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Mothers of extremely preterm infants experience high rates of mental health disorders that impair maternal-infant interaction and lead to worse infant developmental outcomes. Therapist Education and Massage for Parent-Infant Outcomes (TEMPO) is a therapist-led program that standardizes the nature and frequency of parent education through weekly scheduled therapy sessions. Using a family-centered approach, the therapist facilitates positive maternal-infant interactions and massage interventions from birth throughout hospitalization with the goal of improving maternal mental health. This qualitative study presents the results of 19 parent interviews and of a focus group of four TEMPO interventionists to elicit feedback about the program. Overall, parents and therapists viewed the program positively. Parents and therapists valued the focus on parent education and engagement to increase parent competence and bonding opportunities. Both groups acknowledged that infant massage had both infant-centered and parent-centered benefits. One area where parent and therapist views did not align was regarding feasibility of TEMPO. Parents noted multiple logistical challenges to regular NICU visitation, but ultimately agreed that attending weekly therapy sessions was feasible. Therapists noted increased time and effort required of TEMPO and felt that institutional and system-level changes would be necessary to implement weekly parent education as standard of care.

We describe an extractionless real-time reverse transcriptase-PCR (rRT-PCR) protocol for SARS-CoV-2 nucleic acid detection using heat as an accurate cost-effective high-capacity solution to COVID-19 testing. We present the effect of temperature, transport media, rRT-PCR mastermixes and gene assays on SARS-CoV-2 gene amplification and limits of detection. Utilizing our heated methodology, our limits of detection were 12.5 and 1 genome copy/reaction for singleplex E- and N1-gene assays, respectively, and 1 genome copy/reaction by utilizing an E/N1 or Orf1ab/N1 multiplex assay combination. Using this approach, we detected up to 98% of COVID-19 positive patient samples analyzed in our various cohorts including a significant percentage of weak positives. Importantly, this extractionless approach will allow for >2-fold increase in testing capacity with existing instruments, circumvent the additional need for expensive extraction devices, provide the sensitivity needed for COVID-19 detection and significantly reduce the turn-around time of reporting COVID-19 test results., Competing Interests: Declaration of competing interest The authors report no conflicts of interest relevant to this article, (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Little is known about rates of joint bleeding among females with FVIII/FIX deficiency or hemophilia carriers. In a cross-sectional study, we tested the hypothesis that females with FVIII or FIX deficiency enrolled in the Universal Data Collection (UDC) project had a reduced mean overall joint range of motion (ROM) compared with historic controls from the Normal Joint Study. Demographics, clinical characteristics, and joint ROM measurements on 303 females without a bleeding disorder and 148 females with FVIII and FIX deficiency, respectively, between the ages of 2-69 years and a body mass index (BMI) ≤ 35 were compared. Multivariate linear regression was performed with the overall joint ROM (sum of the right and left ROM measurements of five joints) as the dependent variable and FVIII or FIX activity as the independent variable adjusting for age, race, BMI, and number of joint bleeds reported over the last 6 months. As FVIII and FIX activity decreased, the mean overall joint ROM became reduced and in most cases was significantly lower than that of the controls regardless of age and clinical hemophilia severity. Further investigation of reduced joint ROM as evidence of subclinical joint bleeding in females with FVIII and FIX deficiency is warranted., (© 2014 Wiley Periodicals, Inc.)

Glioblastoma multiforme is an aggressive and incurable type of brain tumor. A subset of undifferentiated glioblastoma cells, known as glioblastoma tumor initiating cells (GTICs), has an essential role in the malignancy of this disease and also appears to mediate resistance to radiation therapy and chemotherapy. GTICs retain the ability to differentiate into cells with reduced malignant potential, but the signaling pathways controlling differentiation are not fully understood at this time. PTEN loss is a very common in glioblastoma multiforme and leads to aberrant activation of the phosphoinositide 3-kinase pathway. Increased signalling through this pathway leads to activation of multiple protein kinases, including atypical protein kinase C. In Drosophila, active atypical protein kinase C has been shown to promote the self-renewal of neuroblasts, inhibiting their differentiation along a neuronal lineage. This effect is mediated by atypical protein kinase c-mediated phosphorylation and inactivation of Lgl, a protein that was first characterized as a tumour suppressor in Drosophila. The effects of the atypical protein kinase C/Lgl pathway on the differentiation status of GTICs, and its potential link to PTEN loss, have not been assessed previously. Here we show that PTEN loss leads to the phosphorylation and inactivation of Lgl by atypical protein kinase C in glioblastoma cells. Re-expression of PTEN in GTICs promoted their differentiation along a neuronal lineage. This effect was also seen when atypical protein kinase C was knocked down using RNA interference, and when a non-phosphorylatable, constitutively active form of Lgl was expressed in GTICs. Thus PTEN loss, acting via atypical protein kinase C activation and Lgl inactivation, helps to maintain GTICs in an undifferentiated state.

Background: Parvovirus B19 (B19) is known to cause a variety of human diseases in susceptible individuals by close contact via the respiratory route or by transfusion of contaminated blood or blood products. In this study, whether a case of B19 transmission was causally related to the infusion of implicated lots of a solvent/detergent (S/D)-treated, immunoaffinity-purified factor VIII concentrate (antihemophilic factor [human][AHF]) was investigated., Study Design and Methods: Anti-B19 (both immunoglobulin M [IgM] and immunoglobulin G [IgG]) and B19 DNA (by a nucleic acid testing [NAT] procedure) were assayed in two implicated product lots, a plasma pool, and a recipient's serum sample. Analysis of the partial B19 sequences obtained from sequencing clones or direct sequencing of the samples was performed., Results: Only one of the two implicated lots was B19 DNA-positive. It contained 1.3 x 10(3) genome equivalents (geq or international units [IU]) per mL. The negative lot was derived from plasma screened for B19 DNA by NAT in a minipool format to exclude high-titer donations, whereas the positive lot was mostly from unscreened plasma. This high-purity AHF product had no detectable anti-B19 IgG. A 4-week postinfusion serum sample from a recipient, who received both lots and became ill, was positive for the presence of B19 antibodies (both IgM and IgG) as well as B19 DNA. The B19 sequences from the positive lot, its plasma pool, and the recipient's serum sample were closely related., Conclusion: These findings and the recipient's clinical history support a causal relationship between the implicated AHF product and B19 infection in this recipient. The seronegative patient became infected after receiving 2x10(4) IU (or geq) of B19 DNA, which was present in this S/D-treated, high-purity AHF product.

End-stage renal disease (ESRD) Networks are quality improvement organizations that collect, analyze, and report information to clinicians and allied health providers about discrepancies between observed patterns of care of ESRD patients and what has been recommended by clinical practice guidelines. The Networks facilitate response to this information by assisting ESRD treatment centers to develop quality improvement programs to redress inadequate care. The authors evaluated this process of quality improvement by selecting 42 treatment centers in a single ESRD Network with the lowest facility-specific mean urea reduction ratio (URR). The treatment centers were randomly assigned to two intervention strategies: (1) feedback alone; (2) an intensive intervention that included feedback, workshops, distribution of educational materials and clinical practice guidelines, technical assistance with the development of quality improvement plans, and continued monitoring. The intensive intervention had greater improvement in the increased proportions of patients dialyzed with prescribed blood flow (P = 0.02) and documented review of prescription (P = 0.01). Furthermore, the mean center URR increased nearly 3% among intensive intervention centers (from 68.1 to 70.9) but only 0.09% among the feedback centers (68.2 to 69.1) (P = 0.002). Similarly, time on dialysis increased 7.5 min on average among patients in intervention centers but decreased 2 min for patients in comparison centers (P = 0.03). These results demonstrate that Network feedback, coupled with the intensive intervention, resulted in improvement in care that would otherwise not have occurred.

End-stage renal disease (ESRD) patients treated with hemodialysis have a high mortality rate, which is largely due to inadequate dialysis. Dialysis adequacy, measured by the urea reduction ratio (URR), tends to be correlated within dialysis facilities with wide variations in average center adequacy. These are characteristics of a center effect, which can have an important impact on dialysis adequacy. This study measured the center effect observed in an ESRD Network before and after a successful quality improvement project (QIP). URR values were recorded on patients sampled from 196 facilities in ESRD Network 6 before (pre-QIP, n = 5309) and after (post-QIP, n = 5753). These data was used to determine the within center correlation (rho) of individual URR values and between center variation in aggregate URR values in both samples. The overall mean URR improved from the pre- to post-QIP sample (mean URR 64.7 +/- 0.1 versus 69.8 +/- 0.1, respectively; P = 0.001). There was a high degree of within center correlation in dialysis adequacy across the facilities, which significantly diminished post-QIP (rho, 0.15 [95% CI, 0.12 to 0.18] versus rho, 0.06 [95% CI, 0.04 to 0.08]). The between center variation in mean URR also declined from the pre-QIP to the post-QIP sample (SD, 3.6 versus 2.8). In conclusion, there is a center effect on dialysis adequacy measurable in an ESRD Network, which diminishes after a successful QIP; therefore, when implementing a QIP to improve dialysis adequacy, changes in the center effect should be considered a potential indicator of the efficacy of the intervention.

Recent literature has urged caution in the interpretation of vancomycin serum concentrations in patients with end-stage renal disease (ESRD), because falsely elevated levels in excess of 70% have been reported with the most commonly used fluorescence polarization immunoassay (FPIA). The purpose of this study was to evaluate the performance of a recently modified FPIA assay for use in patients with ESRD, in comparison to high-performance liquid chromatography (HPLC) and an enzyme-mediated immunoassay technique (EMIT). Serum vancomycin samples were prospectively collected from adults with ESRD undergoing chronic hemodialysis. Each sample was stored at -70 degrees C until analyzed in duplicate by FPIA, EMIT, and HPLC. In an in vitro experiment, blank serum samples with 15 microg/ml vancomycin were spiked with increasing amounts of CDP and analyzed in duplicate with the modified FPIA assay. When compared to HPLC, no statistically significant difference was found in patients with ESRD with the use of the modified FPIA assay (mean concentrations, HPLC 14.92 microg/ml, FPIA 15.96 microg/ml), with FPIA exhibiting a positive bias of 0.64 microg/ml and a precision of +/-3.49 microg/ml (n = 18, p = 0.44). The mean EMIT concentration was 18.34 microg/ml, with a positive bias of 3.43 microg/ml and a precision of +/-5.17 microg/ml (p < 0.01). The addition of increasing amounts of CDP to vancomycin in vitro resulted in concentrations similar to those expected in the absence of significant cross-reactivity with the modified FPIA assay. The modified FPIA assay is a satisfactory tool for monitoring vancomycin serum concentrations in patients with ESRD undergoing hemodialysis. Results obtained with EMIT were not as precise as with FPIA.