Tumor-Experienced Human NK Cells Express High Levels of PD-L1 and Inhibit CD8+ T Cell Proliferation.

Natural Killer (NK) cells play a key role in cancer immunosurveillance. However, NK cells from cancer patients display an altered phenotype and impaired effector functions. In addition, evidence of a regulatory role for NK cells is emerging in diverse models of viral infection, transplantation, and autoimmunity. Here, we analyzed clear cell renal cell carcinoma (ccRCC) datasets from The Cancer Genome Atlas (TCGA) and observed that a higher expression of NK cell signature genes is associated with reduced survival. Analysis of fresh tumor samples from ccRCC patients unraveled the presence of a high frequency of tumor-infiltrating PD-L1+ NK cells, suggesting that these NK cells might exhibit immunoregulatory functions. In vitro, PD-L1 expression was induced on NK cells from healthy donors (HD) upon direct tumor cell recognition through NKG2D and was further up-regulated by monocyte-derived IL-18. Moreover, in vitro generated PD-L1hi NK cells displayed an activated phenotype and enhanced effector functions compared to PD-L1- NK cells, but simultaneously, they directly inhibited CD8+ T cell proliferation in a PD-L1-dependent manner. Our results suggest that tumors might drive the development of PD-L1-expressing NK cells that acquire immunoregulatory functions in humans. Hence, rational manipulation of these regulatory cells emerges as a possibility that may lead to improved anti-tumor immunity in cancer patients.

The relation between glycemic control and HDL-C in type 2 diabetes: a preliminary step forward?

Low high-density lipoprotein cholesterol (HDL-C) levels are associated with cardiovascular (CV) disease in type 2 diabetes (T2D). Unfortunately available drugs to increase HDL-C have failed to demonstrate a reduction in CV risk. We assessed the effect of improving glycemic control on HDL-C levels. A 6-month intervention resulted in significant improvement in HbA1c but not in HDL-C levels. However, when considering the subgroup of subjects with low levels of HDL-C at baseline, we found a significant and inverse relation between improvement in HbA1c and HDL-C levels.

Sigmoid colon injury due to blunt abdominal trauma. A case report.

We present a case of sigmoid colon injury after blunt abdominal trauma. The patient was submitted to sigmoid resection with primary end-to-end colo-colic anastomosis. He died 22 days after operation with septic shock and acute respiratory failure. Post-mortem examination showed left lung generalized pneumonia with no signs of intra-abdominal pathology; colo-colic anastomosis was intact. We reviewed the literature about the management of this rare trauma.

Inhibition of Amazon deforestation and fire by parks and indigenous lands.

Conservation scientists generally agree that many types of protected areas will be needed to protect tropical forests. But little is known of the comparative performance of inhabited and uninhabited reserves in slowing the most extreme form of forest disturbance: conversion to agriculture. We used satellite-based maps of land cover and fire occurrence in the Brazilian Amazon to compare the performance of large (> 10,000 ha) uninhabited (parks) and inhabited (indigenous lands, extractive reserves, and national forests) reserves. Reserves significantly reduced both deforestation and fire. Deforestation was 1.7 (extractive reserves) to 20 (parks) times higher along the outside versus the inside of the reserve perimeters and fire occurrence was 4 (indigenous lands) to 9 (national forests) times higher. No strong difference in the inhibition of deforestation (p = 0. 11) or fire (p = 0.34) was found between parks and indigenous lands. However, uninhabited reserves tended to be located away from areas of high deforestation and burning rates. In contrast, indigenous lands were often created in response to frontier expansion, and many prevented deforestation completely despite high rates of deforestation along their boundaries. The inhibitory effect of indigenous lands on deforestation was strong after centuries of contact with the national society and was not correlated with indigenous population density. Indigenous lands occupy one-fifth of the Brazilian Amazon-five times the area under protection in parks--and are currently the most important barrier to Amazon deforestation. As the protected-area network expands from 36% to 41% of the Brazilian Amazon over the coming years, the greatest challenge will be successful reserve implementation in high-risk areas of frontier expansion as indigenous lands are strengthened. This success will depend on a broad base of political support.

Effect of haemorrhage on plasma propofol concentrations in a patient undergoing orthotopic liver transplantation.

We report a patient who underwent repeat orthotopic liver transplantation complicated by intraoperative blood loss of more than 59 litre. During liver transplantation, a constant rate propofol infusion was given and plasma samples were obtained throughout the procedure for propofol assay. Before the anhepatic phase of the procedure, plasma propofol concentrations reached a plateau at 1 microgram ml-1, and these concentrations were consistent with those predicted using a pharmacokinetic model. During the anhepatic phase of surgery, serum propofol concentrations increased progressively and exceeded those predicted by the pharmacokinetic model. Large intravascular fluid shifts associated with blood loss and subsequent blood replacement influenced plasma propofol concentrations observed in this patient.

Mental health professionals' attire.

OBJECTIVE: Our aim was to obtain mental health patients' views on psychiatrists' and case managers' attire. METHODS: Eighty-six patients treated at a community mental health service were surveyed. Various types of commonly worn attire were listed. Respondents were asked to choose what they thought was most appropriate for their psychiatrist and case manager to wear. RESULTS: Over 50% of respondents felt that psychiatrist or case manager dress was not an important issue. However, those who felt that it was preferred less formal attire. CONCLUSIONS: Psychiatrists and case managers in a community mental health team could consider adopting less formal attire. This conclusion is limited by the small sample and may be relevant to rural areas only. Further research is needed in urban centres. Implications of these findings are discussed.

[Role of noninvasive diagnosis in cardiac echinococcosis: pulmonary embolization from right atrial localization]. / Ruolo della diagnostica non invasiva nella echinococcosi cardiaca: embolizzazione polmonare da localizzazione atriale destra.

We report the case of a young woman died of pulmonary embolism from a hydatid cyst of the right atrium. Cardiac involvement in hydatid disease is rare, particularly when it is intracavitary and not intramyocardial. The role of invasive and noninvasive techniques, such as echocardiography, computed tomography and nuclear magnetic resonance, is discussed.

Sporotrichosis of the knee. A case report.

Articular infections due to the fungus Sporothrix schenkii are rare. Only 46 cases of Sporotrichosis arthritis have been well-documented in the English literature to date. The presentation may be limited to a monoarticular synovitis, hence the diagnosis may be confused with other more common causes resulting in costly delays in proper treatment. Reported is a case of Sporotrichosis of the knee misdiagnosed multiple times over a three-year period yet illustrating important clinical features that could lead to earlier diagnosis and management.