Effect of dry cow therapy products on the in vitro phagocytic function of goat milk leukocytes

O uso de medicamentos antimamíticos específicos para vacas no período seco é indicado para prevenção de infecções na lactação seguinte. Não obstante, a ação das células envolvidas no período de secagem tem fundamental importância para a involução da glândula mamária e seu restabelecimento para a lactação subseqüente. A indisponibilidade de tais medicamentos para uso em cabras tem resultado na extrapolação do uso de produtos recomendados para vacas sem que se considerem as particularidades e diferenças anátomo-fisiológicas entre as espécies bovina e caprina. O presente estudo teve por objetivo avaliar a influência de cinco antimamíticos específicos para vacas secas sobre a função dos fagócitos provenientes de leite caprino. Para tal, fez-se o isolamento de células somáticas de 20 amostras de leite provenientes de 10 cabras lactantes, sem antecedentes de tratamento de mamite nos últimos 30 dias, sob condições higiênico-sanitárias de colheita e com resultados negativos ao cultivo microbiológico do leite. As células aderidas a lamínulas de vidro foram confrontadas com formulações contendo princípios ativos disponíveis no mercado como Gentamicina (M1), Cefalônio Anidro (M2), Ampicilina (M3), Cloxacilina Benzatínica (M4) e Cefapirina Benzatínica (M5). Avaliou-se, por microscopia, a fagocitose de partículas de Zymosan. As médias dos índices de fagocitose das células submetidas ao tratamento com M2 (15,12% ± 16,22), M3 (6,02% ± 7,96), M4 (4,54% ± 5,45) e M5 (2,47% ± 4,64) foram menores (p<0,001) que a média dos índices de fagocitose do grupo controle (40,67% ± 19,68). A média dos índices de fagocitose das células submetidas ao tratamento com M2 foi maior (p<0,05) que as médias dos tratamentos com M3, M4 e M5 enquanto estas foram estatisticamente iguais entre si. As amostras celulares submetidas ao medicamento M1 exibiram adesão insuficiente ou ausente às lamínulas, inviabilizando a avaliação da fagocitose por meio da técnica utilizada. Os resultados obtidos permitem concluir que os medicamentos estudados exerceram influência negativa sobre os fagócitos do leite, porém, esta interferência sobre as funções das células somáticas não pode por si só determinar o insucesso da terapia proposta para o período seco, pois deve ser considerada, outrossim, a eficácia do princípio ativo sobre o patógeno causador do processo infeccioso.The use of specific anti-mastitis drugs is indicated in dry cow therapy to prevent infections in the following lactation. Nonetheless, cells active in the dry period are of fundamental importance for the involution of the mammary gland and its recovery for the following lactation. Since there are no specific drugs for dry goat therapy, the dry cow therapy drugs tend to be misused in goats despite of the anatomical and physiological differences apart from the particularities of the two species. The objective of the present study was to evaluate the influence of five drugs specific for dry cow therapy on the function of goat milk phagocytes. Somatic cells were isolated from 20 milk samples of 10 lactating goats that had not been treated for mastitis during the previous 30 days. Milk samples were collected properly and microbiological culture yielded negative results. Cells adherent to glass coverslips were treated with commercially available dry cow therapy drugs containing active principles such as Gentamicin (M1), Cephalonium anhydrous (M2), Ampicillin (M3), Cloxacillin benzathine (M4) and Cephapirin benzathine (M5). Phagocytosis of Zymosan particles was evaluated. Mean phagocytosis indexes of cells treated with M2 (15.12% ± 16.22), M3 (6.02% ± 7.96), M4 (4.54% ± 5.45) and M5 (2.47% ± 4.64) were lower (p<0.001) than mean phagocytosis index of the control group (40.67% ± 19.68). Mean phagocytosis index of cells treated with M2 was greater (p<0.05) than those treated with M3, M4 and M5, whereas means of the latter three treatments were statistically similar. M1-treated cells did not adhere adequately to the cover slips, making it impossible to evaluate phagocytosis in this group. The results obtained enable the conclusion that drugs used affected milk phagocytes negatively. However, interference on somatic cell function is not the sole factor determining an unsuccessful dry period therapy, since the efficacy of the active principle on pathogens responsible for infectious processes also has to be considered

Masses, radii, and orbits of small Kepler planets : The transition from gaseous to rocky planets

We report on the masses, sizes, and orbits of the planets orbiting 22 Kepler stars. There are 49 planet candidates around these stars, including 42 detected through transits and 7 revealed by precise Doppler measurements of the host stars. Based on an analysis of the Kepler brightness measurements, along with high-resolution imaging and spectroscopy, Doppler spectroscopy, and (for 11 stars) asteroseismology, we establish low false-positive probabilities (FPPs) for all of the transiting planets (41 of 42 have an FPP under 1%), and we constrain their sizes and masses. Most of the transiting planets are smaller than three times the size of Earth. For 16 planets, the Doppler signal was securely detected, providing a direct measurement of the planet's mass. For the other 26 planets we provide either marginal mass measurements or upper limits to their masses and densities; in many cases we can rule out a rocky composition. We identify six planets with densities above 5 g cm-3, suggesting a mostly rocky interior for them. Indeed, the only planets that are compatible with a purely rocky composition are smaller than 2 R ⊕. Larger planets evidently contain a larger fraction of low-density material (H, He, and H2O).Peer reviewedFinal Accepted Versio

A European research agenda for somatic symptom disorders, bodily distress disorders, and functional disorders: Results of an estimate-talk-estimate delphi expert study

Background: Somatic Symptom Disorders (SSD), Bodily Distress Disorders (BDD) and functional disorders (FD) are associated with high medical and societal costs and pose a substantial challenge to the population and health policy of Europe. To meet this challenge, a specific research agenda is needed as one of the cornerstones of sustainable mental health research and health policy for SSD, BDD, and FD in Europe. Aim: To identify the main challenges and research priorities concerning SSD, BDD, and FD from a European perspective. Methods: Delphi study conducted from July 2016 until October 2017 in 3 rounds with 3 workshop meetings and 3 online surveys, involving 75 experts and 21 European countries. EURONET-SOMA and the European Association of Psychosomatic Medicine (EAPM) hosted the meetings. Results: Eight research priorities were identified: (1) Assessment of diagnostic profiles relevant to course and treatment outcome. (2) Development and evaluation of new, effective interventions. (3) Validation studies on questionnaires or semi-structured interviews that assess chronic medical conditions in this context. (4) Research into patients preferences for diagnosis and treatment. (5) Development of new methodologic designs to identify and explore mediators and moderators of clinical course and treatment outcomes (6). Translational research exploring how psychological and somatic symptoms develop from somatic conditions and biological and behavioral pathogenic factors. (7) Development of new, effective interventions to personalize treatment. (8) Implementation studies of treatment interventions in different settings, such as primary care, occupational care, general hospital and specialty mental health settings. The general public and policymakers will benefit from the development of new, effective, personalized interventions for SSD, BDD, and FD, that will be enhanced by translational research, as well as from the outcomes of research into patient involvement, GP-patient communication, consultation-liaison models and implementation. Conclusion: Funding for this research agenda, targeting these challenges in coordinated research networks such as EURONET-SOMA and EAPM, and systematically allocating resources by policymakers to this critical area in mental and physical well-being is urgently needed to improve efficacy and impact for diagnosis and treatment of SSD, BDD, and FD across Europe

Multi-ancestry genome-wide association study accounting for gene-psychosocial factor interactions identifies novel loci for blood pressure traits

Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP, taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from five ancestry groups. In the combined meta-analyses of stages 1 and 2, we identified 59 loci (p value &lt; 5e−8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel&nbsp;loci supports a major role for genes implicated in the immune response (PLCL2), synaptic function and neurotransmission (LIN7A and PFIA2), as well as genes previously implicated in neuropsychiatric or stress-related disorders (FSTL5 and CHODL). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms