This course could be an effective model, and one that other institutions could employ, for improving communication skills and empathy in the next generation of health care professionals. Next steps include advocating for communication skills training to be embedded throughout the curriculum of a four-year medical school program.
To characterize the role of neurotrophin receptors on macrophages, we investigated the ability of nerve growth factor (NGF) and its precursor, proNGF, to regulate human macrophage phenotype. The p75 neurotrophin receptor (p75NTR) and TrkA were concentrated within overlapping domains on membrane ruffles. NGF stimulation of macrophages increased membrane ruffling, calcium spiking, phagocytosis and growth factor secretion. In contrast, proNGF induced podosome formation, increased migration, suppressed calcium spikes and increased neurotoxin secretion. These results demonstrate opposing roles of NGF and proNGF in macrophage regulation providing new avenues for pharmacological intervention during neuroinflammation.
Objective To assess the role of HIV and monocytes/macrophages in adipose tissue dysregulation. Methods Cross-sectional study in 5 groups: HIV seronegative, HIV+ antiretroviral therapy (ART)-naive, HIV+ nonlipoatrophic on zidovudine- and/or stavudine-containing ART, HIV+ lipoatrophic on similar ART, and HIV+ on abacavir- or tenofovir-containing ART. HIV DNA in circulating monocyte subsets was quantitated by real-time polymerase chain reaction. Biopsied subcutaneous fat was examined for macrophage content by CD68 staining. Isolated adipocytes and macrophages were cultured and the supernatant assayed for secretory products by Luminex multiplex cytokine technology. Results Sixty-nine subjects were enrolled. Lipoatrophic subjects had higher median HIV DNA levels (270.5 copies/106 cells) in circulating peripheral CD14+CD16+ co-expressing monocyte subsets compared with subjects who were ART-naive (25.0 copies), non-lipoatrophic (15.0 copies), or on abacavir/tenofovir (57.5 copies), P < 0.01. Group differences in adipocytes and adipose macrophage content were marginal. Although adipocyte secretory products were similar, HIV-infected subjects had higher adipose macrophage–derived interleukin (IL)-12p40, IL-6, IL-8, and monocyte inflammatory protein 1 alpha and lower eotaxin and interferon gamma levels than HIV seronegative subjects (P < 0.05). Within HIV-infected subjects, adipose macrophage secretory products were comparable between subjects naive with ART versus those on ART. Conclusions Circulating HIV-infected and proinflammatory CD14+CD16+ monocyte subsets contribute to the pathogenesis of HIV-associated lipoatrophy. Among HIV-infected individuals, macrophages, rather than adipocytes, are the primary source of low-grade inflammation in subcutaneous adipose tissue. HIV infection modifies these macrophages to a more proinflammatory phenotype, and these changes are not substantially mitigated by the use of ART.
Epithelial cells of the gut, antennal glands, integument, and gills of crustaceans regulate the movements of ions into and across these structures and thereby influence the concentrations of ions in the hemolymph. Specific transport proteins serving cations and anions are found on apical and basolateral cell membranes of epithelia in these tissues. In recent years, a considerable research effort has been directed at elucidating their physiological and molecular properties and relating these characteristics to the overall biology of the organisms. Efforts to describe ion transport in crustaceans have focused on the membrane transfer properties of Na+/H+ exchange, calcium uptake as it relates to the molt cycle, heavy metal sequestration and detoxification, and anion movements into and across epithelial cells. In addition to defining the properties and mechanisms of cation movements across specific cell borders, work over the past 5 yr has also centered on defining the molecular nature of certain transport proteins such as the Na+/H+ exchanger in gill and gut tissues. Monovalent anion transport proteins of the gills and gut have received attention as they relate to osmotic and ionic balance in euryhaline species. Divalent anion secretion events of the gut have been defined relative to potential roles they may have in hyporegulation of the blood and in hepatopancreatic detoxification events involving complexation with cationic metals.
Vocalizations produced by a neonate male bottlenosed dolphin during the first 5 days after birth were compared to the vocalizations of two adult female bottlenosed dolphins housed in the same enclosure. Audio and video recordings were made of the focal mother and her calf from birth. Calf vocalizations were identified as sounds that occurred concurrently with the emission of bubble streams by the calf. Adult vocalizations were recorded prior to, during, and after the birth of the calf. Initial calf vocalizations were of a single sound type varying in duration from 0.35 to 1.4 s. The sounds produced by the calf were broadband signals with spectral energy from approximately 0.5 to 9 kHz and peak energy levels between 1.2 and 1.6 kHz. Spectrographic and aural analyses of sounds made by the calf and adults revealed that calf vocalizations were more similar to the burst-pulse sounds of both adults than to any other vocalizations of either dolphin. Evolution of the calf’s sounds toward narrow-band frequency-modulated whistles was evident in later recordings. These results contrast with previous reports that bottlenosed dolphins produce whistles from birth and elucidate relationships between the production of whistles and burst-pulse sounds and their ontogeny.
In the current era of highly active antiretroviral therapy (HAART), the prevalence of HIV-associated non-Hodgkin lymphoma (H-NHL) is not as high as in the beginning of the acquired immunodeficiency syndrome (AIDS) epidemic, but still remains above that of non-HIV-infected individuals. Therefore, the epidemiology suggests that the pathogenesis of H-NHL may be multifactoral, involving the interaction of the immune system with HIV or other pathogens. Although HIV is a retrovirus, it is not characterized with the typical oncogenic potential associated with insertional mutagenesis. HIV integration occurs as a necessary step in the life cycle allowing for replication and transcription of the viral genome to take place. While HIV is thought to integrate randomly, more recent studies have suggested that integration occasionally occurs in a less random fashion. While the majority of H-NHL may be secondary to immune dysfunction, this non-random integration may be a factor leading to pathogenesis of a small subset of H-NHL since the pathways involved in malignancies usually require an accumulation of abnormalities leading to proliferation and transformation. A common element among lymphomas in this setting of immune dysfunction is the inability to control a pathogen that acts as an ongoing immune activator. Thus, an increased risk of H-NHL emerges from the combination of immunodeficiency, increased immune activation and possible HIV insertional mutagenesis. The focus of this review will be on the role viral pathogenesis plays in oncogenic transformation.
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