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Background: As clinical laboratories struggle to maintain their financial footing and as patients face mounting out-of-pocket expenses for diagnostic testing, being able to perform financial analysis of laboratory stewardship efforts has become an increasingly important skill., Content: Understanding the revenue cycle as it relates to diagnostic testing is fundamental to selecting, designing, implementing, and evaluating laboratory stewardship interventions for maximum financial return. Leveraging the data and processes driving the revenue cycle can inform informatics-based interventions (such as clinical decision support) and allow deliberate financial analyses of stewardship-focused projects. For labs striving not only to ensure their own financial health but also to help their patients avoid financial toxicity, the most effective strategies often depend on developing productive partnerships with key players along the revenue cycle., Summary: Financial laboratory analytics is an emerging skill set that can power laboratory stewardship efforts and whose benefits accrue to patients, clinicians, laboratories, and health systems., (© Association for Diagnostics & Laboratory Medicine 2025. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Microbiology laboratories are pivotal hubs for exploring the potential of microorganisms and addressing global challenges. Particularly, Environmental Microbiology facilities hold substantial influence in advancing knowledge and capabilities crucial for achieving the United Nations Sustainable Development Goals. This raises the imperative of integrating sustainable practices to mitigate the environmental impact of research activities and foster a culture of responsibility. Such an approach not only aligns with global sustainability objectives but also catalyses innovative, eco-conscious methodologies in scientific research aimed at tackling pressing environmental issues. Concerns regarding the environmental footprint of laboratory practices have stimulated innovative improvements within the scientific community, ranging from resource-efficient initiatives to the management of essential commodities like water and energy. This perspective discusses specific areas where microbiology laboratories can enhance their sustainability efforts, drawing on reports and case studies of pioneering groups. Additionally, it explores potential collaborators to support these endeavours and emphasises the pivotal role of early career researchers in driving this transition. By initiating discussions and sparking curiosity within the environmental microbial community, this commentary seeks to propel the microbial ecology field toward a greener future, starting from within the laboratory environment., (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)

Objectives: Positive culture results from non-sterile sites (NSSs) are poorly predictive of clinical infection. Despite this, these results are often interpreted as an indication for antibiotics, even in patients with limited signs of infection. We sought to quantify the influence of NSS culture results on post-report antibiotic initiation (PRAI) in patients who had not been started on antibiotics pre-report., Methods: All community wound/skin swab and sputum cultures were matched to antibiotic dispensing records from February 2017 to July 2022. Prescribing behaviour was assessed pre- and post-report. Sampling without treatment pre-report was termed 'test-and-wait' (TaW). Following TaW, PRAI was identified if antibiotics were started within 5 days post-report., Results: There were 65 480 wound/skin swabs and 8126 sputum samples, with TaW occurring in 21 740 (35.1%) and 4185 (54.4%), respectively. Following a TaW approach PRAI occurred in 43.3% when an organism was reported, versus 10.8% (P < 0.01) for a 'no growth' report for wound/skin swabs. For the same comparison with sputum, PRAI occurred in 47.9% versus 10.8% (P < 0.01). On multivariate analysis reporting an organism remained strongly associated with PRAI., Conclusions: Reporting an organism in those not already on antibiotics was strongly associated with PRAI. We hypothesize that for many patients TaW suggests limited evidence of infection (i.e. insufficient to justify antibiotic treatment at time of sampling), meaning positive NSS results may be driving a considerable volume of potentially unnecessary antibiotic use. Further study on this topic is required, but strategies to reduce PRAI may offer laboratories an opportunity to meaningfully impact antimicrobial stewardship efforts., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Health promotion is thus not only a participatory practice, but a practice for empowerment and social justice. The study describes findings from a community-based participatory and challenge-driven research program. that aimed to improve health through health promotion platform in an ethnically diverse low-income neighbourhood of Malmö, Sweden. Local residents together with lay health promoters living in the area were actively involved in the planning phase and decided on the structure and content of the program. Academic, public sector and commercial actors were involved, as well as NGOs and residents. Empowerment was used as a lens to analyse focus group interviews with participants (n=322) in six co-creative health-promoting labs on three occasions in the period 2017-2019. The CBPR interview guide focused on the dimensions of participation, collaboration and experience of the activities. The CBPR approach driven by community member contributed to empowerment processes within the health promotion labs: Health promotors building trust in social places for integration, Participants motivate each other by social support and Participants acting for community health in wider circle. CBPR Health promotion program should be followed up longitudielly with community participants to be able to see the processes of change and empowerment on the community level., (© The Author(s) 2021. Published by Oxford University Press.)

On December 19, 2018, Altria announced an offer of $12.8 billion for Juul Labs, combining the largest U.S. cigarette manufacturer with the largest U.S. e-cigarette company. This deal is currently being challenged by the Federal Trade Commission (FTC). We consider the antitrust implications. We also consider population health implications, which we argue are essential to a comprehensive analysis of the impact on consumers. Although the FTC antitrust investigation has focused on closed vaping systems, we argue that the relevant market is the broader nicotine delivery product market, which includes all vaping products along with tobacco products. With Altria having a large market share in the key nicotine delivery product submarkets and with important entry barriers, the merger potentially places Altria in a dominant position in the relevant market. In particular, competition in the vaping submarket is reduced, thereby likely to reduce the availability of less harmful alternatives to cigarettes., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: Living labs are user-focused experimental environments in which users and producers co-create innovative solutions in real-life settings. The aim of this study was to review and synthesize health-related studies that used the living labs approach., Methods: An integrative literature review of 15 studies was conducted on the application of living lab principles and their usefulness for investing health problems. Three reviewers independently used methodological assessment tools to evaluate the data quality., Results: Twelve of 15 studies were published during the past 5 years, while 14 of the 15 studies were conducted in Europe. Older adults were the target population in 9 of the 15 studies. The research topics varied, including detecting and monitoring daily life, fall prevention and social support. All the studies applied multi-method approaches and a real-life setting. Use of the living lab approach appeared to improve the quality of life, physical and social health and cognitive function of the target populations., Conclusions: The results showed that the living lab approach was more commonly used to investigate health problems in older adult populations. Living lab appears to be an appropriate method for developing innovative solutions to improve the health of vulnerable groups., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.)

Measurements of the dose equivalent at different distances from the isocenter of the proton therapy center at iThemba LABS were previously performed with a tissue-equivalent proportional counter (TEPC). These measurements showed that the scattered radiation levels were one or two orders of magnitude higher in comparison to other passive scattering delivery systems. In order to reduce these radiation levels, additional shielding was installed shortly after the measurements were done. Therefore, the aim of this work is to quantify and assess the reduction of the secondary doses delivered in the proton therapy room at iThemba LABS after the installation of the additional shielding. This has been performed by measuring microdosimetric spectra with a TEPC at 11 locations around the isocenter when a clinical modulated beam of 200 MeV proton was impinging onto a water phantom placed at the isocenter.

The Romer Labs RapidChek® Listeria monocytogenes test system (Performance Tested Method 011805) was validated against the U.S. Department of Agriculture-Food Safety and Inspection Service Microbiology Laboratory Guidebook (USDA-FSIS/MLG), U.S. Food and Drug Association Bacteriological Analytical Manual (FDA/BAM), and AOAC Official Methods of Analysis (AOAC/OMA) cultural reference methods for the detection of L. monocytogenes on selected foods including hot dogs, frozen cooked breaded chicken, frozen cooked shrimp, cured ham, and ice cream, and environmental surfaces including stainless steel and plastic in an unpaired study design. The RapidChek method uses a proprietary enrichment media system, a 44-48 h enrichment at 30 ± 1°C, and detects L. monocytogenes on an immunochromatographic lateral flow device within 10 min. Different L. monocytogenes strains were used to spike each of the matrixes. Samples were confirmed based on the reference method confirmations and an alternate confirmation method. A total of 140 low-level spiked samples were tested by the RapidChek method after enrichment for 44-48 h in parallel with the cultural reference method. There were 88 RapidChek presumptive positives. One of the presumptive positives was not confirmed culturally. Additionally, one of the culturally confirmed samples did not exhibit a presumptive positive. No difference between the alternate confirmation method and reference confirmation method was observed. The respective cultural reference methods (USDA-FSIS/MLG, FDA/BAM, and AOAC/OMA) produced a total of 63 confirmed positive results. Nonspiked samples from all foods were reported as negative for L. monocytogenes by all methods. Probability of detection analysis demonstrated no significant differences in the number of positive samples detected by the RapidChek method and the respective cultural reference method.

In this report, we describe 2 instances in which expert use of an electronic health record (EHR) system interfaced to an external clinical laboratory information system led to unintended consequences wherein 2 patients failed to have laboratory tests drawn in a timely manner. In both events, user actions combined with the lack of an acknowledgment message describing the order cancellation from the external clinical system were the root causes. In 1 case, rapid, near-simultaneous order entry was the culprit; in the second, astute order management by a clinician, unaware of the lack of proper 2-way interface messaging from the external clinical system, led to the confusion. Although testing had shown that the laboratory system would cancel duplicate laboratory orders, it was thought that duplicate alerting in the new order entry system would prevent such events., (© The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: As the cost of sequencing continues to fall, smaller groups increasingly initiate and manage larger sequencing projects and take on the complexity of data storage for high volumes of samples. This has created a need for low-cost laboratory information management systems (LIMS) that contain flexible fields to accommodate the unique nature of individual labs. Many labs do not have a dedicated information technology position, so LIMS must also be easy to setup and maintain with minimal technical proficiency. MetaLIMS is a free and open-source web-based application available via GitHub. The focus of MetaLIMS is to store sample metadata prior to sequencing and analysis pipelines. Initially designed for environmental metagenomics labs, in addition to storing generic sample collection information and DNA/RNA processing information, the user can also add fields specific to the user's lab. MetaLIMS can also produce a basic sequencing submission form compatible with the proprietary Clarity LIMS system used by some sequencing facilities. To help ease the technical burden associated with web deployment, MetaLIMS options the use of commercial web hosting combined with MetaLIMS bash scripts for ease of setup. MetaLIMS overcomes key challenges common in LIMS by giving labs access to a low-cost and open-source tool that also has the flexibility to meet individual lab needs and an option for easy deployment. By making the web application open source and hosting it on GitHub, we hope to encourage the community to build upon MetaLIMS, making it more robust and tailored to the needs of more researchers., (© The Authors 2017. Published by Oxford University Press.)

Study Objective: We determine the incidence of clinically significant findings within mandatory screening studies during medical clearance of patients for psychiatric care., Methods: This is a retrospective review of emergency department patients medically cleared for psychiatric care over 11 months. All patients evaluated for behavioral health-related issues are recorded on a daily report which was used to locate subjects. Laboratory studies were reviewed during that visit for the presence of abnormalities. If abnormalities were noted, the individual chart was reviewed. Our primary outcome was the incidence of clinically significant findings that warranted admission to a medical or surgical unit., Results: 204 psychiatric patient reports were reviewed. 191 of these patients had screening studies performed. Seven patients were admitted to a nonpsychiatric unit. These admissions were all for elevated ethanol levels. These patients were admitted until their ethanol level decreased, and then transferred to a psychiatric facility. The total screening lab cost during this study period was $27,893., Conclusions: Routine screening has limited utility in this population and comes at significant cost. Further research should be directed to determine which patients may benefit from screening studies., (Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.)

A NE213 proton recoil detector using the time-of-flight technique was used to measure neutron beam fluence energy distributions at the neutron time-of-flight facility of iThemba Labs. A comparison was performed between neutron beam fluence energy distributions calculated by the Monte Carlo code MCNPX and that measured for neutron beams of energies up to ∼64 MeV for the calibration of detectors. The results obtained showed good agreement between the calculated and measured distributions., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Summary: We present the Sample-based Laboratory Information Management System (SLIMS), a powerful and user-friendly open source web application that provides all members of a laboratory with an interface to view, edit and create sample information. SLIMS aims to simplify common laboratory tasks with tools such as a user-friendly shopping cart for subjects, samples and containers that easily generates reports, shareable lists and plate designs for genotyping. Further key features include customizable data views, database change-logging and dynamically filled pre-formatted reports. Along with being feature-rich, SLIMS' power comes from being able to handle longitudinal data from multiple time-points and biological sources. This type of data is increasingly common from studies searching for susceptibility genes for common complex diseases that collect thousands of samples generating millions of genotypes and overwhelming amounts of data. LIMSs provide an efficient way to deal with this data while increasing accessibility and reducing laboratory errors; however, professional LIMS are often too costly to be practical. SLIMS gives labs a feasible alternative that is easily accessible, user-centrically designed and feature-rich. To facilitate system customization, and utilization for other groups, manuals have been written for users and developers., Availability: Documentation, source code and manuals are available at http://genapha.icapture.ubc.ca/SLIMS/index.jsp. SLIMS was developed using Java 1.6.0, JSPs, Hibernate 3.3.1.GA, DB2 and mySQL, Apache Tomcat 6.0.18, NetBeans IDE 6.5, Jasper Reports 3.5.1 and JasperSoft's iReport 3.5.1.

Motivation: The rapid expansion of whole-genome copy number (CN) studies brings a demand for increased precision and resolution of CN estimates. Recent studies have obtained CN estimates from more than one platform for the same set of samples, and it is natural to want to combine the different estimates in order to meet this demand. Estimates from different platforms show different degrees of attenuation of the true CN changes. Similar differences can be observed in CNs from the same platform run in different labs, or in the same lab, with different analytical methods. This is the reason why it is not straightforward to combine CN estimates from different sources (platforms, labs and analysis methods)., Results: We propose a single-sample multi source normalization that brings full-resolution CN estimates to the same scale across sources. The normalized CNs are such that for any underlying CN level, their mean level is the same regardless of the source, which make them better suited for being combined across sources, e.g. existing segmentation methods may be used to identify aberrant regions. We use microarray-based CN estimates from 'The Cancer Genome Atlas' (TCGA) project to illustrate and validate the method. We show that the normalized and combined data better separate two CN states at a given resolution. We conclude that it is possible to combine CNs from multiple sources such that the resolution becomes effectively larger, and when multiple platforms are combined, they also enhance the genome coverage by complementing each other in different regions., Availability: A bounded-memory implementation is available in aroma.cn.

In the last 10 to 15 years, privatization has been used as a policy instrument to reduce the involvement of the public sector in the provision of a variety of services. The purpose of this paper is to discuss models of privatization in the dental technician market and to report on the findings of an analysis of the functioning and efficiency of such services within the framework of the Israel Defence Forces (IDF). We also develop a method for assessing the quality and efficiency with which such services are produced and assess the need for privatization of the service. Currently, the IDF employs a mixed model of privatization whereby some dental technician services are produced in-house and others are contracted out to the civilian private market. A comparative quantitative analysis of the efficiency, quality, and cost of services indicates that the civilian labs are able to produce prosthetic services at a lower cost per unit of output and at a higher level of quality than are the IDF labs. The highly competitive nature of the industry as well as the relative ease with which the IDF could monitor the quality of service further supports the case for privatization of the entire service. The analysis and method described in this paper can serve as a paradigm for evaluating dental technician services in a variety of settings.

The degree of residual structure retained by proteins while passing through biological membranes is a fundamental mechanistic question of protein translocation. Proteins are generally thought to be unfolded while transported through canonical proteinaceous translocons, including the translocons of the outer and inner chloroplast envelope membranes (TOC and TIC). Here, we readdressed the issue and found that the TOC/TIC translocons accommodated the tightly folded dihydrofolate reductase (DHFR) protein in complex with its stabilizing ligand, methotrexate (MTX). We employed a fluorescein-conjugated methotrexate (FMTX), which has slow membrane transport rates relative to unconjugated MTX, to show that the rate of ligand accumulation inside chloroplasts is faster when bound to DHFR that is actively being imported. Stromal accumulation of FMTX is ATP dependent when DHFR is actively being imported but is otherwise ATP independent, again indicating DHFR/FMTX complex import. Furthermore, the TOC/TIC pore size was probed with fixed-diameter particles and found to be greater than 25.6 Å, large enough to support folded DHFR import and also larger than mitochondrial and bacterial protein translocons that have a requirement for protein unfolding. This unique pore size and the ability to import folded proteins have critical implications regarding the structure and mechanism of the TOC/TIC translocons., (© 2018 American Society of Plant Biologists. All rights reserved.)

Objective: To examine the associations of peer victimization with internalizing symptoms, externalizing symptoms, social competence, and academic performance in a clinical sample of adolescents with severe obesity, and whether self-worth and social support affect these associations., Methods: Multisite cross-sectional data from 139 adolescents before weight loss surgery ( M age = 16.9; 79.9% female, 66.2% White; M Body Mass Index [BMI] = 51.5 kg/m 2 ) and 83 nonsurgical comparisons ( M age = 16.1; 81.9% female, 54.2% White; M BMI = 46.9 kg/m 2 ) were collected using self-reports with standardized measures., Results: As a group, participants did not report high levels of victimization. Self-worth mediated the effects of victimization on a majority of measures of adjustment, and further analyses provided evidence of the buffering effect of social support for some mediational models., Conclusions: Self-worth and social support are important targets for prevention and intervention for both victimization and poor adjustment in adolescent severe obesity., (© The Author 2016. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Photosynthesis occurs in thylakoids, a highly specialized membrane system. In the cyanobacterium Synechocystis sp PCC 6803 (hereafter Synechocystis 6803), the thylakoids are arranged parallel to the plasma membrane and occasionally converge toward it to form biogenesis centers. The initial steps in PSII assembly are thought to take place in these regions, which contain a membrane subcompartment harboring the early assembly factor PratA and are referred to as PratA-defined membranes (PDMs). Loss of CurT, the Synechocystis 6803 homolog of Arabidopsis thaliana grana-shaping proteins of the CURVATURE THYLAKOID1 family, results in disrupted thylakoid organization and the absence of biogenesis centers. As a consequence, PSII is less efficiently assembled and accumulates to only 50% of wild-type levels. CurT induces membrane curvature in vitro and is distributed all over the thylakoids, with local concentrations at biogenesis centers. There it forms a sophisticated tubular network at the cell periphery, as revealed by live-cell imaging. CurT is part of several high molecular mass complexes, and Blue Native/SDS-PAGE and isoelectric focusing demonstrated that different isoforms associate with PDMs and thylakoids. Moreover, CurT deficiency enhances sensitivity to osmotic stress, adding a level of complexity to CurT function. We propose that CurT is crucial for the differentiation of membrane architecture, including the formation of PSII-related biogenesis centers, in Synechocystis 6803., (© 2016 American Society of Plant Biologists. All rights reserved.)

In plants, algae, and cyanobacteria, photosystem II (PSII) catalyzes the light-driven oxidation of water. The oxygen-evolving complex of PSII is a Mn4CaO5 cluster embedded in a well-defined protein environment in the thylakoid membrane. However, transport of manganese and calcium into the thylakoid lumen remains poorly understood. Here, we show that Arabidopsis thaliana PHOTOSYNTHESIS AFFECTED MUTANT71 (PAM71) is an integral thylakoid membrane protein involved in Mn(2+) and Ca(2+) homeostasis in chloroplasts. This protein is required for normal operation of the oxygen-evolving complex (as evidenced by oxygen evolution rates) and for manganese incorporation. Manganese binding to PSII was severely reduced in pam71 thylakoids, particularly in PSII supercomplexes. In cation partitioning assays with intact chloroplasts, Mn(2+) and Ca(2+) ions were differently sequestered in pam71, with Ca(2+) enriched in pam71 thylakoids relative to the wild type. The changes in Ca(2+) homeostasis were accompanied by an increased contribution of the transmembrane electrical potential to the proton motive force across the thylakoid membrane. PSII activity in pam71 plants and the corresponding Chlamydomonas reinhardtii mutant cgld1 was restored by supplementation with Mn(2+), but not Ca(2+) Furthermore, PAM71 suppressed the Mn(2+)-sensitive phenotype of the yeast mutant Δpmr1 Therefore, PAM71 presumably functions in Mn(2+) uptake into thylakoids to ensure optimal PSII performance., (© 2016 American Society of Plant Biologists. All rights reserved.)

Study Question: Which recommendations can be provided by the European Society of Human Reproduction and Embryology Special Interest Group (ESHRE SIG) Embryology to support laboratory specialists in the organization and management of IVF laboratories and the optimization of IVF patient care?, Summary Answer: Structured in 13 sections, the guideline development group formulated recommendations for good practice in the organization and management of IVF laboratories, and for good practice of the specific procedures performed within the IVF laboratory., What Is Known Already: NA., Study Design, Size, Duration: The guideline was produced by a group of 10 embryologists representing different European countries, settings and levels of expertise. The group evaluated the document of 2008, and based on this assessment, each group member rewrote one or more sections. Two 2-day meetings were organized during which each of the recommendations was discussed and rewritten until consensus within the guideline group was reached. After finalizing the draft, the members of the ESHRE SIG embryology were invited to review the guideline., Participants/materials, Setting, Methods: NA., Main Results and the Role of Chance: The guideline provides recommendations on the general organization of an IVF laboratory (staffing and direction, quality management, laboratory safety), and on the specific aspects of the procedures performed in IVF laboratories (Identification of patients and traceability of their reproductive cells, consumables, handling of biological material, oocyte retrieval, sperm preparation, insemination of oocytes, scoring for fertilization, embryo culture and transfer, and cryopreservation). A last section provides recommendations regarding an Emergency plan for IVF laboratories., Limitations, Reasons for Caution: Evidence on most of the issues described is scarce, and therefore it was decided not to perform a formal search for and assessment of scientific evidence. However, recommendations published in the EUTCD and relevant and recent documents, manuals and consensus papers were taken into account when formulating the recommendations., Wider Implications of the Findings: Despite the limitations, the guideline group is confident that this document will be helpful to directors and managers involved in the management and organization of IVF laboratories, but also to embryologists and laboratory technicians performing daily tasks., Study Funding/competing Interests: The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings. The guideline group members did not receive payment. Dr Coticchio reports speaker's fees from IBSA and Cook, outside the submitted work; Dr Lundin reports grants from Vitrolife, personal fees from Merck Serono, non-financial support from Unisense, outside the submitted work; Dr. Rienzi reports personal fees from Merck Serono, personal fees from MSD, grants from GFI, outside the submitted work; the other authors had nothing to disclose., Trial Registration Number: NA., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: To characterize prevalence and correlates of child maltreatment (CM) in a clinical sample of adolescents with severe obesity., Method: Multicenter baseline data from 139 adolescents undergoing weight loss surgery (Mage = 16.9; 79.9% female, 66.2% White; Mbody mass index [BMI] = 51.5 kg/m(2)) and 83 nonsurgical comparisons (Mage = 16.1; 81.9% female, 54.2% White; MBMI = 46.9 kg/m(2)) documented self-reported CM (Childhood Trauma Questionnaire) and associations with psychopathology, quality of life, self-esteem and body image, high-risk behaviors, and family dysfunction. , Results: CM prevalence (females: 29%; males: 12%) was similar to national adolescent base rates. Emotional abuse was most prevalent. One in 10 females reported sexual abuse. For females, CM rates were higher in comparisons, yet correlates were similar for both cohorts: greater psychopathology, substance use, and family dysfunction, and lower quality of life., Conclusion: While a minority of adolescents with severe obesity reported a CM history, they carry greater psychosocial burden into the clinical setting., (© The Author 2015. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Thylakoids of land plants have a bipartite structure, consisting of cylindrical grana stacks, made of membranous discs piled one on top of the other, and stroma lamellae which are helically wound around the cylinders. Protein complexes predominantly located in the stroma lamellae and grana end membranes are either bulky [photosystem I (PSI) and the chloroplast ATP synthase (cpATPase)] or are involved in cyclic electron flow [the NAD(P)H dehydrogenase (NDH) and PGRL1-PGR5 heterodimers], whereas photosystem II (PSII) and its light-harvesting complex (LHCII) are found in the appressed membranes of the granum. Stacking of grana is thought to be due to adhesion between Lhcb proteins (LHCII or CP26) located in opposed thylakoid membranes. The grana margins contain oligomers of CURT1 proteins, which appear to control the size and number of grana discs in a dosage- and phosphorylation-dependent manner. Depending on light conditions, thylakoid membranes undergo dynamic structural changes that involve alterations in granum diameter and height, vertical unstacking of grana, and swelling of the thylakoid lumen. This plasticity is realized predominantly by reorganization of the supramolecular structure of protein complexes within grana stacks and by changes in multiprotein complex composition between appressed and non-appressed membrane domains. Reversible phosphorylation of LHC proteins (LHCPs) and PSII components appears to initiate most of the underlying regulatory mechanisms. An update on the roles of lipids, proteins, and protein complexes, as well as possible trafficking mechanisms, during thylakoid biogenesis and the de-etiolation process complements this review.

Chloroplasts of land plants characteristically contain grana, cylindrical stacks of thylakoid membranes. A granum consists of a core of appressed membranes, two stroma-exposed end membranes, and margins, which connect pairs of grana membranes at their lumenal sides. Multiple forces contribute to grana stacking, but it is not known how the extreme curvature at margins is generated and maintained. We report the identification of the CURVATURE THYLAKOID1 (CURT1) protein family, conserved in plants and cyanobacteria. The four Arabidopsis thaliana CURT1 proteins (CURT1A, B, C, and D) oligomerize and are highly enriched at grana margins. Grana architecture is correlated with the CURT1 protein level, ranging from flat lobe-like thylakoids with considerably fewer grana margins in plants without CURT1 proteins to an increased number of membrane layers (and margins) in grana at the expense of grana diameter in overexpressors of CURT1A. The endogenous CURT1 protein in the cyanobacterium Synechocystis sp PCC6803 can be partially replaced by its Arabidopsis counterpart, indicating that the function of CURT1 proteins is evolutionary conserved. In vitro, Arabidopsis CURT1A proteins oligomerize and induce tubulation of liposomes, implying that CURT1 proteins suffice to induce membrane curvature. We therefore propose that CURT1 proteins modify thylakoid architecture by inducing membrane curvature at grana margins.

Objective: The localized form of pigmented villonodular synovitis of the knee joint is a rare disease with limited alteration of the synovial membrane, the pathogenesis of which is the subject of controversial discussion., Methods: Eighteen cases have been documented in our hospital since 1976. All of the patients had additional cartilage or meniscus damage. Treatment consisted of excision of the lesion and the adjacent synovial membrane, as well as therapy of the additional damage., Results: The patients who had received such therapy were followed for 3-9 yr, without any clinical, sonographic or magnetic resonance tomographic signs of recurrence. In addition to the lack of a tendency towards recurrence, none of the cases displayed any further characteristics of the diffuse form of villonodular synovitis, such as invasiveness or malignant transformation., Conclusions: We therefore suggest that pigmented villonodular synovitis of the knee joint should be classified more strictly than before into a potentially neoplastic (diffuse) form and a reactive granulomatous (local) form. From the cases observed, we conclude that degenerative joint lesions may be the cause of the reactive granulomatous form.

Introduction: Hypoxia presents a physiological challenge to the Warfighters during military aviation and subterranean warfare operations by decreasing the supply of oxygen to the brain, which results in a reduced cognitive function depending on the magnitude and duration of hypoxic exposure. Moderate hypoxic exposures, fractions of inspired oxygen (FiO2) of 0.11 to 0.14, show no effects on simple tasks, but complex tasks like working memory may be hindered. Unfortunately, people often cannot recognize their own symptoms of hypoxemia, which are individualistic at moderate hypoxic exposure. Thus, screening tools, like gamified cognitive assessments, during moderate hypoxia may provide personnel objective feedback to initiate safety protocols before a possible accident. However, whether gamified assessments of working memory are sensitive to moderate hypoxia is unknown. Therefore, we tested the hypothesis which moderate normobaric hypoxia decreases gamified working memory performance when accounting for the individualistic responses of arterial blood oxygen saturations., Materials and Methods: Following 3 consecutive days of 2 practice sessions per day, 30 healthy adults (25 ± 5 years, 10 women) completed three 1-min rounds of the tablet-based working memory game (Backtracker, Statespace Labs, Inc.) at baseline and 60 and 90 min after exposure to FiO2 (= 0.138 ± 0.002 [hypoxia] and 0.201± 0.004 [normoxia] oxygen). Both conditions were completed on the same day and administered in a single-blind, block randomized manner. Arterial oxyhemoglobin saturation was estimated via forehead pulse oximetry (SpO2). Data were analyzed using linear mixed effects modeling., Results: Compared to normoxia (99 ± 1%), SpO2 was lower (P < .001) at 60 (90 ± 2%) and 90 (90 ± 2%) min of hypoxia. A decrease in SpO2 was associated with a statistically significant decrease in the proportion of both tiles with the correct location (P < .02; -0.016) and correct order of appearance recalled (P < .01; -0.016). A decrease in SpO2 was associated with a statistically significant decrease in median time to first tap (P < .01; -0.041 s) and median time between taps (P < .01; -0.030 s). A significant interaction effect between the SpO2 decrease and baseline performance was found for proportion of tiles with the correct location recalled (P < .05; -0.014), median time to first tap (P < .01; -0.070 s), and median time between taps (P < .01; -0.037 s). A significant interaction effect between the SpO2 decrease and the path length was found for the proportion of tiles with the correct location recalled (P < .01; +0.021), median time to first tap (P < .01; -0.036 s), and median time between taps (P < .01; -0.043 s)., Conclusions: These findings indicate that greater decreases in SpO2 during moderate hypoxic exposure hinder performance on a gamified assessment of working memory as measured by the proportion of correctly identified order and location of tiles. Considering the statistically significant decrease in both median time to first tap and median time between taps associated with the decrease in SpO2, participants are taking less time to plan or execute movements, which may compound or independently contribute to spatial and temporal memory mistakes., (© The Association of Military Surgeons of the United States 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

The clinical manifestation of Parkinson's disease exhibits significant heterogeneity in the prevalence of non-motor symptoms and the rate of progression of motor symptoms, suggesting that Parkinson's disease can be classified into distinct subtypes. In this study, we aimed to explore this heterogeneity by identifying a set of subtypes with distinct patterns of spatiotemporal trajectories of neurodegeneration. We applied Subtype and Stage Inference (SuStaIn), an unsupervised machine learning algorithm that combined disease progression modelling with clustering methods, to cortical and subcortical neurodegeneration visible on 3 T structural MRI of a large cross-sectional sample of 504 patients and 279 healthy controls. Serial longitudinal data were available for a subset of 178 patients at the 2-year follow-up and for 140 patients at the 4-year follow-up. In a subset of 210 patients, concomitant Alzheimer's disease pathology was assessed by evaluating amyloid-β concentrations in the CSF or via the amyloid-specific radiotracer 18F-flutemetamol with PET. The SuStaIn analysis revealed three distinct subtypes, each characterized by unique patterns of spatiotemporal evolution of brain atrophy: neocortical, limbic and brainstem. In the neocortical subtype, a reduction in brain volume occurred in the frontal and parietal cortices in the earliest disease stage and progressed across the entire neocortex during the early stage, although with relative sparing of the striatum, pallidum, accumbens area and brainstem. The limbic subtype represented comparative regional vulnerability, which was characterized by early volume loss in the amygdala, accumbens area, striatum and temporal cortex, subsequently spreading to the parietal and frontal cortices across disease stage. The brainstem subtype showed gradual rostral progression from the brainstem extending to the amygdala and hippocampus, followed by the temporal and other cortices. Longitudinal MRI data confirmed that 77.8% of participants at the 2-year follow-up and 84.0% at the 4-year follow-up were assigned to subtypes consistent with estimates from the cross-sectional data. This three-subtype model aligned with empirically proposed subtypes based on age at onset, because the neocortical subtype demonstrated characteristics similar to those found in the old-onset phenotype, including older onset and cognitive decline symptoms (P < 0.05). Moreover, the subtypes correspond to the three categories of the neuropathological consensus criteria for symptomatic patients with Lewy pathology, proposing neocortex-, limbic- and brainstem-predominant patterns as different subgroups of α-synuclein distributions. Among the subtypes, the prevalence of biomarker evidence of amyloid-β pathology was comparable. Upon validation, the subtype model might be applied to individual cases, potentially serving as a biomarker to track disease progression and predict temporal evolution., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

We previously described a novel Plasmodium vivax invasion mechanism into human reticulocytes via the PvRBP2a-CD98 receptor-ligand pair. Using linear epitope mapping, we assessed the PvRBP2a epitopes involved in CD98 binding and recognized by antibodies from patients who were infected. We identified 2 epitope clusters mediating PvRBP2a-CD98 interaction. Cluster B (PvRBP2a431-448, TAALKEKGKLLANLYNKL) was the target of antibody responses in humans infected by P vivax. Peptides from each cluster were able to prevent live parasite invasion of human reticulocytes. These results provide new insights for development of a malaria blood-stage vaccine against P vivax., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Electronic nicotine-delivery systems (ENDS) can reduce tobacco-related health risks for adults who smoke cigarettes (AWS) by facilitating complete switching away from cigarettes. However, little is known about ENDS use and switching among subpopulations that have been disproportionately affected by smoking., Aims and Methods: AWS (age ≥ 21 years) were recruited following their first purchase of a JUUL Starter Kit in 2018. Participants who self-reported switching (no past-30-day cigarette smoking) at 1-, 2-, 3-, 6-, 9-, 12-, 15-, 18-, 21-, and 24-month follow-ups. Percent switched and percent with substantial smoking reduction (≥50% decrease in cigarettes per day among those who continued smoking) were calculated. Analyses focused on racial and ethnic minorities, persons with low income and education levels, sexual minorities, and those with mental and physical health conditions., Results: Overall rates of switching away from cigarettes increased across follow-ups to 51.2% (month-12) to 58.6% (month-24, 87% of whom used ENDS). Among those who continued to smoke at 24 months, 45.4% reduced cigarettes per day by ≥ 50%. Rates of switching and substantial smoking reduction were largely similar across subgroups, with some statistically significant, but small, differences in month-24 switching rates (eg, education, mental and physical health conditions; switch rate range: 42%-57%)., Conclusions: AWS demonstrated progressively increasing switching rates over 2 years after purchasing JUUL products. Similar trends in switching and smoking reduction were observed across populations disproportionately affected by smoking. By facilitating switching and smoking reduction, ENDS products such as JUUL may provide an opportunity to reduce smoking-related harm among some populations disproportionately affected by smoking, potentially reducing tobacco-related health disparities., Implications: ENDS have the potential to benefit population health if they can replace cigarettes. This benefit must extend to populations disproportionately affected by smoking. In this real-world study, 59% of JUUL purchasers reported complete switching 2 years later (no past-30-day smoking, with most continuing to use ENDS). Furthermore, 45% of those who continued to smoke reduced cigarette consumption by at least half. These rates of switching and smoking reduction were largely comparable across populations disproportionately affected by smoking (defined, eg, by ethnicity and income). ENDS can serve as an effective harm reduction strategy to complement current efforts to reduce tobacco-related disparities., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Limited throughput represents a substantial drawback during bioprocess development. In recent years, several commercial microbioreactor systems have emerged featuring parallelized experimentation with optical monitoring. However, many devices remain limited to batch mode and do not represent the fed-batch strategy typically applied on an industrial scale. A workflow for 32-fold parallelized microscale cultivation of protein secreting Corynebacterium glutamicum in microtiter plates incorporating online monitoring, pH control and feeding was developed and validated. Critical interference of the essential media component protocatechuic acid with pH measurement was revealed, but was effectively resolved by 80% concentration reduction without affecting biological performance. Microfluidic pH control and feeding (pulsed, constant and exponential) were successfully implemented: Whereas pH control improved performance only slightly, feeding revealed a much higher optimization potential. Exponential feeding with µ = 0.1 h -1 resulted in the highest product titers. In contrast, other performance indicators such as biomass-specific or volumetric productivity resulted in different optimal feeding regimes.

The RNA-guided CRISPR-associated (Cas) enzyme Cas12a cleaves specific double-stranded (ds-) or single-stranded (ss-) DNA targets (in cis), unleashing non-specific ssDNA cleavage (in trans). Though this trans-activity is widely coopted for diagnostics, little is known about target determinants promoting optimal enzyme performance. Using quantitative kinetics, we show formation of activated nuclease proceeds via two steps whereby rapid binding of Cas12a ribonucleoprotein to target is followed by a slower allosteric transition. Activation does not require a canonical protospacer-adjacent motif (PAM), nor is utilization of such PAMs predictive of high trans-activity. We identify several target determinants that can profoundly impact activation times, including bases within the PAM (for ds- but not ssDNA targets) and sequences within and outside those complementary to the spacer, DNA topology, target length, presence of non-specific DNA, and ribose backbone itself, uncovering previously uncharacterized cleavage of and activation by RNA targets. The results provide insight into the mechanism of Cas12a activation, with direct implications on the role of Cas12a in bacterial immunity and for Cas-based diagnostics., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Objectives: National societies recommend against performing routine daily laboratory testing without a specific indication. Unnecessary testing can lead to patient harm, such as hospital-acquired anemia. The objective of this study was to reduce repeat complete blood counts (CBCs) after initial testing., Methods: This was a quality improvement initiative implemented across 11 safety net hospitals in New York City. A best practice advisory (BPA) was implemented that asked the user to remove a CBC if the last 2 CBCs within 72 hours had normal white blood cell and platelet counts and unchanged hemoglobin levels. The outcome measure was the rate of CBCs per 1000 patient days preintervention (January 8, 2020, to December 22, 2020) to postintervention (December 23, 2020, to December 7, 2021). The process measure was the acceptance rate of the BPA, defined as the number of times the repeat CBC order was removed through the BPA divided by the total number of times the BPA triggered., Results: Across 11 hospitals, repeat CBC testing decreased by 12.3% (73.05 to 64.04 per 1000 patient days, P < .001). Six of the 11 hospitals exhibited statistically significant decreases, ranging from a 10% to 48.9% decrease of repeat CBCs. The overall BPA action rate was 20.0% (24,029 of 119,944 repeat CBCs)., Conclusions: This low-effort, electronic health record-based intervention can effectively reduce unnecessary laboratory testing., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Real-world evidence on exposure to harmful and potentially harmful constituents (HPHCs) and on biological effects in cigarette smokers who switch to electronic nicotine delivery systems (ENDS) can inform the health effects of switching., Aims and Methods: This cross-sectional, observational study assessed adults who had smoked ≥10 cigarettes/day for ≥10 years, comparing 124 continuing cigarette smokers (Smokers) to 140 former smokers who switched to JUUL-brand ENDS exclusively for ≥6 months (Switchers). Assessments included biomarkers of exposure (BOEs) to select HPHCs, biomarkers of potential harm (BOPHs) related to smoking-related diseases, psychometric assessments of dependence on cigarettes and ENDS, respectively, and respiratory symptoms. Planned analyses compared geometric means, adjusted for demographic covariates; further analyses adjusted for additional lifestyle and smoking history covariates., Results: Nicotine levels were significantly higher in Switchers (median time switched = 3 years), who were unusually heavy users of JUUL. All other BOEs, including NNAL and HPMA3 (primary endpoints), were significantly lower in Switchers than Smokers. Most BOPHs (sICAM-1 [primary], and eg, white blood cell count, MCP1, HbA1c) were significantly lower in Switchers than Smokers; HDL was significantly higher. Switchers reported significantly lower dependence on JUUL than Smokers did on cigarettes, and respiratory symptom scores were significantly lower among Switchers than Smokers., Conclusions: Compared to continuing smokers, smokers who switched to JUUL had substantially lower exposures to multiple HPHCs, favorable differences in markers of inflammation, endothelial function, oxidative stress, and cardiovascular risk, and fewer respiratory symptoms. These findings suggest that switching from cigarettes to JUUL likely reduces smokers' health risks., Implications: Short-term confinement studies and randomized clinical trials demonstrate that adult smokers who switch completely to ENDS experience substantial reductions in exposure to many smoking-related toxicants. This study extends those findings to longer periods of switching to JUUL-brand ENDS (almost 3 years on average) under naturalistic use conditions in real-world settings and also found that switching to JUUL resulted in favorable differences in BOPHs more proximally related to smoking-induced disease, as well as in respiratory symptoms. Smokers who switch to ENDS reduce their exposure to toxicants, likely reducing their disease risk., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The black carpenter ant (Camponotus pennsylvanicus) is a pest species found widely throughout North America. From a single individual I used long-read nanopore sequencing to assemble a phased diploid genome of 306 Mb and 60X coverage, with quality assessed by a 97.0% BUSCO score, improving upon other ant assemblies. The mitochondrial genome reveals minor rearrangements from other ants. The reads also allowed assembly of parasitic and symbiont genomes. I include a complete Wolbachia bacterial assembly with a size of 1.2 Mb, as well as a commensal symbiont Blochmannia pennsylvanicus, at 791 kb. DNA methylation and hydroxymethylation were measured at base-pair resolution level from the same reads and confirmed extremely low levels seen in the Formicidae family. There was moderate heterozygosity, with 0.16% of bases being biallelic from the parental haplotypes. Protein prediction yielded 14 415 amino acid sequences with 95.8% BUSCO score and 86% matching to previously known proteins. All assemblies were derived from a single MinION flow cell generating 20 Gb of sequence for a cost of $1047 including consumable reagents. Adding fixed costs for equipment brings the total for an ant-sized genome to less than $5000. All analyses were performed in 1 week on a single desktop computer., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Summary: Here, we introduce RatesTools, an automated pipeline to infer de novo mutation rates from parent-offspring trio data of diploid organisms. By providing a reference genome and high-coverage, whole-genome resequencing data of a minimum of three individuals (sire, dam and offspring), RatesTools provides a list of candidate de novo mutations and calculates a putative mutation rate. RatesTools uses several quality filtering steps, such as discarding sites with low mappability and highly repetitive regions, as well as sites with low genotype and mapping qualities to find potential de novo mutations. In addition, RatesTools implements several optional filters based on post hoc assumptions of the heterozygosity and mutation rate of the organism. Filters are highly customizable to user specifications in order to maximize utility across a wide range of applications., Availability and Implementation: RatesTools is freely available at https://github.com/campanam/RatesTools under a Creative Commons Zero (CC0) license. The pipeline is implemented in Nextflow (Di Tommaso et al., 2017), Ruby (http://www.ruby-lang.org), Bash (https://www.gnu.org/software/bash/) and R (R Core Team, 2020) with reliance upon several other freely available tools. RatesTools is compatible with macOS and Linux operating systems., Supplementary Information: Supplementary data are available at Bioinformatics online., (Published by Oxford University Press 2022.)

Dens are a crucial component of the life history of most shallow water octopuses. However, den usage dynamics have only been explored in a few species over relatively short durations, and Octopus rubescens denning behavior has never been explored in situ. We built four underwater camera traps to observe the behavior of O. rubescens in and around their dens. To distinguish individuals, octopuses were captured and given a unique identifiable visible implant elastomer tag on the dorsal side of their mantle. After being tagged and photographed, each octopus was released back to its original capture site within its original den bottle. The site is unique in that octopuses reside almost exclusively in discarded bottles, therefore aiding in locating and monitoring dens. Motion-activated cameras were suspended in a metal field-of-view above bottle dens of released octopuses to observe den-associated behaviors. Cameras were regularly retrieved and replaced to allow continuous monitoring of den locations in 71 h intervals for over a month. We found that O. rubescenswas primarily active during the day and had frequent interactions with conspecifics (other members within the species). We also found that rockfish and red rock crabs tended to frequent den locations more often when octopuses were not present, while kelp greenling both visited dens more frequently and stayed longer when octopuses were present. Our results, demonstrate the utility of motion-activated camera traps for behavioral and ecological studies of nearshore mobile organisms., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.)

Aims: To investigate if Clostridium (Clostridioides) difficile infection (CDI), traditionally thought of as hospital-acquired, can be genomically linked to hospital or community environmental sources, and to define possible importation routes from the community to the hospital., Methods and Results: In 2019, C. difficile was isolated from 89/300 (29.7%) floor and 96/300 (32.0%) shoe sole samples at a tertiary hospital in Western Australia. Non-toxigenic C. difficile ribotype (RT) 010 predominated among floor (96.6%) and shoe sole (73.2%) isolates, while toxigenic RT 014/020 was most prevalent among contemporaneous clinical cases (33.0%) at the hospital. Whole-genome sequencing and high-resolution core genome single nucleotide polymorphism (cgSNP) analysis on C. difficile strains from hospital and community sources showed no clinical C. difficile RT 014/020 strains were genetically related, and evidence of frequent long-distance, multi-directional spread between humans, animals and the environment. In addition, cgSNP analysis of environmental RT 010 strains suggested transportation of C. difficile via shoe soles., Conclusions: While C. difficile RT 014/020 appears to spread via routes outside the healthcare system, RT 010 displayed a pattern of possible importation from the community into the hospital., Significance and Impact of Study: These findings suggest developing community-based infection prevention and control strategies could significantly lower rates of CDI in the hospital setting., (© 2021 The Society for Applied Microbiology.)

Members of the marine Roseobacter group are key players in the global carbon and sulfur cycles. While over 300 species have been described, only 2% possess reduced genomes (mostly 3-3.5 Mbp) compared to an average roseobacter (>4 Mbp). These taxonomic minorities are phylogenetically diverse but form a Pelagic Roseobacter Cluster (PRC) at the genome content level. Here, we cultivated eight isolates constituting a novel Roseobacter lineage which we named 'CHUG'. Metagenomic and metatranscriptomic read recruitment analyses showed that CHUG members are globally distributed and active in marine pelagic environments. CHUG members possess some of the smallest genomes (~2.6 Mb) among all known roseobacters, but they do not exhibit canonical features of typical bacterioplankton lineages theorized to have undergone genome streamlining processes, like higher coding density, fewer paralogues and rarer pseudogenes. While CHUG members form a genome content cluster with traditional PRC members, they show important differences. Unlike other PRC members, neither the relative abundances of CHUG members nor their relative gene expression levels are correlated with chlorophyll a concentration across the global samples. CHUG members cannot utilize most phytoplankton-derived metabolites or synthesize vitamin B 12 , a key metabolite mediating the roseobacter-phytoplankton interactions. This combination of features is evidence for the hypothesis that CHUG members may have evolved a free-living lifestyle decoupled from phytoplankton. This ecological transition was accompanied by the loss of signature genes involved in roseobacter-phytoplankton symbiosis, suggesting that relaxation of purifying selection owing to lifestyle shift is likely an important driver of genome reduction in CHUG., (© 2021. The Author(s), under exclusive licence to International Society for Microbial Ecology.)

The transfer of antimicrobial resistance genes commonly occurs via vertical and horizontal gene transfer, as such genes are often found on the same mobile genetic element. This occurrence can lead to the co-selection of resistance to antimicrobials without their application. Dairy cattle located in the south-western United States were enrolled in a matched-pair longitudinal study to evaluate the effects of a two-dose ceftiofur treatment for metritis on levels of third-generation cephalosporin resistance among faecal Escherichia coli temporally. Escherichia coli chosen for further investigation were isolated on selective media, harboured extended-spectrum beta-lactam, fluoroquinolone and macrolide resistance genes. This combination has previously been unreported; importantly, it included genes encoding for resistance to antibiotics that can only be used in dairy cattle less than 20 months of age. Fluoroquinolones, macrolides and third and higher generation cephalosporins are considered critically important and highest priority for human medicine by the World Health Organization., (© 2020 The Society for Applied Microbiology.)

Background: Preoperative laboratory testing is commonplace in the clinical setting and is often utilized at surgeon discretion. We searched the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) data set to determine the impact of preoperative laboratory testing in ambulatory plastic surgery patients., Objective: The authors assess the utilization and predictive value of preoperative laboratory testing in outpatient plastic surgery procedures., Methods: Patients undergoing ambulatory plastic surgery were identified from the 2005 to 2010 NSQIP databases. Laboratory tests were categorized by group: hematologic, chemistry, coagulation, and liver function tests (LFT). We defined complications in 2 groups: major postoperative and wound complications. Multivariate analyses were used to identify patient characteristics associated with testing and to assess the ability of laboratory testing to predict postoperative complications., Results: A total of 5359 (62.0%) patients underwent testing; 881 (16.4%) tests were performed on the day of surgery. In patients with no defined NSQIP comorbidities, 59.4% underwent preoperative testing and had a significantly lower rate of abnormal findings (33.4% vs 25.3%, P < .0001). In multivariate analyses, testing was associated with older age, American Society of Anesthesiologists class >2, Hispanic or African American race, body contouring procedures, epidural or spinal procedures, and with diabetes, hypertension, and cancer. Major complications occurred in 0.34% of patients. Our analysis demonstrated that neither testing nor abnormal results were associated with postoperative complications, either major (P = .178) or wound (P = .150)., Conclusions: We found no association between abnormal laboratory testing and postoperative morbidity. Preoperative testing in low-risk ambulatory plastic surgery patients may be costly and has limited direct clinical benefit.

Objective: Chronic inflammatory diseases, like Systemic Lupus Erythematosus (SLE), carry an increased risk for atherosclerosis and cardiovascular events, accompanied by impairment of atheroprotective properties of high-density lipoprotein (HDL). In SLE, serum B cell-activating factor (BAFF), a cytokine implicated in disease progression, has been correlated with subclinical atherosclerosis. We investigated the impact of treatment with belimumab -an anti-BAFF monoclonal antibody- on HDL atheroprotective properties and composition in SLE patients., Methods: Serum samples were collected from 35 SLE patients with active disease despite conventional therapy, before and after 6-month add-on treatment with belimumab, and 26 matched healthy individuals. We measured cholesterol efflux and antioxidant capacities, paraoxonase-1 (PON1) activity, serum amyloid A1 (SAA1), myeloperoxidase (MPO) and lipid peroxidation product levels of HDL. LC-MS/MS was performed to analyse the HDL lipidome., Results: Following treatment with belimumab, cholesterol efflux and antioxidant capacities of HDL were significantly increased in SLE patients and restored to levels of control subjects. HDL-associated PON1 activity was also increased, whereas lipid peroxidation products were decreased following treatment. HDL cholesterol efflux and antioxidant capacities correlated negatively with the disease activity. Changes were noted in the HDL lipidome of SLE patients following belimumab treatment, as well as between SLE patients and healthy individuals, and specific changes in lipid species correlated with functional parameters of HDL., Conclusions: HDL of SLE patients with active disease displays impaired atheroprotective properties accompanied by distinct lipidomic signatures compared with controls. Belimumab treatment may improve the HDL atheroprotective properties and modify the HDL lipidomic signature in SLE patients, thus potentially mitigating atherosclerosis development., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: The most frequently ordered laboratory test worldwide is the complete blood count (CBC). As clinical chemists are increasingly assigned to assist or direct laboratories outside of the traditional clinical chemistry sections, such as the automated hematology section, expertise must be established. This review article is a dedication to that ongoing effort., Content: In this primer, the white blood cell (WBC) test components of the CBC are introduced, followed by a discussion of the laboratory evaluation of leukopenia and leukocytosis., Summary: The laboratorian's approach to consult cases should be guided by the patient's clinical history and presentation while being able to provide key laboratory-based insights to assist in resolving result discrepancies that may otherwise go unnoticed., (© Association for Diagnostics & Laboratory Medicine 2025. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Identification of N,N-dimethylpentylone (DMP) in counterfeit "Ecstasy" and "Molly" tablets poses risk to public health due to its adverse effects. Little information is available regarding the pharmacological activity or relevant blood or tissue concentrations of DMP, and even less is known about other structurally related beta-keto methylenedioxyamphetamine analogues on recreational drug markets, such as N-propyl butylone. Here, a novel toxicological assay utilizing liquid chromatography-tandem quadrupole mass spectrometry (LC-QQQ-MS) was developed and validated for the quantitation of DMP and five related synthetic cathinones (eutylone, pentylone, N-ethyl pentylone (NEP), N-propyl butylone, and N-cyclohexyl butylone), with chromatographic resolution from isomeric variants and quantitation performed by standard addition. A forensic series of 125 cases is presented for DMP and related analogs, along with pharmacological activity assessments using monoamine transporter and mouse behavioral assays. The blood concentration range for DMP in postmortem forensic cases was 3.3-4,600 ng/mL (mean: 320±570 ng/mL, median: 150 ng/mL), whereas pentylone, the primary N-desmethyl metabolite of DMP, was identified in 98% of cases with a concentration range 1.3-710 ng/mL (mean±SD: 105±120 ng/mL, median: 71 ng/mL). N-Propyl butylone, a newly identified synthetic cathinone, was quantitated in seven cases (mean±SD: 82±75 ng/mL, median: 50 ng/mL, range: 1.7-200 ng/mL). DMP displayed potent uptake inhibition at the dopamine transporter (IC50=49 nM), with 100-fold weaker potency at the serotonin transporter (IC50=4990 nM). DMP was a locomotor stimulant in mice (ED50=3.5 mg/kg) exhibiting potency relatively similar to eutylone, N-ethyl pentylone, and pentylone. Our results show that DMP is a psychomotor stimulant associated with adverse clinical outcomes leading to death. Forensic laboratories must continue to update testing methods to capture emerging drugs, with specific emphasis on resolution and identification of isomeric species. Following the scheduling of DMP in early-2024, there could be an anticipated market shift towards a new unregulated synthetic stimulant to replace DMP., (© The Author(s) 2025. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)