RESUMO
We investigated mechanisms by which TLR9 signaling promoted the development of the protective response to Cryptococcus neoformans in mice with cryptococcal pneumonia. The afferent (week 1) and efferent (week 3) phase immune parameters were analyzed in the infected wild-type (TLR9(+/+)) and TLR-deficient (TLR9(-/-)) mice. TLR9 deletion diminished 1) accumulation and activation of CD11b(+) dendritic cells (DCs), 2) the induction of IFN-γ and CCR2 chemokines CCL7, CCL12, but not CCL2, at week 1, and 3) pulmonary accumulation and activation of the major effector cells CD4(+) and CD8(+) T cells, CD11b(+) lung DCs, and exudate macrophages at week 3. The significance of CCL7 induction downstream of TLR9 signaling was investigated by determining whether CCL7 reconstitution would improve immunological parameters in C. neoformans-infected TLR9(-/-) mice. Early reconstitution with CCL7 1) improved accumulation and activation of CD11b(+) DCs at week 1, 2) restored early IFN-γ production in the lungs, and 3) restored the accumulation of major effector cell subsets. CCL7 administration abolished the difference in lung fungal burdens between TLR9(+/+) and TLR9(-/-) mice at week 3; however, significant reduction of fungal burdens between PBS- and CCL7-treated mice has not been observed, suggesting that additional mechanism(s) apart from early CCL7 induction contribute to optimal fungal clearance in TLR9(+/+) mice. Collectively, we show that TLR9 signaling during the afferent phase contributes to the development of protective immunity by promoting the early induction of CCL7 and IFN-γ and the subsequent early recruitment and activation of DCs and additional effector cells in mice with cryptococcal pneumonia.
Assuntos
Quimiocina CCL7/imunologia , Criptococose/imunologia , Cryptococcus neoformans , Pulmão/imunologia , Pneumonia/imunologia , Animais , Antígeno CD11b/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Comunicação Celular/imunologia , Contagem de Colônia Microbiana , Criptococose/complicações , Criptococose/microbiologia , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Feminino , Interferon gama/imunologia , Pulmão/metabolismo , Pulmão/microbiologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Proteínas Quimioatraentes de Monócitos/imunologia , Pneumonia/complicações , Pneumonia/microbiologia , Transdução de Sinais , Receptor Toll-Like 9/deficiência , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/imunologiaRESUMO
BACKGROUND AND OBJECTIVES: The proper documentation of Hierarchical Condition Category (HCC) codes is essential for risk-adjusted reimbursement, chart accuracy, and clinical communication within primary care, but represents a significant training gap in resident education. Our goal was to improve the understanding and confidence level of family medicine residents with HCC coding during outpatient primary care visits. METHODS: We developed and distributed a web-based, interactive module to family medicine residents at our academic institution. We assessed module impact through pre- and postsurveys focusing on knowledge, confidence, and experience with HCC coding. RESULTS: Twenty-eight of 48 preeducation surveys were returned (response rate of 58%), including 16 junior (PGY-1-2) and 12 senior (PGY-3-4) residents. A majority of residents answered each HCC knowledge question correctly. Median baseline confidence with HCC coding for all respondents was 4 (interquartile range [IQR]: 2, 6; scale 0-10; 10=most confident): senior residents 6 (IQR: 5, 7) versus junior residents 2 (IQR: 2, 4). Forty-six percent of respondents noted some previous education on HCC codes, including 75% of senior vs 25% of junior residents. Twenty-six residents completed the educational module. Posttest surveys (n=5, response rate: 19%) demonstrated median confidence of 7 (IQR: 4, 8.5). CONCLUSIONS: Family medicine residents displayed a high degree of knowledge but low confidence with HCC coding. Posteducation surveys suggest the possibility of a positive impact of our e-module, though further intervention roll out and data collection are needed to evaluate this effect.
Assuntos
Medicina de Família e Comunidade , Internato e Residência , Competência Clínica , Documentação , Humanos , Internet , Inquéritos e QuestionáriosRESUMO
Diet and nutrition are moving to the forefront of modern primary and preventive care to help address the rising burden of chronic diseases among the general population. Such a movement has yet to occur formally across the field of transplantation. We therefore looked to establish the current base of knowledge regarding diet, nutrition and solid-organ transplantation. A limited number of focused studies looking into the dietary habits of solid-organ transplant patients have been performed and many of the available studies have detailed the nutritional status in the peri-operative period. Frequently described, however, is the heavy incidence of metabolic abnormalities, such as obesity, dyslipidemia and diabetes, occurring after solid-organ transplantation. Optimistically, several studies have noted improvement in several metabolic abnormalities with the use of dietary interventions in the post-transplant period. Despite these positive results, few consensus guidelines for post-transplant diet have been established and nutritional support among transplant programs remains limited. Although there are many hurdles to implementation of detailed dietary recommendations and nutritional support for transplant patients, creating such programs and guidelines could dramatically impact long-term outcomes and burden of chronic metabolic disease for transplant recipients.