Nucleolar stress enhances lytic reactivation of the Kaposi's sarcoma-associated herpesvirus.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a human tumorigenic virus exhibiting two forms of infection, latent and lytic. Latent infection is abortive and allows the virus to establish lifelong infection, while lytic infection is productive, and is needed for virus dissemination within the host and between hosts. Latent infection may reactivate and switch towards the lytic cycle. This switch is a critical step in the maintenance of long-term infection and for the development of KSHV-related neoplasms. In this study, we examined the effect of nucleolar stress, manifested by failure in ribosome biogenesis or function and often coupled with p53 activation, on lytic reactivation of KSHV. To this end, we induced nucleolar stress by treatment with Actinomycin D, CX-5461 or BMH-21. Treatment with these compounds alone did not induce the lytic cycle. However, enhancement of the lytic cycle by these compounds was evident when combined with expression of the viral protein K-Rta. Further experiments employing combined treatments with Nutlin-3, knock-down of p53 and isogenic p53+/+ and p53-/- cells indicated that the enhancement of lytic reactivation by nucleolar stress does not depend on p53. Thus, our study identifies nucleolar stress as a novel regulator of KSHV infection, which synergizes with K-Rta expression to increase lytic reactivation. This suggests that certain therapeutic interventions, which induce nucleolar stress, may affect the outcome of KSHV infection.

Triage and air evacuation strategy for mass casualty events: a model based on combat experience.

BACKGROUND: Management of combat casualties should optimize outcomes by appropriate patient triage, prehospital care, and rapid transport to the most capable medical facility, while avoiding overwhelming individual facilities. METHODS: Planning the medical support for the campaign was done by the medical department of the IDF Southern command in cohort with the medical department of the Homefront command. Data collection and analysis were done by the Trauma Branch of the Medical corp. RESULTS: 339 soldiers were injured, among them were 10 fatalities. Five hospitals received casualties, although the 2 regional hospitals received 84% of the primary evacuation load. The majority of urgently injured soldiers (90%) were evacuated by air, as opposed to 59% of non-urgently injured soldiers. CONCLUSIONS: In a cross border setting, airlifting the urgent casualties to farther away level I trauma centers provides appropriate care for them, while not crossing the "surge capacity" line for the near-by medical centers.

QuikClot Combat Gauze use for hemorrhage control in military trauma: January 2009 Israel Defense Force experience in the Gaza Strip--a preliminary report of 14 cases.

BACKGROUND: Standard gauze field dressings and direct pressure occasionally are inadequate for the control of hemorrhage. QuikClot® Combat Gauze™ (QCG) combines surgical gauze with an inorganic material and is approved by the Food and Drug Administration and by the Israeli Standards Institute for external hemorrhage control. The purpose of this article is to report clinical use of this dressing during Operation Cast Lead in the Gaza strip during January 2009. METHODS: QuikClot Combat Gauze and the QCG guidelines were issued to advanced life support (ALS) providers during the preparations for the Operation. All cases of injuries involving hemorrhage were reviewed, as well as interviews with the ALS providers (physicians and paramedics) and injured soldiers. RESULTS: Fourteen uses of QCG were reported and reviewed (out of a total of 56 hemostatic interventions in 35 cases). Dressings were applied to injuries to the head, neck, axilla, buttocks, abdomen, back, and pelvis in 10 cases, and to extremities in four cases. In 13 cases (93%), injuries were caused by blast or gunshot mechanisms. The success rate was reported as 79% (11/14). Failure to control hemorrhage was reported in three cases in three different locations: neck, buttock, and thigh. All failures were attributed to severe soft tissue and vascular injuries. No complications or adverse events were reported. CONCLUSIONS: This report on the clinical field use of the QCG dressing by ALS providers suggests that it is an effective and safe product, and applicable for prehospital treatment of combat casualties. This report further suggests that QCG should be issued to medics as well as ALS providers. Larger clinical investigations are needed to confirm these findings.

Anatomic distribution of bullet head injuries in combat fatalities.

BACKGROUND: Gun-shot wound head injury comprises a substantial fraction of combat injuries and a major cause of death in the battlefield. Current shielding gear is totally ineffective against bullets, because bullet-proof materials are too heavy to be worn on the head. The aim of this work was to describe the anatomic distribution of bullet entry wounds to the head in combat fatalities and to discern whether distribution is random (null hypothesis) or not. METHODS: We retrospectively examined the forensic external examination reports of all Israeli Defense Forces combat fatalities during the years 2000 to 2004, the Second Lebanon War (2006), and Operation Cast Lead (2009) and mapped the exact anatomic location of all bullet entry wounds to the calvaria. RESULTS: We found 76 gun-shot entry wounds to the heads of 49 fatalities. Among these wounds, the occipital and anterior-temporal regions were found to be hit significantly more often than expected compared with their relative surface area (p < 0.001 and p < 0.001, respectively). Fifty-five percent of all injuries occurred within 15% of the surface area of skull. CONCLUSIONS: These findings imply that gun-shot entry wounds to the head are unevenly distributed. A partially bullet-proof protective helmet may prevent a substantial fraction of injuries (and fatalities) without a significant weight addition to the helmet.