Microbubble Contrast-Enhanced Transcutaneous Ultrasound Enables Real-Time Spinal Cord Perfusion Monitoring Following Posterior Cervical Decompression.

INTRODUCTION: Ultrasound imaging is inexpensive, portable, and widely available. The development of a real-time transcutaneous spinal cord perfusion monitoring system would allow more precise targeting of mean arterial pressure goals following acute spinal cord injury (SCI). There has been no prior demonstration of successful real-time cord perfusion monitoring in humans. METHODS: Four adult patients who had undergone posterior cervical decompression and instrumentation at a single center were enrolled into this prospective feasibility study. All participants had undergone cervical laminectomies spanning ≥2 contiguous levels ≥2 months prior to inclusion with no history of SCI. The first two underwent transcutaneous ultrasound without contrast and the second two underwent contrast-enhanced ultrasound (CEUS) with intravenously injected microbubble contrast. RESULTS: Using non-contrast ultrasound with or without Doppler (n=2), the dura, spinal cord, and vertebral bodies were apparent however ultrasonography was insufficient to discern intramedullary perfusion or clear white-gray matter differentiation. With application of microbubble contrast (n=2), it was possible to quantify differential spinal cord perfusion within and between cross-sectional regions of the cord. Further, it was possible to quantify spinal cord hemodynamic perfusion using CEUS by measuring peak signal intensity and the time to peak signal intensity after microbubble contrast injection. Time-intensity curves were generated and area under the curves were calculated as a marker of tissue perfusion. CONCLUSION: CEUS is a viable platform for monitoring real-time cord perfusion in patients who have undergone prior cervical laminectomies. Further development has the potential to change clinical management acute SCI by tailoring treatments to measured tissue perfusion parameters.

Early administration of high dose enoxaparin after traumatic brain injury.

BACKGROUND: Early enoxaparin 30 mg BID administration at 24 h post-injury has been demonstrated in patients with traumatic brain injury (TBI). However this dose can also yield subtherapeutic anti-Xa levels in 30-50% of trauma patients, suggesting that larger doses may be required for adequate prophylaxis against venous thromboembolism (VTE). The safety of enoxaparin 40 mg BID in trauma patients has previously been shown - however, these studies have largely excluded TBI patients. Therefore, we sought to demonstrate the safety of early enoxaparin 40 mg BID in a low-risk group of TBI patients. METHODS: A retrospective review of TBI patients at a Level 1 trauma center was performed. Patients with stable computed tomography (CT) of the head at 6 to 24 h post-injury who received enoxaparin 40 mg BID were included and serial GCS evaluations to identify possible clinical complications. To evaluate the safety of this dosing regimen, data was then compared to patients from our institution with similar TBI profiles who had received 5,000 units (U) of subcutaneous heparin (SQH) prophylaxis. RESULTS: 199 TBI patients were identified over a nine month period, 40/199 (19.7%) received DVT prophylaxis after traumatic injury. Of these 40, 19 (47.5%) received enoxaparin 40 mg BID and 21 (52.5%) received 5,000U of SQH. Low risk TBI patients who were either given enoxaparin (n = 7) or SQH (n = 4), demonstrated no clinical decline in mental status during their inpatient stay. CONCLUSION: Prior studies have demonstrated that enoxaparin 40 mg BID dosing is superior to traditional VTE prophylaxis in trauma patients. However, TBI patients are often excluded from this dosing due to concern for progression. Our study showed no clinical decline in mental status in a small cohort of low-risk TBI patients who received enoxaparin 40 mg BID.

Cervical cancer prevention: Human papillomavirus testing as primary screening.

Low- and middle-income countries carry a high burden of preventable cervical cancer cases and deaths. Because human papillomavirus DNA-based testing is increasingly becoming the preferred method of screening for cervical cancer prevention, this commentary discusses next steps and key considerations for its expansion.

FinaleDB: a browser and database of cell-free DNA fragmentation patterns.

SUMMARY: Circulating cell-free DNA (cfDNA) is a promising biomarker for the diagnosis and prognosis of many diseases, including cancer. The genome-wide non-random fragmentation patterns of cfDNA are associated with the nucleosomal protection, epigenetic environment and gene expression in the cell types that contributed to cfDNA. However, current progress on the development of computational methods and understanding of molecular mechanisms behind cfDNA fragmentation patterns is significantly limited by the controlled-access of cfDNA whole-genome sequencing (WGS) dataset. Here, we present FinaleDB (FragmentatIoN AnaLysis of cEll-free DNA DataBase), a comprehensive database to host thousands of uniformly processed and curated de-identified cfDNA WGS datasets across different pathological conditions. Furthermore, FinaleDB comes with a fragmentation genome browser, from which users can seamlessly integrate thousands of other omics data in different cell types to experience a comprehensive view of both gene-regulatory landscape and cfDNA fragmentation patterns. AVAILABILITY AND IMPLEMENTATION: FinaleDB service: http://finaledb.research.cchmc.org/. FinaleDB source code: https://github.com/epifluidlab/finaledb_portal, https://github.com/epifluidlab/finaledb_workflow. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Renal T cell infiltration occurs despite attenuation of development of hypertension with hydralazine in Envigo's female Dahl rat maintained on a low-Na+ diet.

Many studies have suggested that renal T cell infiltration contributes to the pathogenesis of salt-sensitive hypertension. To investigate this mechanism further, we determined T cell profiles in the kidney and lymphoid tissues as a function of blood pressure in the female Envigo Dahl salt-sensitive (SS) rat maintained on low-Na+ (LS) diet. Mean arterial pressure and heart rate were measured by telemetry in SS rats from 1 mo old (juvenile) to 4 mo old. Normotensive salt-resistant (SR) rats were included as controls. Frequencies of T helper (CD4+) cells were greater in the kidney, lymph nodes, and spleen in 4-mo-old hypertensive SS rats compared with normotensive SR animals and SS juvenile rats, suggesting that renal T cell infiltration contributes to hypertension in the SS rat on a LS diet. At 1.5 mo, half of the SS rats were treated with vehicle (Veh), and the rest received hydralazine (HDZ; 25 mg·kg-1·day-1) for 11 wk. HDZ impeded the development of hypertension compared with Veh-treated control rats [mean arterial pressure: 157 ± 4 mmHg in the Veh-treated group (n = 6) vs. 133 ± 3 mmHg in the HDZ-treated group (n = 7), P < 0.001] without impacting T helper cell frequencies in the tissues, suggesting that HDZ can overcome mechanisms of hypertension driven by renal T cell infiltration under the LS diet. Renal frequencies of CD4+CD25+ and CD4+CD25+FoxP3+ regulatory T cells were significantly higher in 4-mo-old hypertensive rats compared with normotensive SR rats and SS juvenile rats, suggesting that these T cell subpopulations play a compensatory role in the development of hypertension. Greater understanding of these T cell populations could lead to new therapeutic targets for treating inflammatory diseases associated with hypertension.

A Synthetic Isoprenoid Lipoquinone, Menaquinone-2, Adopts a Folded Conformation in Solution and at a Model Membrane Interface.

Menaquinones (naphthoquinones, MK) are isoprenoids that play key roles in the respiratory electron transport system of some prokaryotes by shuttling electrons between membrane-bound protein complexes acting as electron acceptors and donors. Menaquinone-2 (MK-2), a truncated MK, was synthesized, and the studies presented herein characterize the conformational and chemical properties of the hydrophobic MK-2 molecule. Using 2D NMR spectroscopy, we established for the first time that MK-2 has a folded conformation defined by the isoprenyl side-chain folding back over the napthoquinone in a U-shape, which depends on the specific environmental conditions found in different solvents. We used molecular mechanics to illustrate conformations found by the NMR experiments. The measured redox potentials of MK-2 differed in three organic solvents, where MK-2 was most easily reduced in DMSO, which may suggest a combination of solvent effect (presumably in part because of differences in dielectric constants) and/or conformational differences of MK-2 in different organic solvents. Furthermore, MK-2 was found to associate with the interface of model membranes represented by Langmuir phospholipid monolayers and Aerosol-OT (AOT) reverse micelles. MK-2 adopts a slightly different U-shaped conformation within reverse micelles compared to within solution, which is in sharp contrast to the extended conformations illustrated in literature for MKs.

A GPU-Based Gibbs Sampler for a Unidimensional IRT Model.

Item response theory (IRT) is a popular approach used for addressing large-scale statistical problems in psychometrics as well as in other fields. The fully Bayesian approach for estimating IRT models is usually memory and computationally expensive due to the large number of iterations. This limits the use of the procedure in many applications. In an effort to overcome such restraint, previous studies focused on utilizing the message passing interface (MPI) in a distributed memory-based Linux cluster to achieve certain speedups. However, given the high data dependencies in a single Markov chain for IRT models, the communication overhead rapidly grows as the number of cluster nodes increases. This makes it difficult to further improve the performance under such a parallel framework. This study aims to tackle the problem using massive core-based graphic processing units (GPU), which is practical, cost-effective, and convenient in actual applications. The performance comparisons among serial CPU, MPI, and compute unified device architecture (CUDA) programs demonstrate that the CUDA GPU approach has many advantages over the CPU-based approach and therefore is preferred.

Effectiveness of a positive youth development program for secondary 1 students in Macau: a pilot study.

With the rapid change to society after the opening of the gaming licensure by the government and the potential attraction to youth caused by the casinos, a well-tested and comprehensive adolescent development program previously established in Hong Kong was adopted and modified to be used in Macau. It is expected to help our adolescents achieve positive growth and be better prepared for future challenges. The aim of this study is to examine the effectiveness of the modified positive youth development program for Secondary 1 Students in Macau. Specifically, two research questions will be asked: (1) How does the positive youth development program affect positive growth for youth in Macau?; and (2) Is youth growth related to different factors such as gender, age, family financial condition, and parents' marital status? A mixed research method with a quantitative approach using a pre- and post-test pre-experimental design, and a qualitative approach using a focus group for the participants is carried out. The study sample included 232 Secondary 1 Students in two schools. The objective outcome evaluation showed that, overall, 123 (53%) of the participants had significant improvement on the total scores of the Chinese Positive Youth Development Scale (CPYDS) and the two composite scores. However, there were some increases in the behavioral intention of alcohol drinking and participation in gambling activities. The "happiness of the family life" was found to have significant differences in the score of the CPYDS, which was shown to be the factor related to youth growth. The focus group interviews revealed that both positive and negative feedback was obtained from the discussion; however, the majority of the participants perceived benefits to themselves from the program. With reference to the principle of triangulation, the present study suggests that, based on both quantitative and qualitative evaluation findings, it should be concluded that there is positive evidence supporting the effectiveness of the Tier 1 Program of the Hong Kong Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes), which was adopted and modified for Macau. In addition, special attention should be paid to the behavioral intention of alcohol drinking and participation in gambling activities in the local context.