with 305MY can provide additional targets for genomic selection to continue to improve 305MY in dairy cattle.

Gene set enrichment analysis of SNP data in dairy and beef cattle with bovine respiratory disease.

Bovine respiratory disease (BRD) is a complex disease that is associated with infection by bacterial and viral pathogens when cattle fail to adequately respond to stress. The objective of this study was to use gene set enrichment analysis of SNP data (GSEA-SNP) and a network analysis (ingenuity pathway analysis) to identify gene sets, genes within gene sets (leading-edge genes) and upstream regulators associated with BRD in pre-weaned dairy calves and beef feedlot cattle. BRD cases and controls were diagnosed using the McGuirk health scoring system. Holstein calves were sampled from commercial calf-raising facilities in California (1003 cases and 1011 controls) and New Mexico (376 cases and 372 controls). Commercial feedlot cattle were sampled from Colorado (500 cases and 499 controls) and Washington (504 cases and 497 controls). There were 102 and 237 unique leading-edge genes identified in the dairy calf and beef cattle populations respectively. Six leading-edge genes (ADIPOQ, HTR2A, MIF, PDE6G, PRDX3 and SNCA) were associated with BRD in both dairy and beef cattle. Network analysis identified glucose as the most influential upstream regulator in dairy cattle, whereas in beef cattle, TNF was the most influential upstream regulator. The genes, gene sets and upstream regulators associated with BRD have common functions associated with immunity, inflammation and pulmonary disease and provide insights into the mechanisms that are critical to BRD susceptibility in cattle.

Low colostrum yield in Jersey cattle and potential risk factors.

Consumption of an adequate volume of high-quality colostrum is vital to a dairy calf's ability to survive and become a productive herd member. However, some dairy herds have reported a deficiency of colostrum production, which ranges from a low volume to no colostrum produced, by cows during fall and winter. Little information regarding this phenomenon exists. The purpose of this study was to characterize the syndrome and identify potential risk factors for low colostrum yield. A 2,500-cow Jersey dairy farm was enrolled in a prospective cohort study in May 2016, to evaluate possible effects of photoperiod, temperature, and cow factors on colostrum production. Dairy personnel were trained to collect, weigh, and evaluate colostrum quality. Information on parity, previous lactation length, previous 305-d mature-equivalent milk production, and dry period length were collected through the farm's dairy management software. Weather and photoperiod data were also collected. Over the year of enrollment, 2,988 eligible cows calved and had colostrum weights recorded and 38% were primiparous (n = 1,143), 25% were in their second lactation (n = 752), and 37% were in their third or greater lactation (n = 1,093). The overall average colostrum yield was 6.6 kg/cow in June 2016, 2.5 kg/cow in December 2016, and 4.8 kg/cow in May 2017. Multiparous cows had a larger decline in colostrum production between June and December (6.6 to 1.3 kg/cow) compared with primiparous animals (6.5 to 4.2 kg/cow). Overall, average colostrum production decreased by 0.17 kg/cow per week during this time, 0.22 kg for multiparous cows and 0.08 kg for primiparous cows. A logistic regression model was constructed for all cows to evaluate effects of cow factors on low colostrum production (<2.7 kg at first milking). Dry period length, calf sex, singleton or twin, age at freshening, month of calving and previous lactation length were significantly associated with the probability of low colostrum yield (<2.7 kg at first milking). A cross-correlation function analysis between the time series for colostrum yield and photoperiod revealed a high correlation at the time of calving and 1 mo prior, particularly for multiparous cows. A pedigree analysis showed that extreme colostrum yield (low vs. high) followed some sire lines. Low colostrum production in this herd could have an economic effect on the dairy and calf health and appears to have a strong seasonal and, potentially, a genetic component.

Identification of genes associated with susceptibility to Mycobacterium avium ssp. paratuberculosis (Map) tissue infection in Holstein cattle using gene set enrichment analysis-SNP.

Multiple genome-wide association analyses have investigated susceptibility to bovine paratuberculosis, but few loci have been identified across independent cattle populations. A SNP-based gene set enrichment analysis (GSEA-SNP) allows expanded identification of genes with moderate effects on a trait through the enrichment of gene sets instead of identifying only few loci with large effects. Therefore, the objective of this study was to identify genes that were moderately associated with Mycobacterium avium ssp. paratuberculosis (Map) tissue infection using GSEA-SNP in Holstein cattle from the Pacific Northwest (PNW; n = 205) and from the PNW and Northeast (PNW+NE; n = 245) which were previously genotyped with the Illumina BovineSNP50 BeadChip. The GSEA-SNP utilized 4389 gene sets from five databases. For each annotated gene in the UMD3.1 assembly (n = 19,723), the most significant SNP within each gene and its surrounding region (10 kb up- and downstream) was selected as a proxy for that gene. Any gene set with a normalized enrichment score > 2.5 was considered enriched. Thirteen gene sets (8 PNW GSEA-SNP; 5 PNW+NE) were enriched in these analyses and all have functions that relate to nuclear factor kappa beta. Nuclear factor kappa beta is critical to gut immune responses, implicated in host immune responses to other mycobacterial diseases, and has established roles in inflammation as well as cancer. Gene sets and genes moderately associated with Map infection could be used in genomic selection to allow producers to select for less susceptible cattle, lower the prevalence of the disease, and reduce economic losses.

Rapid Communication: Subclinical bovine respiratory disease - loci and pathogens associated with lung lesions in feedlot cattle.

Bovine respiratory disease (BRD) is an economically important disease of feedlot cattle that is caused by viral and bacterial pathogen members of the BRD complex. Many cases of subclinical BRD go untreated and are not detected until slaughter, when lung lesions are identified. The objectives of this study were to identify which BRD pathogens were associated with the presence of lung lesions at harvest and to identify genomic loci that were associated with susceptibility to lung lesions as defined by consolidation of the lung and/or the presence of fibrin tissue. Steers from a Colorado feedlot ( = 920) were tested for the presence of viral and bacterial pathogens using deep pharyngeal and mid-nasal swabs collected on entry into the study. Pathogen profiles were compared between cattle with or without lung consolidation (LC), fibrin tissue in the lung (FT), a combination of LC and FT in the same lung (lung lesions [LL]), and hyperinflated lungs (HIF) at harvest. Genotyping was conducted using the Illumina BovineHD BeadChip. Genomewide association analyses (GWAA) were conducted using EMMAX (efficient mixed-model association eXpedited), and pseudoheritabilities were estimated. The pathogen profile comparisons revealed that LC ( = 0.01, odds ratio [OR] = 3.37) and LL cattle ( = 0.04, OR = 4.58) were more likely to be infected with bovine herpes virus-1 and that HIF cattle were more likely to be infected with spp. ( = 0.04, OR = 4.33). Pseudoheritability estimates were 0.25 for LC, 0.00 for FT, 0.28 for LL, and 0.13 for HIF. Because pseudoheritability for FT was estimated to be 0, GWAA results for FT were not reported. There were 4 QTL that were moderately associated ( < 1 × 10) with only LC, 2 that were associated with only LL, and 1 that was associated with LC and LL. Loci associated with HIF included 12 that were moderately associated and 3 that were strongly associated (uncorrected P < 5 × 10-7). A 24-kb region surrounding significant lead SNP was investigated to identify positional candidate genes. Many positional candidate genes underlying or flanking the detected QTL have been associated with signal transduction, cell adhesion, or gap junctions, which have functional relevance to the maintenance of lung health. The identification of pathogens and QTL associated with the presence of lung abnormalities in cattle exhibiting subclinical BRD allows the identification of loci that may not be detected through manifestation of clinical disease alone.

Identification of loci associated with susceptibility to subspecies () tissue infection in cattle.

Johne's disease is a contagious bacterial infection of cattle caused by ssp. (). A previous genome-wide association analysis (GWAA) in Holstein cattle identified QTL on BTA3 and BTA9 that were highly associated (P < 5 × 10) and on BTA1, BTA16, and BTA21 that were moderately associated (P < 5 × 10) with Map tissue infection. The objectives of this study were to validate previous GWAA results in Jersey cattle ( = 57), Holstein cattle from the Pacific Northwest (PNW, = 205) and a combined Holstein population from the PNW and the Northeast (PNW + NE, = 423), and also identify new loci associated with tissue infection. DNA was genotyped using the Illumina BovineSNP50 BeadChip, and the PNW + NE data was also imputed to whole genome sequence level using Run4 of the 1000 Bull Genomes project with Beagle v 4.1 and FImpute. Cases were ileocecal node positive and controls were negative for by quantitative PCR (qPCR). Individuals were removed for SNP call rate < 90%, and SNP were removed for genotype call rate < 90% or minor allele frequency < 1%. For the Jersey, PNW, and PNW + NE, GWAA were conducted using an allelic dosage model. For the PNW and the PNW + NE, an additional efficient mixed-model association eXpedited (EMMAX) analysis was performed using additive, dominance and recessive models. Seven QTL on BTA22 were identified in the Jersey population with the most significant ( = 4.45 × 10) located at 21.7 megabases (Mb). Six QTL were associated in the PNW and the PNW + NE analyses, including a QTL previously identified on BTA16 in the NE population. The most significant locus for the PNW was located on BTA21 at 61 Mb ( = 8.61 × 10) while the most significant locus for the PNW + NE was on BTA12 at 90 Mb ( = 2.33 × 10). No additional QTL were identified with the imputed GWAA. Putative positional candidate genes were identified within 50 kb 5' and 3' of each QTL. Two positional candidate genes were identified in Jersey cattle, 1 identified in the PNW and 8 in the PNW + NE populations. Many identified positional candidate genes are involved in signal transduction, have immunological functions, or have putative functional relevance in entry into host cells. This study supported 2 previously identified SNP within a QTL on BTA16 and identified 16 new QTL, including 2 found in the PNW and the PNW+NE, associated with tissue infection.

Modeling Ribavirin-Induced Anemia in Patients with Chronic Hepatitis C Virus.

Ribavirin remains an important component of hepatitis C treatment in certain clinical scenarios, but it causes hemolytic anemia. A quantitative understanding of the ribavirin exposure-anemia relationship is important in dose individualization/optimization. We developed a model relating ribavirin triphosphate (RTP) exposure in red blood cells (RBCs), RBC lifespan, feedback regulation of RBC production when anemia occurs, and the resulting hemoglobin decline. Inosine triphosphatase (ITPA) and interleukin 28B (IL28B) genetics were found to be significant covariates. Clinical trial simulations predicted that anemia is least severe in IL28B non-CC (rs12979860, CT or TT), ITPA variant subjects, followed by IL28B non-CC, ITPA wild-type, IL28B CC, ITPA variant, and IL28B CC, ITPA wild-type subjects (most severe). Reducing the ribavirin dose from 1,200/1,000 mg to 800/600 mg could reduce the proportions of grade 2 anemia by about half. The resulting model framework will aid the development of dosing strategies that minimize the incidence of anemia in treatment regimens that include ribavirin.

Motion-induced interruptions and postural equilibrium in linear lateral accelerations.

This study assesses lateral tipping motion-induced interruptions (MIIs) in a simulated motion environment. The objective is to revisit MII occurrence and sway motion relationship by focusing on the frequency and acceleration of the lateral motion stimulus. Results verify that MIIs increase with increasing peak sway acceleration, but the effect of sway frequency is not as clear as that of acceleration. Complex multidirectional motions create more tipping MIIs than unidirectional motion. Research should incorporate acceleration, frequency and motion complexity as factors influencing MII occurrence. To describe a temporary loss of balance without tipping, the term 'probable' MII is introduced. This term fills the gap between the theoretical definition and a human-centred perception of an MII where loss of balance is not a binary phenomenon. The 'probable' MIIs were 16-67% more common than the 'definite' MIIs. The developed mathematical model of MII occurrence versus sway acceleration (amplitude, frequency) approximated the observed MIIs with less than 9% difference.

History of the meat animal evaluation contest: a pedagogical stimulant.

A century ago students were exposed to livestock judging and meat judging, though each was taught as an independent entity. Fifty years ago universities started combining subjects involving the evaluation process, whether characteristics involved traits of the live animal or those related to meat value. Universities developed a meat animal evaluation contest (MAEC) that included breeding livestock, market livestock, and meat products. Using production records, students culled, ranked, priced, and answered questions about breeding and market cattle, swine, and sheep. For market livestock, ranks and values were scored on carcass data after the livestock were harvested. Students graded, ranked, answered questions, and priced meat products. A communications component involved students being given a problem to be discussed as a group presentation. In 1964, the first MAEC was conducted at Rath Packing Co., Waterloo, IA, and included 40 students. In 1967, the contest was held at The Farmbest Co. and IBP of Denison, IA, and included 87 students. In 1968, the MAEC moved to the Knights of Ak-Sar-Ben, Omaha, NE, and by 1988, 187 students (22 universities) competed. In 1995, the MAEC moved to the United Stockyards Co., St. Joseph, MO. Starting in 2004, it moved to various universities (South Dakota State University, Oklahoma State University, University of Nebraska, and Texas Tech University). The MAEC has stimulated students to better learn and understand the details of meat animal evaluation and has encouraged the development of evaluation courses as well as satellite and symposia programs. To date, over 6,000 students representing 40 universities have participated.

Practice guidelines: development, application to clinical care, and role in provider education.

Substantial progress has been made in the past several decades toward the application of evidence-based medicine. Practice guidelines, which assist providers in clinical decision making, have played a valuable role in this initiative. This article highlights the attributes of good practice guidelines, along with their role in the education of health-care providers, and examines the development, revision, and limitations of practice guidelines for emerging infections.

The effect of lopinavir/ritonavir on the renal clearance of tenofovir in HIV-infected patients.

We determined the effects of lopinavir/ritonavir on tenofovir renal clearance. Human immunodeficiency virus-infected subjects taking tenofovir disoproxil fumarate (TDF) were matched on age, race, and gender and were enrolled into one of the following two groups: group 1: subjects taking TDF plus lopinavir/ritonavir plus other nucleoside reverse transcriptase inhibitors (NRTIs); group 2: subjects taking TDF plus NRTIs and/or non-NRTIs but no protease inhibitors. Twenty-four-hour blood and urine collections were carried out in subjects for tenofovir quantification. Drug transporter genotype associations with tenofovir pharmacokinetics were examined. In 30 subjects, median (range) tenofovir apparent oral clearance, renal clearance, and fraction excreted in urine were 34.6 l/h (20.6-89.5), 11.3 l/h (6.2-22.6), and 0.33 (0.23-0.5), respectively. After adjusting for renal function, tenofovir renal clearance was 17.5% slower (P=0.04) in subjects taking lopinavir/ritonavir versus those not taking a protease inhibitor, consistent with a renal interaction between these drugs. Future studies should clarify the exact mechanism and whether there is an increased risk of nephrotoxicity.

Nutritional risk in an urban homebound older population. The nutrition and healthy aging project.

PURPOSE: To establish the prevalence of nutritional problems and their related socio-demographic and health-related risk factors in the homebound elderly population. METHODS: Subjects included 239 men and women, ages 65 to 105 years. Trained, two-person field teams conducted comprehensive in-home assessments. Medical record reviews assessed co-morbidity and medication use. RESULTS: The majority of these urban study subjects are of very advanced age (mean age 81 years), female (72%), non-white (73%), living alone (51%), of low income (76%), and somewhat socially isolated (26% had no weekly social contact). More older women than men were widowed (60 vs. 33%, respectively) and poor (80 vs. 67%). The disease burden and functional dependency were both high in men and women; 77% had three or more chronic medical conditions; 76% were functionally dependent in one or more ADL's and 95% in one or more IADL's. Poor dietary quality was universal in these older men and women; half or more consumed diets that deviated from recommended standards for at least 13 of the 24 nutritional guidelines studied. Five percent of subjects were underweight (Body Mass Index (BMI) <18.5); 22% were overweight (BMI 25.0-29.9); and 33% were obese (BMI >30.0). Fasting albumin, hemoglobin, and absolute lymphocyte concentrations were borderline to very low in 18-32%. Dyslipidemia was more common in women; however, men and women had similar Total:HDL cholesterol ratios. CONCLUSIONS: Nutritional status is poor in homebound persons of very advanced age with substantial co-morbidity and functional dependency. The complexities of nutritional risk necessitate multi-disciplinary and individualized nutritional intervention strategies.

Relationship between infant sleep position and motor development in preterm infants.

To determine whether motor development in premature infants varies according to sleep position, we evaluated 213 infants <1750 g birth weight enrolled in the Collaborative Home Infant Monitoring Evaluation (CHIME). At 56 weeks postconceptional age (PCA), sleep position was determined by maternal report, and the Bayley Scales of Infant Development 2nd Edition (BSID-II) were performed. Infants who slept supine were less likely than infants who slept prone to receive credit for maintaining the head elevated to 45 degrees (p = .021), and infants who slept nonprone were less likely than prone sleepers to receive credit for maintaining the head elevated to 90 degrees and lowering with control (p = .001). The Psychomotor and Mental Development Indices at 56 and 92 weeks PCA were not altered by usual sleep position at 56 weeks PCA. In summary, infants sleeping supine are less able to lift the head and lower with control at 56 weeks PCA, but global developmental status was unaffected. Supine sleeping has been associated with decreased risk for sudden infant death syndrome, but compensatory strategies while awake may be needed to avoid delayed acquisition of head control.

Effect of sildenafil on subjective and physiologic parameters of the female sexual response in women with sexual arousal disorder.

Sexual dysfunction is a complaint of 30-50% of American women. Aside from hormone replacement therapy, there are no current FDA-approved medical treatments for female sexual complaints. The goal of this pilot study was to determine safety and efficacy of sildenafil for use in women with sexual arousal disorder (SAD). Evaluations were completed on 48 women with complaints of SAD. Physiologic measurements, including genital blood flow, vaginal lubrication, intravaginal pressure-volume changes, and genital sensation were recorded pre- and postsexual stimulation at baseline and following 100 mg sildenafil. Subjective sexual function was assessed using a validated sexual function inventory at baseline and following 6 weeks of home use of sildenafil. At termination of the study patients also completed an intervention efficacy index (FIEI). Following sildenafil, poststimulation physiologic measurements improved significantly compared to baseline. Baseline subjective sexual function complaints, including low arousal, low desire, low sexual satisfaction, difficulty achieving orgasm, decreased vaginal lubrication, and dyspareunia also improved significantly following 6 weeks home use of sildenafil. Sildenafil appears to significantly improve both subjective and physiologic parameters of the female sexual response. Double-blind, placebo-controlled studies are currently in progress to further determine efficacy of this medication for treatment of female sexual dysfunction complaints in different populations of women.

Short-term supplementation therapy does not affect elastin degradation in severe alpha(1)-antitrypsin deficiency. The American-Italian AATD Study Group.

We evaluated the ability of intravenous supplementation therapy with alpha(1)-antitrypsin (AAT) to reduce the rate of urinary excretion of desmosine (DES), a specific marker of elastin degradation, in eight men and four women with emphysema due to severe, congenital deficiency of AAT (range 17-69 mg/dl). Nine were former cigarette smokers, two were current smokers, and one reported never smoking; their mean age was 54 (SD 12) yr and their mean FEV(1) was 41 (18%) of predicted. Urinary DES was measured by isotope dilution and HPLC. Prior to the start of AAT supplementation, mean DES excretion was 13.0 (5.0) microg/g creatinine, 73% higher than in healthy nonsmokers. During 8 wk of supplementation therapy, mean urinary DES excretion was 13.0 (5.9) microg/g creatinine, unchanged from the baseline period (p = 0.85 by repeated measures ANOVA). We conclude that baseline levels of elastin degradation in emphysematous patients with severe AAT deficiency were abnormally high and that 8 wk of AAT supplementation therapy did not appreciably reduce the rate of elastin degradation. These findings raise the possibilities that protective levels of AAT in the lungs are insufficient or that elastin degradation in the lungs of these subjects is not dependent upon neutrophil elastase at this time.

Fibrinogen is an important determinant of the metastatic potential of circulating tumor cells.

Detailed studies of tumor cell-associated procoagulants and fibrinolytic factors have implied that local thrombin generation and fibrin deposition and dissolution may be important in tumor growth and dissemination. To directly determine whether fibrin(ogen) or plasmin(ogen) are determinants of the metastatic potential of circulating tumor cells, this study examined the impact of genetic deficits in each of these key hemostatic factors on the hematogenous pulmonary metastasis of 2 established murine tumors, Lewis lung carcinoma and the B16-BL6 melanoma. In both tumor models, fibrinogen deficiency strongly diminished, but did not prevent, the development of lung metastasis. The quantitative reduction in metastasis in fibrinogen-deficient mice was not due to any appreciable difference in tumor stroma formation or tumor growth. Rather, tumor cell fate studies indicated an important role for fibrin(ogen) in sustained adhesion and survival of tumor cells within the lung. The specific thrombin inhibitor, hirudin, further diminished the metastatic potential of circulating tumor cells in fibrinogen-deficient mice, although the inhibitor had no apparent effect on tumor cell proliferation in vitro. The absence of plasminogen and plasmin-mediated fibrinolysis had no significant impact on hematogenous metastasis. The authors concluded that fibrin(ogen) is a critical determinant of the metastatic potential of circulating tumor cells. Furthermore, thrombin appears to facilitate tumor dissemination through at least one fibrin(ogen)-independent mechanism. These findings suggest that therapeutic strategies focusing on multiple distinct hemostatic factors might be beneficial in the containment of tumor metastasis.

Self-reported factors that affect glycemic control in college students with type 1 diabetes.

PURPOSE: This study examined the self-reported impact of different factors on the overall diabetes care of college students with type 1 diabetes. METHODS: An 18-item questionnaire was mailed to 164 students with type 1 diabetes attending college away from home; results from 42 students fulfilled study criteria and were analyzed. Metabolic control was assessed by relative changes in glycosylated hemoglobin (HbA1c) levels from medical records. RESULTS: HbA1c levels did not change significantly between high school and college, yet most college students reported that diabetes was more difficult to manage in college. Commonly reported barriers to diabetes control included diet, irregular schedules, lack of parental involvement, peer pressure, drugs and alcohol, fear of hypoglycemia, and finances. Factors identified as improving diabetes control were an increased sense of responsibility, increased frequency of blood glucose testing, exercise, contact with healthcare providers, fear of hyperglycemia, and knowledge of the results of the Diabetes Control and Complications Trial. Many students reported testing their blood more frequently and taking more injections than in high school; most were on intensive insulin regimens. CONCLUSIONS: Despite the perception that diabetes management was more difficult in college, metabolic control was maintained during college, possibly due to a more intensive treatment approach.

Development and characterization of a Staphylococcus aureus nasal colonization model in mice.

Staphylococcus aureus nasal carriage is a risk factor for infection in humans, particularly in the hospital environment. Attenuation of carriage has proven effective in reducing the prevalence of infection in some high-risk groups. To study staphylococcal factors that influence nasal colonization, a mouse model of S. aureus nasal colonization was developed. Mice were inoculated intranasally with S. aureus Reynolds, and nasal carriage was evaluated by quantitating cultures of the nasal tissues from mice sacrificed at various time points after inoculation. The majority of mice inoculated with 10(8) CFU of S. aureus maintained nasal carriage for at least 20 days. Nasal colonization rates were similar for inbred (BALB/c and C57BL/6) and outbred (ICR) mice. Colonization was not affected by mouse passage of strain Reynolds. Lower inoculum doses (<10(7) CFU) resulted in reduced colonization after 7 days. However, mice given streptomycin in their drinking water developed long-term carriage of S. aureus, and they were colonized with inocula as low as 10(5) CFU. Nasal colonization was also established with two other S. aureus strains (one strain each of human and murine origins). S. aureus recovered from the nares of experimentally colonized mice expressed high levels of capsule, and the ability of a capsule-defective mutant to persist in the nares was reduced in comparison to that of the parent strain. This nasal colonization model should prove useful for studies of factors that mediate S. aureus colonization and for assessment of targets for antimicrobial intervention or vaccine development.