MiR-342 controls Mycobacterium tuberculosis susceptibility by modulating inflammation and cell death.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that places a heavy strain on public health. Host susceptibility to Mtb is modulated by macrophages, which regulate the balance between cell apoptosis and necrosis. However, the role of molecular switches that modulate apoptosis and necrosis during Mtb infection remains unclear. Here, we show that Mtb-susceptible mice and TB patients have relatively low miR-342-3p expression, while mice with miR-342-3p overexpression are more resistant to Mtb. We demonstrate that the miR-342-3p/SOCS6 axis regulates anti-Mtb immunity by increasing the production of inflammatory cytokines and chemokines. Most importantly, the miR-342-3p/SOCS6 axis participates in the switching between Mtb-induced apoptosis and necrosis through A20-mediated K48-linked ubiquitination and RIPK3 degradation. Our findings reveal several strategies by which the host innate immune system controls intracellular Mtb growth via the miRNA-mRNA network and pave the way for host-directed therapies targeting these pathways.

Predictors of mortality in pediatric urban firearm injuries.

BACKGROUND: Although firearms account for less than 5 % of all pediatric injuries, they have the highest associated case fatality rate. METHODS: The registry at a Level-1 trauma center was used to identify firearm injuries (<18 years of age) from 1991 to 2011. Descriptive statistics and risk-adjusted multivariate analyses (MVA) were performed. RESULTS: Overall, 1085 patients were identified. Immediate operations were performed in 33 % (n = 358) of patients with most having abdominal surgery (n = 214). Survival was 86 %, but higher for African Americans (OR = 1.92) than for Hispanics (p = 0.006). African Americans were more likely to sustain extremity (OR = 2.26) and less head (OR = 0.36) injuries than Hispanics (p < 0.001). Analysis by injury location showed that head (OR = 14.1) had the highest associated mortality. Other significant predictors included multiple major injury (defined by Abbreviated Injury Scale) with central nervous system involvement (OR = 7.30) and single injuries to the chest (OR = 2.68). These findings were compared to abdominal injuries as the baseline (p < 0.02). MVA demonstrated that Caucasian children had higher mortality (OR = 6.12) vs. Hispanics (p = 0.031). Children admitted with initial pH ≤ 7.15 (OR = 14.8), initial hematocrit ≤30 (OR = 3.24), or Injury Severity Score (ISS) > 15 (OR = 1.08) had higher mortality rates (p < 0.05). CONCLUSION: Independent significant indicators of mortality include low initial pH or hematocrit, Caucasian race, high ISS, and those who sustain head injuries.

Healthcare-associated viral respiratory infections in paediatric intensive care unit settings: More than just a sneeze.

Healthcare-associated infections (HAIs) affect patient health. Patients with Paediatric Intensive Care Unit (PICU) acquired viral respiratory infections had longer use of respiratory support. We found it's uncommon in ICUs to have high risk HAIs. RSV, parainfluenza, and hMPV are the most common, and 1/3 of patients required escalation in respiratory support and/or escalation in antibiotics. All patients had underlying comorbidities. In our series there were two deaths within 2 weeks of infection.

MicroRNA-325-3p Facilitates Immune Escape of Mycobacterium tuberculosis through Targeting LNX1 via NEK6 Accumulation to Promote Anti-Apoptotic STAT3 Signaling.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis that poses threats to the public. M. tuberculosis survives in macrophages by escaping from immune surveillance and clearance, which exacerbates the bacterial proliferation. However, the molecular mechanisms of this immune escape have not yet been fully understood. Using multiple cell and mouse models, we found that microRNA-325-3p (miR-325-3p) is upregulated after M. tuberculosis infection and Mir325-deficient mice show resistance to M. tuberculosis We demonstrated that miR-325-3p directly targets LNX1, an E3 ubiquitin ligase of NEK6, and that this hampers the proteasomal degradation of NEK6 in macrophages. The abnormal accumulation of NEK6 leads to the activation of STAT3 signaling, thus inhibiting the process of apoptosis and promoting the intracellular survival of M. tuberculosis Our findings not only reveal a new immune escape pathway of M. tuberculosis but also may provide new insights into the development of therapeutic approaches for drug-resistant TB.IMPORTANCE Intracellular survival of Mycobacterium tuberculosis results in bacterial proliferation and the spread of infection in lungs, consequently deteriorating the conditions of tuberculosis (TB) patients. This research discovers a new immune escape pathway of M. tuberculosis by modulating host miR-325-3p expression, thus leading to the intracellular survival of M. tuberculosis These findings make a contribution to the understanding of the immune escape of M. tuberculosis, and they provide a theoretical basis for the development of therapeutic approaches for drug-resistant TB.

911 Emergency Medical Services and Re-Triage to Level I Trauma Centers.

BACKGROUND: Interfacility transfer of undertriaged patients to higher-level trauma centers has been found to result in a delay of appropriate care and an increase in mortality. To address this, for the last 10 years our region has used 911 emergency medical services (EMS) paramedics for rapid re-triage of undertriaged patients to our institution's Level I trauma center. We sought to determine whether using 911 EMS for re-triage to our institution was associated with worse outcomes-with mortality as the primary end point-compared with direct EMS transport from point of injury. STUDY DESIGN: We retrospectively reviewed all trauma activations to our institution during a 16-month period; 3,394 active traumas were analyzed. RESULTS: Two hundred and seventy patients (8%) arrived via 911 EMS re-triage and 3,124 (92%) arrived via direct EMS transport. Total EMS transport time was significantly longer (122.5 minutes vs 33.7 minutes; p < 0.001) between the 2 groups, but there was no significant difference in mortality rates (4.1% vs 3.6%; p = 0.67). CONCLUSIONS: These data show that although using 911 EMS for re-triage is associated with an increase in total transport time, it does not result in an increase in mortality compared with direct EMS transport. We conclude that the use of 911 EMS can be considered a safe method to re-triage patients to higher-level trauma centers.

Cost varies with procedure type in pediatric GI foreign bodies.

BACKGROUND/PURPOSE: In pediatric cases of ingested foreign bodies, gastrointestinal foreign bodies (GIFB) have distinct factors contributing to longer and more costly hospitalizations. METHODS: Patients admitted with ingested foreign bodies were identified in the Kids' Inpatient Database (1997-2009). RESULTS: Overall, 7480 cases were identified. Patients were most commonly <5years of age (44%), male (54%), and Caucasian (57%). A total of 2506 procedures were performed, GI surgical procedures (57%) most frequently, followed by GI endoscopy (24%), esophagoscopy (11%), and bronchoscopy - in cases of inhaled objects (9%). On multivariate analysis, length of stay increased when cases were associated with intestinal obstruction (OR=1.7), esophageal perforation (OR=40.0), intestinal perforation (OR=4.4), exploratory laparotomy (OR=1.9), and gastric (OR=2.9), small bowel (OR=1.5), or colon surgery (OR=2.5), all p<0.02. Higher total charges (TC) were associated with intestinal obstruction (OR=2.0), endoscopy of esophagus (OR=1.8), stomach (OR=2.1), or colon (OR=3.3), and exploratory laparotomy (OR=3.6) or surgery of stomach (OR=5.6), small bowel (OR=6.4), or colon (OR=3.4), all p<0.001. CONCLUSIONS: Surgical or endoscopic procedures are performed in approximately one third of GIFB cases. Associated psychiatric disorder or self-inflicted injury is seen in more than 20% of GIFB patients. Resource utilization is determined heavily by associated diagnoses and treatment procedures.