The Bio-Hermes Study: Biomarker database developed to investigate blood-based and digital biomarkers in community-based, diverse populations clinically screened for Alzheimer's disease.

Introduction: Alzheimer's disease (AD) trial participants are often screened for eligibility by brain amyloid positron emission tomography/cerebrospinal fluid (PET/CSF), which is inefficient as many are not amyloid positive. Use of blood-based biomarkers may reduce screen failures.

Methods: We recruited 755 non-Hispanic White, 115 Hispanic, 112 non-Hispanic Black, and 19 other minority participants across groups of cognitively normal (n = 417), mild cognitive impairment (n = 312), or mild AD (n = 272) participants.

Opportunities for Regulatory Changes to Promote Pediatric Device Innovation in the United States: Joint Recommendations From Pediatric Innovator Roundtables.

Objective: The purpose of this report is to provide insight from pediatric stakeholders with a shared desire to facilitate a revision of the current United States regulatory pathways for the development of pediatric healthcare devices.

Methods: On August 5, 2020, a group of innovators, engineers, professors and clinicians met to discuss challenges and opportunities for the development of new medical devices for pediatric health and the importance of creating a regulatory environment that encourages and accelerates the research and development of such devices. On January 6, 2021, this group joined regulatory experts at a follow-up meeting.

Cryo scanning transmission x-ray microscope optimized for spectrotomography.

A cryo scanning transmission X-ray microscope, the cryo-STXM, has been designed and commissioned at the Canadian Light Source synchrotron. The instrument is designed to operate from 100 to 4000 eV (λ = 12.4 - 0.

Using non-invasive magnetic resonance imaging (MRI) to assess the reduction of Cr(VI) using a biofilm-palladium catalyst.

Industrial waste streams may contain contaminants that are valuable like Pd(II) and/or toxic and mutagenic like Cr(VI). Using Serratia sp. biofilm the former was biomineralized to produce a supported nanocrystalline Pd(0) catalyst, and this biofilm-Pd heterogeneous catalyst was then used to reduce Cr(VI) to less dangerous Cr(III) at room temperature, with formate as the electron donor.

Extending the dynamic range of phase contrast magnetic resonance velocity imaging using advanced higher-dimensional phase unwrapping algorithms.

Phase contrast magnetic resonance velocity imaging is a powerful technique for quantitative in vivo blood flow measurement. Current practice normally involves restricting the sensitivity of the technique so as to avoid the problem of the measured phase being 'wrapped' onto the range -pi to +pi. However, as a result, dynamic range and signal-to-noise ratio are sacrificed.

Branch cut surface placement for unwrapping of undersampled three-dimensional phase data: application to magnetic resonance imaging arterial flow mapping.

We demonstrate in both simulated and real cases the effect that undersampling of a three-dimensional (3D) wrapped phase distribution has on the geometry of phase singularity loops and their branch cut surfaces. The more intuitive two-dimensional (2D) problem of setting branch cuts between dipole pairs is taken as a starting point, and then branch cut surfaces in flat and ambiguous 3D loops are discussed. It is shown that the correct 2D branch cuts and 3D branch cut surfaces should be placed where the gradient of the original phase distribution exceeded pi rad voxel(-1).

Early detection of tumour immune-rejection using magnetic resonance imaging.

Dynamic contrast agent-enhanced magnetic resonance imaging measurements of the perfusion of an immunogenic murine tumour showed that immune rejection was preceded by an increase in the apparent vascular volume of the tumour. This increase in vascularity, which has been observed previously in other tumours undergoing immune rejection, was confirmed by histological analysis of tumour sections obtained postmortem. Magnetic resonance imaging measurements similar to this could be used in the clinic to monitor the early responses of tumours to immunotherapy, before there is any change in tumour growth rate or volume.

Differential sensitivity of two adenocarcinoma xenografts to the anti-vascular drugs combretastatin A4 phosphate and 5,6-dimethylxanthenone-4-acetic acid, assessed using MRI and MRS.

The effects of two anti-vascular agents, combretastatin A4 phosphate (CA4P), and 5,6-dimethylxanthenone-4-acetic acid (DMXAA), on the perfusion of two human colon adenocarcinomas implanted in SCID mice, were assessed for up to 3 h using non-invasive magnetic resonance imaging (MRI) and spectroscopy techniques (MRS). MRI measurements of GdDTPA inflow showed that treatment with CA4P had little effect on the perfusion of HT29 tumours. Localized (31)P MRS measurements also showed that the drug had no significant effect on tumour cell energy status, as assessed from the ratio of the integrals of the signals from inorganic phosphate (P(i)) and nucleoside triphosphates.

Non-invasive detection of apoptosis using magnetic resonance imaging and a targeted contrast agent.

The C2 domain of synaptotagmin I, which binds to anionic phospholipids in cell membranes, was shown to bind to the plasma membrane of apoptotic cells by both flow cytometry and confocal microscopy. Conjugation of the protein to superparamagnetic iron oxide nanoparticles allowed detection of this binding using magnetic resonance imaging. Detection of apoptotic cells, using this novel contrast agent, was demonstrated both in vitro, with isolated apoptotic tumor cells, and in vivo, in a tumor treated with chemotherapeutic drugs.

Potent anti-metastatic activity of combretastatin-A4.

The requirement for tumour vascularisation to permit the expansion of solid tumours beyond a threshold size of approximately 1 mm diameter has focussed attention on anti-vascular and anti-angiogenic agents for cancer therapy. Combretastatin-A4 (cis CA-4P) is a tubulin-binding agent that is cytotoxic for proliferating endothelial cells in vitro and causes anti-vascular effects in the established tumour vessels of some primary tumours. Preliminary data from Phase I clinical trials indicate that cis CA-4 may also be effective in targeting the vasculature of human tumours.

The susceptibility of tumors to the antivascular drug combretastatin A4 phosphate correlates with vascular permeability.

The acute effects of the antivascular drug, combretastatin A4 phosphate, on tumor energy status and perfusion were assessed using magnetic resonance imaging (MRI) and spectroscopy. Localized (31)P magnetic resonance spectroscopy showed that LoVo and RIF-1 tumors responded well to drug treatment, with significant increases in the P(i)/nucleoside triphosphate ratio within 3 h, whereas SaS, SaF, and HT29 tumors did not respond to the same extent. This variable response was also seen in MRI experiments in which tumor perfusion was assessed by monitoring the kinetics of inflow of the contrast agent, gadolinium diethylenetriaminepentaacetate.

Diagnosis of glaucoma using telemedicine--the effect of compression on the evaluation of optic nerve head cup-disc ratio.

A photograph of the optic nerve head requires a lot of disk space (over 1 MByte) for storage and may require substantial bandwidth and time for transmission to a remote practitioner for a second opinion. To test whether compression degrades the image quality of the images, 302 slides were digitized at an optical resolution of 2400 pixels/inch (945 pixels/cm) and 30 bit/pixel. The images were saved both in non-compressed TIFF format and in compressed JPEG (compression ratio of 60) format.

The intellectual property cookbook: a guide for the novice health-care telemedicine provider working with industry.

Telemedicine is a new field and many health-care providers are developing their own products with the help of industry. Most practitioners are novices in the legal tools necessary to protect their own work with regard to any future commercialization. To summarize these issues for the telemedicine practitioner, a review of intellectual property protection has been performed.

Collaborative telemedicine between optometry and ophthalmology: an initiative from the University of Houston.

The University of Houston College of Optometry (UHCO) has developed a strong Telemedicine Optometry/Ophthalmology program. Patient care, clinical teaching and research benefit from utilizing Telemedicine technology. This initiative between Optometry and Ophthalmology is at the forefront of eyecare! Presented here: clinical teaching opportunities via tele-education including retinal, uveitic, neuro-ophthalmic disorders and glaucoma.

Magnetic resonance imaging and spectroscopy of combretastatin A4 prodrug-induced disruption of tumour perfusion and energetic status.

The effects of combretastatin A4 prodrug on perfusion and the levels of 31P metabolites in an implanted murine tumour were investigated for 3 h after drug treatment using nuclear magnetic resonance imaging (MRI) and spectroscopy (MRS). The area of regions of low signal intensity in spin-echo images of tumours increased slightly after treatment with the drug. These regions of low signal intensity corresponded to necrosis seen in histological sections, whereas the expanding regions surrounding them corresponded to haemorrhage.

Semiquantitation of cooperativity in binding of vancomycin-group antibiotics to vancomycin-susceptible and -resistant organisms.

The association of vancomycin group antibiotics with the growing bacterial cell wall was investigated by using the cell wall precursor analog di-N-acetyl-Lys-D-Ala-D-Ala in competition binding experiments. The affinities of the antibiotics for the -D-Ala-D-Ala-containing cell wall precursors of Bacillus subtilis ATCC 6633 (a model for vancomycin-susceptible gram-positive bacteria) and for the -D-Ala-D-Lac-containing cell wall precursors of Leuconostoc mesenteroides (a model for vancomycin-resistant strains of Enterococcus faecium and Enterococcus faecalis) were determined by a whole-cell assay. The binding of strongly dimerizing antibiotics such as eremomycin to the bacterial surface was thus shown to be enhanced by up to 2 orders of magnitude (relative to the binding in free solution) by the chelate effect, whereas weakly dimerizing antibiotics like vancomycin and antibiotics carrying lipid tails (teicoplanin) benefited less (ca.

Cooperativity between non-polar and ionic forces in the binding of bacterial cell wall analogues by vancomycin in aqueous solution.

The clinically important glycopeptide antibiotic vancomycin binds to bacterial cell wall peptides of Gram-positive bacteria which terminate in -Lys-D-Ala-D-Ala, thereby inhibiting cell wall synthesis resulting in cell death. We have removed the N-terminal leucine residue of vancomycin by an Edman degradation and acylated the exposed amino group of residue 2 with N-Me-Gly, N-Me-D-Ala, acetyl, butyl, and isohexyl groups to generate novel vancomycin analogues. The binding of vancomycin and these vancomycin analogues to the bacterial cell wall analogue di-N-Ac-L-Lys-D-Ala-D-Ala (DALAA) was studied by NMR techniques and UV spectroscopy.

Dimerization and membrane anchors in extracellular targeting of vancomycin group antibiotics.

Antibiotics of the vancomycin group are shown to enhance their affinities for the bacterial cell wall by the devices of either dimerization (vancomycin and other glycopeptides which dimerize even more strongly) or use of a membrane anchor (teicoplanin); a chelate mechanism is suggested in both cases, as supported by antagonism experiments with the cell wall analog di-N-acetyl-L-Lys-D-Ala-D-Ala. These results may have implications for other binding processes which occur near membrane surfaces.

Modified glycine precipitation technique for the preparation of factor VIII concentrate of high purity and high stability.

A modification of the glycine precipitation method for the production of factor VIII concentrate is reported. In this procedure, cryoprecipitate was prepared, washed and dissolved in buffer. Contaminating fibrinogen was precipitated by the addition of 2.