Track E Implementation Science, Health Systems and Economics

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138412/1/jia218443.pd

Melanoma Cell-Intrinsic PD-1 Receptor Functions Promote Tumor Growth

Summary Therapeutic antibodies targeting programmed cell death 1 (PD-1) activate tumor-specific immunity and have shown remarkable efficacy in the treatment of melanoma. Yet, little is known about tumor cell-intrinsic PD-1 pathway effects. Here, we show that murine and human melanomas contain PD-1-expressing cancer subpopulations and demonstrate that melanoma cell-intrinsic PD-1 promotes tumorigenesis, even in mice lacking adaptive immunity. PD-1 inhibition on melanoma cells by RNAi, blocking antibodies, or mutagenesis of melanoma-PD-1 signaling motifs suppresses tumor growth in immunocompetent, immunocompromised, and PD-1-deficient tumor graft recipient mice. Conversely, melanoma-specific PD-1 overexpression enhances tumorigenicity, as does engagement of melanoma-PD-1 by its ligand, PD-L1, whereas melanoma-PD-L1 inhibition or knockout of host-PD-L1 attenuate growth of PD-1-positive melanomas. Mechanistically, the melanoma-PD-1 receptor modulates downstream effectors of mTOR signaling. Our results identify melanoma cell-intrinsic functions of the PD-1:PD-L1 axis in tumor growth and suggest that blocking melanoma-PD-1 might contribute to the striking clinical efficacy of anti-PD-1 therapy

Hematological parameters in Nile Tilápia, Oreochromis niloticus exposed to sub-letal concentrations of mercury

Mercury toxicity in tilapia, Oreochromis niloticus, (Linnaeus, 1758) was investigated by the hematological parameters after long-term (14 days) exposure to various Hg concentrations (0.02, 0.002, 0.0002mg/L Hg). Test groups were set up with three replicates for each concentration, plus the control group. Blood samples were collected from six individuals for each concentration at 0, 3, 7, 10 and 14 days of exposure. The hematological parameters analyzed were: total red blood cell count (RBC), hemoglobin concentration (Hb), hematocrit (Ht), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), total white blood cell count (WBC) and differential leukocyte counts and total thrombocyte count (Tr). There were no significant differences among the mean hematological values at the different Hg concentrations indicating that Hg at the concentrations studied was not toxic to tilapia.<br>A toxicidade do mercúrio foi avaliada em tilápia, Oreochromis niloticus (Linnaues, 1758) através da análise dos parâmetros hematológicos após exposição a diferentes concentrações sub-letais, durante um período de 14 dias. O bioensaio foi conduzido no laboratório de toxicologia do Instituto de Pesca, SP. Foram utilizados alevinos (12.44 ± 0.84 cm, e 27.13 ± 4.67 g) e aquários com capacidade para 50 litros e preenchidos com água declorada e mais a quantidade de solução de mercúrio (HgCl2) correspondendo as seguintes concentrações: 0,02; 0,002; 0.0002 mg.L-1 Hg. Foram utilizadas 3 repetições de cada concentração e grupo controle. Amostras de sangue foram coletadas de seis animais de cada concentração nos tempos 0, 3, 7, 10 e 14 dias de exposição. Foram avaliados: a contagem de eritrócitos (RBC), concentração de hemoglobina (Hb), hematócrito (Ht), volume corpuscular médio (VCM), hemoglobina corpuscular média (HCM) e concentração de hemoglobina corpuscular média (CHCM), trombócitos totais (Tr), contagem diferencial e total de leucócitos (Lc). Os resultados demonstram que as concentrações de Hg testadas, não alteraram significativamente os parâmetros hematológicos, permitindo concluir que a quantidade de Hg na água não foram suficientes para afetar o quadro hematológico de Oreochromis niloticus

International Nosocomial Infection Control Consortiu (INICC) report, data summary of 43 countries for 2007-2012. Device-associated module

We report the results of an International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2007-December 2012 in 503 intensive care units (ICUs) in Latin America, Asia, Africa, and Europe. During the 6-year study using the Centers for Disease Control and Prevention's (CDC) U.S. National Healthcare Safety Network (NHSN) definitions for device-associated health care–associated infection (DA-HAI), we collected prospective data from 605,310 patients hospitalized in the INICC's ICUs for an aggregate of 3,338,396 days. Although device utilization in the INICC's ICUs was similar to that reported from ICUs in the U.S. in the CDC's NHSN, rates of device-associated nosocomial infection were higher in the ICUs of the INICC hospitals: the pooled rate of central line–associated bloodstream infection in the INICC's ICUs, 4.9 per 1,000 central line days, is nearly 5-fold higher than the 0.9 per 1,000 central line days reported from comparable U.S. ICUs. The overall rate of ventilator-associated pneumonia was also higher (16.8 vs 1.1 per 1,000 ventilator days) as was the rate of catheter-associated urinary tract infection (5.5 vs 1.3 per 1,000 catheter days). Frequencies of resistance of Pseudomonas isolates to amikacin (42.8% vs 10%) and imipenem (42.4% vs 26.1%) and Klebsiella pneumoniae isolates to ceftazidime (71.2% vs 28.8%) and imipenem (19.6% vs 12.8%) were also higher in the INICC's ICUs compared with the ICUs of the CDC's NHSN