Toward a Predictive Assessment of Stab-Penetration Forces.

Collaborative research between the disciplines of forensic pathology and biomechanics was undertaken to investigate the hyperelastic properties of human skin, to determine the force required for sharp instrument penetration of skin, and to develop a finite element model, which reflects the mechanisms of sharp instrument penetration. These studies have led to the development of a "stab metric," based on simulations, to describe the force magnitudes in stabbing incidents. Such a metric should, in time, replace the crudely quantitative descriptors of stabbing forces currently used by forensic pathologists.

Hospitalist management of vaso-occlusive pain crisis in patients with sickle cell disease using a pathway of care.

Background: Patients with sickle cell disease (SCD) suffer from intermittent vaso-occlusive pain crises (VOCs). These crises lead to frequent hospitalizations, significant morbidity, and increased mortality risk. Care pathways can enhance efficiency and quality of care.

High-resolution analysis of gene activity during the Xenopus mid-blastula transition.

The Xenopus mid-blastula transition (MBT) marks the onset of large-scale zygotic transcription, as well as an increase in cell cycle length and a loss of synchronous cell divisions. Little is known about what triggers the activation of transcription or how newly expressed genes interact with each other. Here, we use high-resolution expression profiling to identify three waves of gene activity: a post-fertilisation wave involving polyadenylation of maternal transcripts; a broad wave of zygotic transcription detectable as early as the seventh cleavage and extending beyond the MBT at the twelfth cleavage; and a shorter post-MBT wave of transcription that becomes apparent as development proceeds.

The influence of acceleration loading curve characteristics on traumatic brain injury.

To prevent brain trauma, understanding the mechanism of injury is essential. Once the mechanism of brain injury has been identified, prevention technologies could then be developed to aid in their prevention. The incidence of brain injury is linked to how the kinematics of a brain injury event affects the internal structures of the brain.

Body mass index and diabetes status do not affect postoperative infection rates after bariatric surgery.

Background: Obesity predisposes general surgical patients to infections such as surgical site infection and respiratory tract infection. The infection rates vary by surgical approach and the type of surgery undertaken. Bariatric surgery is increasingly used to treat obesity and obesity related co-morbidities.

Who needs inpatient detox? Development and implementation of a hospitalist protocol for the evaluation of patients for alcohol detoxification.

Background: Clinicians caring for patients seeking alcohol detoxification face many challenges, including lack of evidence-based guidelines for treatment and high recidivism rates.

Objectives: To develop a standardized protocol for determining which alcohol dependent patients seeking detoxification need inpatient versus outpatient treatment, and to study the protocol's implementation.

Design: Review of best evidence by ad hoc task force and subsequent creation of standardized protocol.

A combined experimental and numerical study of stab-penetration forces.

The magnitude of force used in a stabbing incident can be difficult to quantify, although the estimate given by forensic pathologists is often seen as 'critical' evidence in medico-legal situations. The main objective of this study is to develop a quantitative measure of the force associated with a knife stabbing biological tissue, using a combined experimental and numerical technique. A series of stab-penetration tests were performed to quantify the force required for a blade to penetrate skin at various speeds and using different 'sharp' instruments.

The influence of dynamic response and brain deformation metrics on the occurrence of subdural hematoma in different regions of the brain.

Object: The purpose of this study was to examine how the dynamic response and brain deformation of the head and brain-representing a series of injury reconstructions of which subdural hematoma (SDH) was the outcome-influence the location of the lesion in the lobes of the brain.

Methods: Sixteen cases of falls in which SDH was the outcome were reconstructed using a monorail drop rig and Hybrid III headform. The location of the SDH in 1 of the 4 lobes of the brain (frontal, parietal, temporal, and occipital) was confirmed by CT/MR scan examined by a neurosurgeon.

Evidence for finely-regulated asynchronous growth of Toxoplasma gondii cysts based on data-driven model selection.

Toxoplasma gondii establishes a chronic infection by forming cysts preferentially in the brain. This chronic infection is one of the most common parasitic infections in humans and can be reactivated to develop life-threatening toxoplasmic encephalitis in immunocompromised patients. Host-pathogen interactions during the chronic infection include growth of the cysts and their removal by both natural rupture and elimination by the immune system.

Diurnal cortisol patterns and psychiatric symptoms in pregnancy: short-term longitudinal study.

Alteration in the HPA axis is a robust biomarker of anxiety and depression in adults, but questions remain about this association in pregnancy. We examined the longitudinal links between diurnal cortisol and mood symptoms from self-report questionnaire and diagnostic interview in an ethnically diverse, psychosocially at-risk sample of 101 women at mid-pregnancy and early third trimester. There were modest but significant associations between depression and elevated cortisol, indexed by a decreased morning level and diminished diurnal decline; the effects were strongest for diagnostic data from clinical interview.

Neural stem cell-mediated delivery of irinotecan-activating carboxylesterases to glioma: implications for clinical use.

CPT-11 (irinotecan) has been investigated as a treatment for malignant brain tumors. However, limitations of CPT-11 therapy include low levels of the drug entering brain tumor sites and systemic toxicities associated with higher doses. Neural stem cells (NSCs) offer a novel way to overcome these obstacles because of their inherent tumor tropism and ability to cross the blood-brain barrier, which enables them to selectively target brain tumor sites.

In vivo T-box transcription factor profiling reveals joint regulation of embryonic neuromesodermal bipotency.

The design of effective cell replacement therapies requires detailed knowledge of how embryonic stem cells form primary tissues, such as mesoderm or neurectoderm that later become skeletal muscle or nervous system. Members of the T-box transcription factor family are key in the formation of these primary tissues, but their underlying molecular activities are poorly understood. Here, we define in vivo genome-wide regulatory inputs of the T-box proteins Brachyury, Eomesodermin, and VegT, which together maintain neuromesodermal stem cells and determine their bipotential fates in frog embryos.

Magnetic resonance imaging tracking of ferumoxytol-labeled human neural stem cells: studies leading to clinical use.

Numerous stem cell-based therapies are currently under clinical investigation, including the use of neural stem cells (NSCs) as delivery vehicles to target therapeutic agents to invasive brain tumors. The ability to monitor the time course, migration, and distribution of stem cells following transplantation into patients would provide critical information for optimizing treatment regimens. No effective cell-tracking methodology has yet garnered clinical acceptance.

Mechanical characterization of brain tissue in simple shear at dynamic strain rates.

During severe impact conditions, brain tissue experiences a rapid and complex deformation, which can be seen as a mixture of compression, tension and shear. Diffuse axonal injury (DAI) occurs in animals and humans when both the strains and strain rates exceed 10% and 10/s, respectively. Knowing the mechanical properties of brain tissue in shear at these strains and strain rates is thus of particular importance, as they can be used in finite element simulations to predict the occurrence of brain injuries under different impact conditions.

A lipobead microarray assembled by particle entrapment in a microfluidic obstacle course and used for the display of cell membrane receptors.

Platforms which can display cell membrane ligands and receptors as a microarray library of probes for screening against a target are essential tools in drug discovery, biomarker identification, and pathogen detection. Membrane receptors and ligands require their native bilayer environment to retain their selectivity and binding affinity, and this complicates displaying them in a microarray platform. In this study, a design is developed in which the probes are first incorporated in supported lipid bilayers formed around micron-sized particles (lipobeads), and the microbeads themselves are then arrayed on a surface by hydrodynamic capture in a microfluidic obstacle course of traps.

Efficient high-throughput sequencing of a laser microdissected chromosome arm.

Background: Genomic sequence assemblies are key tools for a broad range of gene function and evolutionary studies. The diploid amphibian Xenopus tropicalis plays a pivotal role in these fields due to its combination of experimental flexibility, diploid genome, and early-branching tetrapod taxonomic position, having diverged from the amniote lineage ~360 million years ago. A genome assembly and a genetic linkage map have recently been made available.

A large pseudoautosomal region on the sex chromosomes of the frog Silurana tropicalis.

Sex chromosome divergence has been documented across phylogenetically diverse species, with amphibians typically having cytologically nondiverged ("homomorphic") sex chromosomes. With an aim of further characterizing sex chromosome divergence of an amphibian, we used "RAD-tags" and Sanger sequencing to examine sex specificity and heterozygosity in the Western clawed frog Silurana tropicalis (also known as Xenopus tropicalis). Our findings based on approximately 20 million genotype calls and approximately 200 polymerase chain reaction-amplified regions across multiple male and female genomes failed to identify a substantially sized genomic region with genotypic hallmarks of sex chromosome divergence, including in regions known to be tightly linked to the sex-determining region.

Influence of preservation temperature on the measured mechanical properties of brain tissue.

The large variability in experimentally measured mechanical properties of brain tissue is due to many factors including heterogeneity, anisotropy, age dependence and post-mortem time. Moreover, differences in test protocols also influence these measured properties. This paper shows that the temperature at which porcine brain tissue is stored or preserved prior to testing has a significant effect on the mechanical properties of brain tissue, even when tests are conducted at the same temperatures.

A centric/non-centric impact protocol and finite element model methodology for the evaluation of American football helmets to evaluate risk of concussion.

American football reports high incidences of head injuries, in particular, concussion. Research has described concussion as primarily a rotation dominant injury affecting the diffuse areas of brain tissue. Current standards do not measure how helmets manage rotational acceleration or how acceleration loading curves influence brain deformation from an impact and thus are missing important information in terms of how concussions occur.

A novel high throughput 1536-well Notch1 γ -secretase AlphaLISA assay.

The Notch pathway plays a crucial role in cell fate decisions through controlling various cellular processes. Overactive Notch signal contributes to cancer development from leukemias to solid tumors. γ-Secretase is an intramembrane protease responsible for the final proteolytic step of Notch that releases the membrane-tethered Notch fragment for signaling.

Effect of dietary nitrate on blood pressure, endothelial function, and insulin sensitivity in type 2 diabetes.

Diets rich in green, leafy vegetables have been shown to lower blood pressure (BP) and reduce the risk of cardiovascular disease. Green, leafy vegetables and beetroot are particularly rich in inorganic nitrate. Dietary nitrate supplementation, via sequential reduction to nitrite and NO, has previously been shown to lower BP and improve endothelial function in healthy humans.

Tether-supported biomembranes with α-helical peptide-based anchoring constructs.

The strict requirement of constructing a native lipid environment to preserve the structure and functionality of membrane proteins is the starting constraint when building biomaterials and sensor systems from these biomolecules. To enhance the viability of supported biomembranes systems and build new ligand display interfaces, we apply rationally designed peptides partitioned into the lipid bilayer interface. Peptides designed to form membrane-spanning α-helical anchoring domains are synthesized using solid-phase peptide synthesis.

Effects of short-term dietary nitrate supplementation on blood pressure, O2 uptake kinetics, and muscle and cognitive function in older adults.

Dietary nitrate (NO(3)(-)) supplementation has been shown to reduce resting blood pressure and alter the physiological response to exercise in young adults. We investigated whether these effects might also be evident in older adults. In a double-blind, randomized, crossover study, 12 healthy, older (60-70 yr) adults supplemented their diet for 3 days with either nitrate-rich concentrated beetroot juice (BR; 2 × 70 ml/day, ∼9.