Photoactivatable Ruthenium Complexes Containing Minimal Straining Benzothiazolyl-1,2,3-triazole Chelators for Cancer Treatment.

Ruthenium(II) complexes containing diimine ligands have contributed to the development of agents for photoactivated chemotherapy. Several approaches have been used to obtain photolabile Ru(II) complexes. The two most explored have been the use of monodentate ligands and the incorporation of steric effects between the bidentate ligands and the Ru(II). However, the introduction of electronic effects in the ligands has been less explored. Herein, we report a systematic experimental, theoretical, and photocytotoxicity study of a novel series of Ru(II) complexes Ru1-Ru5 of general formula [Ru(phen)2(N∧N')]2+, where N∧N' are different minimal strained ligands based on the 1-aryl-4-benzothiazolyl-1,2,3-triazole (BTAT) scaffold, being CH3 (Ru1), F (Ru2), CF3 (Ru3), NO2 (Ru4), and N(CH3)2 (Ru5) substituents in the R4 of the phenyl ring. The complexes are stable in solution in the dark, but upon irradiation in water with blue light (λex = 465 nm, 4 mW/cm2) photoejection of the ligand BTAT was observed by HPLC-MS spectrometry and UV-vis spectroscopy, with t1/2 ranging from 4.5 to 14.15 min depending of the electronic properties of the corresponding BTAT, being Ru4 the less photolabile (the one containing the more electron withdrawing substituent, NO2). The properties of the ground state singlet and excited state triplet of Ru1-Ru5 have been explored using density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations. A mechanism for the photoejection of the BTAT ligand from the Ru complexes, in H2O, is proposed. Phototoxicity studies in A375 and HeLa human cancer cell lines showed that the new Ru BTAT complexes were strongly phototoxic. An enhancement of the emission intensity of HeLa cells treated with Ru5 was observed in response to increasing doses of light due to the photoejection of the BTAT ligand. These studies suggest that BTAT could serve as a photocleavable protecting group for the cytotoxic bis-aqua ruthenium warhead [Ru(phen)2(OH2)2]2+.

FACT regulates pluripotency through proximal and distal regulation of gene expression in murine embryonic stem cells.

BACKGROUND: The FACT complex is a conserved histone chaperone with critical roles in transcription and histone deposition. FACT is essential in pluripotent and cancer cells, but otherwise dispensable for most mammalian cell types. FACT deletion or inhibition can block induction of pluripotent stem cells, yet the mechanism through which FACT regulates cell fate decisions remains unclear. RESULTS: To explore the mechanism for FACT function, we generated AID-tagged murine embryonic cell lines for FACT subunit SPT16 and paired depletion with nascent transcription and chromatin accessibility analyses. We also analyzed SPT16 occupancy using CUT&RUN and found that SPT16 localizes to both promoter and enhancer elements, with a strong overlap in binding with OCT4, SOX2, and NANOG. Over a timecourse of SPT16 depletion, nucleosomes invade new loci, including promoters, regions bound by SPT16, OCT4, SOX2, and NANOG, and TSS-distal DNaseI hypersensitive sites. Simultaneously, transcription of Pou5f1 (encoding OCT4), Sox2, Nanog, and enhancer RNAs produced from these genes' associated enhancers are downregulated. CONCLUSIONS: We propose that FACT maintains cellular pluripotency through a precise nucleosome-based regulatory mechanism for appropriate expression of both coding and non-coding transcripts associated with pluripotency.

PCR screening reveals abundance of bovicin-like bacteriocins among ruminal Streptococcus spp. isolated from beef and dairy cattle.

AIMS: To investigate the inhibitory activity and the distribution of biosynthetic genes encoding bovicin-like bacteriocins among ruminal Streptococcus isolated from beef and dairy cattle. METHODS AND RESULTS: Most isolates were classified as Streptococcus equinus and Streptococcus lutetiensis based on 16S rRNA sequencing. The antimicrobial activity of 150 ruminal streptococci isolated from beef and dairy cattle were tested by deferred inhibition assays and their genetic diversity was characterized by BOX-PCR. The frequency of biosynthetic genes associated with the biosynthesis of bovicin-like bacteriocins (bovicin HC5 and bovicin 255) was investigated by PCR screening. Approximately 33% of the ruminal streptococci isolated from Nellore heifers showed inhibitory activity in vitro with the majority harbouring genes for bacteriocin biosynthesis. In contrast, streptococci from Holstein cows showed limited inhibitory activity and a lower frequency of bacteriocin biosynthetic genes. CONCLUSIONS: Streptococcus from the rumen of beef and dairy cattle exhibit remarkable differences in inhibitory activity and distribution of genes associated with the biosynthesis of prototypical bovicins (bovicin HC5 and bovicin 255). SIGNIFICANCE AND IMPACT OF THE STUDY: Our findings demonstrate that bovicin HC5 is distributed among ruminal streptococci from different breeds of cattle. The high degree of conservation of the bovicin HC5 structural gene among strains of ruminal streptococci suggests that random genetic drift is not a dominant force in the evolution of this bacteriocin.

Pre-transplant assessment of pp65-specific CD4 T cell responses identifies CMV-seropositive patients treated with rATG at risk of late onset infection.

Assessment of CMV-specific T cell immunity might be a useful tool in predicting CMV infection after solid organ transplantation. We have investigated CD4 and CD8 T-cell responses to CMV pp65 and IE-1 antigens in a prospective study of 28 CMV-seropositive kidney transplant recipients who were administered lymphocyte-depleting antibodies (Thymoglobulin®) as induction treatment and with universal prophylaxis for CMV infection. The response was analyzed by intracellular flow cytometry analysis of IFN-γ production in pretransplant samples and at 1, 6, 12 and 24 months post-transplant. Overall, only pretransplant CD4 T-cell responses to pp65 were significantly lower (p = .004) in patients with CMV replication post-transplant. ROC curve analysis showed that pre-transplant frequencies of pp65-specific CD4 + T cells below 0.10% could predict CMV infection with 75% sensitivity and 83.33% specificity (AUC: 0.847; 95% CI: 0.693-1.001; p = .0054) and seem to be mandatory for efficient control of CMV viral replication by the host immune system. In conclusion, the functional assessment of CMV-specific CD4 T-cell immunity pretransplant in seropositive patients may allow the identification of Thymoglobulin®-treated kidney transplant recipients at risk of developing CMV infection post-transplantation.

A standard set of person-centred outcomes for diabetes mellitus: results of an international and unified approach.

AIMS: To select a core list of standard outcomes for diabetes to be routinely applied internationally, including patient-reported outcomes. METHODS: We conducted a structured systematic review of outcome measures, focusing on adults with either type 1 or type 2 diabetes. This process was followed by a consensus-driven modified Delphi panel, including a multidisciplinary group of academics, health professionals and people with diabetes. External feedback to validate the set of outcome measures was sought from people with diabetes and health professionals. RESULTS: The panel identified an essential set of clinical outcomes related to diabetes control, acute events, chronic complications, health service utilisation, and survival that can be measured using routine administrative data and/or clinical records. Three instruments were recommended for annual measurement of patient-reported outcome measures: the WHO Well-Being Index for psychological well-being; the depression module of the Patient Health Questionnaire for depression; and the Problem Areas in Diabetes scale for diabetes distress. A range of factors related to demographic, diagnostic profile, lifestyle, social support and treatment of diabetes were also identified for case-mix adjustment. CONCLUSIONS: We recommend the standard set identified in this study for use in routine practice to monitor, benchmark and improve diabetes care. The inclusion of patient-reported outcomes enables people living with diabetes to report directly on their condition in a structured way.

Amino-Functionalized Mesoporous Silica Nanoparticle-Encapsulated Octahedral Organoruthenium Complex as an Efficient Platform for Combatting Cancer.

In the process of synthesis of a new drug, as important as the drug itself is the formulation used, because the same compound can present a very different efficacy depending on how it is administered. In this work, we demonstrate how the antitumor capacity of a new octahedral organoruthenium complex, [Ru(ppy-CHO)(phen)2][PF6] is affected by its encapsulation in different types of mesoporous silica nanoparticles. The interactions between the Ru complex and the silica matrix and how these interactions are affected at two different pHs (7.4 and 5.4, mimicking physiological and endolysosomal acidic conditions, respectively) have been studied. The encapsulation has also been shown to affect the induction of apoptosis and necrosis and progression of the cell cycle compared to the free drug. The encapsulation of the Ru complex in nanoparticles functionalized with amino groups produced very high anticancer activity in cancer cells in vitro, especially against U87 glioblastoma cells, favoring cellular internalization and significantly increasing the anticancer capacity of the initial non-encapsulated Ru complex.

Invasive Lactococcus lactis producing mycobacterial Hsp65 ameliorates intestinal inflammation in acute TNBS-induced colitis in mice by increasing the levels of the cytokine IL-10 and secretory IgA.

AIMS: To investigate the anti-inflammatory activity of an invasive and Hp65-producing strain Lactococcus lactis NCDO2118 FnBPA+ (pXYCYT:Hsp65) in acute 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced colitis in mice as an innovative therapeutic strategy against Crohn's disease (CD). METHODS AND RESULTS: The pXYCYT:Hsp65 plasmid was transformed into the L. lactis NCDO2118 FnBPA+ strain, resulting in the L. lactis NCDO2118 FnBPA+ (pXYCYT:Hsp65) strain. Then, the functionality of the strain was evaluated in vitro for Hsp65 production by Western blotting and for invasion into Caco-2 cells. The results demonstrated that the strain was able to produce Hsp65 and efficiently invade eukaryotic cells. Subsequently, in vivo, the anti-inflammatory capacity of the recombinant strain was evaluated in colitis induced with TNBS in BALB/c mice. Oral administration of the recombinant strain was able to attenuated the severity of colitis by mainly reducing IL-12 and IL-17 levels and increasing IL-10 and secretory immunoglobulin A levels. CONCLUSIONS: The L. lactis NCDO2118 FnBPA+ (pXYCYT:Hsp65) strain contributed to a reduction in inflammatory damage in experimental CD. SIGNIFICANCE AND IMPACT OF THE STUDY: This study, which used L. lactis for the production and delivery of Hsp65, has scientific relevance because it shows the efficacy of this new strategy based on therapeutic protein delivery into mammalian enterocytes.

Helminth Parasites and Diet of Leptodactylus Petersii (Steindachner, 1864) (Anura: Leptodactylidae) from Amapá State, Eastern Amazon, Brazil.

Leptodactylus petersii is a species of anuran found in both terrestrial and aquatic habitats and occurs from South America to southern North America and the West Indies. Studies involving the fauna of anuran parasites offer complementary information related to ecology. Thus, since there are few studies on the natural history of this species, this research aims to analyze the diet and the presence of endoparasitic helminths of Leptodactylus petersii from the state of Amapá, Brazil. We found 10 different taxonomic categories of prey in stomach contents, with the categories Hymenoptera (Formicidae) with 32.26 % (n = 12) being the most representative. Among the 12 individuals of L. petersii that were analyzed for helminth parasites, 83.3 % were infected with at least one species of helminths allocated to Phylum Nematoda. Our results report a new occurrence site for Rhabdias breviensis, originally described for Leptodactylus petersii in the state of Pará, as well as the second report of Ortleppascaris sp. in Brazil.

Cystic fibrosis in Afro-Brazilians: XK haplotypes analysis supports the European origin of p.F508del mutation.

Cystic fibrosis (CF) is a common autosomal recessive disorder, being the p.F508del the most frequent mutation. Also, a nearby restriction fragment length polymorphism (RFLP) named XK (KM19 and XV2C) is non-randomly associated with specific CF alleles. Our aim was to analyze the occurrence of the p.F508del mutation and XK haplotypes in Afro-Brazilians CF patients and controls, since these data is available for the other two main ethnic groups found in Brazil (Euro-Brazilians and Brazilian Amerindians), contributing for the whole comprehension of these haplotypes in the Brazilian population. A total of 103 patients and 54 controls were studied. PCR and PCR-RFLP methodologies were used to identify the presence of the p.F508del and the XK haplotype in the subjects. The combined data show that 84.2% of p.F508del mutation is associated with haplotype B and only 15.8% with haplotype A; no other haplotypes were found to be associated with this mutation. Our data suggest that the occurrence of p.F508del mutation and haplotype B in Afro-Brazilian patients occurs probably due to admixture with Euro-descendants. Therefore this mutation and haplotype could be used as a admixture marker.

Structure, Spectra, and DFT Simulation of Nickel Benzazolate Complexes with Tris(2-aminoethyl)amine Ligand.

Benzazolate complexes of Ni(II), [Ni(pbz)(tren)]ClO4 (pbz = 2-(2'-hydroxyphenyl)-benzimidazole (pbm), 1, 2-(2'-hydroxyphenyl)-benzoxazole (pbx), 2, 2-(2'-hydroxyphenyl)-benzothiazole (pbt), 3; tren = tris(2-aminoethyl)amine), are prepared by self-assembly reaction and structurally characterized. Theoretical DFT simulations are carried out to reproduce the features of their crystal structures and their spectroscopic and photophysic properties. The three complexes are moderately luminescent at room temperature both in acetonitrile solution and in the solid state. The simulations indicate that the absorption spectrum is dominated by two well-defined transitions, and the electronic density concentrates in three MOs around the benzazole ligands. The Stokes shifts of the emission spectra of complexes 1-3 are determined by optimizing the electronic excited state.

Influence of different surfactants on the physicochemical properties of elastic liposomes.

Elastic liposomes are capable to improve drug transport through the skin by acting as penetration enhancers due to the high fluidity and elasticity of the liposome membranes. Therefore, elastic liposomes were prepared and characterized to facilitate the transdermal transport of bioactive molecules. Liposomes consisted of dimyristoylphosphatidylcholine (DMPC) as the structural component, with different surfactants derived from lauric acid as elastic components: C12E5 (polyoxyethylene-5-lauryl ether), PEG4L (polyethyleneglycol-4-lauryl ester), PEG4DL (polyethylene glycol-4-dilauryl ester), PEG8L (polyethylene glycol-8-lauryl ester) and PEG8DL (polyethylene glycol-8-dilauryl ester). The elastic liposomes were characterized in terms of their phospholipid content, mean diameter, size distribution, elasticity and stability during storage, as well as their ability to incorporate surfactant and permeate through 50 nm pore size membranes. The results showed that the phospholipid phase transition temperature, the fluidity of the lipid bilayer resulting from incorporation of the surfactant and the preservation of particle integrity were factors determining the performance of the elastic liposomes in permeating through nanoporous membranes. The best results were obtained using DMPC combined with the surfactants PEG8L or PEG8DL. The findings demonstrate the potential of using elastic liposomes for transdermal administration of drugs.

Validation of an Argentine version of Lupus Quality of Life questionnaire.

OBJECTIVE: To determine reproducibility and validity of an Argentine version of the Lupus Quality of Life questionnaire (LupusQoL) and to determine cut-off values in the questionnaire. MATERIALS AND METHODS: One hundred and forty-seven systemic lupus erythematosus patients (American College of Rheumatology 1982/1997) were assessed from April 2014 to July 2014. Demographic and socioeconomic variables were collected, as well as SELENA/SLEDAI, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index Score, comorbidities and treatment data. Patients completed LupusQoL-Argentine version and European Quality of Life Questionnaire (EuroQoL-5D). Internal consistency and reliability were examined. Convergent validity with EuroQoL-5D was assessed through analysis of latent classes, which established homogeneous categories from the responses of each domain of LupusQoL and for the total. RESULTS: Out of 147 patients, 93.2% were female, mean age 36.4 ± 11.1 years, mean disease duration 2.7 ± 9 years, mean SELENA/SLEDAI 2.7 ± 3 points. The cut-off point that defined good or bad quality of life was 0.739 for EuroQoL 5D and 63 for LupusQoL. Cut-off values for each LupusQoL domain were also defined, creating two classes in each of them. There was moderate to high concordance to classify quality of life (Kappa = 0.74, 95% confidence interval = 0.54, 0.95). CONCLUSION: The Argentine version of LupusQoL is a valid, reliable and reproducible instrument to assess quality of life. In this study, cut-off points that allow the classification of patients regarding whether they have good or bad quality of life are established for the first time.

Mid-Term Outcomes after Percutaneous Closure of the Secundum Atrial Septal Defect with the Figulla-Occlutech Device.

OBJECTIVES: To evaluate the mid-term outcomes after percutaneous closure of the secundum atrial septal defects (ASD) using the Figulla-Occlutech device (FOD). BACKGROUND: Transcatheter closure has become the method of choice for most patients with ASD. Although the FOD may have some advantageous characteristics there is a paucity of data on later outcomes after the use of this relatively new device. METHODS: Observational, single arm study including 200 non-consecutive patients who underwent ASD closure between 04/09 and 07/15 in 2 centers. Device performance, deployment technique, and immediate and mid-term outcomes were assessed. RESULTS: Median age and weight were 24 years (4-72) and 58 kg (15-92), respectively. Single defects were observed in 171 patients (median size of 19 mm). The remainder had multiple or multifenestrated defects. Implantation of FOD (median size of 24 mm) was successful in all (99%), but 2 patients (1 with deficient postero-inferior rim; 1 with a large ASD for the size of the child). Embolization with device retrieval occurred in 2 (1%). Median follow-up of 36 months was obtained in 172 patients. Serial echocardiographic assessment showed complete closure in all but 2 patients, in whom an additional small non-significant posterior defect was purposely left untouched. There have been no episodes of late arrhythmias, device embolization, cardiac erosion, endocarditis, thromboembolism, wire fracture, or death. CONCLUSIONS: Transcatheter closure of ASDs in older children, adolescents, and adults using the FOD was highly successful in a wide range of anatomical scenarios with high closure rates and no complications in mid-term follow-up.

Host preference, population growth and injuries assessment of Polyphagotarsonemus latus (banks) (ACARI: Tarsonemidae) on Capsicum annuum L. Genotypes.

Despite the continued efforts on the search for different genotypes, Capsicum annuum (L.) is quite susceptible to attack by pest arthropods, especially the broad mite Polyphagotarsonemus latus Banks. Thus, the host preference, population growth and the injuries assessment of P. latus was studied on six C. annuum genotypes used in Brazil (Atlantis, California Wonder, Impact, Palloma, Rubia and Tendence). Host preference was accessed in choice tests, pairing the several genotypes, and the population growth was observed through non-choice tests in laboratory. The injuries assessments were evaluated in the greenhouse, comparing the injury level among the six genotypes. The results indicate that California Wonder and Palloma genotypes were more preferred by P. latus, and Impact and Tendence were less preferred. P. latus presented positive population growth rates (ri) on all the genotypes, however, Palloma and California Wonder showed the highest values of population growth rate (ri = 0.344 and ri = 0.340, respectively), while Impact had the lowest value (ri = 0.281). All the evaluated C. annuum genotypes showed low tolerance to P. latus and exhibited several injuries, but there was no statistical difference between them. California Wonder had the highest average number of mites/leaf (57.15), while Impact and Tendence obtained the lowest values (36.67 and 35.12, respectively) at the end of the evaluation period. The total average of injuries notes at the end of the bioassay did not differ between the genotypes. The number of mites/leaf was growing for the injury scale to the note 3.0, but when the injury scale approached the note 4.0, there was observed a decrease in the number of mites/leaf for all the genotypes.

Inclusion of cytoplasmic lineage effect and direct-maternal genetic covariance for genetic evaluation of growth traits in Nellore cattle.

We evaluated the impact of cytoplasmic lineage effects (Lc) for growth traits on genetic evaluation, including the genetic covariance between direct and maternal effects (σam). Pedigree data from 496,190 Nellore animals and observations on birth weight (BW, N = 243,391), weaning weight (WW, N = 431,681), and post-weaning weight gain adjusted to 345 days (PWG, N = 172,131) were analyzed. Four univariate models were used to obtain estimates of (co)variance components using the restricted maximum likelihood method in the BLUPF90 program. Model 1 included Lc and σam. Model 2 included Lc and σam was set to zero. Model 3 did not include Lc. Model 4 did not include Lc and σam was set to zero. These models considered the effects of the Lc as random. Phenotypic variance obtained through cytoplasmic lineage effects was determined for all traits, ranging from 0.07 to 0.15, 0.15 to 0.03, and 0.05 to 0.03% for BW, WW, and PWG, respectively, for models 1 and 2. Correlations between direct and maternal genetic components were positive for WW and negative for BW and PWG. No differences were observed for genetic parameter estimates or animal ranking with the inclusion of σam. For BW, the likelihood ratio suggested that model 1 best fits the data, while model 4 was the most appropriate for WW and PWG. Thus, these models are recommended for genetic evaluations. Despite the low magnitude of cytoplasmic lineages, this effect could predict breeding value and improve the selection of animals for BW in this Nellore population.

Parameters of a dynamic mechanistic model of cattle growth retain enough biological interpretation for genotype-to-phenotype mapping.

This study aimed to investigate the predictability of a phenotype when using a dynamic model of cattle growth. Genotypic and phenotypic information on Nellore (Bos indicus) cattle were used in a genome-wide association analysis designed to contrast the biological interpretation of core parameters [conversion efficiency of metabolizable energy to net energy for gain (kg) and adjusted final shrunk body weight (AFSBW)] to their associated genomic regions and nearby quantitative trait loci (QTLs). Single nucleotide polymorphisms (SNPs) were used to develop prediction equations for kg and AFSBW, which enter the model for simulative prediction purposes. QTLs and genes, one related to mature body weight and another to growth efficiency, are consistent with the model equations. Significantly associated SNPs were used to compute parameters, which yielded reasonable model outcomes when compared with regular parameter computations. Our results provide evidence of the biological validity of using such parameters as component traits of higher phenotypes and the possibility of using genomic data for genotype-to-parameter mapping.

Systems genetics and genome-wide association approaches for analysis of feed intake, feed efficiency, and performance in beef cattle.

Feed intake, feed efficiency, and weight gain are important economic traits of beef cattle in feedlots. In the present study, we investigated the physiological processes underlying such traits from the point of view of systems genetics. Firstly, using data from 1334 Nellore (Bos indicus) cattle and 943,577 single nucleotide polymorphisms (SNPs), a genome-wide association analysis was performed for dry matter intake, average daily weight gain, feed conversion ratio, and residual feed intake with a Bayesian Lasso procedure. Genes within 50-kb SNPs, most relevant for explaining the genomic variance, were annotated and the biological processes underlying the traits were inferred from Database for Annotation, Visualization and Integrated Discovery (DAVID) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Our results indicated several putative genomic regions associated with the target phenotypes and showed that almost all genomic variances were in the SNPs located in the intergenic and intronic regions. We further identified five main metabolic pathways related to ion transport, body composition, and feed intake control, which influenced the four phenotypes simultaneously. The systems genetics approach used in this study revealed novel pathways related to feed efficiency traits in beef cattle.

Genetic variation of the weaning weight of beef cattle as a function of accumulated heat stress.

The objective of this study was to identify the genetic variation in the weaning weight (WW) of beef cattle as a function of heat stress. The WWs were recorded at approximately 205 days of age in three Brazilian beef cattle populations: Nelore (93,616), Brangus (18,906) and Tropical Composite (62,679). In view of the cumulative nature of WW, the effect of heat stress was considered as the accumulation of temperature and humidity index units (ACTHI) from the animal's birth to weaning. A reaction norm model was used to estimate the (co)variance components of WW across the ACTHI scale. The accumulation of THI units from birth to weaning negatively affected the WW. The definition of accumulated THI units as an environmental descriptor permitted to identify important genetic variation in the WW as a function of heat stress. As evidence of genotype by environment interaction, substantial heterogeneity was observed in the (co)variance components for WW across the environmental gradient. In this respect, the best animals in less stressful environments are not necessarily the best animals in more stressful environments. Furthermore, the response to selection for WW is expected to be lower in more stressful environments.

Inbreeding depression in Zebu cattle traits.

The productivity of herds may be negatively affected by inbreeding depression, and it is important to know how intense is this effect on the livestock performance. We performed a comprehensive analysis involving five Zebu breeds reared in Brazil to estimate inbreeding depression in productive and reproductive traits. Inbreeding depression was estimated for 13 traits by including the individual inbreeding rate as a linear covariate in the standard genetic evaluation models. For all breeds and for almost all traits (no effect was observed on gestation length), the performance of the animals was compromised by an increase in inbreeding. The average inbreeding depression was -0.222% and -0.859% per 1% of inbreeding for linear regression coefficients scaled on the percentage of mean (ßm ) and standard deviation (ßσ ), respectively. The means for ßm (and ßσ ) were -0.269% (-1.202%) for weight/growth traits and -0.174% (-0.546%) for reproductive traits. Hence, inbreeding depression is more pronounced in weight/growth traits than in reproductive traits. These findings highlight the need for the management of inbreeding in the respective breeding programmes of the breeds studied here.

Impact of patient and navigator race and language concordance on care after cancer screening abnormalities.

BACKGROUND: Patient navigation improves the timely diagnosis of cancer among minorities, but little is known about the effects of patient and navigator race and language concordance on health outcomes. METHODS: The authors investigated the effects of patient and navigator race and language concordance on the time to diagnosis of cancer screening abnormalities among participants in the Boston Patient Navigation Research Program, a clinical effectiveness trial for women who had breast or cervical cancer screening abnormalities identified from January 1, 2007 to December 31, 2008. Hazard ratios and 95% confidence intervals were estimated using proportional hazards regression adjusting for clinical and demographic factors. RESULTS: In total, 1257 women had breast cancer screening abnormalities (n = 655) or cervical cancer screening abnormalities (n = 602) identified, and 56% were nonwhite. Language concordance was associated with timelier resolution for all patients in the cervical cancer screening abnormalities group during the first 90 days (adjusted hazard ratio, 1.46; 95% confidence interval, 1.18-1.80), and specifically for Spanish speakers during the first 90 days (adjusted hazard ratio, 1.43; 95% confidence interval, 1.10-1.84), but no difference was observed after 90 days for women who had cervical cancer screening abnormalities or at any time for those who had breast cancer screening abnormalities. Race concordance was associated with significant decreases in the time to diagnosis for minority women with breast and cervical cancer screening abnormalities in analyses stratified by race, but no differences were observed in analyses that included all women. CONCLUSIONS: Patient navigator race and language concordance improved the timeliness of care in a minority population. Patient navigators who are racially/ethnically diverse and multilingual may help address barriers to care and improve cancer outcomes for low-income minorities.