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Subclinical endotoxemia (low levels of circulating bacterial endotoxin) has been observed in patients suffering from chronic inflammatory diseases such as atherosclerosis, diabetes, and obesity. However, the link between this condition and chronic inflammation is poorly understood. Previous work from our lab has shown that chronic exposure to super-low doses of bacterial endotoxin (LPS) aggravates atherosclerosis resulting in increased plaque size and instability in a macrophage-dependent manner in a mouse model of atherosclerosis. Further, we showed that super-low dose LPS (SLD-LPS) treatment was able to inhibit lysosomal fusion in immortalized macrophages. However, this was done under more acute treatment conditions. The aim of this project was to examine the molecular mechanisms by which chronic SLD-LPS may polarize macrophages to a non-resolving pro-inflammatory state consistent with chronic inflammation. This was carried out in two projects, the first a more broad phenotypic paper showing the disruption in homeostasis by chronic SLD-LPS in immortalized macrophages, while the second uses primary bone marrow-derived mouse macrophages to identify specific molecular signaling pathways used by chronic SLD-LPS. Here we show that chronic SLD-LPS led to the novel upregulation of pro-inflammatory mediators p62 and ccl2 with simultaneous downregulation of homeostatic mediators Nrf2 and slc40a1 in immortalized wild-type mouse macrophages. Further we showed this effect was reversed using the homeostatic restorative agent sodium phenylbutyrate (4-PBA), a newly reported activity for this reagent in mouse macrophages. This indicated that a disruption in homeostasis, possibly involving autophagy, may be responsible for the non-resolving pro-inflammatory polarization of macrophages. Therefore, in our second project, we further explored the effect of chronic SLD-LPS treatment on the homeostatic arm of the response by focusing on the Nrf2 inhibitor Keap1. Here we show that chronic SLD-LPS results in an accumulation of Keap1 in mouse bone marrow-derived macrophages, an effect specific to chronic SLD-LPS, as high doses of LPS failed to induce Keap1. We suggest that this effect may be related to a disruption in lysosomal fusion as evidenced by accumulation of autophagy flux markers MLKL and p62. Further, we show that these effects are dependent on the non-traditional TLR4 adaptor TRAM, suggesting an alternative dose-dependent signaling pathway for LPS. Together this work identifies novel signaling mechanisms involved in non-resolving pro-inflammatory polarization of murine macrophages, providing new insight behind how chronic super-low dose LPS exposure may lead to chronic inflammation. / Doctor of Philosophy / Inflammation is the body's natural response to injury or insult and can be beneficial in certain contexts such as pathogen clearance. However, left un-checked, chronic inflammation can exacerbate or even lead to disease pathology, such as is the case with modern diseases such as atherosclerosis, obesity, diabetes, etc. Despite the high prevalence of these diseases, effective treatments and therapies are still lacking. Recently it was discovered that many patients suffering from chronic inflammatory diseases had low levels bacterial endotoxin (LPS) in their circulation, a condition referred to as subclinical endotoxemia. However, possible links between this condition and chronic inflammatory disease remain poorly understood. Using a mouse model of atherosclerosis, previous research from our lab showed that persistent exposure to super-low doses of bacterial endotoxin (similar to those observed in humans) lead to aggravated atherosclerosis with both increased plaque size and instability. Further, we showed that this effect was primarily mediated by pro-inflammatory polarized immune cells called macrophages, but the molecular mechanism behind this polarization is still unclear. Further research into these molecular mechanisms may provide better targets for the development of future chronic inflammatory disease treatments. Here using a combination of mouse cell line and primary cell cultures, we discuss how chronic exposure to super-low doses of bacterial endotoxin leads to the chronic non-resolving pro-inflammatory polarization of macrophage immune cells, with particular emphasis on the distinct molecular signaling mechanisms induced by chronic super-low dose LPS.

Although subclinical eating disorders are more common than clinical eating disorders, they have received significantly less empirical attention. Subclinical symptoms of eating disorders often surface during adolescence and young adulthood and are far more common among females than males. Despite knowledge that the larger sociocultural context may contribute to the development of eating disorders, few studies have examined feminist-informed factors that may serve as protective mechanisms for young women who are influenced by Western capitalist culture and exhibit some symptomology, but do not develop clinically disordered eating. Using the feminist-relational model (feminist-relational Model (Jordan, 1997; Maine and Bunnell, 2008; Surrey, 1991) as a guide, this study sought to fill this gap. Informed by feminist grounded theory methodology, this study qualitatively examined socio-relational and socio-political contexts as potential protective factors for young women ages 18-25 whose subclinical eating disorder symptoms had not yet developed into a clinical eating disorder. Using constructivist grounded theory methodology, an emerging model was developed which demonstrates how participants spoke of their eating disorder symptoms in an externalized way. This was termed the "eating disorder voice." Findings highlight how feminist-informed protective factors helped participants resolve the tension between their genuine voice and eating disorder voice, and act in accordance with their preferred values. Participants were then more likely to be open about their symptoms and invest in their relationships. The main protective factors that emerged included, support people who provide emotional and tangible support, support people who challenge the eating disorder, a personal sense of agency, and community activism and involvement. The present study adds to the feminist theory and the feminist-relational model by providing a conceptualization of the symbiotic relationship between feminist-informed protective factors, suggesting through supportive relationships, individuals experience increased empowerment and agency. Clinical findings indicate that protecting symptoms, misperceptions regarding subclinical symptoms, and stigma served as barriers to seeking treatment. Implications for future research and practice are discussed. / Ph. D.

Dairy cattle characteristically exhibit decreased milk yield and reproductive performance, as well as increased uterine infection rates during periods of high stress. Chromium supplementation has demonstrated efficacy as a feed additive capable of reducing the detrimental effects of stress. As such, its application in dairy production may help to alleviate economic losses associated with seasonal heat stress and the stress experienced during the early postpartum period. Therefore, the objective of the work described in this thesis was to evaluate the potential benefits of short-duration, high-dose chromium (Cr) supplementation in early postpartum dairy cows during the summer months. Multiparous, early postpartum cows (20.95 ± 0.21 DIM, 658.29 ± 13.61 kg) were assigned to one of two treatment groups: 1) normal TMR (Con; n=10) and 2) normal TMR + Cr propionate supplementation (CrPro; 12 mg/h/d Cr; n=12). Body weight (BW), milk yield, and feed intake were measured each day of the experiment. Ambient temperature and humidity were monitored, and the temperature-humidity index (THI) was calculated for the duration of the study as an indicator of the severity of the heat stress experienced by the cows. Transrectal ultrasonography was performed every three days to assess ovarian follicular and luteal dynamics. Respiration rates (RR), rectal temperatures (RT), and blood glucose were recorded concurrently with ovarian ultrasonography. Plasma was collected and used for analysis of progesterone concentrations. Every six days in conjunction with ultrasonography, endometrial cytology samples were collected via cytobrush from each cow to determine the incidences of subclinical endometritis (SCE), as determined by polymorphonuclear leukocyte (PMNL) %. There were no treatment-based differences in RR, RT, blood glucose, feed intake, milk yield, or BW. However, the supplementation strategy did improve reproductive parameters. Within the Con group, there was an increase in PMNL % between samples five and six. Furthermore, at cytology sample six, the Con group had a greater percentage of PMNL than the CrPro group (P=0.01). Chromium consumption did not affect the counts or sizes of most follicles, with the exception being the 6-9 mm category where the CrPro group had a greater average diameter and tended to have more follicles in this category. While CL numbers or size did not differ between treatments, the ratio of progesterone (P4) to corpus luteum (CL) volume was greater in the CrPro group compared to the Con group (P=0.03). The results from this study indicate that the proposed supplementation strategy does not influence DMI or milk yield in cows experiencing stress. Nonetheless, short-duration, high-dose Cr supplementation strategy could benefit reproductive performance and thereby limit economic losses experienced by dairy producers during periods of stress. / Master of Science / Dairy producers continue to experience monetary losses due to the decrease in production performance by dairy cows resulting from physiological changes in response to stress. Elevated ambient temperature and humidity conditions can lead to heat stress, which has been found to decrease both milk and reproductive performance on dairy operations. The period after calving, known as the postpartum period, can also lead to metabolic changes in a cow due to the stress of giving birth and beginning to produce milk. Chromium is an essential trace mineral that can be supplemented with cattle feed to improve the impacts of such stressful periods on production parameters. This study evaluated the effect of a short-duration, high-dose chromium supplementation strategy on reproduction and lactation of early postpartum dairy cattle during summer months. Twenty-two cows were assigned to two treatment groups: control (standard feed only) and chromium supplement (standard feed plus chromium propionate supplementation). Cows receiving the chromium supplement did not experience any changes in respiration rate, rectal temperature, blood glucose levels, feed intake, milk yield, or body weight. Reproductive analyses determined that cows receiving the chromium supplementation had a lower number of immune cells present in the uterus by the end of the experiment, which may be indicative of a healthier uterine environment. Chromium supplemented cows also had a greater level of progesterone concentration to corpus luteum volume compared to cows in the control group. These results indicate that the short-duration, high-dose chromium supplementation strategy could benefit reproductive performance and limit losses experienced by dairy cows under stress conditions.

Background: Annually, over 150,000 cardiovascular events occur among individuals ,65 years old in the United States, including asymptomatic ones. Coronary artery calcium (CAC), a subclinical marker of coronary artery disease (CAD), enhances risk stratification among asymptomatic individuals. This study assessed the prevalence of CAC in a rural population and determined relationships between traditional risk factors for CAD and CAC scores. Methods: During January 2011 to December 2012, asymptomatic individuals from central Appalachia were screened for CAC in the largest tertiary cardiovascular institute. Based on Agatston scale, participants were grouped into 4 CAC scores: zero (CAC 5 0), mild (CAC 5 1-99), moderate (CAC 5 100-399) and severe (CAC $ 400). Multinomial logistic regression was used to examine associations between potential risk factors of CAD and CAC score. Results: Of 1,674 participants, 55.4% had positive CAC score (CAC . 0). Increasing age and being male were positively associated with higher CAC scores. Although there was significant association between mild CAC and hypertension and family history of CAD, moderate CAC was positively associated with smoking status. Except hypercholesterolemia and sedentary lifestyle, severe CAC was significantly associated with major health conditions (obesity, diabetes and hypertension), lifestyle (smoking) and family history of CAD. Conclusions: More than half of participants in the CAC screening had subclinical CAD (CAC score . 0). The association between CAC score and CAD risk factors suggests that education about subclinical atherosclerosis among asymptomatic individuals in this region with high cardiovascular disease prevalence is needed because CAC improves CAD risk stratification, and the knowledge of CAC enhances medication adherence and motivates individuals towards beneficial behavioral/lifestyle modification.

Objective: To perform systematic review of the effects of screening for coronary artery calcium (CAC), a subclinical marker of coronary artery disease (CAD), on behavioral or lifestyle modification, risk perception, and medication adherence. Methods: We searched through CINAHL, PsychInfo, Web of Science, Cochrane Central Register of Control Trials, and PubMed (Medline) for studies on the effects of CAC screening in asymptomatic individuals across three major domains: behavioral modification, risk perception for CAD, and medication adherence. We extracted data from the retrieved studies, assessed and synthesized the information. Results: Of the 15 retrieved studies, three were randomized control trials and 12 were observational studies. CAC score was ascertained either as total score, quartiles, or standardized Agatston's ordinal scale. While all the 15 studies involved issues related to behavioral and medication adherence, four involved risk perception of CAD. Although no standardized approach was used in these studies, CAC screening enhanced medication adherence in 13 of the 15 studies, while the others were mixed. Conclusion: CAC screening improved medication adherence and could likely motivated individuals for beneficial behavioral or lifestyle changes to improve CAD. The mixed results suggest the need for further research because screening for subclinical atherosclerosis has significant implications for early detection and prevention of future cardiovascular events by aggressive risk factors modification.

The present study aimed to research links between autistic traits and creativity in the average adult population. The sample consisted of 108 adults,​ 60 females, 48 males, age 18-66 (M=34,90; SD=10,85), from 20 different social media pages who participated in the study through self-report questionnaires about autistic traits and creativity. The result shows that the autistic traits of difficulties in imagination and difficulties in social skills has associations with difficulties in creativity, while the autistic trait of attention to detail has associations with benefits in creativity. The creativity domains, differences between men and women and the method of self-report are discussed.

O elevado custo dos tratamentos tradicionais da mastite bovina, associado à redução de produção e inviabilidade de tratamento das mastites subclínicas durante a lactação, bem como a exigência cada vez mais rigorosa da ausência de resíduos de antimicrobianos por parte de instituições nacionais e internacionais, impulsiona o desenvolvimento de novas alternativas terapêuticas que visem minimizar o impacto das medidas tradicionais de tratamento. A homeopatia surge como importante alternativa, sendo aceita nacional e internacionalmente. O objetivo do trabalho foi avaliar o tratamento homeopático com Phytolacca decandra 30CH durante a lactação de vacas com mastite subclínica, utilizando parâmetros de qualidade do leite como Califórnia Mastitis Test (CMT), contagem de células somáticas (CCS) totais, porcentagens de polimorfonucleares (PMN) e de mononucleares (MN), teores de proteína, lactose, gordura, sólidos totais (ST) e extrato seco desengordurado (ESD), além da mensuração da produção leiteira. Foram selecionadas 26 vacas, CMT 2+ e 3+ sem sinais de mastite clínica, entre o terceiro e sexto mês de lactação, pluríparas e divididas em dois grupos, um com tratamentos medicamentosos mensais e outro com tratamentos quinzenais. Mensalmente foram colhidas duas amostras de leite de cada glândula mamária (teto) que apresentava mastite subclínica. Uma das amostras foi utilizada para CCS e análise dos componentes do leite, e a outra para identificação microbiológica. Nos grupos tratados, foi administrado o medicamento homeopático Phytolaca decandra 30CH diluído em água e aspergido nas mucosas oro-nasais e vaginais, enquanto que nos grupos denominados controle foi administrado placebo da mesma maneira. A pesagem da produção láctea de ambos os grupos foi realizada quinzenalmente até o final do experimento. Verificou-se então que não houve diferença significativa entre a produção láctea, CCS e a presença de microrganismos na secreção láctea das glândulas quando comparadas antes e depois do tratamento homeopático, dentro de cada grupo, bem como quando comparados os grupos entre si. As medianas de CMT e porcentagens de PMN foram compatíveis com infecções mamárias agudas, embora os animais tenham sido diagnosticados como portadores de mastites crônicas e em nenhum momento desenvolveram sinais clínicos. / The high cost of traditional treatments of bovine mastitis, with the reduction of production and impracticable treatment of subclinical mastitis during lactation, as well as the requirement of an increased demand for absence of antimicrobial agents residues by national and international institutions, drives the development of new therapeutic alternatives in order to minimizing the impact of traditional treatment measures. The homeopathy appears as an important alternative, accepted domestically and internationally. The objective of this work was to evaluate homeopathic treatment with Phytolacca decandra 30CH during the lactation of cows with subclinical mastitis, using some milk quality parameters as California Mastitis Test (CMT), total somatic cell count (SCC), percentages of polymorphonuclear (PMN) and mononuclear (MN) cells, levels of protein, lactose, fat, total solids and dry defatted matter, in addition to the measurement of milk production. Twenty-six cows were selected with CMT 2 + and 3 + without any signs of clinical mastitis, between the third and sixth month of lactation, pluriparous and they were divided into two groups, with monthly or biweekly drug treatments. Monthly were collected two milk samples from each mammary gland (teat) that presented subclinical mastitis. One of the samples was used for analysis of SCC and milk components, and the other one for microbiological identification. In the treated groups, was given the homeopathic medicine Phytolaca decandra 30CH diluted in water and sprayed in the oral-nasal and vaginal mucosa, while to the control group was given placebo following the same method. The weighing of the milk production for both groups was performed fortnightly until the end of the experiment. There was no significant difference between milk production, SCC and the presence of microorganisms in milk gland secretion compared before and after homeopathic treatment, within each group as well as comparing the groups together. The medians of CMT and percentages of PMN were compatible with acute mammary infection, in spite of they have been diagnosed as carriers of chronic mastitis, and at any time no clinical signs have been developed.

The general objectives of the present thesis were to evaluate: (i) the effects of subclinical mastitis (SM) caused by major pathogens on SCC, milk leukocyte differentials (MLD) and milk yield; (ii) milk yield losses caused by SM at the cow and quarter level; and (iii) the economic impact of SM caused by major pathogens. The thesis was structured in four studies. In study 1, quarter milk samples (n = 302) from 78 cows with SCC gt;200,000 cells/mL were analyzed by milk leukocyte differential (MLD) methodology and by microbiological culture (MC). Quarters with positive-culture results were obtained from 102/156 (65.4%) of MLD-positive milk samples, while 28/135 (20.7%) of MLD-negative milk samples were MC-positive. When MC was considered the gold standard for mastitis diagnosis, the sensitivity (Se) of the MLD was 65.4% (IC95% = 57.4 to 72.8%) and the specificity (Sp) was 79.3% (IC95% = 71.4% to 85.7%). In conclusion, the use of the MLD on cows with monthly composite SCC > 200×103 cells/mL for screening at quarter level identified quarters more likely to be culture-positive. In study 2, the effect of different pathogens was evaluated by comparison of contralateral (healthy and infected) mammary quarters of 146 lactating cows. The impact of SM on economic return (quarter milk yield × milk price) was determined by applying milk payment estimates on milk collected from healthy versus infected glands. The milk losses ranged from 0.07 Kg/quarter.milking to 2.9 Kg/quarter.milking, and varied according to the pathogen causing SM. Economic losses were higher for SM caused by Enterococcus spp. (US$0.43/quarter.milking), Strep. Dysgalactiae (US$ 0.74/quarter.milking) and E. coli (US$0.98/quarter.milking). Additionally, there was a trend for Staph. aureus and Citrobacter spp. To induce economic losses of US$ 0.26 and 0.29/quarter.milking, respectively. In general, the economic return was lower in quarters with SM caused by environmental and contagious pathogens (US$ 0.18 and 0.22/quarter.milking, respectively) when compared to their healthy contralateral quarters. In study 3, a total of 146 out of 650 lactating cows were selected from seven dairy herds for having composite milk SCC > 200,000 cells/mL in combination with the isolation of a major mastitis pathogen. From these selected cows, 1,436 quarter milk samples were collected during three successive sampling occasions at intervals of 15-20 days. Quarter milk yield was measured by milking the mammary quarters individually using three successive milk samplings over time. Bacterial isolates were identified by microbiological culture, MALDI-TOF MS and partial sequencing of the 16S rRNA gene. Milk losses and economic returns varied according to the type of mastitis-causing pathogen: 0.24 to -0.87 kg/quarter.milking for environmental streptococci, and -1.57 to -1.69 kg/quarter.milking for Staph. aureus. Overall, mammary quarters that were cured from SM caused by Staph. aureus and environmental streptococci exhibited an increase in economic return of approximately 0.47 and 0.69 US$/quarter.milking, respectively. In study 4, test day records (n = 1,200,002) were obtained from the Paraná State Holstein Association, which included data from 92,560 lactating cows, from 781 herds, from January 2010 to December 2015. A segmented regression was fitted to estimate the cut-off point of Log10SCC scale where milk yield started to be affected by mastitis: 0.90 (~7,963 cells/mL). In conclusion, first lactation cows have a reduction of 1.37 to 2.28 kg/cow/d of milk yield for each increase of one unit of Log10SCC over the cutoff point, whereas second and later lactation cows are expected to have milk yield losses of 2.36 to 4.20 kg/cow/d for each unit increase of Log10SCC over the cutoff point. Overall, the results of this thesis indicated that milk losses depend on the type of pathogen causing SM. Major pathogens have showed greater effects on milk quality than when it was observed using the approach of culture results of negative or positive. The methodology for evaluation of subclinical mastitis effect on milk yield interferes in the estimation of milk losses, and should include factors such as DIM and number of parity. / Os objetivos gerais da tese foram avaliar: (i) os efeitos da mastite subclínica (MS) causada por patógenos primários sobre a CCS, contagem diferencial de células e produção de leite; (ii) perdas de produção de leite ocasionadas pela MS, em nível de vacas e quartos mamários; e (iii) o impacto econômico da MS causado por patógenos primários. A tese foi estruturada em quatro estudos. No estudo 1, amostras de leite de quartos mamários (n = 302) foram submetidas a cultura microbiológica (CM) e contagem diferencial de leucócitos (MLD). Quartos com resultados cultura-positiva apresentaram 102/156 (65,4%) amostras de leite MLD-positivas, e 28/135 (20,7%) das amostras de leite MLD-negativas tiveram CM-positivas. Quando a CM foi considerada o padrão-ouro para o diagnóstico da mastite, o diagnóstico por meio da MLD apresentou sensibilidade (Se) de 65,4% (IC95% = 57,4 a 72,8%) e especificidade (Sp) de 79,3% (IC95% = 71,4% a 85,7%). Em conclusão, o uso da MLD em vacas com CCS mensal > 200,000 células/mL para triagem de quartos identificou os mais prováveis de ser cultura-positivos. No estudo 2, o efeito de diferentes tipos de patógenos foi estudado avaliando pares de quartos mamários contralaterais (sadios e infectados) de 146 vacas em lactação. O impacto da MS sobre o retorno econômico (produção de leite × preço do leite) foi determinado pela aplicação de estimativas de pagamento do leite de quartos sadios e infectados. As perdas de leite variaram de 0,07 Kg/quarto.ordenha a 2,9 Kg/quarto.ordenha de acordo com o patógeno causador de MS. As perdas econômicas foram maiores em casos de MS causados por Enterococcus spp. (US$ 0,43/quarto.ordenha), Strep. dysgalactiae (US$ 0,74/quarto.ordenha) e E. coli (US$ 0,98/quarto.ordenha). Além disso, houve uma tendência de Staph. aureus e Citrobacter spp. ocasionar perdas de US$ 0,26 e 0,29/quarto.ordenha, respectivamente. Em geral, o retorno econômico foi menor em quartos com MS causada por patógenos ambientais e contagiosos (US$ 0,18 e 0,22/quarto.ordenha, respectivamente) quando comparados com os quartos contralaterais sadios. No estudo 3, um total de 146 das 650 vacas em lactação foram selecionadas de sete rebanhos por apresentar amostras compostas de leite com alta CCS (> 200.000 células/mL) e isolamento de patógeno primário causador de MS. Destas vacas selecionadas, 1.436 amostras de leite de quartos foram coletadas durante três amostragens sucessivas com intervalos de 15-20 dias. A produção de leite em nível de quartos mamários foi mensurada por meio de ordenha completa e individual. Os isolados bacterianos foram identificados por CM, MALDI-TOF MS e sequenciamento parcial do gene 16S rRNA. As perdas de leite e os retornos econômicos variaram de acordo com o tipo de patógeno causador da mastite: - 0,24 a -0,87 kg/quarto.ordenha (Streptococcus ambientais) e -1,57 a -1,69 kg/quarto.ordenha (Staph. aureus). Em geral, os quartos mamários que apresentaram cura da MS causada por Staph. aureus e Streptococcus ambientais apresentaram aumento no retorno econômico de aproximadamente 0,47 e 0,69 US$/quarto.ordenha, respectivamente. No estudo 4, registros do controle leiteiro (n = 1.200.002) foram obtidos da associação Paranaense do gado Holandês, os quais incluíram dados de 92.560 vacas Holandesas em lactação de 781 rebanhos, de janeiro de 2010 a dezembro de 2015. Uma regressão segmentada foi ajustada para estimar o ponto de corte na escala Log10CCS em que a produção de leite começou a ser afetada pela MS: 0.90 (~ 7.963 células/mL). Como conclusão, vacas de primeira cria apresentaram redução de 1,37 a 2,28 kg/vaca/dia na produção de leite para cada aumento de uma unidade Log10CCS acima do ponto de corte, enquanto vacas com duas ou mais crias apresentaram perdas de 2,36 a 4,20 kg/vaca/dia. Em geral, os resultados desta tese indicaram que as perdas de leite dependem do tipo de patógeno que causa SM. Os patógenos primários mostraram maiores efeitos sobre a qualidade do leite do que quando foram observados pela abordagem com base nos resultados de cultura negativa ou positivos. A metodologia de avaliação do efeito da mastite subclínica sobre a produção de leite interfere na estimativa das perdas de leite e deve incluir fatores como DIM e número de paridade.

Este estudo objetivou avaliar a: a) eficiência da antibioticoterapia associada à vacinação, de infecções intramamárias (IIM) causadas por Staphylococcus aureus (S. aureus) durante a lactação e secagem; b) variabilidade genética de S. aureus de acordo com a resposta ao tratamento, antibiograma e técnica de Polimorfismo do Comprimento de Fragmentos Amplificados (AFLP). Para a avaliação da eficiência da terapia durante a lactação, foram selecionadas 117 vacas com mastite subclínica causada por S. aureus, a partir de 5 rebanhos leiteiros, as quais foram distribuídas aleatoriamente em três tratamentos: a) controle (sem tratamento), b) antibioticoterapia intramamária + injetável, c) antibioticoterapia intramamária + injetável + vacinação contra S. aureus. Para avaliar a eficiência da antibioticoterapia associada à vacinação contra S. aureus na secagem, foram selecionadas 136 vacas com mastite subclínica causada por S. aureus, as quais foram distribuídas aleatoriamnte em quatro tratamentos: a) antibioticoterapia intramamária, b) antibioticoterapia intramamária + injetável, c) antibioticoterapia intramamária + vacina, d) antibioticoterapia intramamária + injetável + vacina. Para os protocolos de tratamento (lactação e secagem), foi utilizada a vacina antimastítica TopVac (Hipra, Espanha). O antibiótico injetável foi a enrofloxacina (Kinetomax®, Bayer, Brasil), dose única (7,5 mg/kg). A antibioticoterapia intramamária durante a lactação foi realizada com ampicilina 75 mg + cloxacilina 250 mg (Bovigam L, Bayer, Irlanda do Norte), e na secagem, com ampicilina 200 mg + cloxacilina 500 mg (Bovigam ®VS, Bayer, Irlanda do Norte). Um total de 117 isolados de S. aureus foram submetidos à técnica de AFLP. A taxa de cura dos quartos tratados com antibioticoterapia, durante a lactação e na secagem, foi de 80,5% (n = 82) e 91,5% (n = 106), respectivamente. A vacinação contra S. aureus não aumentou a taxa de cura do tratamento durante a lactação, porém reduziu a CCS das vacas vacinada em comparação com as vacas do tratamento controle. No tratamento durante a lactação, primíparas e vacas com apenas um quarto infectado apresentaram maior taxa de cura (79 e 70%, respectivamente) do que pluríparas e vacas com dois ou mais quartos infectados (11 e 17%, respectivamente), respectivamente. A resistência à penicilina não afetou a taxa de cura dos isolados de S. aureus. A probabilidade de um isolado não adaptado à glândula mamária ser multirresistente e resistente à oxacilina foi maior do que a de um isolado adaptado, porém a taxa de cura dos isolados não adaptados foi maior do que a de isolados adaptados. Em conclusão, a antibioticoterapia foi eficiente para tratamento de mastite subclínica causada por S. aureus durante a lactação e secagem, e o resultado de antibiograma foi associado à classificação dos isolados em adaptados e não adaptados, porém não foi associado à resposta a antibioticoterapia / The objectives of this study were to evaluate: a) treatment effectiveness, using antibiotics and vaccination, in cows with intramammary infections caused by S. aureus during lactation and dry period; b) the genetic variability of S. aureus strains according to treatment responses, antibiogram and the AFLP technique. To evaluate the effectiveness of the lactation therapy, 117 icows with S. aureus subclinical mastitis, from 5 herds, were randomly distributed into 3 treatments: a) control; b) Intramammary + Injectable; c) Intramammary + injectable + Vaccine. To evaluate the effectiveness of the dry off therapy, 136 cows with S. aureus subclinical mastitis were randomly distributed into 4 treatments: a) Intramammary; b) Intramammary + Injectable (INT + INJ); c) Intramammary + Vaccine (INT + VAC); d) Intramammary + Injectable + Vaccine (INT + INJ + VAC). For both therapies (lactation and dry off), the antimastitis vaccine was the TopVac (Hipra, Spain). The injetable antibiotic was enrofloxacin (Kinetomax®, Bayer S. A., Brasil) single dose (7,5 mg/kg). The intramammary therapy was, during lactation, with ampicillin 75 mg + cloxacilin 200 mg (Bovigam L, Bayer, North Ireland) and at dry off with ampicillin 250 mg + cloxacilin 500 mg (Bovigam ®VS, Bayer, North Ireland). S. aureus isolates (117) were submitted to the AFLP technique. The cure rate of quarters treated with antibiotics during lactation and dry period was 80,5% (n = 82) e 91,5% (n = 106), respectively. Vaccination against S. aureus didn't raise the cure rate during lactation, but lowered the SCC of vaccinated cows compared to control cows. In the lactation therapy, primiparous and cows with one infected quarter had higher cure rates (79 and 70%, respectively) than pluriparous and cows with more than one infected quarter (11 and 17%, respectively), respectively. Resistence to penicillin did not affect S. aureus isolates cure rate. The probability of a non adapted S. aureus isolate to be multiresistant and resistant to oxacilin was higher than an adapted isolate, but cure rates of non adapted isolates was higher than adapted isolates. In conclusion, antibiotic therapy was efficient to treat S. aureus subclinical mastitis during lactation and dry period, and the antibiogram result was associated with the isolates classification in adapted and non adapted, but was not associated with the response to therapy