Y-switch: a spring-loaded synthetic gene switch for robust DNA/RNA signal amplification and detection.

Nucleic acid tests (NATs) are essential for biomedical diagnostics. Traditional NATs, often complex and expensive, have prompted the exploration of toehold-mediated strand displacement (TMSD) circuits as an economical alternative. However, the wide application of TMSD-based reactions is limited by 'leakage'-the spurious activation of the reaction leading to high background signals and false positives.

Pharmacokinetics, pharmacodynamics, and safety of fesomersen, a novel antisense inhibitor of factor XI, in healthy Chinese, Japanese, and Caucasian volunteers.

The inhibition of coagulation factor XI (FXI) presents an attractive approach for anticoagulation as it is not expected to increase the risk of clinically relevant bleeding and is anticipated to be at least as effective as currently available anticoagulants. Fesomersen is a conjugated antisense oligonucleotide that selectively inhibits the expression of FXI. The article describes three clinical studies that investigated the safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of fesomersen after subcutaneous (s.

Amphiphilic Block Copolymers PEG--PMTCs: Synthesis, Self-Assembly, Degradation Properties and Biocompatibility.

As a hydrophilic cyclic ketene acetal (CKA), 2-methylene-1,3,6-trioxocane (MTC) has recently attracted a lot of attention owing to its ability to promote a quicker (bio)degradation as compared to other heavily studied CKAs. Here, we prepared amphiphilic block copolymers based on poly-MTC with varying chain lengths by radical ring opening polymerization. Self-assemblies of these amphiphiles were performed in PBS buffer to generate nanoparticles with sizes from 40 to 105 nm, which were verified by dynamic light scattering, electron microscopy, and static light scattering (Zimm plots).

Noise Exposure and Hearing Loss among Workers at a Hammer Forge Company.

The National Institute for Occupational Safety and Health (NIOSH) evaluated continuous and impact noise exposures and hearing loss among workers at a hammer forge company. Full-shift personal noise exposure measurements were collected on forge workers across 15 different job titles; impact noise characteristics and one-third octave band noise levels were assessed at the forge hammers; and 4,750 historic audiometric test records for 483 workers were evaluated for hearing loss trends. Nearly all workers' noise exposures exceeded regulatory and/or recommended exposure limits.

Dynamic matrices with DNA-encoded viscoelasticity for cell and organoid culture.

Three-dimensional cell and organoid cultures rely on the mechanical support of viscoelastic matrices. However, commonly used matrix materials lack control over key cell-instructive properties. Here we report on fully synthetic hydrogels based on DNA libraries that self-assemble with ultrahigh-molecular-weight polymers, forming a dynamic DNA-crosslinked matrix (DyNAtrix).

Effects of Rapamycin on the Expression of Redox Enzymes in Aortic Vascular Smooth Muscle Cells from Marfan Syndrome Mice.

Activation of the mechanistic target of rapamycin (mTOR) pathway has been implicated in an increasing number of diseases, including Marfan syndrome (MFS), an inherited connective tissue disorder. mTOR-dependent reactive oxygen species (ROS) formation has also been suggested to play a role in aortic aneurysm formation in MFS patients. This study aimed to characterize the effects of mTOR inhibition by rapamycin on key redox enzymes and NADPH oxidases (NOX) in cultured vascular smooth muscle cells of a murine MFS model.

Temporary and Permanent Auditory Effects Associated with Occupational Coexposure to Low Levels of Noise and Solvents.

This study aimed to assess temporary and permanent auditory effects associated with occupational coexposure to low levels of noise and solvents. Cross-sectional study with 25 printing industry workers simultaneously exposed to low noise (<80 dBA TWA) and low levels of solvents. The control group consisted of 29 industry workers without the selected exposures.

Single-molecule mechanical fingerprinting with DNA nanoswitch calipers.

Decoding the identity of biomolecules from trace samples is a longstanding goal in the field of biotechnology. Advances in DNA analysis have substantially affected clinical practice and basic research, but corresponding developments for proteins face challenges due to their relative complexity and our inability to amplify them. Despite progress in methods such as mass spectrometry and mass cytometry, single-molecule protein identification remains a highly challenging objective.

Work-Related Risk Factors for Rotator Cuff Syndrome in a Prospective Study of Manufacturing and Healthcare Workers.

Objective: This prospective study assessed the risk of developing rotator cuff syndrome (RCS) with separate or specific combinations of biomechanical exposures measures, controlling for individual confounders.

Background: Compared with other musculoskeletal disorders, rates of work-related shoulder musculoskeletal disorders have been declining more slowly.

Method: We conducted up to 2 years of individual, annual assessments of covariates, exposures, and health outcomes for 393 U.

Safe patient handling and mobility (SPHM) for increasingly bariatric patient populations: Factors related to caregivers' self-reported pain and injury.

This study was conducted at 5 Veterans Administration Medical Centers (VAMCs). A cross sectional survey was administered to 134 workers who routinely lift and mobilize patients within their workplaces' safe patient handling and mobility (SPHM) programs, which are mandated in all VAMCs. The survey was used to examine a comprehensive list of SPHM and non-SPHM variables, and their associations with self-reported musculoskeletal injury and pain.

Role of computed tomography texture analysis using dual-energy-based bone marrow imaging for multiple myeloma characterization: comparison with histology and established serologic parameters.

Objective: To identify textural features on dual-energy CT (DECT)-based bone marrow images in myeloma which correlate with serum markers of myeloma activity and the degree of medullary involvement.

Methods: A total of 110 patients (63.0 ± 11.

Mid-term response assessment in multiple myeloma using a texture analysis approach on dual energy-CT-derived bone marrow images - A proof of principle study.

Purpose: To identify textural features on dual-energy CT (DECT)-generated virtual non calcium (VNC) bone marrow images in a small group of patients with multiple myeloma undergoing systemic treatment which could potentially help for mid-term response assessment.

Methods: 44 patients (59.1 ± 11.

A smart polymer for sequence-selective binding, pulldown, and release of DNA targets.

Selective isolation of DNA is crucial for applications in biology, bionanotechnology, clinical diagnostics and forensics. We herein report a smart methanol-responsive polymer (MeRPy) that can be programmed to bind and separate single- as well as double-stranded DNA targets. Captured targets are quickly isolated and released back into solution by denaturation (sequence-agnostic) or toehold-mediated strand displacement (sequence-selective).

Trends in Work-Related Musculoskeletal Disorders From the 2002 to 2014 General Social Survey, Quality of Work Life Supplement.

Objective: To update trends in prevalence of back and upper limb musculoskeletal symptoms and risk factors from the 2014 Quality of Work Life (QWL) Survey.

Methods: Quadrennial QWL Surveys, 2002 to 2014 (with N = 1455, 1537, 1019, and 1124 in 2002, 2006, 2010, and 2014 surveys respectively) were analyzed for reports of back pain and pain in arms.

Results: In the fourth analysis of this survey, 12-year trends continue to show a decline in back pain and pain in arms.

Rapid in vitro production of single-stranded DNA.

There is increasing demand for single-stranded DNA (ssDNA) of lengths >200 nucleotides (nt) in synthetic biology, biological imaging and bionanotechnology. Existing methods to produce high-purity long ssDNA face limitations in scalability, complexity of protocol steps and/or yield. We present a rapid, high-yielding and user-friendly method for in vitro production of high-purity ssDNA with lengths up to at least seven kilobases.

Noise exposures and perceptions of hearing conservation programs among wildland firefighters.

Wildland firefighters are exposed to numerous noise sources that may be hazardous to their hearing. This study examined the noise exposure profiles for 264 wildland firefighters across 15 job categories. All 264 firefighters completed questionnaires to assess their use of hearing protection devices, enrollment in hearing conservation programs, and their overall perception of their noise exposure.

Noncovalent Aqua Materials Based on Perylene Diimides.

Most robust functional organic materials are currently based on polymers. These materials exhibit high stability, but once formed they are difficult to modify, adapt to their environment, and recycle. Materials based on small molecules that are held together by noncovalent interactions can offer an alternative to conventional polymer materials for applications that require adaptive and stimuli-responsive features.

Auditory system dysfunction in Brazilian gasoline station workers.

To examine the auditory system of Brazilian gasoline station workers using an extensive audiological test battery. This was a cross-sectional study. The audiological evaluation included a questionnaire, pure-tone audiometry, acoustic immittance tests, transient-evoked otoacoustic emissions (TEOAEs), distortion product otoacoustic emissions (DPOAEs), auditory brainstem response (ABR) and P300 auditory-evoked potentials.

The relationships between blood lead levels and serum thyroid stimulating hormone and total thyroxine in the third National Health and Nutrition Examination Survey.

Regression analysis was used to estimate and test for relationships between the blood lead concentration and the concentrations of serum thyroid stimulating hormone and serum total thyroxine in adults, 20 years and older, participating in the third National Health and Nutrition Examination Survey. No relationship was found between the blood lead level and the concentration of serum thyroid stimulating hormone. The serum total thyroxine concentration decreased as the blood lead level increased in women, but not in men.

Field evaluation of onsite near real-time monitors for surface contamination by 5-fluorouracil.

Objectives: In order to produce near real-time onsite results to detect surface contamination by antineoplastic drugs, the National Institute for Occupational Safety and Health developed monitors for 5-fluorouracil, which use surface wiping and lateral flow immunoassay for measurement. The monitors were tested in the laboratory to assess the sensitivity of detection on laboratory-produced contaminated surfaces. A field evaluation to assess the capability of the monitors to make measurements in healthcare workplaces was carried out in collaboration with a medical device company and the results are presented in this report.

Selective Nascent Polymer Catch-and-Release Enables Scalable Isolation of Multi-Kilobase Single-Stranded DNA.

Scalable methods currently are lacking for isolation of long ssDNA, an important material for numerous biotechnological applications. Conventional biomolecule purification strategies achieve target capture using solid supports, which are limited in scale and susceptible to contamination owing to nonspecific adsorption and desorption on the substrate surface. We herein disclose selective nascent polymer catch and release (SNAPCAR), a method that utilizes the reactivity of growing poly(acrylamide-co-acrylate) chains to capture acrylamide-labeled molecules in free solution.

Self-Assembly of Perylenediimide-Single-Strand-DNA Conjugates: Employing Hydrophobic Interactions and DNA Base-Pairing To Create a Diverse Structural Space.

The self-assembly behavior of DNA conjugates possessing a perylenediimide (PDI) head group and an N-oligonucleotide tail has been investigated using a combination of optical spectroscopy and cryogenic transmission electron microscopy (cryo-TEM) imaging. To obtain insight into the interplay between PDI hydrophobic interactions and DNA base-pairing we employed systematic variation in the length and composition of the oligo tails. Conjugates with short (TA) or (CG) oligo tails (n≤3) form helical or nonhelical fibers constructed from π-stacked PDI head groups with pendent oligo tails in aqueous solution.

Associations between urinary biomarkers of polycyclic aromatic hydrocarbon exposure and reproductive function during menstrual cycles in women.

Essentially all women are exposed to polycyclic aromatic hydrocarbons (PAHs), formed during incomplete combustion of organic materials, including fossil fuels, wood, foods, and tobacco. PAHs are ovarian toxicants in rodents, and cigarette smoking is associated with reproductive abnormalities in women. Biomonitoring of hydroxylated PAH (OH-PAH) metabolites in urine provides an integrated measure of exposure to PAHs via multiple routes and has been used to characterize exposure to PAHs in humans.

Inter-laboratory comparison of three earplug fit-test systems.

The National Institute for Occupational Safety and Health (NIOSH) sponsored tests of three earplug fit-test systems (NIOSH HPD Well-Fit, Michael & Associates FitCheck, and Honeywell Safety Products VeriPRO). Each system was compared to laboratory-based real-ear attenuation at threshold (REAT) measurements in a sound field according to ANSI/ASA S12.6-2008 at the NIOSH, Honeywell Safety Products, and Michael & Associates testing laboratories.