Rapid immunoassays for diagnosis of heparin-induced thrombocytopenia: Comparison of diagnostic accuracy, reproducibility, and costs in clinical practice.

Immunoassays are crucial in the work-up of patients with suspected heparin-induced thrombocytopenia (HIT) and rapid tests have been recently developed. However, comparative data on diagnostic accuracy, reproducibility, and analytical costs of different immunoassays in clinical practice are limited. Samples of 179 consecutive patients evaluated for suspected HIT in clinical practice using a polyspecific enzyme-linked immunoabsorbent assay (GTI diagnostics; ELISA) and a rapid particle gel immunoassay (PaGIA), were additionally analysed with a IgG-specific chemiluminescent immunoassay (AcuStar HIT-IgG). Presence of HIT was defined as a positive functional heparin-induced platelet aggregation test. Diagnostic accuracy was determined for low, intermediate and high thresholds as previously established (ELISA: optical density 0.4, 1.3, and 2.0 respectively; PaGIA: positive/negative, titre of 4, titre of 32; AcuStar HIT-IgG: 1.0 U/ml, 2.8, 9.4) and reproducibility was assessed by repeated measurements. Costs of test determination were calculated taking reagents, controls, and working time of technicians according to Swiss health care system into account. Data on PaGIA results were available for 171 patients (95.5%), ELISA for 144 patients (80.4%), and AcuStar HIT-IgG for 179 patients (100%). Sensitivity was above 95% for all assays at low and intermediate thresholds. Specificity increased with higher thresholds and was above 90% for all assays with intermediate and high thresholds. Specificity of AcuStar HIT-IgG (92.8%; 95% CI 87.7, 96.2) was significantly higher than PaGIA (83.0%; 95% CI 76.3, 88.5) and higher than ELISA (81.8%, 95% CI 74.2, 88.0) at low threshold (p<0.05). Reproducibility was adequate for all assays. Total costs per test were CHF 51.02 for ELISA, 117.70 for AcuStar HIT-IgG, and 83.13 for PaGIA. We observed favourable diagnostic accuracy measures and a high reproducibility for PaGIA and AcuStar HIT-IgG. Implementation into 24-hours-service might improve patient care but the results must be confirmed in other settings and larger populations as well

Antibacterial mono- and sesquiterpene esters of benzoic acids from Iranian propolis

<p>Abstract</p> <p>Background</p> <p>Propolis (bee glue) has been used as a remedy since ancient times. Propolis from unexplored regions attracts the attention of scientists in the search for new bioactive molecules.</p> <p>Results</p> <p>From Iranian propolis from the Isfahan province, five individual components were isolated: the prenylated coumarin suberosin <b>1</b>, and four terpene esters: tschimgin (bornyl <it>p</it>-hydroxybenzoate) <b>2</b>, tschimganin (bornyl vanillate) <b>3</b>, ferutinin (ferutinol <it>p</it>-hydroxybenzoate) <b>4, </b>and tefernin (ferutinol vanillate) <b>5</b>. All of them were found for the first time in propolis. Compounds <b>2 </b>- <b>5 </b>demonstrated activity against <it>Staphylococcus aureus</it>.</p> <p>Conclusions</p> <p>The results of the present study are consistent with the idea that propolis from unexplored regions is a promising source of biologically active compounds.</p

The charmonium and bottomonium mass spectroscopy with a simple approximaton of the kinetic term

In this paper we propose a particular description of meson spectroscopy, with emphasis in heavy bound states like charmonia and bottomonia, after working on the main aspects of the construction of an effective potential model. We use the prerogatives from ``soft QCD'' to determine the effective potential terms, establishing the asymptotic Coulomb term from one gluon exchange approximation. At the same time, a linear confinement term is introduced in agreement with QCD and phenomenological prescription. The main aspect of this work is the simplification in the calculation, consequence of a precise and simplified description of the kinetic term of the Hamiltonian. With this proposition we perform the calculations of mass spectroscopy for charmonium and bottomonium mesons and we discuss the real physical possibilities of developing a generalized potential model, its possible advantages relative to experimental parameterization and complexity in numerical calculations

Mannan-Binding Lectin Levels and Activity Are Not Altered in Atopic Dermatitis Patients with a History of Eczema Herpeticum

Background. Eczema herpeticum (EH) is a potentially serious, systemic complication in subjects with atopic dermatitis (AD) caused by herpes simplex virus (HSV). The innate immune dysregulation that predisposes these subjects to cutaneous viral infections is not well understood. We tested the hypothesis that defects in mannan-binding lectin (MBL) may be associated with an increased risk of EH. Methods. We evaluated serum MBL levels and functional activity in 13 AD subjects with a history of EH (EH+) and 21 AD subjects with no history of EH (EH−). MBL levels were detected by enzyme immunoassay. MBL pathway functional activity was evaluated by determining MBL C4b deposition capacity. Results. We found no statistical difference in MBL serum levels or function between EH+ and EH− groups. Conclusion. Considering the limitations of this study (e.g., small samples size) our findings suggest that MBL defects do not play a role in EH

EXCHANGE-2: investigating the efficacy of add-on plasma exchange as an adjunctive strategy against septic shock—a study protocol for a randomized, prospective, multicenter, open-label, controlled, parallel-group trial

Background Sepsis is as a life-threatening organ dysfunction caused by a dysregulated host response to an infection. The mortality of sepsis and particular of septic shock is very high. Treatment mostly focuses on infection control but a specific intervention that targets the underlying pathological host response is lacking to the present time. The investigators hypothesize that early therapeutic plasma exchange (TPE) will dampen the maladaptive host response by removing injurious mediators thereby limiting organ dysfunction and improving survival in patients with septic shock. Although small prospective studies demonstrated rapid hemodynamic stabilization under TPE, no adequately powered randomized clinical trial has investigated hard outcomes. Methods This is a randomized, prospective, multicenter, open-label, controlled, parallel-group interventional trial to test the adjunctive effect of TPE in patients with early septic shock. Patients with a refractory (defined as norepinephrine (NE) ≥ 0.4 μg/kg/min ≥ 30 min OR NE 0.3 μg/kg/min + vasopressin) and early (shock onset < 24 h) septic shock will be included. The intervention is a standard TPE with donor fresh frozen plasma (1.2 × individual plasma volume) performed within 6 h after randomization and will be compared to a standard of care (SOC) control arm. The primary endpoint is 28 days mortality for which the power analysis revealed a group size of 137 / arm (n = 274) to demonstrate a benefit of 15%. The key secondary objective will be to compare the extent of organ failure indicated by mean SOFA over the first 7 days as well as organ support-free days until day 28 following randomization. Besides numerous biological secondary, safety endpoints such as incidence of bleeding, allergic reactions, transfusion associated lung injury, severe thrombocytopenia, and other severe adverse events will be assessed during the first 7 days. For exploratory scientific analyses, biomaterial will be acquired longitudinally and multiple predefined scientific subprojects are planned. This study is an investigator-initiated trial supported by the German Research Foundation (DFG, DA 1209/7–1), in which 26 different centers in Germany, Switzerland, and Austria will participate over a duration of 33 months. Discussion This trial has substantial clinical relevance as it evaluates a promising adjunctive treatment option in refractory septic shock patients suffering from an extraordinary high mortality. A positive trial result could change the current standard of care for this septic subgroup. The results of this study will be disseminated through presentations at international congresses, workshops, and peer-reviewed publications. Trial registration ClinicalTrials.gov NCT05726825, Registered on 14 February 2023

Portuguese propolis disturbs glycolytic metabolism of human colorectal cancer in vitro

Propolis is a resin collected by bees from plant buds and exudates, which is further processed through the activity of bee enzymes. Propolis has been shown to possess many biological and pharmacological properties, such as antimicrobial, antioxidant, immunostimulant and antitumor activities. Due to this bioactivity profile, this resin can become an alternative, economic and safe source of natural bioactive compounds.Antitumor action has been reported in vitro and in vivo for propolis extracts or its isolated compounds; however, Portuguese propolis has been little explored. The aim of this work was to evaluate the in vitro antitumor activity of Portuguese propolis on the human colon carcinoma cell line HCT-15, assessing the effect of different fractions (hexane, chloroform and ethanol residual) of a propolis ethanol extract on cell viability, proliferation, metabolism and death. METHODS: Propolis from Angra do Heroísmo (Azores) was extracted with ethanol and sequentially fractionated in solvents with increasing polarity, n-hexane and chloroform. To assess cell viability, cell proliferation and cell death, Sulforhodamine B, BrDU incorporation assay and Anexin V/Propidium iodide were used, respectively. Glycolytic metabolism was estimated using specific kits. RESULTS: All propolis samples exhibited a cytotoxic effect against tumor cells, in a dose- and time-dependent way. Chloroform fraction, the most enriched in phenolic compounds, appears to be the most active, both in terms of inhibition of viability and cell death. Data also show that this cytotoxicity involves disturbance in tumor cell glycolytic metabolism, seen by a decrease in glucose consumption and lactate production. CONCLUSION: Our results show that Portuguese propolis from Angra do Heroísmo (Azores) can be a potential therapeutic agent against human colorectal cancer.We thank the Portuguese Science and Technology Foundation (FCT) for VMG fellowship (ref. SFRH/BI/33503/2008). The authors thank Mr. Antonio Marques from Frutercoop - Azores, who kindly collected and provided the propolis sample for the study

Analytical methods applied to diverse types of Brazilian propolis

Propolis is a bee product, composed mainly of plant resins and beeswax, therefore its chemical composition varies due to the geographic and plant origins of these resins, as well as the species of bee. Brazil is an important supplier of propolis on the world market and, although green colored propolis from the southeast is the most known and studied, several other types of propolis from Apis mellifera and native stingless bees (also called cerumen) can be found. Propolis is usually consumed as an extract, so the type of solvent and extractive procedures employed further affect its composition. Methods used for the extraction; analysis the percentage of resins, wax and insoluble material in crude propolis; determination of phenolic, flavonoid, amino acid and heavy metal contents are reviewed herein. Different chromatographic methods applied to the separation, identification and quantification of Brazilian propolis components and their relative strengths are discussed; as well as direct insertion mass spectrometry fingerprinting

In vitro antiproliferative activity of partially purified Trigona laeviceps propolis from Thailand on human cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Cancers are some of the leading causes of human deaths worldwide and their relative importance continues to increase. Since an increasing proportion of cancer patients are acquiring resistance to traditional chemotherapeutic agents, it is necessary to search for new compounds that provide suitable specific antiproliferative affects that can be developed as anticancer agents. Propolis from the stingless bee, <it>Trigona laeviceps</it>, is one potential interesting source that is widely available and cultivatable (as bee hives) in Thailand.</p> <p>Methods</p> <p>Propolis (90 g) was initially extracted by 95% (v/v) ethanol and then solvent partitioned by sequential extractions of the crude ethanolic extract with 40% (v/v) MeOH, CH₂Cl₂and hexane. After solvent removal by evaporation, each extract was solvated in DMSO and assayed for antiproliferative activity against five cancer (Chago, KATO-III, SW620, BT474 and Hep-G2) and two normal (HS27 fibroblast and CH-liver) cell lines using the MTT assay. The cell viability (%) and IC₅₀values were calculated.</p> <p>Results</p> <p>The hexane extract provided the highest <it>in vitro </it>antiproliferative activity against the five tested cancer cell lines and the lowest cytotoxicity against the two normal cell lines. Further fractionation of the hexane fraction by quick column chromatography using eight solvents of increasing polarity for elution revealed the two fractions eluted with 30% and 100% (v/v) CH₂Cl₂in hexane (30DCM and 100DCM, respectively) had a higher anti-proliferative activity. Further fractionation by size exclusion chromatography lead to four fractions for each of 30DCM and 100DCM, with the highest antiproliferative activity on cancer but not normal cell lines being observed in fraction# 3 of 30DCM (IC₅₀value of 4.09 - 14.7 μg/ml).</p> <p>Conclusions</p> <p><it>T. laeviceps </it>propolis was found to contain compound(s) with antiproliferative activity <it>in vitro </it>on cancer but not normal cell lines in tissue culture. The more enriched propolis fractions typically revealed a higher antiproliferative activity (lower IC₅₀value). Overall, propolis from Thailand may have the potential to serve as a template for future anticancer-drug development.</p

Antibody Response to SARS-CoV-2 Vaccination in Patients following Allogeneic Hematopoietic Cell Transplantation

Vaccines against SARS-CoV-2 have been rapidly approved. Although pivotal studies were conducted in healthy volunteers, little information is available on the safety and efficacy of mRNA vaccines in immunocompromised patients, including recipients of allogeneic hematopoietic cell transplantation (allo-HCT). Here we used a novel assay to analyze patient- and transplantation-related factors and their influence on immune responses to SARS-CoV-2 vaccination over an extended period (up to 6 months) in a large and homogenous group of allo-HCT recipients at a single center in Switzerland. We examined longitudinal antibody responses to SARS-CoV-2 vaccination with BNT162b2 (BioNTech/Pfizer) and mRNA-1273 (Moderna) in 110 allo-HCT recipients and 86 healthy controls. Seroprofiling recording IgG, IgA, and IgM reactivity against SARS-CoV-2 antigens (receptor-binding domain, spike glycoprotein subunits S1 and S2, and nucleocapsid protein) was performed before vaccination, before the second dose, and at 1, 3, and 6 months after the second dose. Patients were stratified to 3 groups: 3 to 6 months post-allo-HCT, 6 to 12 months post-allo-HCT, and >12 months post-allo-HCT. Patients in the 3 to 6 months and 6 to 12 months post-allo-HCT groups developed significantly lower antibody titers after vaccination compared with patients in the >12 months post-allo-HCT group and healthy controls (P 65 years (P = .030), those receiving immunosuppression for prevention or treatment of graft-versus-host disease (GVHD) (P = .033), and patients with relapsed disease (P = .014) displayed low humoral immune responses to the vaccine. In contrast, the intensity of the conditioning regimen, underlying disease (myeloid/lymphoid/other), and presence of chronic GVHD had no impact on antibody levels. Antibody titers achieved the highest levels at 1 month after the second dose of the vaccine but waned substantially in all transplantation groups and healthy controls over time. This analysis of long-term vaccine antibody response is of critical importance to allo-HCT recipients and transplant physicians to guide treatment decisions regarding revaccination and social behavior during the SARS-CoV-2 pandemic. Keywords: Allogeneic hematopoietic cell transplantation; SARS-CoV-2; Vaccinatio