TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: The development of human leukocyte antigen (HLA) antibody responses has been associated with worse clinical outcomes, such as bronchiolitis obliterans syndrome (BOS) and death, in lung transplant recipients (LTRs). However, the role of donor-specific HLA antibody (DSA) responses as a risk factor for poor outcomes remains controversial.', 'We prospectively screened 445 LTRs for DSA at our institution at the time of surveillance bronchoscopies for the first 2 years after transplantation between 2003 and 2008, and evaluated clinical outcomes. For this purpose, we used the combination of panel-reactive antibodies (PRA) by enzyme-linked immunosorbent assay (ELISA) and the Luminex single-antigen bead (SAB) assay (One Lambda, Canoga Park, CA).', 'We detected de novo DSA (dnDSA) in 58 of 445 (13%) LTRs in our cohort. Freedom from BOS was significantly reduced in LTRs with dnDSA versus those without dnDSA (p < 0.001). Using a Cox proportional hazards model, the development of dnDSA was associated with a significantly increased hazard ratio (HR = 6.59 [4.53 to 9.59]; p < 0.001) for BOS and high-grade BOS (Stage 2) (HR = 5.76 [3.48 to 9.52]; p < 0.001). Freedom from death was significantly reduced in LTRs with dnDSA (p < 0.001), including mortality attributable to BOS (HR = 9.86 [4.91 to 19.78]; p < 0.001).\Question: Are de novo donor-specific HLA antibodies associated with early and high-grade bronchiolitis obliterans syndrome and death after lung transplantation?

SOLUTION: Taken together, our findings provide evidence that dnDSA is associated with accelerated BOS kinetics and severity, as well as death due to BOS after lung transplantation. In addition, these data support regular monitoring for the development of dnDSA in LTRs and underscore the need for novel strategies to mitigate the increased risk of poor outcomes associated with dnDSA.

PROBLEM: Context: Targeting the energy storing white adipose tissue (WAT) by pharmacological and dietary means in order to promote its conversion to energy expending "brite" cell type holds promise as an anti-obesity approach. Present study was designed to investigate/revisit the effect of capsaicin on adipogenic differentiation with special reference to induction of "brite" phenotype during differentiation of 3T3-L1 preadipocytes.', 'Multiple techniques such as Ca2+ influx assay, Oil Red-O staining, nutrigenomic analysis in preadipocytes and matured adipocytes have been employed to understand the effect of capsaicin at different doses. In addition to in-vitro experiments, in-vivo studies were carried out in high-fat diet (HFD) fed rats treated with resiniferatoxin (RTX) (a TRPV1 agonist) and in mice administered capsaicin.', 'TRPV1 channels are expressed in preadipocytes but not in adipocytes. In preadipocytes, both capsaicin and RTX stimulate Ca2+ influx in dose-dependent manner. This stimulation may be prevented by capsazepine, a TRPV1 antagonist. At lower doses, capsaicin inhibits lipid accumulation and stimulates TRPV1 gene expression, while at higher doses it enhances accumulation of lipids and suppresses expression of its receptor. In doses of 0.1-100 M, capsaicin promotes expression of major pro-adipogenic factor PPAR and some of its downstream targets. In concentrations of 1 M, capsaicin up-regulates anti-adipogenic genes. Low-dose capsaicin treatment of 3T3-L1 preadipocytes differentiating into adipocytes results in increased expression of brown fat cell marker genes. In white adipose of mice, capsaicin administration leads to increase in browning-specific genes. Global TRPV1 ablation (i.p. by RTX administration) leads to increase in locomotor activity with no change in body weight.\Question: Does capsaicin induce '' brite '' phenotype in differentiating 3T3-L1 preadipocytes?

SOLUTION: Our findings suggest the dual modulatory role of capsaicin in adipogenesis. Capsaicin inhibits adipogenesis in 3T3-L1 via TRPV1 activation and induces brown-like phenotype whereas higher doses.

PROBLEM: Context: Uncontrolled intra-abdominal bleeding is a common cause of death in trauma patients in the prehospital and perioperative settings. The detrimental effects of abdominal hypertension are well studied, but the potential therapeutic use of abdominal insufflation for hemostasis has not been fully explored. We measured the effect of abdominal insufflation on blood loss and physiologic outcomes in a swine model of blunt liver injury.', 'Twenty-one anticoagulated swine (32 +/- 3 kg) were anesthesized; laparotomy was performed to localize liver anatomy and to place loose tourniquettes isolating the porta hepatis and supra/infrahepatic vena cava. A captive bolt gun was used to create a grade V hepatic laceration, producing massive parenchymal injury as well as complex tears of the middle and right hepatic veins. Animals were randomized into either control (n = 10) or abdominal insufflation at 20 cm H(2)O pressure (n = 11) groups. Crystalloid was used to maintain a mean arterial pressure of 30 mm Hg. Arterial pressure and other physiologic variables were recorded for 20 minutes. Animals were then sacrificed and blood loss measured.', 'Blood loss was 69% lower in insufflated animals compared with controls (384 +/- 51 versus 1252 +/- 88 cc, p < 0.001). After 20 minutes, insufflated animals had significantly higher mean arterial blood pressure (32.2 +/- 4.2 versus 21.2 +/- 4.0 mm Hg) and lower total resuscitation volume (195 +/- 83 versus 1356 +/- 95 cc). Three pigs died in the control group (30%), whereas no insufflated animals died (p < 0.05).\Question: Does abdominal insufflation decrease blood loss and mortality after porcine liver injury?

SOLUTION:
In a swine model of catastrophic blunt hepatic injury, abdominal insufflation significantly decreased blood loss and mortality.