Effects of Intercept pathogen reduction treatment on extended cold storage of apheresis platelets.

BACKGROUND: Platelets pose the greatest transfusion-transmitted infectious risk among blood products. Refrigeration of platelets can mitigate bacterial contamination and extend platelet shelf life. Implementation of pathogen reduction technologies (PRTs) at blood banks has become increasingly popular to protect against emerging and reemerging infectious diseases. In this study, we sought to evaluate the effects of Intercept PRT on platelets collected on different platforms and cold-stored for up to 21 days in plasma and platelet additive solution (PAS). METHODS: Double-dose apheresis platelets were collected with use of a Trima or Amicus system into either 100% plasma or 65% InterSol PAS/35% plasma and split equally between two bags. One bag served as control, while the other received Intercept PRT treatment. Bags were stored unagitated in the cold and evaluated on Days 1, 7, 14, and 21 to assess platelet metabolism, activation, aggregation, and clot formation and retraction. RESULTS: By Day 14 of storage, lactate levels reached approximately 13 mmol/L for all samples irrespective of Intercept treatment. Mean clot firmness dropped from the 62.2- to 67.5-mm range (Day 1) to the 28.4- to 51.3-mm range (Day 21), with no differences observed between groups. Clot weights of Intercept-treated Trima/plasma samples were significantly higher than control by Day 14 of storage (P = .004), indicating a reduced clot retraction function. Intercept treatment caused a higher incidence of plasma membrane breakdown in plasma-stored platelets (P = .0013; Trima/plasma Day 14 Control vs Intercept). CONCLUSIONS: Intercept treatment of platelets and subsequent cold storage, in plasma or PAS, results in comparable platelet metabolism platelets for up to 14 days of storage but altered clotting dynamics. Pathogen-reduced platelets with an extended shelf life would be beneficial for the deployed setting and would greatly impact transfusion practice among civilian transfusion centers.

TEG PlateletMapping assay results may be misleading in the presence of cold stored platelets.

BACKGROUND: Viscoelastic tests (VETs) are used widely to monitor hemostasis in settings such as cardiac surgery. There has also been renewed interest in cold stored platelets (CSPs) to manage bleeding in this setting. CSPs are reported to have altered hemostatic properties compared to room temperature platelets (RTPs), including activation of GPIIb/IIIa. We investigated whether the functional differences between CSP and RTP affected the performance of the PlateletMapping VET on the TEG 5000 and 6s analyzer. METHOD: Platelet concentrates were divided equally into CSP (stored at 4°C ± 2°C) and RTP (stored at 22°C ± 2°C) fractions. Whole blood was treated to induce platelet dysfunction (WBIPD) by incubating with anti-platelet drugs (1.0 µM ticagrelor and 10 µM aspirin) or by simulating cardiopulmonary bypass. WBIPD samples were then mixed with 20% by volume of CSPs or RTPs to model platelet transfusion before analysis using the PlateletMapping VET. RESULTS: Addition of CSPs to WBIPD increased the PlateletMapping MAFIBRIN and MAADP parameters with the TEG 5000 analyzer (both p < 0.0001 compared to addition of buffer alone). This effect was not observed with RTPs. The differential effect of CSPs on the MAFIBRIN corrected after pre-incubation with the GPIIb/IIIa antagonist tirofiban and was quantitatively less with the PlateletMapping test for the TEG 6s analyzer which contains the GPIIb/IIa antagonist abciximab. DISCUSSION: The PlateletMapping MAFIBRIN and MAADP test results may be misleadingly high with CSPs, particularly with the TEG 5000 analyzer, most likely due to constitutive activation of GPIIb/IIIa on CSPs during storage. TEG PlateletMapping results should be interpreted with caution following CSP transfusion.

Use of Specialized Pro-Resolving Mediators to Alleviate Cold Platelet Storage Lesion.

BACKGROUND: Cold-stored platelets are an attractive option for treatment of actively bleeding patients due to a reduced risk of septic complications and preserved hemostatic function compared to conventional room temperature-stored platelets. However, refrigeration causes increased platelet activation and aggregate formation. Specialized pro-resolving mediators (SPMs), cell signaling mediators biosynthesized from essential fatty acids, have been shown to modulate platelet function and activation. In this study, we sought to determine if SPMs could be used to inhibit cold-stored platelet activation. METHODS: Platelets were collected from healthy donors (n = 4-7) and treated with SPMs (resolvin E1 [RvE1], maresin 1 [MaR1], and resolvin D2 [RvD2]) or vehicle (VEH; 0.1% EtOH). Platelets were stored without agitation in the cold and assayed on Days 0 and 7 of storage for platelet activation levels using flow cytometry, platelet count, aggregation response using impedance aggregometry, and nucleotide content using mass spectrometry. RESULTS: Compared to VEH, SPM treatment inhibited GPIb shedding (all compounds), significantly reduced both PS exposure and activation of GPIIb/IIIa receptor (RvD2, MaR1), and preserved aggregation response to TRAP (RvD2, MaR1) after 7 days of storage. Similar to untreated cold-stored platelets, SPM-treated samples did not preserve platelet counts or block the release of P-Selectin. Nucleotide content was unaffected by SPM treatment in cold-stored platelets. CONCLUSIONS: SPM treatment, particularly Mar1 and RvD2, led to reduced platelet activation and preserved platelet function after 7 days of storage in the cold. Future work is warranted to better elucidate the mechanism of action of SPMs on cold platelet function and activation.

An in vitro pilot study of apheresis platelets collected on Trima Accel system and stored in T-PAS+ solution at refrigeration temperature (1-6°C).

BACKGROUND: Using platelet additive solution (PAS) to dilute fibrinogen during long-term cold storage of platelets (PLTs) decreases PLT activation and increases functional PLT shelf life. We performed a randomized, paired study to assess the in vitro quality of PLTs stored in the cold in T-PAS+ for up to 18 days evaluated against PLTs stored under currently allowable conditions (5-day room temperature-stored PLTs [RTP] and 3-day cold-stored PLTs [CSP]). STUDY DESIGN AND METHODS: PLTs were collected from healthy volunteers (n = 10) and diluted to 65% T-PAS+/35% plasma before cold storage. Double-dose apheresis PLTs (in 100% plasma) were collected from the same donors and split into two bags (one bag RTP, one bag CSP). All bags were sampled on the day of collection (Day 0). CSP and RTP bags were sampled on Days 3 and 5, respectively. T-PAS+ samples were assessed on Days 3, 5, 14, 16, and 18 of storage for metabolism, hemostatic function, and activation. RESULTS: After 18 days of storage in T-PAS+, pH was 6.71 ± 0.04, PLT count was comparable to Day 3 CSP, PLT function (aggregation and clot strength) was comparable to Day 5 RTP, and PLT activation was significantly increased. CONCLUSION: Refrigerated PLTs stored in T-PAS+ for 18 days met FDA pH standards. Functional metrics suggest activity of T-PAS+-stored PLTs and the potential to contribute to hemostasis throughout 18 days of storage. Extending the shelf life of PLTs would increase access to hemostatic resuscitation for bleeding patients in military and civilian settings.

Transitioning towards a sustainable environment: the dynamic nexus between economic complexity index, technological development and human capital with environmental quality in India.

This paper aims to investigate the dynamic nexus between economic complexity index (ECI), technological development (TIN), human capital (HC) and environmental quality in India for transition towards a sustainable environment. This study is based on secondary data covering the period from 1985 to 2018. For empirical analysis, this study applied "Stochastic Impacts by Regression on Population, Affluence, and Technology" (STIRPAT) model framework under the estimation of autoregressive distributed lag (ARDL) model and vector error correction model (VECM) model. The empirical findings of model 1 show ECI, TIN, HC and urbanization (URB) as the helping hands to mitigate the problem of environmental degradation by shrinking the level of EF, whereas for model 2, ECI and TIN failed to influence the CO2 emissions, but HC served as a stimulant for environmental quality enhancement by declining the level of CO2 emissions. In contrast, GDP growth and URB strengthen the CO2 emissions levels. Moreover, in VECM framework, estimated findings reveal that the covariables Granger-cause EF and CO2 emissions, inferring that causality flows asynchronously from its covariables to EF and CO2. Impulse response function (IRF) revealed that the responses in EF and CO2 emissions ascribed to changes in its covariables. The outcome of the study has some implications for environmental policy strategists to prepare sustainable environment policies and other responsible authorities for sustainable development goal (SDGs), academician and scholars. All the stakeholders involved in environmental economics and policymakers can evaluate this study to design proper policy framework with respect to the environment. There are few studies that explore the dynamic nexus between ECI, TIN and HC with environmental quality in the control environment of URB and GDP growth using the STIRPAT model for India.

Fast Track Diagnostic Tools for Clinical Management of Sepsis: Paradigm Shift from Conventional to Advanced Methods.

Sepsis is one of the deadliest disorders in the new century due to specific limitations in early and differential diagnosis. Moreover, antimicrobial resistance (AMR) is becoming the dominant threat to human health globally. The only way to encounter the spread and emergence of AMR is through the active detection and identification of the pathogen along with the quantification of resistance. For better management of such disease, there is an essential requirement to approach many suitable diagnostic techniques for the proper administration of antibiotics and elimination of these infectious diseases. The current method employed for the diagnosis of sepsis relies on the conventional culture of blood suspected infection. However, this method is more time consuming and generates results that are false negative in the case of antibiotic pretreated samples as well as slow-growing microbes. In comparison to the conventional method, modern methods are capable of analyzing blood samples, obtaining accurate results from the suspicious patient of sepsis, and giving all the necessary information to identify the pathogens as well as AMR in a short period. The present review is intended to highlight the culture shift from conventional to modern and advanced technologies including their limitations for the proper and prompt diagnosing of bloodstream infections and AMR detection.

Regulatory and Interacting Partners of PDLIM7 in Thyroid Cancer.

Enigma protein, encoded by the PDLIM7 gene, is overexpressed in thyroid cancer in a stage-dependent manner, suggesting a potential involvement in the initiation and progression of thyroid cancer. The Enigma interacts with several cellular pathways, including PI3K/AKT, MDM2, and BMP-1. The Enigma is regulated by microRNAs. Specifically, we showed that the Enigma protein upregulation corresponds to the downregulation of Let-7 family genes. There is limited research on the interactions and regulation of the Enigma with other proteins/genes in thyroid cancer tissues, indicating a gap in current knowledge. Our aim is to establish the Enigma as a biomarker. We also aim to study the interacting partners of the Enigma signaling pathways and their probable miRNA regulation in thyroid cancer progression. Using Western blotting, densitometric analysis, immunoprecipitation (IP), and reverse IP, we detected the protein expression and protein-protein interactions in the corresponding papillary thyroid carcinomas (PTCs). Utilizing real-time qPCR assay and Pearson's correlation test, we highlighted the correlation between PDLIM7 and Let-7g gene expression in the same tissues. The results showed the differential upregulations of the Enigma protein in different stages of PTCs compared to benign tissues along with AKT, VDR, BMP-1, and MDM2 proteins. Loss of DBP was observed in a subset of PTCs. Strong interactions of the Enigma with PI3K/AKT and MDM2 were noted, along with a weaker BMP-1 interaction. Pearson's correlation coefficient analysis between PDLIM7 and let-7g gene expression was significant (p < 0.05); however, there was a weak inverse correlation (r = -0.27). The study suggests the potential utility of the PDLIM7-qPCR assay as a biomarker for thyroid cancer. The Enigma's interactions with key signaling pathways may provide valuable insights into the development of thyroid cancer. The study contributes to understanding the molecular mechanisms involving the Enigma protein in thyroid cancer and highlights its potential as a biomarker.

What is the recommended approach to asymptomatic patients who develop a reactive PPD?

Clinical evaluation and chest x-ray are recommended for asymptomatic patients with a positive purified protein derivative (PPD) test result, to exclude the slight possibility of active tuberculosis (TB). Patients with radiographic evidence of old (healed) TB infection should also undergo sputum testing (strength of recommendation [SOR]: C, expert opinion). Treatment with isoniazid (INH) monotherapy (300 mg/d) reduces progression of latent tuberculosis to active disease (SOR: A, large randomized controlled trials [RCT]), with 9 months as the optimal treatment length (SOR: B, derivation from RCTs). A 3-month course of combined rifampin (600 mg/d) and INH (300 mg/d) is equivalent in efficacy to INH monotherapy and is associated with similar rates of toxicity (SOR: A, meta-analysis of RCTs), but this regimen is not included in Centers for Disease Control and Prevention recommendations.

PURLs: BP meds: this simple change improves outcomes.

For patients with uncontrolled hypertension, a switch to bedtime dosing is advisable.

PURLs: Another option for patients with liver disease.

Currently used to treat hepatic encephalopathy, rifaximin is effective at preventing this common complication of chronic liver disease, as well.

Medical case teaching on the web.

BACKGROUND: Little is known about strategies for developing teaching cases and strategies for identifying design features that optimize a learner's interactions with Web-based cases. PURPOSES: We examined design features in Web cases that facilitated interactive and engaging learning. METHODS: Nine collaborators reviewed selected Web cases and documented the presence of features that facilitate interactive learning, including opportunities for information gathering, decision making, and receiving feedback. RESULTS: Eighteen Web sites offered cases. These cases mainly were narrated based on biomedical information without patient voices. The cases were organized in a linear structure from patient presentation to follow-up. Many cases presented only a single case. We found little use of features for augmenting a learner's interaction with cases. Only a handful of cases generated feedback on the basis of the learners' responses. CONCLUSION: Our study suggests ways to improve the development of Web cases. These methods contribute to future research in testing cases for educational effectiveness.