Single Penetrating Research Articles

A Catalytic Approach for the Synthesis of Peptide-Oligonucleotides Conjugates in Aqueous Solution or On-Column.

Peptide-oligonucleotide conjugates (POCs) are covalent architectures composed of a DNA or RNA molecules linked to a peptide. These constructs have found widespread applications ranging from hybrid nanomaterials to gene-targeted therapies. Considering the important role of POCs, a new catalytic approach for their preparation is reported here, that could be applied either on solid support in anhydrous media, or post-synthetically in aqueous buffer. Single amino acids, peptides and cell penetrating peptides (CPPs) were conjugated to various oligo(ribo)nucleotides with high conversions and good isolated yields. The applicability of the method was demonstrated on more than 35 examples including an analogue of a commercial therapeutic oligonucleotide. Other conjugation partners, such as deoxycholic acid and biotin were also successfully conjugated to oligonucleotides. To highlight the potential of this catalytic approach, these conditions have been applied to iterative processes, which is of high interest for the development of DNA-Encoded Libraries.

Comparison of the Fixation Strengths of Screws between the Traditional Trajectory and the Single and Double Endplate Penetrating Screw Trajectories Using Osteoporotic Vertebral Body Models Based on the Finite Element Method.

This is a finite element (FE) study. To compare the fixation strength of traditional trajectory (TT) and single and double endplate penetrating screw trajectories (SEPST/DEPST) to the osteoporotic vertebral body model based on the FE method. SEPST/DEPST have been developed to enhance the fixation strength in patients with diffuse idiopathic hyperostosis (DISH). This technique was also applied to patients with osteoporosis. However, determining the superiority of SEPST/ DEPST is difficult because of the heterogeneous patient backgrounds. Twenty vertebrae (T12 and L1) from 10 patients with osteoporosis (two males and eight females; mean age, 74.7 years) were obtained to create the 10 FE models. First, a single screw was placed with TT and SEPST/DEPST, and the fixation strength was compared by axial pullout strength (POS) and multidirectional loading tests. Second, two screws were placed on the bilateral pedicles with TT and SEPST/DEPST, and the fixation force of the vertebrae in the constructs in flexion, extension, lateral flexion, and axial rotation was examined. SEPST and DEPST had 140% and 171% higher POS values than TT, respectively, and the DEPST result was statistically significant (p =0.007). The multidirectional fixation strength was significantly higher in DEPST and SEPST than in TT in the cranial, caudal, and medial directions (p <0.05) but not in the lateral direction (p =0.05). The vertebral fracture strength at the lower instrumented vertebra of the DEPST tended to be higher than that of TT. The vertebral motion angles in SEPST and DEPST were significantly smaller in lateral bending (p =0.02) and tended to be smaller in flexion and extension than in TT (p =0.13). This study may provide useful information for spine surgeons in deciding whether to choose the SEPS or DEPS technique for augmenting fixation in osteoporotic vertebral fracture surgery.

PENETRATING CRANIUM INJURY BY A CONCRETE NAIL: CASE STUDY

The article describes a case study, demonstrating the infliction of a single blind penetrating «gunshot» wound to the head with a concrete nail fired from a powder-actuated fastening tool. Forensic examination of the injury caused by atypical projectiles when fired from atypical firearms can be a difficult task. The results of a thorough autopsy examination of the body and the ante-/post-mortem discovery of atypical projectiles (or other foreign objects) in the victim’s body are the prerequisite for correct interpretation of the injury morphological features. Peer Review History: Received: 22 October 2023; Revised: 26 November; Accepted: 29 December, Available online: 15 January 2024 Academic Editor: Dr. Muhammad Zahid Iqbal, AIMST University, Malaysia, drmmziqbal@gmail.com Received file: Reviewer's Comments: Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 7.0/10 Reviewers: Dr. Rima Benatoui,Laboratory of Applied Neuroendocrinology, Department of Biology, Faculty of Science, Badji Mokhtar University Annaba, Algeria. benattouiryma@gmail.com Dr. Owanaro Peter, Nigeria, Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Niger Delta University, Wilberforce Island, Bayelsa State, Nigeria. owonaropeter@gmail.com

Experimental investigation on micro-fracture evolution and fracture permeability of oil shale heated by water vapor

The study investigated the relationship between the temperature field distribution and fracture connectivity of oil shale heated by water vapor using infrared thermal imaging experiment. High temperature triaxial permeability testing system was then used to study the permeability of oil shale containing single penetrating fracture under the condition of water vapor heating. Finally, micro CT imaging and hot stage microscope imaging experiments were conducted to study the microstructure characteristics of oil shale at different temperatures. It was observed that when the oil shale was heated by water vapor, fractures became the main flow channels, and the connectivity of fractures affected the heating area of oil shale. The magnitude of fracture permeability of oil shale decreased from 10−15 m2 at 25 °C to 10−17 m2 at 350 °C. When the temperature was higher than 350 °C, the permeability of oil shale increased rapidly and recovered to the order of 10−15 m2 after 500 °C. The micro-fractures had little contribution to permeability in the temperature range of 25 °C–350 °C. The decrease in the permeability in this temperature range was caused by the closure of the single penetrating fracture. When the temperature reached 400 °C, some new penetrating fractures appeared. This resulted in the increase in permeability.

Prediction of corneal astigmatism based on corneal tomography after femtosecond laser arcuate keratotomy using a pix2pix conditional generative adversarial network.

PurposeThis study aimed to develop a deep learning model to generate a postoperative corneal axial curvature map of femtosecond laser arcuate keratotomy (FLAK) based on corneal tomography using a pix2pix conditional generative adversarial network (pix2pix cGAN) for surgical planning.MethodsA total of 451 eyes of 318 nonconsecutive patients were subjected to FLAK for corneal astigmatism correction during cataract surgery. Paired or single anterior penetrating FLAKs were performed at an 8.0-mm optical zone with a depth of 90% using a femtosecond laser (LenSx laser, Alcon Laboratories, Inc.). Corneal tomography images were acquired from Oculus Pentacam HR (Optikgeräte GmbH, Wetzlar, Germany) before and 3 months after the surgery. The raw data required for analysis consisted of the anterior corneal curvature for a range of ± 3.5 mm around the corneal apex in 0.1-mm steps, which the pseudo-color corneal curvature map synthesized was based on. The deep learning model used was a pix2pix conditional generative adversarial network. The prediction accuracy of synthetic postoperative corneal astigmatism in zones of different diameters centered on the corneal apex was assessed using vector analysis. The synthetic postoperative corneal axial curvature maps were compared with the real postoperative corneal axial curvature maps using the structural similarity index measure (SSIM) and peak signal-to-noise ratio (PSNR).ResultsA total of 386 pairs of preoperative and postoperative corneal tomography data were included in the training set, whereas 65 preoperative data were retrospectively included in the test set. The correlation coefficient between synthetic and real postoperative astigmatism (difference vector) in the 3-mm zone was 0.89, and that between surgically induced astigmatism (SIA) was 0.93. The mean absolute errors of SIA for real and synthetic postoperative corneal axial curvature maps in the 1-, 3-, and 5-mm zone were 0.20 ± 0.25, 0.12 ± 0.17, and 0.09 ± 0.13 diopters, respectively. The average SSIM and PSNR of the 3-mm zone were 0.86 ± 0.04 and 18.24 ± 5.78, respectively.ConclusionOur results showed that the application of pix2pix cGAN can synthesize plausible postoperative corneal tomography for FLAK, showing the possibility of using GAN to predict corneal tomography, with the potential of applying artificial intelligence to construct surgical planning models.

Designing successive target selection in virtual reality via penetrating the intangible interface with handheld controllers

Empirical research on single target selection in Virtual Reality/Augmented Reality (VR/AR) environments has been studied extensively. However, there is a lack of methods and research on improving the coherence when successively selecting multiple targets. We propose Sewing, a successive target selection method with handheld controllers in VR environments. We leverage real-life sewing as a design metaphor for the selection of multiple targets with one single spatial movement penetrating targets with handheld controllers. We conducted an empirical study to validate the efficiency of selecting multiple targets with Sewing compared with the conventional selection method, which is based on the button pressing metaphor. Results showed that Sewing can provide promising performance and coherence for rapid and accurate target selection. Based on the results, we implemented SewTyping, a Sewing-based VR text entry method to evaluate the applicability of Sewing, and conducted an empirical study to compare the typing performance with two other techniques (Controller Pointing and Drum-like Keyboard). Results showed that 1) SewTyping achieved 26.57 words per minute with a total error rate of 3.68% and 2) users adapted to the sewing-like movement easily and achieved steady performance with essential practice.

Self-inflicted stab injury with abdominal evisceration: A case report

Introduction and importanceSelf-inflicted abdominal stab injury with an intention of self-harm is uncommon. Moreover, self-inflicted injury leading to avulsion of the colon has rarely been reported in the literature. We report a case of a 42-years-female with schizoaffective disorder who presented with self-inflicted stab injury on the abdomen resulting in abdominal evisceration.Presentation of caseA 42-years-female with schizoaffective disorder (F25) for 10 years presented to the emergency department with multiple, self-inflicted injuries on the abdomen. A large free portion of the omentum and segment of the bowel were brought in a plastic carry bag. Examination revealed multiple transverse hesitation cuts in the epigastrium and a single deep penetrating transverse cut resulting in the evisceration of the omentum and colon. Intra-operatively, avulsion of a large portion of the greater omentum and missing segment of the mid transverse colon was observed. The patient underwent an immediate abdominal exploration and side-to-side colo-colic anastomosis along with diversion ileostomy. At three months following primary surgery, ileostomy closure was done.ConclusionPatients with schizophrenia spectrum psychosis are at risk of self-harm and in our case a schizoaffective patient presented with self-inflicted injuries that required an emergency abdominal exploration and repair. This case highlights a multi-disciplinary approach for the management of these cases and mandates clinicians and caregivers to be more vigilant to restrict injuries in the future.

Simulation of steam/air leakage through small-scale cracked concrete specimen

At the Material Testing and Research Institute (MPA Karlsruhe) leakage experiments with concrete specimens containing a single penetrating crack were performed on behalf of GRS. The specimens had a prismatic shape and the dimensions 4.0 cm × 4.0 cm × 11.0 cm. The crack width was adjustable and ranged from 0.05 mm to 0.25 mm in the experiments. On top of the leakage measurement two sets of additional measurements were performed. In leakage experiments with air at room temperature the exit velocity of the leakage flow was measured with a hot-wire anemometer. The measured velocities were compared to the velocities calculated by leakage rate formulas. The formulas compare well to measurement results. Differences depend greatly on the crack width and the respective assumptions on the friction coefficient proposed by the authors. In a second set of experiments, hot air and hot steam/air mixtures were used. At the beginning of the experiment the specimen had room temperature; due to heat transfer from the leaking fluid to the specimen and the thermal expansion of the specimen, the crack width was reduced, and the leakage rate significantly decreased. The leakage process including fluid-structure interaction was simulated using the coupling of the thermal-hydraulic system code ATHLET, which has been developed and validated by GRS, and the structure mechanical finite element code ANSYS Mechanical.

Association of Plaque Features with Infarct Patterns in Patients with Acutely Symptomatic Middle Cerebral Artery Atherosclerotic Disease

Background and PurposeUnderstanding the stroke mechanism of middle cerebral artery (MCA) atherosclerosis is important for stroke triage and future trial design. The aim of this study was to characterize intrinsic MCA plaque and acute cerebral infarct in vivo by using high-resolution black-blood (BB) and diffusion-weighted magnetic resonance (MR) imaging and to investigate the relationship between plaque features and infarct patterns. MethodsA single-center retrospective study was conducted at a tertiary referral center between March 2017 and August 2019. Patients consecutively admitted for acute ischemic stroke with MCA stenosis underwent diffusion-weighted and BB MR imaging. Plaque features and infarct patterns were assessed. The association between plaque features and infarct patterns (binary variable: single/multiple) was evaluated using a multivariate logistic regression model. ResultsOf 49 patients with MCA atherosclerotic stenosis, diffusion-weighted MR imaging showed that 28 patients (57%) had multiple acute cerebral infarcts and 21 patients had single acute cerebral infarcts. In contrast to single infarct, multiple infarcts were associated with greater plaque burden (81.9±7.24 versus 71.3±13.7; P=0.012). A multivariate logistic regression model adjusted for 7 potential confounders confirmed a statistically significant positive association between plaque burden and multiple acute infarcts (adjusted R2 =0.432, P< 0.001). The rate of plaque surface irregularity was significantly greater in patients with multiple infarcts than those with single infarct (71% versus 43%, P=0.044). For single acute penetrating artery infarct, patients with infarct size > 2cm had greater plaque burden compared with patients with infarct size < 2cm (75.3±13.4 versus 63.4±10.9; P = 0.016). ConclusionsIncreased plaque burden, plaque surface irregularity in patients with MCA stenosis is associated with its likelihood to have caused an artery-to-artery embolism that produces multiple cerebral infarcts, especially along the border zone region, and increased plaque burden may promote subcortical single infarct size by occluding penetrating arteries. Our results provide important insight into stroke mechanism of MCA atherosclerosis.

Single Cortical Microinfarcts Lead to Widespread Microglia/Macrophage Migration Along the White Matter

Loss of cognitive function with aging is a complex and poorly understood process. Recently, clinical research has linked the occurrence of cortical microinfarcts to cognitive decline. Cortical microinfarcts form following the occlusion of penetrating vessels and are considered to be restricted to the proximity of the occluded vessel. Whether and how such local events propagate and affect remote brain regions remain unknown. To this end, we combined histological analysis and longitudinal diffusion tensor imaging (DTI), following the targeted-photothrombotic occlusion of single cortical penetrating vessels. Occlusions resulted in distant tissue reorganization across the mouse brain. This remodeling co-occurred with the formation of a microglia/macrophage migratory path along subcortical white matter tracts, reaching the contralateral hemisphere through the corpus callosum and leaving a microstructural signature detected by DTI-tractography. CX3CR1-deficient mice exhibited shorter trail lengths, differential remodeling, and only ipsilateral white matter tract changes. We concluded that microinfarcts lead to brain-wide remodeling in a microglial CX3CR1-dependent manner.

Microembolism of single cortical arterioles can induce spreading depression and ischemic injury; a potential trigger for migraine and related MRI lesions

Increasing epidemiological evidence suggests an association between migraine with aura (MA) and cardiovascular events. There is experimental as well as clinical evidence implying cerebral microembolism as a potential trigger for MA attacks. Microembolism may also account for some of the ischemic MRI lesions more commonly observed in MA than in general population. Limited size of clinically-silent MRI lesions suggests isolated occlusion of a small vessel. However, it is not known whether selective thrombosis of a small arteriole (e.g. single mouse penetrating arteriole – PA), can induce cortical spreading depression (CSD), the putative cause of migraine aura and, hence, trigger an MA attack. For this, we mimiced thrombosis of a small vessel caused by microembolism by selectively occluding a PA just before diving into the cortex (radius; 10–25 µm) in the mouse. Clotting was induced with FeCl3 applied focally over the PA by a glass micropipette for 3 min. DC potential changes were recorded and the alterations in cortical blood flow were monitored by laser speckle contrast imaging. Mice were kept alive for 1–4 weeks and brain sections were stained with H&E or luxol-fast blue to evaluate changes induced by PA occlusion. We found that single PA occlusion consistently triggered a CSD originating from the tissue around the PA soon after occlusion and induced delayed, small ischemic lesions within territory of the affected vessel a few weeks later. These findings suggest that cerebral microembolism can lead to MA attacks and may account for some of the silent brain lesions.

Movement Disorders Syndromes Associated With Lacunar Infarcts, Clinical Case Series

Lacunar infarcts are small (&lt;15 mm diameter) subcortical infarcts that results from occlusion of a single penetrating artery. Lacunar infarcts are associated with clinical lacunar syndromes, one of lacunar syndromes is movement disorders syndrome such as chore, dystonia, hemibolismus and asterixis. Several types of movement disorders have been described with small, deep infarct, majority of these syndrome is caused by penetrating small- artery disease. The movement disorder may appear as the only sign of the infarct or may develop later, after an initial syndrome, different in character, has resolved.Hemichorea – hemiballismus is the most common of movement disorder due to lacunar infarcts.The lacunar size infarcts found in different parts of the striatum including in head of the caudate nucleus and adjacent corona radiate, the subthalamic and the thalamus. The onset is typically abrupt and is usually- unaccompanied by other complaints. The chorea usually involves the forearm, hand, and fingers. In some cases, chorea has been delayed by some weeks or months after the initial occurrence of hemiparesis. Dystonia: Two types of dystonia have been described in cases of lacunes, action- induced and focal dystonia.Case I- in a 63 year old woman with lacunar stroke, with abrupt onset of chorea, chorea involves the foream, hand, and fingers, it was accompanied by hemiparesis that faded within 3 months even though the chorea persisted unchanged.Case II- In a 75 years old man chorea was delayed by some weeks after initial occurrence of hemiparesis due to lacunar infarct.Case III- in a 81 years old woman lacunar infarct, whose putaminal lesions was documented by CT scan, suffer choreic movements of the distal parts of the arm and leg that interfered with normal activity and prevented easy walking for more than a weeks, the examination revealed normal strength, sensation and reflexes.Case IV- A 69 years old man , with lacunar infarct in adjacent corona radiate with action – induced dystonia in the left hand. The finger of the affected hand become flexed in to the palm, leaving only the Thumb free, strength of hand was normal . Activity exacerbated the movements. The left hand and forearm showed involuntary movements that produced an unusual posture.

Dynamic diameter response of intraparenchymal penetrating arteries during cortical spreading depression and elimination of vasoreactivity to hypercapnia in anesthetized mice

Cortical spreading depression (CSD) induces marked hyperemia with a transient decrease of regional cerebral blood flow (rCBF), followed by sustained oligemia. To further understand the microcirculatory mechanisms associated with CSD, we examined the temporal changes of diameter of intraparenchymal penetrating arteries during CSD. In urethane-anesthetized mice, the diameter of single penetrating arteries at three depths was measured using two-photon microscopy during passage of repeated CSD, with continuous recordings of direct current potential and rCBF. The first CSD elicited marked constriction superimposed on the upstrokes of profound dilation throughout each depth of the penetrating artery, and the vasoreaction temporally corresponded to the change of rCBF. Second or later CSD elicited marked dilation with little or no constriction phase throughout each depth, and the vasodilation also temporally corresponded to the increase of rCBF. Furthermore, the peak dilation showed good negative correlations with basal diameter and increase of rCBF. Vasodilation induced by 5% CO2 inhalation was significantly suppressed after CSD passage at any depth as well as hyperperfusion. These results may indicate that CSD-induced rCBF changes mainly reflect the diametric changes of the intraparenchymal arteries, despite the elimination of responsiveness to hypercapnia.

Accuracy assessment of NOGGIN Plus and MALÅ RAMAC X3M single channel ground penetrating RADAR (GPR) for underground utility mapping

Ground Penetrating Radar (GPR) becomes a popular device in investigation of the underground utilities in recent years. GPR analyses the type and position of utility objects. However, the performance accuracy of GPR models is an important issue that should be considered. This study conducts the accuracy analysis between two models of single channel GPR; NOGGIN PLUS and MALÅ RAMAC X3M, by focusing on the basic principles of single channel GPR, accuracy analysis and calibration methods implemented on GPR. The survey work has been performed to identify the most accurate instrument to detect underground utility objects. In addition, data analysis was carried out to compare between two models of single channel GPR. This study provides proper guidelines and assists surveyors to select the suitable instruments regarding on applications especially on utility mapping in terms of accuracy.

Allopurinol protects against ischemic insults in a mouse model of cortical microinfarction

Microinfarcts are common in patients with cognitive decline and dementia. Allopurinol (ALLO), a xanthine oxidase (XO) enzyme inhibitor, has been found to reduce proinflammatory molecules and oxidative stress in the vasculature. We here examined the effect of pre-treatment with allopurinol on the cortical microinfarction. C57BL/6J mice were subjected to a permanent single penetrating arteriole occlusion induced by two-photon laser irradiation. Infarction volume, the activation of glial cells and nitrosative stress in the ischemic brain was assessed using immunohistochemistry. Pre-treatment with ALLO achieved 42% reduction of infarct volume and significantly reduced microglia infiltration, astrocyte proliferation and nitrosative stress in the ischemic brain. These data indicate that ALLO protects against microinfarcts possibly through inhibition of nitrosative stress and attenuation of microglia infiltration as well as astrocytes reactivation.

BBB leakage, astrogliosis, and tissue loss correlate with silicon microelectrode array recording performance

The clinical usefulness of brain machine interfaces that employ penetrating silicon microelectrode arrays is limited by inconsistent performance at chronic time points. While it is widely believed that elements of the foreign body response (FBR) contribute to inconsistent single unit recording performance, the relationships between the FBR and recording performance have not been well established. To address this shortfall, we implanted 4X4 Utah Electrode Arrays into the cortex of 28 young adult rats, acquired electrophysiological recordings weekly for up to 12 weeks, used quantitative immunohistochemical methods to examine the intensity and spatial distribution of neural and FBR biomarkers, and examined whether relationships existed between biomarker distribution and recording performance. We observed that the FBR was characterized by persistent inflammation and consisted of typical biomarkers, including presumptive activated macrophages and activated microglia, astrogliosis, and plasma proteins indicative of blood-brain-barrier disruption, as well as general decreases in neuronal process distribution. However, unlike what has been described for recording electrodes that create only a single penetrating injury, substantial brain tissue loss generally in the shape of a pyramidal lesion cavity was observed at the implantation site. Such lesions were also observed in stab wounded animals indicating that the damage was caused by vascular disruption at the time of implantation. Using statistical approaches, we found that blood–brain barrier leakiness and astrogliosis were both associated with reduced recording performance, and that tissue loss was negatively correlated with recording performance. Taken together, our data suggest that a reduction of vascular damage at the time of implantation either by design changes or use of hemostatic coatings coupled to a reduction of chronic inflammatory sequela will likely improve the recording performance of high density intracortical silicon microelectrode arrays over long indwelling periods and lead to enhanced clinical use of this promising technology.

Fatal Penetrating Lacerated Wound By Tusk of Indian Wild Boar

Attack of wild boar is rare and death by single injury on body due to attack of wild boar is rarest of rare. Although wild boars do not generally pose a threat to people, they occasionally attack humans. Due to the clearing of natural boar habitats, the number of interactions, including aggressive ones, between humans and boars has increased. When dealing aggressively with a human, boar will charge at them. When ramming into a person, the boar will slash the tusks upwards, creating sizeable open lacerations on the skin. Due to the height of the boar relative to a human, most wounds are inflicted to the upper legs, fatalities do occasionally occur. Wild boar attacks are under reported. There are very few cases of human attack by wild boars mentioned in literature. This case is reported for single fatal penetrating lacerated injury to lower limb inflicted by tusk of wild boar.

Evolving Concept of Small Vessel Disease through Advanced Brain Imaging.

Imaging plays a crucial role in studying and understanding cerebral small vessel disease. Several important findings have emerged from recent applications of advanced brain imaging methods. In patients with acute lacunar syndromes, diffusionweighted MRI studies have shown that the diagnostic precision of using clinical features alone or combined with CT scan findings to diagnose small vessel disease as the underlying cause is poor. Followup imaging studies on patients with acute infarcts related to small vessel disease have shown that the infarct may cavitate, merge into white matter disease abnormalities, or become invisible with time. High resolution MRI may demonstrate intracranial atherosclerosis in larger arteries (that may block orifices of penetrating arteries and cause small deep infarcts), but abnormalities in single penetrating arteries cannot as yet be consistently and reliably visualized for use in clinical practice. The epidemiology and risk factors of silent cerebral infarcts have been further delineated. Patterns of new incident silent infarcts appear related to existing white matter disease, suggesting similarities in pathophysiology. Silent deep infarcts causes local cortical atrophy, and can affect connectivity in the brain. Studies on cerebral microbleeds have shown consistent patterns in their effects on prognosis for a large number of outcomes, but the implications of cerebral microbleeds for treatment decisions remain to be established. Cortical microinfarcts represent the latest addition to the spectrum of small vessel disease in the brain, and appears as the most prevalent SVD entity. An important consensus document on neuroimaging standards for small vessel disease has been recently published.

Peptide-bridged dinuclear Ru(II) complex for mitochondrial targeted monitoring of dynamic changes to oxygen concentration and ROS generation in live mammalian cells.

A novel mitochondrial localizing ruthenium(II) peptide conjugate capable of monitoring dynamic changes in local O2 concentrations within living cells is presented. The complex is comprised of luminescent dinuclear ruthenium(II) polypyridyl complex bridged across a single mitochondrial penetrating peptide, FrFKFrFK-CONH2 (r = D-arginine). The membrane permeability and selective uptake of the peptide conjugate at the mitochondria of mammalian cells was demonstrated using confocal microscopy. Dye co-localization studies confirmed very precise localization and preconcentration of the probe at the mitochondria. This precision permitted collection of luminescent lifetime images of the probe, without the need for co-localizing dye and permitted semiquantitative determination of oxygen concentration at the mitochondria using calibration curves collected at 37 °C for the peptide conjugate in PBS buffer. Using Antimycin A the ability of the probe to respond dynamically to changing O2 concentrations within live HeLa cells was demonstrated. Furthermore, based on lifetime data it was evident that the probe also responds to elevated reactive oxygen species (ROS) levels within the mitochondria, where the greater quenching capacity of these species led to luminescent lifetimes of the probe at longer Antimycin A incubation times which lay outside of the O2 concentration range. Although both the dinuclear complex and a mononuclear analogue conjugated to an octaarginine peptide sequence exhibited some cytotoxicity over 24 h, cells were tolerant of the probes over periods of 4 to 6 h which facilitated imaging. These metal-peptide conjugated probes offer a valuable opportunity for following dynamic changes to mitochondrial function which should be of use across domains in which the metabolic activity of live cells are of interest from molecular biology and drug discovery.

To TQIP or Not to TQIP? that is the Question

The Trauma Quality Improvement Program (TQIP) reports a feasible mortality prediction model. We hypothesize that our institutional characteristics differ from TQIP aggregate data, questioning its applicability. We conducted a 2-year (2008 to 2009) retrospective analysis of all trauma activations at a Level 1 trauma center. Data were analyzed using TQIP methodology (three groups: blunt single system, blunt multisystem, and penetrating) to develop a mortality prediction model using multiple logistic regression. These data were compared with TQIP data. Four hundred fifty-seven patients met TQIP inclusion criteria. Penetrating and blunt trauma differed significantly at our institution versus TQIP aggregates (61.9 vs 7.8%; 38.0 vs 92.2%, P < 0.01). There were more firearm mechanisms of injury and less falls compared with TQIP aggregates (28.9 vs 4.2%; 8.5 vs 34.8%, P < 0.01). All other mechanisms were not significantly different. Variables significant in the TQIP model but not found to be predictors of mortality included Glasgow Coma Score motor 2 to 5, systolic blood pressure greater than 90 mmHg, age, initial pulse rate in the emergency department, mechanism of injury, head Abbreviated Injury Score, and abdominal Abbreviated Injury Score. External benchmarking of trauma center performance using mortality prediction models is important in quality improvement for trauma patient care. From our results, TQIP methodology from the pilot study may not be applicable to all institutions.