Toll-Interacting Protein in Resolving and Non-Resolving Inflammation

Innate leukocytes manifest dynamic and distinct inflammatory responses upon challenges with rising dosages of pathogen-associated molecular pattern molecules such as lipopolysaccharide (LPS). To differentiate signal strengths, innate leukocytes may utilize distinct intracellular signaling circuitries modulated by adaptor molecules. Toll-interacting protein (Tollip) is one of the critical adaptor molecules potentially playing key roles in modulating the dynamic adaptation of innate leukocytes to varying dosages of external stimulants. While Tollip may serve as a negative regulator of nuclear factor κ of activated B cells signaling pathway in cells challenged with higher dosages of LPS, it acts as a positive regulator for low-grade chronic inflammation in leukocytes programmed by subclinical low-dosages of LPS. This review aims to discuss recent progress in our understanding of complex innate leukocyte dynamics and its relevance in the pathogenesis of resolving versus non-resolving chronic inflammatory diseases

Extension of the Carter-Yang polynomial growth curve model to allow unique times of measurement for subjects

A PC program extending the procedure due to Carter and Yang (Commun Stat: Theory Methods, 8 (1986) 2507-2526) to allow unique times of measurement for subjects is described, illustrated and made available. Given longitudinal observations on each of N subjects comprising a single group, this program determines the lowest degree polynomial in time adequate to fit the average growth curve (AGC); estimates this curve and provides confidence bands for the AGC, and confidence intervals for the corresponding polynomial regression coefficients; and so-called prediction intervals which, with a given level of confidence, will contain the growth curve of a `new' subject from the same population of which the N subjects constitute a random sample. Two kinds of missing data are accommodated. First, in the context of studies planned so that subjects will be measured at identical times and, second, in unstructured studies where subjects may present with their own, unique times of measurement.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31277/1/0000183.pd

DESIGN, ENGINEERING, AND ASSESSMENT OF MOBILE MINEFIELDS

Naval mine warfare typically supports a sea denial strategy through the denial and/or delay of the enemy’s use of the water space or by controlling sea traffic in a designated area. Sea mines have been effective for decades. However, with technological progress, mine countermeasure (MCM) efforts have reduced the risks of a minefield by detecting and/or neutralizing mines to establish and maintain a Q-route for safe passage. The concept of a mobile minefield is proposed to increase the difficulty of the enemy’s MCM and improve the survivability of the minefield by adding mobility. This research explores both the physical design concepts and the operational effectiveness of mobile mines based on simulations and models. The simulation results show that, compared to static mines, mobile mines improved the number of enemy ships destroyed by at least 200% and increased the time it took the enemy to transition through the minefield by 50%. The results suggest that the mobile minefield would be operationally useful for the Department of the Navy and this technology is worth pursing and exploring.Distribution Statement A. Approved for public release: Distribution is unlimited.Captain, Singapore ArmyCaptain, Singapore ArmyMajor, Singapore ArmyLieutenant, Taiwan NavyMajor, United States ArmyCivilian, Department of the NavyLieutenant, United States NavyCivilian, Singapore Technologies Engineering, SingaporeMajor, Singapore ArmyMajor, Singapore ArmyMajor, Singapore ArmyCommander, United States NavyCivilian, Defense Science and Technology Agency (DSTA), SingaporeMajor, Singapore ArmyMajor, Republic of Singapore Air ForceTenente-Coronel, Brazilian Air ForceLieutenant, United States NavyCivilian, Department of the ArmyMajor, Singapore ArmyMajor, Israel Defense ForcesCivilian, Defense Science Organisation, SingaporeCaptain, Singapore Arm

Evaluation of Bacteria and Fungi DNA Abundance in Human Tissues

Whereas targeted and shotgun sequencing approaches are both powerful in allowing the study of tissue-associated microbiota, the human: microorganism abundance ratios in tissues of interest will ultimately determine the most suitable sequencing approach. In addition, it is possible that the knowledge of the relative abundance of bacteria and fungi during a treatment course or in pathological conditions can be relevant in many medical conditions. Here, we present a qPCR-targeted approach to determine the absolute and relative amounts of bacteria and fungi and demonstrate their relative DNA abundance in nine different human tissue types for a total of 87 samples. In these tissues, fungi genomes are more abundant in stool and skin samples but have much lower levels in other tissues. Bacteria genomes prevail in stool, skin, oral swabs, saliva, and gastric fluids. These findings were confirmed by shotgun sequencing for stool and gastric fluids. This approach may contribute to a more comprehensive view of the human microbiota in targeted studies for assessing the abundance levels of microorganisms during disease treatment/progression and to indicate the most informative methods for studying microbial composition (shotgun versus targeted sequencing) for various samples types

Consensus Recommendations for the Use of Automated Insulin Delivery (AID) Technologies in Clinical Practice

International audienceThe significant and growing global prevalence of diabetes continues to challenge people with diabetes (PwD), healthcare providers and payers. While maintaining near-normal glucose levels has been shown to prevent or delay the progression of the long-term complications of diabetes, a significant proportion of PwD are not attaining their glycemic goals. During the past six years, we have seen tremendous advances in automated insulin delivery (AID) technologies. Numerous randomized controlled trials and real-world studies have shown that the use of AID systems is safe and effective in helping PwD achieve their long-term glycemic goals while reducing hypoglycemia risk. Thus, AID systems have recently become an integral part of diabetes management. However, recommendations for using AID systems in clinical settings have been lacking. Such guided recommendations are critical for AID success and acceptance. All clinicians working with PwD need to become familiar with the available systems in order to eliminate disparities in diabetes quality of care. This report provides much-needed guidance for clinicians who are interested in utilizing AIDs and presents a comprehensive listing of the evidence payers should consider when determining eligibility criteria for AID insurance coverage

Phosphorylation by Dyrk1A of Clathrin Coated Vesicle-Associated Proteins: Identification of the Substrate Proteins and the Effects of Phosphorylation

Dyrk1A phosphorylated multiple proteins in the clathrin-coated vesicle (CCV) preparations obtained from rat brains. Mass spectrometric analysis identified MAP1A, MAP2, AP180, and α- and β-adaptins as the phosphorylated proteins in the CCVs. Each protein was subsequently confirmed by [32P]-labeling and immunological methods. The Dyrk1A-mediated phosphorylation released the majority of MAP1A and MAP2 and enhanced the release of AP180 and adaptin subunits from the CCVs. Furthermore, Dyrk1A displaced adaptor proteins physically from CCVs in a kinase-concentration dependent manner. The clathrin heavy chain release rate, in contrast, was not affected by Dyrk1A. Surprisingly, the Dyrk1A-mediated phosphorylation of α- and β-adaptins led to dissociation of the AP2 complex, and released only β-adaptin from the CCVs. AP180 was phosphorylated by Dyrk1A also in the membrane-free fractions, but α- and β-adaptins were not. Dyrk1A was detected in the isolated CCVs and was co-localized with clathrin in neurons from mouse brain sections and from primary cultured rat hippocampus. Previously, we proposed that Dyrk1A inhibits the onset of clathrin-mediated endocytosis in neurons by phosphorylating dynamin 1, amphiphysin 1, and synaptojanin 1. Current results suggest that besides the inhibition, Dyrk1A promotes the uncoating process of endocytosed CCVs

The immediate and long-term effects of exercise and patient education on physical, functional, and quality-of-life outcome measures after single-level lumbar microdiscectomy: a randomized controlled trial protocol

BACKGROUND: Low back pain remains a costly quality-of-life-related health problem. Microdiscectomy is often the surgical procedure of choice for a symptomatic, single-level, lumbar disc herniation in younger and middle-aged adults. The question of whether a post-microdiscectomy exercise program enhances function, quality of life, and disability status has not been systematically explored. Thus, the overall purpose of this study is to assess immediate and long-term outcomes of an exercise program, developed at University of Southern California (USC), targeting the trunk and lower extremities (USC Spine Exercise Program) for persons who have undergone a single-level microdiscectomy for the first time. METHODS/DESIGN: One hundred individuals between the ages of 18 and 60 who consent to undergo lumbar microdiscectomy will be recruited to participate in this study. Subjects will be randomly assigned to one of two groups: 1) one session of back care education, or 2) a back care education session followed by the 12-week USC Spine Exercise Program. The outcome examiners (evaluators), as well as the data managers, will be blinded to group allocation. Education will consist of a one-hour "one-on-one" session with the intervention therapist, guided by an educational booklet specifically designed for post-microdiscectomy care. This session will occur four to six weeks after surgery. The USC Spine Exercise Program consists of two parts: back extensor strength and endurance, and mat and upright therapeutic exercises. This exercise program is goal-oriented, performance-based, and periodized. It will begin two to three days after the education session, and will occur three times a week for 12 weeks. Primary outcome measures include the Oswestry Disability Questionnaire, Roland-Morris Disability Questionnaire, SF-36(® )quality of life assessment, Subjective Quality of Life Scale, 50-foot Walk, Repeated Sit-to-Stand, and a modified Sorensen test. The outcome measures in the study will be assessed before and after the 12-week post-surgical intervention program. Long-term follow up assessments will occur every six months beginning one year after surgery and ending five years after surgery. Immediate and long-term effects will be assessed using repeated measures multivariate analysis of variance (MANOVA). If significant interactions are found, one-way ANOVAs will be performed followed by post-hoc testing to determine statistically significant pairwise comparisons. DISCUSSION: We have presented the rationale and design for a randomized controlled trial evaluating the effectiveness of a treatment regimen for people who have undergone a single-level lumbar microdiscectomy

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

Peer reviewe

CfA3: 185 Type Ia Supernova Light Curves from the CfA

We present multi-band photometry of 185 type-Ia supernovae (SN Ia), with over 11500 observations. These were acquired between 2001 and 2008 at the F. L. Whipple Observatory of the Harvard-Smithsonian Center for Astrophysics (CfA). This sample contains the largest number of homogeneously-observed and reduced nearby SN Ia (z < 0.08) published to date. It more than doubles the nearby sample, bringing SN Ia cosmology to the point where systematic uncertainties dominate. Our natural system photometry has a precision of 0.02 mag or better in BVRIr'i' and roughly 0.04 mag in U for points brighter than 17.5 mag. We also estimate a systematic uncertainty of 0.03 mag in our SN Ia standard system BVRIr'i' photometry and 0.07 mag for U. Comparisons of our standard system photometry with published SN Ia light curves and comparison stars, where available for the same SN, reveal agreement at the level of a few hundredths mag in most cases. We find that 1991bg-like SN Ia are sufficiently distinct from other SN Ia in their color and light-curve-shape/luminosity relation that they should be treated separately in light-curve/distance fitter training samples. The CfA3 sample will contribute to the development of better light-curve/distance fitters, particularly in the few dozen cases where near-infrared photometry has been obtained and, together, can help disentangle host-galaxy reddening from intrinsic supernova color, reducing the systematic uncertainty in SN Ia distances due to dust.Comment: Accepted to the Astrophysical Journal. Minor changes from last version. Light curves, comparison star photometry, and passband tables are available at http://www.cfa.harvard.edu/supernova/CfA3