2021 Patient Preferences for Point of Care Testing Survey: More Acceptance and Less Concern.

BACKGROUND: The evolving opinions of our community members provide insights into how end-users perceive the value and identify key point-of-care test (POCT) characteristics. METHODS: We deployed our validated 45-item English-language survey to uncompensated volunteers and compared the results from 1264 respondents in 2021 with those obtained in 2020. RESULTS: Average responses for items regarding the benefits of POCTs demonstrated that the 2021 respondents indicated agreement with all 14 potential benefits. Average responses for items regarding concerns were distinctly different from those for benefits. The only concern item that scored in the agree range was "not having insurance coverage for POCTs." Average responses to the other 13 concern items were in the disagree range. For 8 of these items, the magnitude of disagreement was greater in the 2021 survey than was observed for the 2020 survey. Differences in POCT exposure over time and by US regions suggest that higher levels of exposure to POCTs in the East are associated with stronger public support. CONCLUSIONS: Community members strongly support the development of accurate, convenient, easy-to-use, affordable, equitably available, in-home POCTs that produce immediate results. This empowers patients and home caregivers to diagnose, manage, enhance their adherence to medical treatments, and more efficiently engage their physicians.

Mapping the biological oxidative damage of engineered nanomaterials.

Novel engineered nanomaterials (ENMs) are being introduced into the market rapidly with little understanding of their potential toxicity. Each ENM is a complex combination of diverse sizes, surface chemistries, crystallinity, and metal impurities. Variability in physicochemical properties is poorly understood but is critically important in revealing adverse effects of ENMs. A need also exists for discovering broad relationships between variations in these physicochemical parameters and toxicological endpoints of interest. Biological oxidative damage (BOD) has been recognized as a key mechanism of nanotoxicity. An assortment of 138 ENMs representing major classes are evaluated for BOD elicited (net decrease in the antioxidant capacity of ENM-exposed human blood serum, as compare to unexposed serum) using the 'Ferric Reducing Ability of Serum' (FRAS) assay. This robust and high-throughput approach has the ability to determine the co-effects which multiple physicochemical characteristics impart on oxidative potential, and subsequently to identify and quantify the influence of individual factors. FRAS BOD approach demonstrated the potential for preliminary evaluation of potential toxicity of ENMs, mapping the within- and between-class variability of ENMs, ranking the potential toxicity by material class, and prioritizing the ENMs for further toxicity evaluation and risk assessment.

Biological oxidative damage by carbon nanotubes: fingerprint or footprint?

Carbon nanotubes (CNTs) have received much attention for performance and toxicity, but vary substantially in terms of impurity type and content, morphology, and surface activity. This study determined the decrease of antioxidant capacity, defined as biological oxidative damage (BOD), of CNTs-exposed serum. The variability in several physicochemical properties of CNTs and their links to BOD elicited in human serum were explored. Tremendous variation in transition metal type and content (104-fold), specific surface area (SSA, nine-fold), and BOD were observed. Mass specific BOD (mBOD) varied from 0.006-0.187 µmol TEU mg(-1), whereas surface area specific BOD (sBOD) varied from 0.068-0.42 µmol TEU m(-2). The sBOD increased in a stepwise fashion from ∼0.1-0.32 µmol TEU m(-2) for tubes with outer diameter less than 10 nm. The mBOD and sBOD may be useful denominators of surface activity and impurity content and assist in designing safer CNTs.

Dietary deficiency increases presenilin expression, gamma-secretase activity, and Abeta levels: potentiation by ApoE genotype and alleviation by S-adenosyl methionine.

Apolipoprotein E4 (ApoE4) is a risk factor for Alzheimer's disease (AD). Whether this risk arises from a deficient function of E4 or the lack of protection provided by E2 or E3 is unclear. Previous studies demonstrate that deprivation of folate and vitamin E, coupled with dietary iron as a pro-oxidant, for 1 month displayed increased presenilin 1 (PS-1) expression, gamma-secretase, and Abeta generation in mice lacking ApoE (ApoE-/- mice). While ApoE-/- mice are a model for ApoE deficiency, they may not reflect the entire range of consequences of E4 expression. We therefore compared herein the impact of the above deficient diet on mice expressing human E2, E3, or E4. As folate deficiency is accompanied by a decrease in the major methyl donor, S-adenosyl methionine (SAM), additional mice received the deficient diet plus SAM. E2 was more protective than murine ApoE or E3 and E4. Surprisingly, PS-1 and gamma-secretase were over-expressed in E3 to the same extent as in E4 even under a complete diet, and were not alleviated by SAM supplementation. Abeta increased only in E4 mice maintained under the complete diet, and was alleviated by SAM supplementation. These findings suggest dietary compromise can potentiate latent risk factors for AD.

Has enhanced folate status during pregnancy altered natural selection and possibly Autism prevalence? A closer look at a possible link.

The inverse association between maternal folate status and incidence of infants born with neural tube defects (NTD's) was recognized over twenty years ago and led the US health agencies in the early 1990s to recommend that women of childbearing age consume 400 microg of folic acid each day. The FDA followed by mandating that certain foods be fortified with folic acid and this has resulted in a significant enhancement of maternal folate status to levels that are often difficult to otherwise achieve naturally. At least one study indicates that this has decreased the incidence of NTD's. However, this same time period directly coincides with what many feel is the apparent beginning and continuous increase in the prevalence of Autism and related Autism Spectrum Disorders (ASD's) in the US. Are these similar time frames of changes in maternal folate status and possible Autism prevalence a random event or has improved maternal (and fetal) folate status during pregnancy played a role? It is not only plausible but highly likely. A particular polymorphic form to a key enzyme required to activate folate for methylation in neurodevelopment, 5-methylenetetrahydrofolate reductase (MTHFR), demonstrates reduced activity under low or normal folate levels but normal activity under conditions of higher folate nutritional status. A consequence of the presence of the polymorphic form of this enzyme during normal or reduced folate status are higher plasma homocysteine levels than noncarriers and the combination of these factors have been shown in several studies to result in an increase rate of miscarriage via thrombotic events. However, the incidence of hyperhomocysteinemia in the presence of the polymorphism is reduced under the common condition of enhanced folate status and thereby masks the latent adverse effects of the presence of this enzyme form during pregnancy. Of great importance is that this polymorphism, although common in the normal population, is found in significantly higher frequency in Autisic individuals. It is hypothesized here that the enhancement of maternal folate status before and during pregnancy in the last 15 years has altered natural selection by increasing survival rates during pregnancy of infants possessing the MTHFR C677T polymorphism, via reduction in hyperhomocysteinemia associated with this genotype and thereby miscarriage rates. This also points directly to an increased rate of births of infants with higher postnatal requirements for folic acid needed for normal methylation during this critical neurodevelopmental period. If these numbers have increased then so have the absolute number of infants that after birth fail to maintain the higher folate status experienced in utero thus leading to an increased number of cases of developmental disorders such as Autism. Detection of the C677T polymorphism as well as other methionine cycle enzymes related to folate metabolism and methylation at birth as part of newborn screening programs could determine which newborns need be monitored and maintained on diets or supplements that ensure adequate folate status during this critical postnatal neurodevelopment period.

Response of drug resistant isolates of Schistosoma mansoni to antischistosomal agents

The susceptibility of four isolates of Schistosoma mansoni (BH, MAP, MPR-1 and K) to four multiple doses of anti-schistosomal agents (hycanthone, niridazole, oxamniquire, and praziquantel) were evaluated in infected female Swiss albino mice. These schistosomal isolates had been maintained in the laboratory without further drug pressure for 20 to 30 generations. Multiple dosage regimens were used for each drug against each isolate of S. mansoni to generate ED50 (effective dose 50%) values. Results demonstrated that the K isolate is resistant to niridazole, the MPR-1 isolate to oxamniquine, and the MAP isolate to both hycanthone and oxamniquine. The BH isolate was susceptible to all drugs and was used as the reference isolate. All isolates were susceptible to praziquantel. The significance of the difference in response of the MPR-1 and MAP isolates is discussed. These results confirm the resistance of these isolates of S. mansoni of three schistosomicides and demonstrate that the resistance of these isolates are stable over long periods of time without exposure to drugs