In Vivo rapid delivery of vasopressin from an implantable drug delivery micro-electro-mechanical device

A miniaturized implantable rapid drug delivery device based on micro-electro-mechanical-systems technology was recently developed and characterized. This device is intended to address acute conditions in high-risk subjects. This work provides an in vivo proof-of-concept for the device in a rabbit model, by releasing a physiologically active dose of vasopressin, a vasoconstrictor. The devices were implanted subcutaneously and activated to rapidly release vasopressin, with monitoring of mean arterial pressure and plasma levels.Device releases showed a rapid and measurable effect on mean arterial pressure as well as a continuous diffusion of vasopressin into the bloodstream, consistent with a depot effect. Plasma levels in rabbits receiving vasopressin with the device rose monotonically to 24.4 ± 2.9 ng/mL after one hour. Bioavailability after one hour was calculated to be 6.2 ± 2.8 % (mean ± s.d.).A new modality for rapid and controlled drug delivery has been developed. The device can be used as a new implantable device controlled by medical algorithms (based on heart rate or mean arterial pressure, for example) for autonomous operation in high-risk populations that require immediate ambulatory intervention.Keywords: Subcutaneous drug delivery; vasopressin; MEMS; rabbit; bioavailability

In Vivo rapid delivery of vasopressin from an implantable drug delivery micro-electro-mechanical device

A miniaturized implantable rapid drug delivery device based on micro-electro-mechanical-systems technology was recently developed and characterized. This device is intended to address acute conditions in high-risk subjects. This work provides an in vivo proof-of-concept for the device in a rabbit model, by releasing a physiologically active dose of vasopressin, a vasoconstrictor. The devices were implanted subcutaneously and activated to rapidly release vasopressin, with monitoring of mean arterial pressure and plasma levels.Device releases showed a rapid and measurable effect on mean arterial pressure as well as a continuous diffusion of vasopressin into the bloodstream, consistent with a depot effect. Plasma levels in rabbits receiving vasopressin with the device rose monotonically to 24.4 ± 2.9 ng/mL after one hour. Bioavailability after one hour was calculated to be 6.2 ± 2.8 % (mean ± s.d.).A new modality for rapid and controlled drug delivery has been developed. The device can be used as a new implantable device controlled by medical algorithms (based on heart rate or mean arterial pressure, for example) for autonomous operation in high-risk populations that require immediate ambulatory intervention.Keywords: Subcutaneous drug delivery; vasopressin; MEMS; rabbit; bioavailability

Underdiagnosis of mild cognitive impairment: A consequence of ignoring practice effects

INTRODUCTION: Longitudinal testing is necessary to accurately measure cognitive change. However, repeated testing is susceptible to practice effects, which may obscure true cognitive decline and delay detection of mild cognitive impairment (MCI). METHODS: We retested 995 late-middle-aged men in a ∼6-year follow-up of the Vietnam Era Twin Study of Aging. In addition, 170 age-matched replacements were tested for the first time at study wave 2. Group differences were used to calculate practice effects after controlling for attrition effects. MCI diagnoses were generated from practice-adjusted scores. RESULTS: There were significant practice effects on most cognitive domains. Conversion to MCI doubled after correcting for practice effects, from 4.5% to 9%. Importantly, practice effects were present although there were declines in uncorrected scores. DISCUSSION: Accounting for practice effects is critical to early detection of MCI. Declines, when lower than expected, can still indicate practice effects. Replacement participants are needed for accurately assessing disease progression.Published versio

Efficient Iterative Algorithms for the Stochastic Finite Element Method with Application to Acoustic Scattering

In this study, we describe the algebraic computations required to implement the stochastic finite element method for solving problems in which uncertainty is restricted to right hand side data coming from forcing functions or boundary conditions. We show that the solution can be represented in a compact outer product form which leads to efficiencies in both work and storage, and we demonstrate that block iterative methods for algebraic systems with multiple right hand sides can be used to advantage to compute this solution. We also show how to generate a variety of statistical quantities from the computed solution. Finally, we examine the behavior of these statistical quantities in one setting derived from a model of acoustic scattering. UMIACS-TR-2002-10

Photosystem I light-harvesting proteins regulate photosynthetic electron transfer and hydrogen production

Linear electron flow (LEF) and cyclic electron flow (CEF) compete for light-driven electrons transferred from the acceptor side of photosystem I (PSI). Under anoxic conditions, such highly reducing electrons also could be used for hydrogen (H2) production via electron transfer between ferredoxin and hydrogenase in the green alga Chlamydomonas reinhardtii. Partitioning between LEF and CEF is regulated through PROTON-GRADIENT REGULATION5 (PGR5). There is evidence that partitioning of electrons also could be mediated via PSI remodeling processes. This plasticity is linked to the dynamics of PSI-associated light-harvesting proteins (LHCAs) LHCA2 and LHCA9. These two unique light-harvesting proteins are distinct from all other LHCAs because they are loosely bound at the PSAL pole. Here, we investigated photosynthetic electron transfer and H2 production in single, double, and triple mutants deficient in PGR5, LHCA2, and LHCA9. Our data indicate that lhca2 and lhca9 mutants are efficient in photosynthetic electron transfer, that LHCA2 impacts the pgr5 phenotype, and that pgr5/lhca2 is a potent H2 photo-producer. In addition, pgr5/lhca2 and pgr5/lhca9 mutants displayed substantially different H2 photo-production kinetics. This indicates that the absence of LHCA2 or LHCA9 impacts H2 photo-production independently, despite both being attached at the PSAL pole, pointing to distinct regulatory capacities

Patient experience of care in a student-faculty collaborative practice

Student Run Clinics (SRCs) are a popular means of caring for the underserved while providing valuable medical education opportunities. Reports of patient experience surveys are rare in this setting. This is troublesome because it is possible that underserved patients, who are more likely to receive care at SRCs, are not receiving the same level of care as at more traditional medical practices. The purpose of this research was to measure patient experience in a student-led medical clinic. The method included the use of patient experience surveys, which were self-administered pre-visit and self- and interviewer administered post-visit. The key results, 100% of patients felt treated with respect. 81.4% of patients would “definitely” and 16.3% would “somewhat” refer their family and friends to the clinic. 87% reported being seen within 15 minutes of their appointment time; 60% reported that they knew they would be seen by medical students and a doctor. This data has been useful to our student-led clinic in streamlining clinic flow, reducing wait times and building awareness of our structure. Our hope is this study will encourage others SRCs to adopt similar student-faculty collaborative research based practices to enhance care for SRC patients while teaching students to use patient feedback to improve quality of care

Enriched protein screening of human bone marrow mesenchymal stromal cell secretions reveals MFAP5 and PENK as novel IL-10 modulators

The secreted proteins from a cell constitute a natural biologic library that can offer significant insight into human health and disease. Discovering new secreted proteins from cells is bounded by the limitations of traditional separation and detection tools to physically fractionate and analyze samples. Here, we present a new method to systematically identify bioactive cell-secreted proteins that circumvent traditional proteomic methods by first enriching for protein candidates by differential gene expression profiling. The bone marrow stromal cell secretome was analyzed using enriched gene expression datasets in combination with potency assay testing. Four proteins expressed by stromal cells with previously unknown anti-inflammatory properties were identified, two of which provided a significant survival benefit to mice challenged with lethal endotoxic shock. Greater than 85% of secreted factors were recaptured that were otherwise undetected by proteomic methods, and remarkable hit rates of 18% in vitro and 9% in vivo were achieved

Amyotrophic lateral sclerosis–specific quality of life–short form (ALSSQOL‐SF): A brief, reliable, and valid version of the ALSSQOL‐R

Introduction: The Amyotrophic Lateral Sclerosis (ALS)‐Specific Quality of Life instrument and its revised version (ALSSQOL and ALSSQOL‐R) have strong psychometric properties, and have demonstrated research and clinical utility. In this study we aimed to develop a short form (ALSSQOL‐SF) suitable for limited clinic time and patient stamina. Methods: The ALSSQOL‐SF was created using Item Response Theory and confirmatory factor analysis on 389 patients. A cross‐validation sample of 162 patients assessed convergent, divergent, and construct validity of the ALSSQOL‐SF compared with psychosocial and physical functioning measures. Results: The ALSSQOL‐SF consisted of 20 items. Compared with the ALSSQOL‐R, optimal precision was retained, and completion time was reduced from 15–25 minutes to 2–4 minutes. Psychometric properties for the ALSSQOL‐SF and its subscales were strong. Discussion: The ALSSQOL‐SF is a disease‐specific global QOL instrument that has a short administration time suitable for clinical use, and can provide clinically useful, valid information about persons with ALS. Muscle Nerve 58: 646–654, 2018Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146574/1/mus26203_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146574/2/mus26203.pd

Influence of young adult cognitive ability and additional education on later-life cognition

How and when education improves cognitive capacity is an issue of profound societal importance. Education and later-life education-related factors, such as occupational complexity and engagement in cognitive-intellectual activities, are frequently considered indices of cognitive reserve, but whether their effects are truly causal remains unclear. In this study, after accounting for general cognitive ability (GCA) at an average age of 20 y, additional education, occupational complexity, or engagement in cognitive-intellectual activities accounted for little variance in late midlife cognitive functioning in men age 56-66 (n = 1009). Age 20 GCA accounted for 40% of variance in the same measure in late midlife and approximately 10% of variance in each of seven cognitive domains. The other factors each accounted for <1% of the variance in cognitive outcomes. The impact of these other factors likely reflects reverse causation-namely, downstream effects of early adult GCA. Supporting that idea, age 20 GCA, but not education, was associated with late midlife cortical surface area (n = 367). In our view, the most parsimonious explanation of our results, a meta-analysis of the impact of education, and epidemiologic studies of the Flynn effect is that intellectual capacity gains due to education plateau in late adolescence/early adulthood. Longitudinal studies with multiple cognitive assessments before completion of education would be needed to confirm this speculation. If cognitive gains reach an asymptote by early adulthood, then strengthening cognitive reserve and reducing later-life cognitive decline and dementia risk may really begin with improving educational quality and access in childhood and adolescence.Peer reviewe