Frequent mild head injury promotes trigeminal sensitivity concomitant with microglial proliferation, astrocytosis, and increased neuropeptide levels in the trigeminal pain system.

BACKGROUND: Frequent mild head injuries or concussion along with the presence of headache may contribute to the persistence of concussion symptoms. METHODS: In this study, the acute effects of recovery between mild head injuries and the frequency of injuries on a headache behavior, trigeminal allodynia, was assessed using von Frey testing up to one week after injury, while histopathological changes in the trigeminal pain pathway were evaluated using western blot, ELISA and immunohistochemistry. RESULTS: A decreased recovery time combined with an increased mild closed head injury (CHI) frequency results in reduced trigeminal allodynia thresholds compared to controls. The repetitive CHI group with the highest injury frequency showed the greatest reduction in trigeminal thresholds along with greatest increased levels of calcitonin gene-related peptide (CGRP) in the trigeminal nucleus caudalis. Repetitive CHI resulted in astrogliosis in the central trigeminal system, increased GFAP protein levels in the sensory barrel cortex, and an increased number of microglia cells in the trigeminal nucleus caudalis. CONCLUSIONS: Headache behavior in rats is dependent on the injury frequency and recovery interval between mild head injuries. A worsening of headache behavior after repetitive mild head injuries was concomitant with increases in CGRP levels, the presence of astrocytosis, and microglia proliferation in the central trigeminal pathway. Signaling between neurons and proliferating microglia in the trigeminal pain system may contribute to the initiation of acute headache after concussion or other traumatic brain injuries

Effective Regge QCD

A new framework for a high energy limit of quantum gauge field theories is introduced. Its potency is illustrated on a new derivation of the reggeization of the gluon.Comment: Latex, 9 pages + 2 figures as PS-file, extended version, to appear in Phys. Rev. Let

Uncontrolled mitochondrial calcium uptake underlies the pathogenesis of neurodegeneration in MICU1-deficient mice and patients

Dysregulation of mitochondrial Ca2+ homeostasis has been linked to neurodegenerative diseases. Mitochondrial Ca2+ uptake is mediated via the calcium uniporter complex that is primarily regulated by MICU1, a Ca2+-sensing gatekeeper. Recently, human patients with MICU1 loss-of-function mutations were diagnosed with neuromuscular and cognitive impairments. While studies in patient-derived cells revealed altered mitochondrial calcium signaling, the neuronal pathogenesis was difficult to study. To fill this void, we created a neuron-specific MICU1-KO mouse model. These animals show progressive, abnormal motor and cognitive phenotypes likely caused by the degeneration of motor neurons in the spinal cord and the cortex. We found increased susceptibility to mitochondrial Ca2+ overload-induced excitotoxic insults and cell death in MICU1-KO neurons and MICU1-deficient patient-derived cells, which can be blunted by inhibiting the mitochondrial permeability transition pore. Thus, our study identifies altered neuronal mitochondrial Ca2+ homeostasis as causative in the clinical symptoms of MICU1-deficient patients and highlights potential therapeutic targets

Disposable Platform Provides Visual and Color-Based Point-of-Care Anemia Self-Testing

Anemia, or low blood hemoglobin (Hgb) levels, afflicts 2 billion people worldwide. Currently, Hgb levels are typically measured from blood samples using hematology analyzers, which are housed in hospitals, clinics, or commercial laboratories and require skilled technicians to operate. A reliable, inexpensive point-of-care (POC) Hgb test would enable cost-effective anemia screening and chronically anemic patients to self-monitor their disease. We present a rapid, standalone, and disposable POC anemia test that, via a single drop of blood, outputs color-based visual results that correlate with Hgb levels. METHODS. We tested blood from 238 pediatric and adult patients with anemia of varying degrees and etiologies and compared hematology analyzer Hgb levels with POC Hgb levels, which were estimated via visual interpretation using a color scale and an optional smartphone app for automated analysis. RESULTS. POC Hgb levels correlated with hematology analyzer Hgb levels (r = 0.864 and r = 0.856 for visual interpretation and smartphone app, respectively), and both POC test methods yielded comparable sensitivity and specificity for detecting any anemia (n = 178) (/dl) (sensitivity: 90.2% and 91.1%, specificity: 83.7% and 79.2%, respectively) and severe anemia (n = 10) (/dl) (sensitivity: 90.0% and 100%, specificity: 94.6% and 93.9%, respectively). CONCLUSIONS. These results demonstrate the feasibility of this POC color-based diagnostic test for self-screening/self-monitoring of anemia. TRIAL REGISTRATION. Not applicable. FUNDING. This work was funded by the FDA-funded Atlantic Pediatric Device Consortium, the Georgia Research Alliance, Children\u27s Healthcare of Atlanta, the Georgia Center of Innovation for Manufacturing, and the InVenture Prize and Ideas to Serve competitions at the Georgia Institute of Technology

Increased permeability-oedema and atelectasis in pulmonary dysfunction after trauma and surgery: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Trauma and surgery may be complicated by pulmonary dysfunction, acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), but the mechanisms are incompletely understood.</p> <p>Methods</p> <p>We evaluated lung capillary protein permeability non-invasively with help of the ⁶⁷Ga-transferrin pulmonary leak index (PLI) technique and extravascular lung water (EVLW) by the transpulmonary thermal-dye dilution technique in consecutive, mechanically ventilated patients in the intensive care unit within 24 h of direct, blunt thoracic trauma (n = 5, 2 with ARDS), and within 12 h of indirect trauma by transhiatal oesophagectomy (n = 8), abdominal surgery for cancer (n = 6) and bone surgery (n = 4). We studied transfusion history, haemodynamics, oxygenation and mechanics of the lungs. The lung injury score (LIS, 0–4) was calculated. Plain radiography was also done to judge densities and atelectasis.</p> <p>Results</p> <p>The PLI and EVLW were elevated above normal in 61 and 30% of patients, respectively, and the PLI directly related to the number of red cell concentrates given (r_s= 0.69, P < 0.001), without group differences. Oxygenation, lung mechanics, radiographic densities and thus the LIS (1.0 [0.25–3.5]) did not relate to PLI and EVLW. However, groups differed in oxygenation and airway pressures and impaired oxygenation related to the number of radiographic quadrants with densities (r_s= 0.55, P = 0.007). Thoracic trauma patients had a worse oxygenation requiring higher airway pressures and thus higher LIS than the other patient groups, unrelated to PLI and EVLW but attributable to a higher cardiac output and thereby venous admixture. Finally, patients with radiographic signs of atelectasis had more impaired oxygenation and more densities than those without.</p> <p>Conclusion</p> <p>The oxygenation defect and radiographic densities in mechanically ventilated patients with pulmonary dysfunction and ALI/ARDS after trauma and surgery are likely caused by atelectasis rather than by increased permeability-oedema related to red cell transfusion.</p

Metabolomic Analysis in Severe Childhood Pneumonia in The Gambia, West Africa: Findings from a Pilot Study

Pneumonia remains the leading cause of death in young children globally and improved diagnostics are needed to better identify cases and reduce case fatality. Metabolomics, a rapidly evolving field aimed at characterizing metabolites in biofluids, has the potential to improve diagnostics in a range of diseases. The objective of this pilot study is to apply metabolomic analysis to childhood pneumonia to explore its potential to improve pneumonia diagnosis in a high-burden setting. and Random Forests (RF). ‘Unsupervised’ (blinded) data were analyzed by Principal Component Analysis (PCA), while ‘supervised’ (unblinded) analysis was by Partial Least Squares-Discriminant Analysis (PLS-DA) and Orthogonal Projection to Latent Structures (OPLS). Potential markers were extracted from S-plots constructed following analysis with OPLS, and markers were chosen based on their contribution to the variation and correlation within the data set. The dataset was additionally analyzed with the machine-learning algorithm RF in order to address issues of model overfitting and markers were selected based on their variable importance ranking. Unsupervised PCA analysis revealed good separation of pneumonia and control groups, with even clearer separation of the groups with PLS-DA and OPLS analysis. Statistically significant differences (p<0.05) between groups were seen with the following metabolites: uric acid, hypoxanthine and glutamic acid were higher in plasma from cases, while L-tryptophan and adenosine-5′-diphosphate (ADP) were lower; uric acid and L-histidine were lower in urine from cases. The key limitation of this study is its small size.Metabolomic analysis clearly distinguished severe pneumonia patients from community controls. The metabolites identified are important for the host response to infection through antioxidant, inflammatory and antimicrobial pathways, and energy metabolism. Larger studies are needed to determine whether these findings are pneumonia-specific and to distinguish organism-specific responses. Metabolomics has considerable potential to improve diagnostics for childhood pneumonia

Beneficial and Detrimental Effects of Plasmin(ogen) during Infection and Sepsis in Mice

Plasmin has been proposed to be an important mediator during inflammation/infection. In this study, by using mice lacking genes for plasminogen, tissue-type plasminogen activator (tPA), and urokinase-type PA (uPA), we have investigated the functional roles of active plasmin in infection and sepsis. Two models were used: an infection model by intravenous injection of 1×107 CFU of S. aureus, and a sepsis model by intravenous injection of 1.6×108 CFU of S. aureus. We found that in the infection model, wild-type (WT) mice showed significantly higher survival rates than plasminogen-deficient (plg-/-) mice. However, in the sepsis model, plg-/- or tPA-/-/uPA-/- mice showed the highest survival rate whereas WT and tPA+/-/uPA+/- mice showed the lowest survival rate, and plg+/-, tPA-/-, and uPA-/- mice had an intermediate survival rate. These results indicate that the levels of active plasmin are critical in determining the survival rate in the sepsis, partly through high levels of inflammatory cytokines and enhanced STAT3 activation. We conclude that plasmin is beneficial in infection but promotes the production of inflammatory cytokines in sepsis that may cause tissue destruction, diminished neutrophil function, and an impaired capacity to kill bacteria which eventually causes death of these mice

Cut Diagrams for High Energy Scatterings

A new approach is introduced to study QCD amplitudes at high energy and comparatively small momentum transfer. Novel cut diagrams, representing resummation of Feynman diagrams, are used to simplify calculation and to avoid delicate cancellations encountered in the usual approach. Explicit calculation to the 6th order is carried out to demonstrate the advantage of cut diagrams over Feynman diagrams.Comment: uu-encoded file containing a latex manuscript with 14 postscript figure