HIF-1α is a negative regulator of plasmacytoid DC development in vitro and in vivo.

Hypoxia-inducible factors (HIFs) regulate hematopoiesis in the embryo and maintain hematopoietic stem cell function in the adult. How hypoxia and HIFs contribute to hematopoietic lineage differentiation in the adult is ill defined. Here we provide evidence that HIF-1 limits differentiation of precursors into plasmacytoid dendritic cells (pDCs). Low oxygen up-regulated inhibitor of DNA binding 2 (ID2) and suppressed Flt3-L-induced differentiation of bone marrow cells to pDCs in wild-type but not HIF-1α(fl/fl) LysM-Cre bone marrow cells. Moreover, pDC differentiated normally in hypoxic ID2(-/-) bone marrow cultures. Finally, we observed elevated pDC frequencies in bone marrow, blood, and spleen of HIF-1α(fl/fl) LysM-Cre and ID2(-/-), but not HIF-2α(fl/fl) LysM-Cre mice. Our data indicate that the low oxygen content in the bone marrow might limit pDC development. This might be an environmental mechanism to restrict the numbers of these potentially autoreactive cells.

Apoptotic tumor cells induce IL-27 release from human DCs to activate Treg cells that express CD69 and attenuate cytotoxicity.

Intrinsic immunosuppression is a major obstacle for successful cancer therapy. The mechanisms for the induction and regulation of immunosuppression in humans are ill defined. A microenvironmental component that might prevent antitumor immunity is the presence of dying tumor cells, which are abundant following conventional cancer ablation methods such as chemo- or radiotherapy. Shedding of apoptotic debris and/or secretion of factors to the tumor bed or draining lymph nodes thus might have a profound impact on professional phagocytes, such as DCs, and subsequent priming of lymphocytes. Here, we exposed human DCs to supernatants of live, apoptotic, or necrotic human breast cancer cells and cocultured them with autologous T cells. Priming with apoptotic debris prevented DCs from establishing cytotoxicity toward live human tumor cells by inducing a Treg-cell population, defined by coexpression of CD39 and CD69. Immunosuppression via Treg cells was transferable and required the release of sphingosine-1-phosphate (S1P) from apoptotic cells, acting via S1P receptor 4 on DCs to induce IL-27 secretion. We propose that CD69 expression on CD39(+) Treg cells enables them to interact with CD73-expressing CD8(+) T cells to generate adenosine, thereby suppressing cytotoxicity. These findings aid the understanding of how dying tumor cells limit antitumor immunity.

Characteristics of Iraqi Patients Treated During Operation Inherent Resolve by a Forward Surgical Team.

INTRODUCTION: The combat experience during the re-entry stages of Operation Inherent Resolve was distinct from other recent operations, but there is no published literature regarding these "initial entry operations" experiences among forward surgical teams (FSTs) deployed to Role 2 facilities A descriptive analysis of patients treated by FSTs may provide valuable information for Role 2 surgical teams preparing to deploy in support of initial entry operations. The purpose of this analysis was to describe injury mechanism, wounding patterns and interventions performed by a small FST in the re-entry phase in Iraq. MATERIALS AND METHODS: From July 17, 2015 to January 31, 2016, a split surgical team with two surgeons and an ER physician documented care for all patients treated by their FST located in Iraq. Given their austere environment, FSTs have limited holding capacity, blood supply, and ability to triage and perform advanced procedures. Patients, who arrived to the Role 2 in asystole, were ineligible for the study. The patient population was Iraqi Security Forces as well as Iraqi civilians. No follow-up data were obtained. Using descriptive statistics, we described the basic demographics, health status, blood utilization, injury severity, and injury pattern of the patient population. RESULTS: The final study population included 300 Iraqi casualties. The majority of patients (96%) were discharged alive. Many patients were 16 years or older (96%), male (96%), Iraqi soldiers (86%), and injured during battle (96%). Over one-third of patients (35%) had a form of metabolic acidosis, 7% were hypothermic, and 18% were in shock at admission. The median amount of blood products used was 6 (interquartile ranges (IQR) = 2-12) units, while the median red blood cells:fresh frozen plasma ratio was 1.2:1. Six or more units of blood were given to 67 (22%) patients. The top three diagnoses were laceration (n = 197, 21%), penetrating injury (n = 185, 19%), and fracture (n = 174, 18%). A high number of injuries occurred in the extremities/pelvis and buttocks (n = 360, 38%) and in the abdomen and pelvic contents (n = 145, 15%). Over a quarter of patients (26%) had critical injuries (i.e., military injury severity score ≥25). CONCLUSIONS: Given the Role 2 configuration, these results demonstrate FSTs must be capable of managing critically ill patients with markedly limited resources. This management will include general operations in both adult and pediatric patients, resuscitation with a limited blood supply, and patient assessment with minimal to no diagnostic tools. This analysis can inform resident training, pre-deployment training, as well as sustainment training for surgeons after residency.

Pneumoperitoneum due to gastric perforation after cardiopulmonary resuscitation: case report.

BACKGROUND: Pneumoperitoneum after cardiopulmonary resuscitation may be due to mediastinal air tracking into the peritoneal cavity via the diaphragmatic hiatus or to gastric perforation. CASE REPORT: A 79-year-old woman received Advanced Cardiac Life Support measures in the intensive care unit. Chest compressions and endotracheal intubation were performed; a stable cardiac rhythm and perfusion were restored. A chest radiograph after resuscitation revealed pneumoperitoneum without pneumomediastinum. The patient underwent laparotomy; a 6-cm perforation of the posterior gastric wall along the lesser curve was detected and repaired. CONCLUSION: Gastric perforation after cardiopulmonary resuscitation should be suspected when chest radiographs obtained after resuscitation show pneumo-peritoneum without pneumomediastinum. Prompt laparotomy allows detection of gastric perforations and decreases the morbidity associated with rupture of a hollow organ. The incidence of gastric perforation after cardiopulmonary resuscitation may be decreased with early endotracheal intubation, avoidance of esophageal intubation, and expeditious placement of an orogastric tube.

Evaluation of Nonvolatile Chemistry Affecting Sensory Bitterness Intensity of Highly Hopped Beers.

The range of different nonvolatile constituents extracted from hops in highly hopped beers suggests that isohumulones may not be the sole contributor to beers' bitterness. Among brewers producing hop-forward beer styles, there is concern that the bitterness unit (BU) is no longer an accurate predictor of beer bitterness. This study examined factors within the beer matrix that influence sensory bitterness perception in highly hopped beers. Over 120 commercial beers were evaluated using sensory and instrumental techniques. Chemical analysis consisted of the BU via spectrophotometry, hop acids via high-performance liquid chromatography, total polyphenols via spectrophotometry, and alcohol content plus real extract via an Alcolyzer. Sensory analysis was conducted over two studies, and the beers' overall bitterness intensities were rated using a 0-20 scale. This study identified that the BU measurement predicts sensory bitterness with a nonlinear response, and it proposed an alternative approach to predicting bitterness based on isohumulones, humulinones, and ethanol concentrations. The study also revealed the importance of oxidized hop acids, humulinones, as a significant contributor to beer bitterness intensity.

Accuracy and Reliability of Triage at the Point of Injury During Operation Enduring Freedom.

BACKGROUND: Accurate point-of-injury reports and casualty evacuation requests allow for optimal resource utilization. However, the accuracy of these reports has not been previously studied. METHODS: All trauma patients treated at one of three forward surgical elements (FSE) in Western Afghanistan during May-August 2012 were prospectively included. North American Treaty Organization (NATO) 9-line medical evacuation request and mechanism, injuries, signs, and treatments (MIST) reports were compared to the initial findings on arrival to the FSE. RESULTS: There were 179 casualty evacuation reports and 298 patients. NATO 9-line and/or MIST reports were available for 70% of these. Triage was accurate for 77%, but there was 17% overtriage and 6% undertriage (k = .619). The number of patients was accurate in 95% of reports, the mechanism of injury was accurate for 98%, and the body region involved was accurate for 92% (k = .850, .943, and .870, respectively). There was no difference between the mean vital signs at the point of injury or on arrival at the FSE. When analyzed individually, however, there was no correlation between each casualty's pulse, mean arterial pressure, or respiratory rate between the two time points. DISCUSSION: There was a high degree of correlation between the triage category of casualty evacuation reports and the patient's actual medical needs. There was also a highly significant association with the number of patients, mechanism of injury, and bodily injuries. However, there was discordance between the vital signs at an individual level, which may represent regression toward the resuscitation threshold.

Presacral epidermoid cyst in a male: a case report and literature review.

Presacral cysts are an uncommon entity most often found incidentally in women. These tumors can arise from any of the 1 or more cell lines present in the presacral space during embryogenesis. We present a case of a 46-year-old male patient who was found to have a well-circumscribed presacral mass on computed tomography (CT) scan, which was obtained for his complaint of vague lower back pain. He underwent transabdominal excision, and pathology revealed a presacral epidermoid cyst filled with keratinaceous material. Presacral cysts are rare, especially in male patients. These tumors originate from an embryologic error during development. Because of the risk of infection and malignant transformation, they should be excised. Surgical options include a posterior approach, transabdominal approach, combined approach, or transrectal approach. The approach is dictated by the tumor size, location, presence of malignancy, and bony invasion.

Enhanced activity during associative encoding in the affected hippocampus in right temporal lobe epilepsy patients.

Mnestic deficits represent the core cognitive impairment of patients with temporal lobe epilepsy (TLE), irrespective of the existence of overt morphological lesions. Compared to controls, patients with symptomatic TLE show altered functional activation patterns in fMRI studies on memory processes. But, so far, such studies have rarely investigated patients with temporal lobe epilepsy of unknown cause. Therefore, in the current study, a small sample of 6 right TLE patients with normal structural MRIs was compared to controls with respect to brain activity during encoding of face-name associations using fMRI. Compared to controls, patients retrieved fewer face-name associations correctly, but showed significantly greater activation of the affected hippocampus for successfully encoded stimuli. Therefore, higher hippocampal activation seems necessary for successful encoding of associations in patients compared to controls. But, this process is not entirely successful since the patients cannot achieve the same performance as controls. In conclusion, the hyperactivation of the hippocampus might represent a compensational but inefficient process.

Fate and effects of azinphos-methyl in a flow through wetland in South Africa.

Our knowledge about the effectiveness of constructed wetlands in retaining agricultural nonpoint-source pesticide pollution is limited. A 0.44-ha vegetated wetland built along a tributary of the Lourens River, Western Cape, South Africa, was studied to ascertain the retention, fate, and effects of spray drift-borne azinphos-methyl (AZP). Composite water samples taken at the inlet and outlet during five spray drift trials in summer 2000 and 2001 revealed an overall reduction of AZP levels by 90 +/- 1% and a retention of AZP mass by 61 +/- 5%. Samples were collected at the inlet outlet, and four platforms within the wetland to determine the fate and effect of AZP in the wetland after direct spray drift deposition in the tributary 200 m upstream of the inlet. Peak concentrations of AZP decreased, and the duration of exposure increased from inlet (0.73 microg/L; 9 h) via platforms 1 and 4 to outlet (0.08 microg/L; 16 h). AZP sorbed to plants or plant surfaces, leading to a peak concentration of 6.8 microg/kg dw. The living plant biomass accounted for 10.5% of the AZP mass initially retained in the wetland, indicating processes such as volatilization, photolysis, hydrolysis, or metabolic degradation as being very important AZP was not detected in sediments. Water samples taken along two 10-m transects situated perpendicular to the shore indicated a homogeneous horizontal distribution of the pesticide: 0.23 +/- 0.02 and 0.14 +/- 0.04 microg/L (n = 5), respectively. Both Copepoda (p = 0.019) and Cladocere (p = 0.027) decreased significantly 6 h postdeposition and remained at reduced densities for at least 7 d. In parallel, the chlorophyll a concentration showed an increase, although not significant, within 6 h of spray deposition. The study highlights the potential of constructed wetlands as a risk-mitigation strategy for spray drift-related pesticide pollution.