RESUMO
A 56-year-old man sought care from a primary care physician (PCP) 5 days after lifting a heavy box produced acute, isolated lumbar pain. The PCP diagnosed a lumbar disc herniation and referred the patient to physical therapy without diagnostic imaging. Due to the presence of multiple red flags leading up to and during examination, the patient was transferred to the emergency department for further evaluation. Magnetic resonance imaging revealed a spinal epidural abscess with an associated multiloculated abscess within the adjacent left paraspinal muscles. J Orthop Sports Phys Ther 2019;49(6):482. doi:10.2519/jospt.2019.8456.
Assuntos
Abscesso/diagnóstico por imagem , Dor Lombar/diagnóstico por imagem , Músculos Paraespinais/diagnóstico por imagem , Abscesso/tratamento farmacológico , Abscesso/microbiologia , Antibacterianos/uso terapêutico , Diagnóstico Diferencial , Humanos , Dor Lombar/tratamento farmacológico , Dor Lombar/microbiologia , Masculino , Pessoa de Meia-Idade , Oxacilina/uso terapêutico , Músculos Paraespinais/efeitos dos fármacos , Músculos Paraespinais/microbiologia , Rifampina/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureusRESUMO
Male and female mammals undergo profound hormonal changes during pregnancy, some of which are sufficiently dramatic to influence offspring survival. In order to understand the proximate mechanisms regulating the variability in reproductive success within and between individuals, we monitored changes in fecal corticosteroid concentrations over the reproductive cycle in male and female oldfield mice (Peromyscus polionotus subgriseus) to test whether corticosteroid concentrations during pregnancy were associated with offspring survival. In females that successfully raised litters to weaning, fecal corticosteroid concentrations were low until mid-gestation and increased significantly towards term; in females that did not raise their pups to weaning, fecal corticosteroid concentrations were significantly higher at mid-gestation, and remained high until late gestation. The difference in fecal corticosteroid concentrations at mid-gestation between successful and unsuccessful females can be explained by the fact that successful females were lactating. Lactation has been associated with a down-regulation of the hypothalamic-pituitary-adrenal (HPA) axis and, accordingly, a decrease in plasma corticosterone (CORT) in several species, including humans. Males that successfully raised their litters had low fecal corticosteroid concentrations throughout their partner's pregnancy. Unsuccessful males, however, had significantly higher fecal corticosteroid concentrations at term than males that raised their pups to weaning. While these preliminary data require further investigation, we suggest that pre-partum fecal corticosteroid concentrations in males were responsible for the variability in reproductive success.
Assuntos
Corticosteroides/metabolismo , Peromyscus/fisiologia , Gravidez/metabolismo , Reprodução/fisiologia , Animais , Comportamento Animal , Fezes , Feminino , Masculino , Camundongos , Radioimunoensaio/métodosRESUMO
Bacterial antimicrobial resistance is an escalating public health threat, yet the current antimicrobial pipeline remains alarmingly depleted, making the development of new antimicrobials an urgent need. Here, we identify a novel, potent, imidazoline antimicrobial compound, SKI-356313, with bactericidal activity against Mycobacterium tuberculosis and Gram-positive cocci, including vancomycin-resistant Enterococcus faecium (VRE) and methicillin-resistant Staphylococcus aureus (MRSA). SKI-356313 is active in murine models of Streptococcus pneumoniae and MRSA infection and is potently bactericidal for both replicating and nonreplicating M. tuberculosis. Using a combination of genetics, whole genome sequencing, and a novel target ID approach using real time imaging of core macromolecular biosynthesis, we show that SKI-356313 inhibits DNA replication and displaces the replisome from the bacterial nucleoid. These results identify a new antimicrobial scaffold with a novel mechanism of action and potential therapeutic utility against nonreplicating M. tuberculosis and antibiotic resistant Gram-positive cocci.