Explore the vast range of titles available.

Safeguarding the environment is one of the most serious modern challenges, as increasing amounts of chemical compounds are produced and released into the environment, causing a serious threat to the future health of the Earth as well as organisms and humans on a global scale. Ecotoxicology is an integrative science involving different physical, chemical, biological, and social aspects concerned with the study of toxic effects caused by natural or synthetic pollutants on any constituents of ecosystems, including animals (including humans), plants, or microorganisms, in an integral context. In recent decades, this science has undergone considerable development by addressing environmental risk assessments through the biomonitoring of indicator species using biomarkers, model organisms, and nanocompounds in toxicological assays. Since a single taxon cannot be representative of complex ecotoxicological effects and mechanisms of action of a chemical, the use of test batteries is widely accepted in ecotoxicology. Test batteries include properly chosen organisms that are easy to breed, adapt easily to laboratory conditions, and are representative of the environmental compartment under consideration. One of the main issues of toxicological and ecotoxicological research is to gain a deeper understanding of how data should be obtained through laboratory and field approaches using experimental models and how they could be extrapolated to humans. There is a tendency to replace animal tests with in vitro systems and to perform them according to standardized analytical methods and the rules of the so-called good laboratory practice (GLP). This paper aims to review this topic to stimulate both efforts to understand the toxicological and ecotoxicological properties of natural and synthetic chemicals and the possible use of such data for application to humans.

D2C7-(scdsFv)-PE38KDEL (D2C7-IT) is a novel recombinant Pseudomonas exotoxin A-based immunotoxin (IT), targeting both wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFR variant III (EGFRvIII) proteins overexpressed in glioblastomas. Initial pre-clinical testing demonstrated the anti-tumor efficacy of D2C7-IT against orthotopic glioblastoma xenograft models expressing EGFRwt, EGFRvIII, or both EGFRwt and EGFRvIII. A good laboratory practice (GLP) manufacturing process was developed to produce sufficient material for a phase I/II clinical trial. D2C7-IT was expressed under the control of the T7 promoter in Escherichia coli BLR (λ DE3). D2C7-IT was produced by a 10-L batch fermentation process and was then purified from inclusion bodies using anion exchange, size exclusion, and an endotoxin removal process that achieved a yield of over 300 mg of purified protein. The final vialed batch of D2C7-IT for clinical testing was at a concentration of 0.12 ± 0.1 mg/mL, the pH was at 7.4 ± 0.4, and endotoxin levels were below the detection limit of 10 EU/mL (1.26 EU/mL). The stability of the vialed D2C7-IT has been monitored over a period of 42 months through protein concentration, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), isoelectric focusing, size exclusion chromatography, cytotoxicity, sterility, and pH measurements. The vialed D2C7-IT is currently being tested in a phase I/II clinical trial by intratumoral convection-enhanced delivery for 72 h in patients with recurrent glioblastoma (NCT02303678, D2C7 for Adult Patients with Recurrent Malignant Glioma; clinicaltrials.gov ).

EHP is a publication of the U.S. government. Publication of EHP lies in the public domain and is therefore without copyright. Research articles from EHP may be used freely; however, articles from the News section of EHP may contain photographs or figures copyrighted by other commercial organizations and individuals that may not be used without obtaining prior approval from both the EHP editors and the holder of the copyright. Use of any materials published in EHP should be acknowledged (for example, \"Reproduced with permission from Environmental Health Perspectives\") and a reference provided for the article from which the material was reproduced.

This paper summarizes the historical and recent research on the aquatic toxicology and bioconcentration potential of tetrabromobisphenol A (TBBPA), a major flame retardant in electronics. Historical studies on TBBPA are presented in detail, and are compared with more recent research. The historical studies have not been published to date, though they were pivotal in regulatory assessments by the European Union, Canada, and the USA. These assessments have enabled the use of TBBPA as a flame retardant in electronic applications, to the present. The studies were conducted under a Test Rule by the US Environmental Protection Agency in 1987, and were sponsored by member companies of the North American Flame Retardants Alliance (NAFRA) through the American Chemistry Council. The studies were conducted under Good Laboratory Practice procedures, and include 6 acute toxicity tests of TBBPA with fish, invertebrates, algae, and microbes, eight chronic tests, and three bioconcentration studies with fish and invertebrates. Methods and empirical data for each study are detailed in an electronic supplement. Results of the NAFRA studies are compared with recent findings on TBBPA toxicity. Molluscan shell growth may be uniquely sensitive to TBBPA, more sensitive than chronic fish or crustacean toxicity endpoints. Several of the NAFRA studies and several independent studies have reported toxicities exceeding the empirical water solubility limits of TBBPA (in the range of 2.0 mg/L depending on pH). The validity of these results is discussed.

While good laboratory practice in a forensic lab minimises the chance of infection of laboratory personnel, in certain cases, possible contamination of pieces of evidence with highly contagious pathogens might call for additional precautions. The number of potential disinfection methods that might be suitable for forensic genetics are surprisingly limited. First and foremost, the ideal technique should not inhibit DNA amplification, it should be effective against a host of pathogens, and it should be applicable on porous surfaces. We examined ozone treatment on extracted DNA samples and mock casework samples. Ozone-treated and control specimens were amplified with Qiagen Investigator ESSplex SE QS kit. Detected allele counts were compared between the treated and untreated sample groups. Following disinfection, concentration of ozone-treated DNA was about half of the control samples, but full STR profiles were recovered. In the case of mock casework samples (disposable surgical masks), there was no significant difference (p = 0.513) between the detected allele counts of control and ozone-treated samples. Sampling location of surgical masks (earloop, nosepiece) showed a statistically significant difference (p = 0.011), though. Comparing the effect of contributors on STR profiling, a significant difference (p = 0.001) was observed, which could be explained with the differences between individuals including shedding capacity, head size or shape. According to our pilot study, ozone treatment does not encumber the routine forensic DNA analysis, the sampling position or the contributor affected the allele counts more than the ozone treatment. •There are no widely accepted methods to disinfect crime scene samples.•Ozone treatment was tested on extracted DNA and mock casework samples.•STR profiling was not inhibited by ozone gas treatment.•This method could be applied on potentially contagious samples.

Sodium dodecyl sulfate (SDS) is a surfactant used and recommended by regulatory agencies as a reference substance in ecotoxicological analyzes. In this work, acute toxicity assays were performed with adults and embryos of the freshwater snail Biomphalaria glabrata, an endemic organism with environmental and public health importance, to evaluate the effects of the surfactant and establish a sensitivity control chart. The organisms were exposed to SDS for 24 h to a range of concentrations, as well as a control group. Six assays were performed to establish the control chart for adults (with a median LC50 of 36.87 mg L−1) and differential sensitivity was observed at each embryonic stage (EC50 = blastulae 33.03, gastrulae 35.03, trochophore 39.71 and veliger 72.55 mg L−1). The following behavioral responses were observed in exposed adult snails: release of hemolymph and mucus, body outside the shell, and penile overexposure. Embryos at the blastulae and gastrulae stages were more sensitive, and teratogenic effects were accentuated in the trochophore stage. The difference in results obtained between adults and embryos underscore the importance of carrying out analyzes at different developmental stages. The serial assays established with SDS for B. glabrata demonstrated efficiency and constancy conditions in the assays with good laboratory practice standards. The wide distribution of Biomphalaria species in several countries, their easy maintenance and cultivation in the laboratory, in addition to ecological importance, make them economical alternatives for ecotoxicological assays.

[LANGUAGE= \"English\"] INTRODUCTION: Appropriate testing is a part of good laboratory practices. “Requesting the right test with the right method, at the right time, to the right patient, to produce the right result at the right cost” has been defined as an appropriate test request. This study was intended to measure the impact of an attend to regulate requests for serum protein electrophoresis tests before and after applying rejection rules and clinical management.METHODS: In a meeting in December 2022, hematologists declared to be more careful about proper testing in electrophoresis. In addition, the laboratory was decided to be involved in test request management through test rejection rules. Multiple myeloma patients with measurable M protein spikes in the gamma regions of serum protein electrophoresis tests were chosen due to relatively well-defined follow-up protocols. Number of hospital visits of the patients and electrophoresis test requests were compared with the year before (2022) and the year after (2023) the meeting.RESULTS: Selected 92 patients visited our hospital 493 times in 2022 and 583 times in 2023 (number of visits). A total of 423 serum protein electrophoresis (SPE) and 416 serum immunofixation electrophoresis (SIFE) tests were requested in 2022 while 427 SPE and 470 SIFE tests were requested in 2023. In 2023, 51 SPE and 36 SIFE test requests were rejected according to the defined test rejection rules.DISCUSSION AND CONCLUSION: From 2022 to 2023 total patient visits increased by 18%, while SPE test requests increased by less than 1% and SIFE test requests increased by 13%. The common will by the Hematology Clinic and the Clinical Biochemistry Laboratory to reduce unnecessary electrophoresis test requests achieved their goal as the rise in test requests were under the rise in hospital visits. After a year of experience, we could confidently propose that our test rejection rules can be adopted by laboratories and used for electrophoresis test management.

The fundamental principle in regulatory toxicology is that all chemicals are toxic and that the severity of effect is proportional to the exposure level. An ancillary assumption is that there are no effects at exposures below the lowest observed adverse effect level (LOAEL), either because no effects exist or because they are not statistically resolvable, implying that they would not be adverse. Chemicals that interfere with hormones violate these principles in two important ways: dose–response relationships can be non-monotonic, which have been reported in hundreds of studies of endocrine disrupting chemicals (EDCs); and effects are often observed below the LOAEL, including all environmental epidemiological studies examining EDCs. In recognition of the importance of this issue, Lagarde et al. have published the first proposal to qualitatively assess non-monotonic dose response (NMDR) relationships for use in risk assessments. Their proposal represents a significant step forward in the evaluation of complex datasets for use in risk assessments. Here, we comment on three elements of the Lagarde proposal that we feel need to be assessed more critically and present our arguments: 1) the use of Klimisch scores to evaluate study quality, 2) the concept of evaluating study quality without topical experts’ knowledge and opinions, and 3) the requirement of establishing the biological plausibility of an NMDR before consideration for use in risk assessment. We present evidence-based logical arguments that 1) the use of the Klimisch score should be abandoned for assessing study quality; 2) evaluating study quality requires experts in the specific field; and 3) an understanding of mechanisms should not be required to accept observable, statistically valid phenomena. It is our hope to contribute to the important and ongoing debate about the impact of NMDRs on risk assessment with positive suggestions.

The Singapore Stem Cell Bank has generated human embryonic stem cell banks from clinical-grade cell lines ESI-017, ESI-035, ESI-049, and ESI-053. All banks were prepared and characterized according to principles of Good Laboratory Practice for quality assurance. Importantly, each cell line has clearly documented and approved ethical provenance and meets recognized standards for performance and safety. The banks are intended to facilitate the translation of stem cell research to clinical medicine by enabling early phase research and development with high-quality, low-cost cells that are also available as clinical-grade stocks.

pGO-1002, a non-viral DNA vaccine that expresses both spike and ORF3a antigens of SARS-CoV-2, is undergoing phase 1 and phase 2a clinical trials in Korea and the US. A preclinical repeated-dose toxicity study in New Zealand white rabbits in compliance with Good Laboratory Practice (GLP) was conducted to assess the potential toxicity, local tolerance, and immunogenicity of the vaccine and GeneDerm suction device. The dose rate was 1.2 mg/head pGO-1002, and this was administered intradermally to a group of animals (eight animals/sex/group) three times at 2-week intervals, followed by a 4-week recovery period. After each administration, suction was applied to the injection site using the GeneDerm device. Mortality, clinical signs, body weight, food consumption, skin irritation, ophthalmology, body temperature, urinalysis, and clinical pathology were also monitored. Gross observations and histopathological evaluation were performed. Overall, pGO-1002 administration-related changes were confined to minor damage or changes at the injection site, increased spleen weight and minimal increased cellularity in white pulp. All changes of injection site were considered local inflammatory changes or pharmacological actions due to the vaccine with the changes in spleen considered consistent with vaccine-induced immune activation. All findings showed reversibility during the 4-week recovery period. Animals vaccinated with pGO-1002, administered by intradermal injection and followed by application of suction with GeneDerm, developed humoral and cellular responses against the SARS-CoV-2 antigens consistent with prior studies in rats. Collectively, it was concluded that the pGO-1002 vaccine was safe and effective under these experimental conditions and these data supported future human study of the vaccine, now known as GLS-5310, for clinical trial use.