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OBJECTIVE: To evaluate experiential pharmacy preceptor perceptions of student pharmacists' ability to administer pediatric immunizations. METHODS: Semi-structured, qualitative key informant interviews using the Outcomes Evaluation Framework were conducted with 10 pharmacist preceptors in outpatient community pharmacies where pediatric immunizations were provided. Interviews were audio-recorded, transcribed, and deidentified prior to analysis by the research team. Qualitative analysis and thematic coding procedures were used to identify relevant themes. RESULTS: Saturation was met after 10 pharmacists participated. All stated that it was beneficial for student pharmacists to administer pediatric vaccines if trained in proper technique. Participants acknowledged that the training students currently receive in immunization administration within the PharmD curriculum is valuable but did identify general confidence and child-comforting techniques during and after vaccination as areas of improvement for students. Just-in-time training, preceptor coaching, and hands-on practice outside of the didactic curriculum were utilized to help build confidence. Barriers to the implementation or expansion of pediatric immunization delivered by students in community pharmacies were identified as competing priorities, time, and reimbursement. CONCLUSION: Student pharmacists can be helpful in easing the challenges of incorporating pediatric immunization services into the community pharmacy setting. Results demonstrate that the integration of student pharmacists into these services is beneficial. Pediatric immunizations are still relatively new to many pharmacists and specific training for pediatric immunization administration may not be integrated into all Doctor of Pharmacy curricula but the experiential education of pediatric immunization training can be beneficial to help prepare student pharmacists for hands-on practice.
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Introduction: As the shortage of primary care providers widens nationwide, access to care utilizing non-physician providers is one strategy to ensure equitable access to care. This study aimed to compare community pharmacist-provided care for minor ailments to care provided at three traditional sites of care: primary care, urgent care, and emergency department, to determine if care provided by pharmacists improved access with comparable quality and reduced financial strain on the healthcare system. Methods: Pharmacy data was provided from 46 pharmacies and 175 pharmacists who participated across five pharmacy corporations over a 3-year period (2016-2019). Data for non-pharmacy sites of care was provided by a large health plan, matching episodes of care for conditions seen in the community pharmacy. Cost-of-care analysis was conducted using superiority study design and revisit data analysis was conducted using noninferiority study design. Results: Median cost-of-care across traditional sites of care was $277.78 higher than care provided at the pharmacies, showing superiority. Noninferiority was demonstrated for revisit care when the initial visit was conducted by a pharmacist compared to traditional sites. Discussion: The authors conclude community pharmacist-provided care for minor ailments improved cost-effective access for patients with comparable quality and reduced financial strains on the healthcare system.
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Introduction: Group living skills (GLS), that is, being tidy and considerate of others, are an important skillset for teams who live and work together. However, this construct does not have a validated measure to enable an understanding of how group living skills influence team dynamics over time. We developed and validated a short measure of group living skills for teams living in extreme work environments. Methods: We collected data from 83 individuals in 24 teams living and working in space and spaceflight analog environments on missions of 45-240 days. Results: We provide evidence of reliability and validity for the GLS Survey over time and identify a two-factor structure. We also demonstrate its use as a measure of team-level dynamics and its utility as a sociometric measure to identify a person's degree of group living skills. Discussion: We outline recommendations for using this new measure in future research and applied settings to understand this unique aspect of teams living and working together.
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Conventional antimicrobial discovery relies on targeting essential enzymes in pathogenic organisms, contributing to a paucity of new antibiotics to address resistant strains. Here, by targeting a non-essential enzyme, Borrelia burgdorferi HtpG, to deliver lethal payloads, we expand what can be considered druggable within any pathogen. We synthesized HS-291, an HtpG inhibitor tethered to the photoactive toxin verteporfin. Reactive oxygen species, generated by light, enables HS-291 to sterilize Borrelia cultures by causing oxidation of HtpG, and a discrete subset of proteins in proximity to the chaperone. This caused irreversible nucleoid collapse and membrane blebbing. Tethering verteporfin to the HtpG inhibitor was essential, since free verteporfin was not retained by Borrelia in contrast to HS-291. For this reason, we liken HS-291 to a berserker, wreaking havoc upon the pathogen's biology once selectively absorbed and activated. This strategy expands the druggable pathogenic genome and offsets antibiotic resistance by targeting non-essential proteins.
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Borrelia burgdorferi , Borrelia burgdorferi/genética , Borrelia burgdorferi/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Verteporfina/metabolismo , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Chaperonas Moleculares/metabolismoRESUMO
Lyme disease, caused by vector-borne Borrelia bacteria, can present with diverse multi-system symptoms that resemble other conditions. The objective of this study was to evaluate disease presentations and Borrelia seroreactivity in individuals experiencing a spectrum of chronic and complex illnesses. We recruited 157 participants from Eastern Canada who reported one or more diagnoses of Lyme disease, neurological, rheumatic, autoimmune, inflammatory, gastrointestinal, or cardiovascular illnesses, or were asymptomatic and presumed healthy. Intake categories were used to classify participants based on their perceived proximity to Lyme disease, distinguishing between those with a disclosed history of Borrelia infection, those with lookalike conditions (e.g. fibromyalgia syndrome), and those with unrelated ailments (e.g. intestinal polyps). Participants completed three questionnaires, the SF-36 v1, SIQR, and HMQ, to capture symptoms and functional burden, and provided blood serum for analysis at an accredited diagnostic lab. Two-tiered IgG and IgM serological assessments (whole cell ELISA and Western blot) were performed in a blinded fashion on all samples. The pattern of symptoms and functional burden were similarly profound in the presumptive Lyme and Lyme-like disease categories. Borrelia seroprevalence across the study cohort was 10% for each of IgG and IgM, and occurred within and beyond the Lyme disease intake category. Western blot positivity in the absence of reactive ELISA was also substantial. Fibromyalgia was the most common individual diagnostic tag disclosed by two-tier IgG-positive participants who did not report a history of Lyme disease. Within the IgG seropositive cohort, the presence of antibodies against the 31 kDa Outer Surface Protein A (OspA) was associated with significantly better health outcomes. Previously, this marker has been linked to treatment-refractory Lyme arthritis. Overall, our findings support prior observations of phenotypic overlap between Lyme and other diseases. Seropositivity associated with non-specific symptoms and functional impairment warrants further mechanistic investigation and therapeutic optimization.
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Borrelia burgdorferi , Borrelia , Fibromialgia , Doença de Lyme , Humanos , Fibromialgia/epidemiologia , Estudos Soroepidemiológicos , Canadá/epidemiologia , Doença de Lyme/diagnóstico , Doença de Lyme/epidemiologia , Doença Crônica , Anticorpos Antibacterianos , Imunoglobulina G , Imunoglobulina MRESUMO
BACKGROUND: Substance use disorders (SUDs) are highly prevalent among adults with persistent pain. Yet, standard competencies for integrating pain and SUD content are lacking across health science student curricula. Additionally, pharmacotherapies to treat SUDs are underutilized. AIM: To address these gaps, a team of health science faculty created an interprofessional simulation activity using a standardized patient and evaluated learner outcomes related to assessment and treatment of comorbid persistent pain and substance use. METHODS: A total of 304 health science students representing nursing, medicine, pharmacy, and social work programs attended virtual learning sessions. Interprofessional student teams developed a team-based care plan for an adult with musculoskeletal pain who takes prescribed opioids while using alcohol. Pre- and post-activity surveys assessing knowledge and confidence were matched for 198 students. Descriptive statistics summarized survey data with inferential analysis of paired data. RESULTS: The largest significant improvements between pre- and post-activity knowledge were observed in items specific to pharmacotherapy options for alcohol and opioid use disorders. Similar gains were noted in students' confidence regarding pharmacotherapies. No significant differences were noted on pre-post-activity knowledge scores between the three main profession groups (medicine, nursing, and pharmacy). CONCLUSIONS: Students attending this interprofessional simulation demonstrated improved knowledge and confidence, particularly in pharmacotherapies for alcohol and opioid use disorders. Replication of such programs can be used to provide consistent content across health science disciplines to heighten awareness and receptivity to medications available to treat SUDs in people treated for persistent pain. The curriculum is freely available from the corresponding author.
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Educação Interprofissional , Transtornos Relacionados ao Uso de Opioides , Humanos , Adulto , Avaliação de Programas e Projetos de Saúde , Currículo , DorRESUMO
Objective.Children with heart failure have higher rates of emergency department utilization, health care expenditure, and hospitalization. Therefore, a need exists for a simple, non-invasive, and inexpensive method of screening for left ventricular (LV) dysfunction. We recently demonstrated the practicality and reliability of a wireless smartphone-based handheld device in capturing carotid pressure waveforms and deriving cardiovascular intrinsic frequencies (IFs) in children with normal LV function. Our goal in this study was to demonstrate that an IF-based machine learning method (IF-ML) applied to noninvasive carotid pressure waveforms can distinguish between normal and abnormal LV ejection fraction (LVEF) in pediatric patients.Approach. Fifty patients ages 0 to 21 years underwent LVEF measurement by echocardiogram or cardiac magnetic resonance imaging. On the same day, patients had carotid waveforms recorded using Vivio. The exclusion criterion was known vascular disease that would interfere with obtaining a carotid artery pulse. We adopted a hybrid IF- Machine Learning (IF-ML) method by applying physiologically relevant IF parameters as inputs to Decision Tree classifiers. The threshold for low LVEF was chosen as <50%.Main results.The proposed IF-ML method was able to detect an abnormal LVEF with an accuracy of 92% (sensitivity = 100%, specificity = 89%, area under the curve (AUC) = 0.95). Consistent with previous clinical studies, the IF parameterω1was elevated among patients with reduced LVEF.Significance.A hybrid IF-ML method applied on a carotid waveform recorded by a hand-held smartphone-based device can differentiate between normal and abnormal LV systolic function in children with normal cardiac anatomy.
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Smartphone , Disfunção Ventricular Esquerda , Humanos , Criança , Recém-Nascido , Lactente , Pré-Escolar , Adolescente , Adulto Jovem , Adulto , Reprodutibilidade dos Testes , Disfunção Ventricular Esquerda/diagnóstico , Função Ventricular Esquerda , Volume Sistólico , Artérias Carótidas/diagnóstico por imagemRESUMO
Early recognition of Lyme carditis is critical to preventing unnecessary pacemaker implantation for conduction abnormalities associated with this tick-born infection. Patients who do receive a pacemaker should be considered for device extraction after the completion of their antibiotic therapy if they recover normal atrioventricular node conduction. (Level of Difficulty: Intermediate.).
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BACKGROUND AND PURPOSE: To describe the implementation of a pediatric vaccination training for student pharmacists and to assess student confidence in providing pediatric vaccinations after taking part in a mixed media, traditional lecture, and active learning, formatted training course. EDUCATIONAL ACTIVITY AND SETTING: Student pharmacists were trained with a two-hour pediatric immunization training module which consisted of materials to detail administration techniques. Students were assessed using a live skills assessment and a multiple-choice knowledge examination. To assess student confidence in these skills, the students were given a pre- and post-instruction survey which was analyzed using the Mann-Whitney U test. FINDINGS: All 170 students enrolled successfully completed the knowledge assessment with an average score of 87% (SD 10%). The skills assessment items most commonly needing remediation were verifying that caregivers received the Vaccine Information Sheet (24%) and reviewing comfort measures and after care instructions with the caregiver (24%). The pre-course survey was completed by 169 out of 170 student pharmacists (99.4%) while the post-course survey was completed by 164 student pharmacists (96.4%) with each item showing a statistically significant increase in perceived confidence in vaccine administration. SUMMARY: Pediatric vaccination training was integrated into a doctor of pharmacy curriculum with the goals of increasing student knowledge and confidence in giving pediatric immunizations. Upon course completion, there was a statistically significant increase in student-perceived knowledge and confidence when administering pediatric immunizations. By expanding access to pediatric immunizers, pharmacists can aid in increasing immunization rates improving public health in their communities.
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Educação em Farmácia , Estudantes de Farmácia , Vacinas , Criança , Educação em Farmácia/métodos , Humanos , Imunização , FarmacêuticosRESUMO
We describe the development, optimization, and validation of a multiplex droplet digital PCR (ddPCR) assay for the simultaneous detection of Babesia, Bartonella, and Borrelia spp. DNA from several sample matrices, including clinical blood samples from animals and humans, vectors, in-vitro infected human and animal cell lines, and tissues obtained from animal models (infected with Bartonella and/or B. burgdorferi). The multiplex ddPCR assay was able to detect 31 Bartonella, 13 Borrelia, and 24 Babesia species, including Theileria equi, T. cervi, and Cytauxzoon felis. No amplification of Treponema or Leptospira spp. was observed. Sensitivity of 0.2-5 genome equivalent DNA copies per microliter was achieved for different members of the Bartonella and Borrelia genus, depending on the species or matrix type (water or spiked blood DNA) tested. The ddPCR assay facilitated the simultaneous detection of co-infections with two and three vector-borne pathogens comprising four different genera (Babesia, Bartonella, Borrelia, and Theileria) from clinical and other sample sources.
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Bartonella bacilliformis (B. bacilliformis), Bartonella henselae (B. henselae), and Bartonella quintana (B. quintana) are bacteria known to cause verruga peruana or bacillary angiomatosis, vascular endothelial growth factor (VEGF)-dependent cutaneous lesions in humans. Given the bacteria's association with the dermal niche and clinical suspicion of occult infection by a dermatologist, we determined if patients with melanoma had evidence of Bartonella spp. infection. Within a one-month period, eight patients previously diagnosed with melanoma volunteered to be tested for evidence of Bartonella spp. exposure/infection. Subsequently, confocal immunohistochemistry and PCR for Bartonella spp. were used to study melanoma tissues from two patients. Blood from seven of the eight patients was either seroreactive, PCR positive, or positive by both modalities for Bartonella spp. exposure. Subsequently, Bartonella organisms that co-localized with VEGFC immunoreactivity were visualized using multi-immunostaining confocal microscopy of thick skin sections from two patients. Using a co-culture model, B. henselae was observed to enter melanoma cell cytoplasm and resulted in increased vascular endothelial growth factor C (VEGFC) and interleukin 8 (IL-8) production. Findings from this small number of patients support the need for future investigations to determine the extent to which Bartonella spp. are a component of the melanoma pathobiome.
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PURPOSE OF REVIEW: Despite the promise of remote patient monitoring (RPM), this technology remained underutilized secondary to a lack of data transparency and systems issues until the COVID-19 pandemic ushered in a new era of telehealth and virtual solutions out of necessity. This review will explore the data supporting the use of RPM via both implantable and wearable devices in the field of cardiology and the role of home monitoring using RPM in the era of COVID-19. RECENT FINDINGS: RPM using implantable cardiac devices is a safe alternative to in-person only visits which leads to enhanced patient satisfaction and improved clinical outcomes. Consumer-grade wearable sensors have drastically expanded RPM capabilities from just the sickest cardiac patients to the entire population aiding in early diagnosis and real-time disease management. Home monitoring enabled by automated alert systems tailored specifically to the needs of the patient by the provider will be the cornerstone of a more continuous, patent-centric healthcare model.
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COVID-19 , Desfibriladores Implantáveis , Telemedicina , Humanos , Pandemias , SARS-CoV-2RESUMO
In December 2019, the novel COVID-19 virus spread from a cluster of pneumonia cases in Wuhan, China, to every corner of the globe, creating a worldwide pandemic pushing hospital systems past capacity and bringing economies worldwide to a halt. The COVID-19 pandemic is unique in comparison to prior coronavirus epidemics in its superior ability to be spread by asymptomatic and presymptomatic patients, allowing the virus to silently evade traditional symptoms-based screening approaches. Countries have implemented cutting-edge digital solutions to enhance traditional contact-tracing methodologies in combination with novel testing strategies to combat the virus, with variable levels of success. Despite having one of the most advanced and expensive health care systems in the world, the United States (U.S.) response is arguably one of the world's largest failures, as it leads the globe in case number as well as deaths. Until a successful vaccine can be broadly distributed, it is imperative that the U.S. curb the viral spread by rapidly developing a framework implementing both enhanced tracing and testing strategies balancing the needs of public health while respecting individual liberties. This review will explore the role of technology-augmented contact-based surveillance in tracking the outbreak in select countries in comparison to the current U.S. approach. It will evaluate barriers in the U.S. to implementing similar technologies, focusing on privacy concerns and a lack of unified testing and tracing strategy. Finally, it will explore strategies for rapidly scaling testing in a cost-effective manner.
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This report describes the development, optimization, and validation of a ddPCR assay for the detection of Bartonella spp. DNA within several sample matrices, including clinical blood samples from patients with or without documented Bartonella spp. bacteremia. The Bartonella spp. ddPCR assay was developed based upon previously published TaqMan-based qPCR assays that can amplify DNA of over 25 Bartonella spp. Host DNA (housekeeping gene) amplification serves as a reference target to facilitate quantification. The efficiency, sensitivity, and specificity of the Bartonella spp. ddPCR assay was assessed by direct comparison with the current qPCR methods used by the Intracellular Pathogens Research Laboratory (North Carolina State University, North Carolina, USA), and Galaxy Diagnostics (Research Triangle Park, North Carolina, USA). Bartonella spp. ddPCR assay parameters were successfully optimized to detect Bartonella concentrations equivalent to 0.5 bacterial genome copies per microliter of blood (0.001 pg/ul of bacterial DNA). The number of droplets detected (resolution) for each concentration was consistent across each of four assessed time points. The Bartonella spp. ddPCR assay detected 16 species/strains including B. henselae; B. quintana; B. vinsonii subsp. berkhoffii (genotypes I, II, III and IV); B. vinsonii subsp. vinsonii; B. melophagi; B. volans; B. monaki; B. alsatica; B. bovis; B. elizabethae; B. clarridgeiae; and B. koehlerae. Bartonella DNA was detected in only one previously negative patient sample (119/120 negative; 99% specificity). The ddPCR sensitivity (53/112) was significantly better than qPCR (6/112) when testing patient blood and enrichment blood culture samples. The development of commercial ddPCR systems with integrated technologies has significantly streamlined the DNA detection process, making it more efficient and standardized for clinical diagnostic testing. The assay described in this work is the first step toward the development of a multiplex ddPCR assay (i.e., using the QX One from Bio-Rad) for the simultaneous detection and absolute quantification of multiple vector-borne pathogens (such as Babesia, Bartonella and Borrelia) within clinical samples.
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Bacteriemia , Infecções por Bartonella , Bartonella , Reação em Cadeia da Polimerase em Tempo Real/métodos , Bacteriemia/diagnóstico , Bacteriemia/microbiologia , Bartonella/genética , Bartonella/isolamento & purificação , Infecções por Bartonella/diagnóstico , Infecções por Bartonella/microbiologia , DNA Bacteriano/isolamento & purificação , HumanosRESUMO
Measurement of cardiac function is vital for the health of pediatric patients with heart disease. Standard tools to measure function including echocardiogram and magnetic residence imaging are time intensive, costly, and have limited accessibility. The Vivio is a novel, non-invasive, handheld device that screens for cardiac dysfunction by analyzing intrinsic frequencies (IF) ω1 and ω2 of carotid artery waveforms. Prior studies demonstrated that left ventricular ejection fraction can be derived from IFs in adults. This study 1) studies whether the Vivio can capture carotid arterial pulse waveform data in children ages 0-19 years old; 2) tests the performance of two sensor head geometries, one larger and smaller than the standard size used in adults, designed for the pediatric population; 3) compares the IFs between pediatric age groups and adults with normal function. The Vivio successfully measured a carotid artery waveform in all children over 5 years old and 28% of children under the age of five. The small head did not accurately measure a waveform in any age group. One-way analysis of variance (ANOVA) demonstrated a difference in the IF ω1 between the adult and pediatric cohorts (F = 7.3, Prob>F = 0.0001). Post host analysis demonstrated a difference between the adult cohort (ω1 = 99 +/- 5 bpm) and the cohorts ages 0-4 (ω1 = 111 +/- 2 bpm; p = 0.0006) and 15-19 years old (ω1 = 105 +/-5 bpm; p = 0.02). One-way ANOVA demonstrated a difference in the IF ω2 between the adult and pediatric cohorts (F = 4.8, Prob>F = 0.003), specifically between the adult (ω2 = 81 +/- 13 bpm) and age 0-4 cohorts (ω2 = 48 +/- 8 bpm; p = 0.002). These results suggest that the Vivio can be used to capture carotid pulse waveform data in pediatric populations and that the data produced can be used to measure intrinsic frequencies.
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Determinação da Frequência Cardíaca/instrumentação , Monitorização Hemodinâmica/instrumentação , Estudo de Prova de Conceito , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Tecnologia sem Fio/instrumentação , Adolescente , Adulto , Artérias Carótidas/fisiologia , Cefalometria , Criança , Pré-Escolar , Estudos de Coortes , Estudos de Viabilidade , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Pulso Arterial , Adulto JovemRESUMO
Congenital complete heart block (CCHB) is a life-threatening medical condition in the unborn fetus with insufficiently validated prenatal interventions. Maternal administration of medications aimed at decreasing the immune response in the fetus and beta-agonists intended to increase fetal cardiac output have shown only marginal benefits. Anti-inflammatory therapies cannot reverse CCHB, but may decrease myocarditis and improve heart function. Advances in prenatal diagnosis and use of strict surveillance protocols for delivery timing have demonstrated small improvements in morbidity and mortality. Ambulatory surveillance programs and wearable fetal heart rate monitors may afford early identification of evolving fetal heart block allowing for emergent treatment. There is also preliminary data suggesting a roll for prevention of CCHB with hydroxychloroquine, but the efficacy and safety is still being studied. To date, intrauterine fetal pacing has not been successful due to the high-risk invasive placement techniques and potential problems with lead dislodgement. The development of a fully implantable micropacemaker via a minimally invasive approach has the potential to pace fetal patients with CCHB and thus delay delivery and allow fetal hydrops to resolve. The challenge remains to establish accepted prenatal interventions capable of successfully managing CCHB in utero until postnatal pacemaker placement is successfully achieved.
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Coração Fetal/diagnóstico por imagem , Bloqueio Cardíaco/congênito , Diagnóstico Pré-Natal/métodos , Feminino , Bloqueio Cardíaco/patologia , Humanos , Gravidez , Cuidado Pré-Natal/métodos , Reprodutibilidade dos TestesRESUMO
Leptospira interrogans (L. interrogans), the causative agent of leptospirosis, is a widespread zoonotic spirochete that lives a dual lifestyle. L. interrogans infects mice, rats, and wildlife in a persistent and asymptomatic fashion, while also causing productive and acute infections in other mammals such as humans and hamsters. Infections in humans can be fatal, accompanied by a cytokine storm and shock-like symptoms. Production of IL-10 has been noted in both rodent and human infections which has led a number of investigators to hypothesize that IL-10 plays a role in the pathogenesis of this disease. To test this hypothesis we have compared bacteremia and the cytokine response of normal and IL-10 deficient C57Bl/6 mice following ip infection with L. interrogans. In normal mice bacterial 16s mRNA was detected in both lung and kidney tissues within a day after infection. Levels of 16s mRNA then dropped in both organs with complete elimination from the lung by day 3 but persistence in the kidney for 7days after infection. In contrast, in IL-10 deficient mice, the organism was eliminated more rapidly from the kidney. We found that infection of both control and IL-10 deficient mice produced similar levels of a number of pro-inflammatory cytokine mRNAs. On the other hand, IFN-γ mRNA was only induced in IL-10 deficient mice. These results support the hypothesis that L. interrogans ability to induce IL-10, which in turn prevents production of IFN-γ and inhibits T cell immunity, may contribute to the persistent growth of this microorganism in the murine kidney.
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Expressão Gênica , Interferon gama/genética , Interleucina-10/deficiência , Rim/imunologia , Rim/metabolismo , Leptospira interrogans/imunologia , Leptospirose/genética , Leptospirose/imunologia , Animais , Anticorpos Antibacterianos/imunologia , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Imunoglobulina M/imunologia , Rim/microbiologia , Leptospirose/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , RNA MensageiroRESUMO
Leptospirosis is a zoonotic disease and is caused by pathogenic species of the Leptospira genus, including Leptospira interrogans (L. interrogans). Humans, domestic and wild animals are susceptible to acute or chronic infection. The innate immune response is a critical defense mechanism against Leptospira interrogans, and has been investigated in mouse models. Murine Toll-like receptors (TLRs) have been shown to be key factors in sensing and responding to L. interrogans infection. Specifically, TLR2, TLR4 and the TLR adaptor molecule MyD88 are essential for host defense against L. interrogans; however, the role of the TLR adaptor molecule TIR-domain-containing adaptor-inducing interferon ß (TRIF) in the response to L. interrogans has not been previously determined. In the present study, TRIF was found to play an important role during leptospiral infection. Following challenge with L. interrogans, Trif(-/-) mice exhibited delayed weight gain compared to wild-type mice. Moreover, Trif(-/-) mice exhibited an increase in L. interrogans burden in the kidneys, lungs, and blood at early time points (less than 7days post infection). Multiple components of the innate immune responses were dampened in response to leptospiral infection including transcription and production of cytokines, and the humoral response, which suggested that TRIF contributes to expression and production of cytokines important for the host defense against L. interrogans.
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Proteínas Adaptadoras de Transporte Vesicular/imunologia , Leptospirose/imunologia , Proteínas Adaptadoras de Transporte Vesicular/genética , Animais , Citocinas/sangue , Citocinas/genética , Citocinas/imunologia , Imunoglobulina A/imunologia , Imunoglobulina M/imunologia , Rim/imunologia , Leptospira/imunologia , Pulmão/imunologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , RNA Mensageiro/metabolismoRESUMO
OBJECTIVE: To design and implement a course in Companion Animal Comparative Counseling that would expose students (N=38) to essential elements of veterinary therapeutics and provide them with the opportunity to apply their knowledge by writing and posting client information sheets (CIS) on an open web site. DESIGN: The elective course was limited to companion animals. Nine different topics were covered over the semester. Class sessions included a didactic component, trivia questions, and field trips. There were 4 major graded assessments: an examination on foundation knowledge, followed by two comparative counseling assessments and evaluation of group-composed CIS. Attendance and participation were also considered. ASSESSMENT: The class learned comparative disease states, how to counsel on common pet prescriptions, where to access informatics about specific veterinary drugs, and how to create their own CIS. CONCLUSION: As pharmacists, these students may have improved their training in veterinary comparative pharmacy.
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Educação em Farmácia , Educação em Veterinária , Avaliação Educacional , Animais , Aconselhamento , Currículo , Cães , Humanos , Internet , Preparações Farmacêuticas/administração & dosagem , Avaliação de Programas e Projetos de Saúde , Estudantes de Farmácia , Inquéritos e Questionários , NavegadorRESUMO
Recombination rate is a complex trait, with genetic and environmental factors shaping observed patterns of variation. Although recent studies have begun to unravel the genetic basis of recombination rate differences between organisms, less attention has focused on the environmental determinants of crossover rates. Here, we test the effect of one ubiquitous environmental pressure-bacterial infection-on global recombination frequency in mammals. We applied MLH1 mapping to assay global crossover rates in male mice infected with the pathogenic bacterium Borrelia burgdorferi, the causative agent of Lyme Disease, and uninfected control animals. Despite ample statistical power to identify biologically relevant differences between infected and uninfected animals, we find no evidence for a global recombination rate response to bacterial infection. Moreover, broad-scale patterns of crossover distribution, including the number of achiasmate bivalents, are not affected by infection status. Although pathogen exposure can plastically increase recombination in some species, our findings suggest that recombination rates in house mice may be resilient to at least some forms of infection stress. This negative result motivates future experiments with alternative house mouse pathogens to evaluate the generality of this conclusion.