Wound Healing in the α2β1 Integrin-Deficient Mouse: Altered Keratinocyte Biology and Dysregulated Matrix Metalloproteinase Expression

The alpha2beta1 integrin, a collagen/laminin receptor, is expressed at high level in the basal cell layer of the epidermis. To define the role of the alpha2beta1 integrin in wound healing, wound repair was extensively evaluated in wild-type and alpha2-null mice in vivo. In addition, the impact of alpha2beta1 integrin-deficiency on the function of primary murine keratinocytes in vitro was analyzed. Our in vivo findings demonstrate that genetic deletion of the alpha2beta1 integrin does not significantly alter the rate of re-epithelialization, collagen deposition, or tensile strength during wound closure in mice. In marked contrast to the observed similarities in wound healing, deletion of the alpha2beta1 integrin resulted in a dramatic increase in neoangiogenesis in the wound microenvironment. In contrast to in vivo studies, primary keratinocytes from alpha2-null mice adhered poorly and displayed impaired migration on type I collagen in vitro. We demonstrate that alpha2beta1 integrin-ligation negatively regulates expression of genes including matrix metalloproteinases both in vivo and in vitro. Furthermore, the changes in gene expression could potentially account for relatively normal wound healing in the alpha2-deficient mouse and our recent observation that suggests an antiangiogenic role for the alpha2beta1 integrin in vivo

Comparison of multiple methods for identification of hyperprolactinemia in the presence of macroprolactin

Macroprolactin is a large, heterogeneous form of prolactin with limited bioavailability. Detection of macroprolactin by different immunoassays varies widely. The objectives of this study were to determine the immunoreactivity of macroprolactin by the Ortho Clinical Diagnostics Vitros ECi prolactin immunoassay, establish the most effective method for interpreting the prolactin concentration after PEG-precipitation, and correlate the clinical features of hyperprolactinemia with the presence of macroprolactin

Recommendations for validation testing of home pregnancy tests (HPTs) in Europe

Homepregnancy tests (HPTs) available in Europe include accuracy and other performance claims listed on their packaging. Due to the lack of guidance on the standardisation of such products, it is often difficult to replicate these claims when tested on a clinical sample, whether in a laboratory setting or by lay users. The In Vitro Diagnostic Regulation is a set of requirements that mandate comprehensive validation data on human pregnancy tests and other in vitro devices. It is due to replace the current European Directive (98/79/EC) and fully implemented in Europe by 2022. In June 2019, a panel of seven experts convened to discuss the validation studies required to provide the information needed to meet the new regulation for HPTs in Europe and proposed 15 recommendations for best practice. Defining best practice at all stages of validation of these important tests may ensure that tests marketed inEurope are fit for purpose, enabling lay users to be confident of the high quality of the HPT results they obtain. The panelists believe that the recommendations proposed here for the validation of HPTs may constructively contribute to improved standardisation of validation procedures in Europe.Peer reviewe

"Inappropriate Off-label Use of a Qualitative, Point-of-care hCG Device" Letter With Response

N/A, letter to the edito

A Cost-Effectiveness Analysis of First Trimester Non-Invasive Prenatal Screening for Fetal Trisomies in the United States

<div><p>Background</p><p>Non-invasive prenatal testing (NIPT) is a relatively new technology for diagnosis of fetal aneuploidies. NIPT is more accurate than conventional maternal serum screening (MSS) but is also more costly. Contingent NIPT may provide a cost-effective alternative to universal NIPT screening. Contingent screening used a two-stage process in which risk is assessed by MSS in the first stage and, based on a risk cutoff, high-risk pregnancies are referred for NIPT. The objective of this study was to (1) determine the optimum MSS risk cutoff for contingent NIPT and (2) compare the cost effectiveness of optimized contingent NIPT to universal NIPT and conventional MSS.</p><p>Study Design</p><p>Decision-analytic model using micro-simulation and probabilistic sensitivity analysis. We evaluated cost effectiveness from three perspectives: societal, governmental, and payer.</p><p>Results</p><p>From a societal perspective, universal NIPT dominated both contingent NIPT and MSS. From a government and payer perspective, contingent NIPT dominated MSS. Compared to contingent NIPT, adopting a universal NIPT would cost $203,088 for each additional case detected from a government perspective and$263,922 for each additional case detected from a payer perspective.</p><p>Conclusions</p><p>From a societal perspective, universal NIPT is a cost-effective alternative to MSS and contingent NIPT. When viewed from narrower perspectives, contingent NIPT is less costly than universal NIPT and provides a cost-effective alternative to MSS.</p></div