The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research.

Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and reproduce the methods and results. Despite considerable levels of endorsement by funders and journals over the years, adherence to the guidelines has been inconsistent, and the anticipated improvements in the quality of reporting in animal research publications have not been achieved. Here, we introduce ARRIVE 2.0. The guidelines have been updated and information reorganised to facilitate their use in practice. We used a Delphi exercise to prioritise and divide the items of the guidelines into 2 sets, the "ARRIVE Essential 10," which constitutes the minimum requirement, and the "Recommended Set," which describes the research context. This division facilitates improved reporting of animal research by supporting a stepwise approach to implementation. This helps journal editors and reviewers verify that the most important items are being reported in manuscripts. We have also developed the accompanying Explanation and Elaboration (E&E) document, which serves (1) to explain the rationale behind each item in the guidelines, (2) to clarify key concepts, and (3) to provide illustrative examples. We aim, through these changes, to help ensure that researchers, reviewers, and journal editors are better equipped to improve the rigour and transparency of the scientific process and thus reproducibility.

Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0.

Improving the reproducibility of biomedical research is a major challenge. Transparent and accurate reporting is vital to this process; it allows readers to assess the reliability of the findings and repeat or build upon the work of other researchers. The ARRIVE guidelines (Animal Research: Reporting In Vivo Experiments) were developed in 2010 to help authors and journals identify the minimum information necessary to report in publications describing in vivo experiments. Despite widespread endorsement by the scientific community, the impact of ARRIVE on the transparency of reporting in animal research publications has been limited. We have revised the ARRIVE guidelines to update them and facilitate their use in practice. The revised guidelines are published alongside this paper. This explanation and elaboration document was developed as part of the revision. It provides further information about each of the 21 items in ARRIVE 2.0, including the rationale and supporting evidence for their inclusion in the guidelines, elaboration of details to report, and examples of good reporting from the published literature. This document also covers advice and best practice in the design and conduct of animal studies to support researchers in improving standards from the start of the experimental design process through to publication.

Adopting workload-based staffing norms at public sector health facilities in Bangladesh: evidence from two districts.

BACKGROUND: Bangladesh's Health system is characterized by severe shortage and unequitable distribution of the formally trained health workforce. In this context, government of Bangladesh uses fixed staffing norms for its health facilities. These norms do not always reflect the actual requirement in reality. This study was conducted in public sector health facilities in two selected districts to assess the existing staffing norms with the purpose of adopting better norms and a more efficient utilization of the existing workforce. METHODS: To carry out this assessment, WHO's Workload Indicators of Staffing Need (WISN) method was applied. Selection of the two districts out of 64 and a total of 24 health facilities were made in consultation with the formally established steering committee of the Ministry of Health. Health facilities, which were performing well in serving the patients during 2016-2017, were selected. This assessment examined staffing requirement of 20 staff categories. RESULTS: Based on the computer-generated WISN results, most of the staff categories were found to have a workload pressure of Very High (seven out of 20 staff categories), followed by Extremely High (five staff categories). Two staff categories had high, three had moderately high, two normal, and one low workload. Nurses were found to be predominantly occupied with support activities (50-60% of working time), instead of actual nursing care. Regarding vacancy, if all the vacant posts were filled, understandably, the workload would reduce, but not yet sufficient to meet the existing staff requirements such as consultants, general physicians and nurses at the district and sub-district/upazila-based hospitals. CONCLUSION: The existing staffing norms fall short of the WISN staffing requirement. The results provide evidence to prompt a revisit of the staffing policies and adopt workload-based norms. This can be supplemented by reviewing the scope of practice of the staff categories in their respective health facilities. In the short term, government might consider redistributing existing workforce as per workload. In the long term, revision of staffing norms is needed to provide quality health services for all.

Informing investment in health workforce in Bangladesh: a health labour market analysis.

BACKGROUND: As the 2016 Global Strategy on Human Resources for Health: Workforce 2030 (GSHRH) outlines, health systems can only function with health workforce (HWF). Bangladesh is committed to achieving universal health coverage (UHC) hence a comprehensive understanding of the existing HWF was deemed necessary informing policy and funding decisions to the health system. METHODS: The health labour market analysis (HLMA) framework for UHC cited in the GSHRH was adopted to analyse the supply, need and demand of all health workers in Bangladesh. Government's information systems provided data to document the public sector HWF. A national-level assessment (2019) based on a country representative sample of 133 geographical units, served to estimate the composition and distribution of the private sector HWF. Descriptive statistics served to characterize the formal and informal HWF. RESULTS: The density of doctors, nurses and midwives in Bangladesh was only 9.9 per 10 000 population, well below the indicative sustainable development goals index threshold of 44.5 outlined in the GSHRH. Considering all HWFs in Bangladesh, the estimated total density was 49 per 10 000 population. However, one-third of all HWFs did not hold recognized roles and their competencies were unknown, taking only qualified and recognized HWFs into account results in an estimated density 33.2. With an estimate 75 nurses per 100 doctors in Bangladesh, the second area, where policy attention appears to be warranted is on the competencies and skill-mix. Thirdly, an estimated 82% of all HWFs work in the private sector necessitates adequate oversight for patient safety. Finally, a high proportion of unfilled positions in the public sector, especially in rural areas where 67% of the population lives, account only 11% of doctors and nurses. CONCLUSION: Bangladesh is making progress on many of the milestones of the GSHRH, notably, the establishment of the HWF unit and reporting through the national health workforce accounts. However, particular investment on strengthening the intersectoral HWF coordination across sectors; regulation for assurance of patient safety and adequate oversight of the private sector; establishing accreditation mechanisms for training institutions; and halving inequalities in access to a qualified HWF are important towards advancing UHC in Bangladesh.

The ARRIVE guidelines 2.0: updated guidelines for reporting animal research.

Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and reproduce the methods and results. Despite considerable levels of endorsement by funders and journals over the years, adherence to the guidelines has been inconsistent, and the anticipated improvements in the quality of reporting in animal research publications have not been achieved. Here, we introduce ARRIVE 2.0. The guidelines have been updated and information reorganised to facilitate their use in practice. We used a Delphi exercise to prioritise and divide the items of the guidelines into 2 sets, the 'ARRIVE Essential 10,' which constitutes the minimum requirement, and the 'Recommended Set,' which describes the research context. This division facilitates improved reporting of animal research by supporting a stepwise approach to implementation. This helps journal editors and reviewers verify that the most important items are being reported in manuscripts. We have also developed the accompanying Explanation and Elaboration document, which serves (1) to explain the rationale behind each item in the guidelines, (2) to clarify key concepts, and (3) to provide illustrative examples. We aim, through these changes, to help ensure that researchers, reviewers, and journal editors are better equipped to improve the rigour and transparency of the scientific process and thus reproducibility.

The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research.

Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and reproduce the methods and results. Despite considerable levels of endorsement by funders and journals over the years, adherence to the guidelines has been inconsistent, and the anticipated improvements in the quality of reporting in animal research publications have not been achieved. Here, we introduce ARRIVE 2.0. The guidelines have been updated and information reorganised to facilitate their use in practice. We used a Delphi exercise to prioritise and divide the items of the guidelines into 2 sets, the "ARRIVE Essential 10," which constitutes the minimum requirement, and the "Recommended Set," which describes the research context. This division facilitates improved reporting of animal research by supporting a stepwise approach to implementation. This helps journal editors and reviewers verify that the most important items are being reported in manuscripts. We have also developed the accompanying Explanation and Elaboration document, which serves (1) to explain the rationale behind each item in the guidelines, (2) to clarify key concepts, and (3) to provide illustrative examples. We aim, through these changes, to help ensure that researchers, reviewers, and journal editors are better equipped to improve the rigour and transparency of the scientific process and thus reproducibility.

The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research.

Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and reproduce the methods and results. Despite considerable levels of endorsement by funders and journals over the years, adherence to the guidelines has been inconsistent, and the anticipated improvements in the quality of reporting in animal research publications have not been achieved. Here, we introduce ARRIVE 2.0. The guidelines have been updated and information reorganised to facilitate their use in practice. We used a Delphi exercise to prioritise and divide the items of the guidelines into 2 sets, the "ARRIVE Essential 10," which constitutes the minimum requirement, and the "Recommended Set," which describes the research context. This division facilitates improved reporting of animal research by supporting a stepwise approach to implementation. This helps journal editors and reviewers verify that the most important items are being reported in manuscripts. We have also developed the accompanying Explanation and Elaboration document, which serves (1) to explain the rationale behind each item in the guidelines, (2) to clarify key concepts, and (3) to provide illustrative examples. We aim, through these changes, to help ensure that researchers, reviewers, and journal editors are better equipped to improve the rigour and transparency of the scientific process and thus reproducibility.

Accuracy in detecting inadequate research reporting by early career peer reviewers using an online CONSORT-based peer-review tool (COBPeer) versus the usual peer-review process: a cross-sectional diagnostic study.

BACKGROUND: The peer review process has been questioned as it may fail to allow the publication of high-quality articles. This study aimed to evaluate the accuracy in identifying inadequate reporting in RCT reports by early career researchers (ECRs) using an online CONSORT-based peer-review tool (COBPeer) versus the usual peer-review process. METHODS: We performed a cross-sectional diagnostic study of 119 manuscripts, from BMC series medical journals, BMJ, BMJ Open, and Annals of Emergency Medicine reporting the results of two-arm parallel-group RCTs. One hundred and nineteen ECRs who had never reviewed an RCT manuscript were recruited from December 2017 to January 2018. Each ECR assessed one manuscript. To assess accuracy in identifying inadequate reporting, we used two tests: (1) ECRs assessing a manuscript using the COBPeer tool (after completing an online training module) and (2) the usual peer-review process. The reference standard was the assessment of the manuscript by two systematic reviewers. Inadequate reporting was defined as incomplete reporting or a switch in primary outcome and considered nine domains: the eight most important CONSORT domains and a switch in primary outcome(s). The primary outcome was the mean number of domains accurately classified (scale from 0 to 9). RESULTS: The mean (SD) number of domains (0 to 9) accurately classified per manuscript was 6.39 (1.49) for ECRs using COBPeer versus 5.03 (1.84) for the journal's usual peer-review process, with a mean difference [95% CI] of 1.36 [0.88-1.84] (p < 0.001). Concerning secondary outcomes, the sensitivity of ECRs using COBPeer versus the usual peer-review process in detecting incompletely reported CONSORT items was 86% [95% CI 82-89] versus 20% [16-24] and in identifying a switch in primary outcome 61% [44-77] versus 11% [3-26]. The specificity of ECRs using COBPeer versus the usual process to detect incompletely reported CONSORT domains was 61% [57-65] versus 77% [74-81] and to identify a switch in primary outcome 77% [67-86] versus 98% [92-100]. CONCLUSIONS: Trained ECRs using the COBPeer tool were more likely to detect inadequate reporting in RCTs than the usual peer review processes used by journals. Implementing a two-step peer-review process could help improve the quality of reporting. TRIAL REGISTRATION: Clinical.Trials.gov NCT03119376 (Registered April, 18, 2017).

Diazepam-induced loss of inhibitory synapses mediated by PLCδ/ Ca2+/calcineurin signalling downstream of GABAA receptors.

Benzodiazepines facilitate the inhibitory actions of GABA by binding to γ-aminobutyric acid type A receptors (GABAARs), GABA-gated chloride/bicarbonate channels, which are the key mediators of transmission at inhibitory synapses in the brain. This activity underpins potent anxiolytic, anticonvulsant and hypnotic effects of benzodiazepines in patients. However, extended benzodiazepine treatments lead to development of tolerance, a process which, despite its important therapeutic implications, remains poorly characterised. Here we report that prolonged exposure to diazepam, the most widely used benzodiazepine in clinic, leads to a gradual disruption of neuronal inhibitory GABAergic synapses. The loss of synapses and the preceding, time- and dose-dependent decrease in surface levels of GABAARs, mediated by dynamin-dependent internalisation, were blocked by Ro 15-1788, a competitive benzodiazepine antagonist, and bicuculline, a competitive GABA antagonist, indicating that prolonged enhancement of GABAAR activity by diazepam is integral to the underlying molecular mechanism. Characterisation of this mechanism has revealed a metabotropic-type signalling downstream of GABAARs, involving mobilisation of Ca2+ from the intracellular stores and activation of the Ca2+/calmodulin-dependent phosphatase calcineurin, which, in turn, dephosphorylates GABAARs and promotes their endocytosis, leading to disassembly of inhibitory synapses. Furthermore, functional coupling between GABAARs and Ca2+ stores was sensitive to phospholipase C (PLC) inhibition by U73122, and regulated by PLCδ, a PLC isoform found in direct association with GABAARs. Thus, a PLCδ/Ca2+/calcineurin signalling cascade converts the initial enhancement of GABAARs by benzodiazepines to a long-term downregulation of GABAergic synapses, this potentially underpinning the development of pharmacological and behavioural tolerance to these widely prescribed drugs.

Core competencies for scientific editors of biomedical journals: consensus statement.

BACKGROUND: Scientific editors are responsible for deciding which articles to publish in their journals. However, we have not found documentation of their required knowledge, skills, and characteristics, or the existence of any formal core competencies for this role. METHODS: We describe the development of a minimum set of core competencies for scientific editors of biomedical journals. RESULTS: The 14 key core competencies are divided into three major areas, and each competency has a list of associated elements or descriptions of more specific knowledge, skills, and characteristics that contribute to its fulfillment. CONCLUSIONS: We believe that these core competencies are a baseline of the knowledge, skills, and characteristics needed to perform competently the duties of a scientific editor at a biomedical journal.

Letter to the editor - round table unites to tackle culture change in an effort to improve animal research reporting.

A round table discussion was held during the LAVA-ESLAV-ECLAM conference on Reproducibility of Animal Studies on the 25th of September 2017 in Edinburgh. The aim of the round table was to discuss how to enhance the rate at which the quality of reporting animal research can be improved. This signed statement acknowledges the efforts that participant organizations have made towards improving the reporting of animal studies and confirms an ongoing commitment to drive further improvements, calling upon both academics and laboratory animal veterinarians to help make this cultural change.

Peer review: tips from field experts for junior reviewers.

This editorial introduces a series of tutorials by experts, who provide tips and advice for junior reviewers on how to conduct peer review based on specific study designs. The aim of these articles is to provide an easy-to-use, quick reference for those who are seeking more guidance on how to peer review biomedical research papers. Unlike previous tips and guides on peer review, this series is the first to provide advice from experts for those in their specific fields.

BMC Medicine: a decade of open access medical research.

On 24 November 2003, BMC Medicine published its first article. Ten years and over 900 articles later we look back at some of the most notable milestones for the journal and discuss advances and innovations in medicine over the last decade. Our editorial board members, Leslie Biesecker, Thomas Powles, Chris Del Mar, Robert Snow and David Moher, also comment on the changes they expect to see in their fields over the coming years.

Enhancing Partnerships of Institutions and Journals to Address Concerns About Research Misconduct: Recommendations From a Working Group of Institutional Research Integrity Officers and Journal Editors and Publishers.

Importance: Institutions and journals strive to promote and protect the integrity of the research record, and both groups are equally committed to ensuring the reliability of all published data. Observations: Three US universities coordinated a series of virtual meetings from June 2021 to March 2022 for a working group composed of senior, experienced US research integrity officers (RIOs), journal editors, and publishing staff who are familiar with managing issues of research integrity and publication ethics. The goal of the working group was to improve the collaboration and transparency between institutions and journals to ensure that research misconduct and publication ethics are managed properly and efficiently. Recommendations address the following: identifying proper contacts at institutions and journals, specifying information to share between institutions and journals, correcting the research record, reconsideration of some fundamental research misconduct concepts, and journal policy changes. The working group identified 3 key recommendations to be adopted and implemented to change the status quo for better collaboration between institutions and journals: (1) reconsideration and broadening of the interpretation by institutions of the need-to-know criteria in federal regulations (ie, confidential or sensitive information and data are not disclosed unless there is a need for an individual to know the facts to perform specific jobs or functions), (2) uncoupling the evaluation of the accuracy and validity of research data from the determination of culpability and intent of the individuals involved, and (3) initiating a widespread change for the policies of journals and publishers regarding the timing and appropriateness for contacting institutions, either before or concurrently under certain conditions, when contacting the authors. Conclusions and Relevance: The working group recommends specific changes to the status quo to enable effective communication between institutions and journals. Using confidentiality clauses and agreements to impede sharing does not benefit the scientific community nor the integrity of the research record. However, a careful and informed framework for improving communications and sharing information between institutions and journals can foster better working relationships, trust, transparency, and most importantly, faster resolution to data integrity issues, especially in published literature.

Assessment of staffing needs for physicians and nurses at Upazila health complexes in Bangladesh using WHO workload indicators of staffing need (WISN) method.

OBJECTIVE: This study aimed to assess the current workload and staffing need of physicians and nurses for delivering optimum healthcare services at the Upazila Health Complexes (UpHCs) in Bangladesh. DESIGN: Mixed-methods, combining qualitative (eg, document reviews, key informant interviews, in-depth interviews, observations) and quantitative methods (time-motion survey). SETTING: Study was conducted in 24 health facilities of Bangladesh. However, UpHCs being the nucleus of primary healthcare in Bangladesh, this manuscript limits itself to reporting the findings from the providers at four UpHCs under this project. PARTICIPANTS: 18 physicians and 51 nurses, males and females. PRIMARY OUTCOME MEASURES: Workload components were defined based on inputs from five experts, refined by nine service providers. Using WHO Workload Indicator of Staffing Need (WISN) software, standard workload, category allowance factor, individual allowance factor, total required number of staff, WISN difference and WISN ratio were calculated. RESULTS: Physicians have very high (WISN ratio 0.43) and nurse high (WISN ratio 0.69) workload pressure. 50% of nurses' time are occupied with support activities, instead of nursing care. There are different workloads among the same staff category in different health facilities. If only the vacant posts are filled, the workload is reduced. In fact, sanctioned number of physicians and nurses is more than actual need. CONCLUSIONS: It is evident that high workload pressures prevail for physicians and nurses at the UpHCs. This reveals high demand for these health workforces in the respective subdistricts. WISN method can aid the policy-makers in optimising utilisation of existing human resources. Therefore, the government should adopt flexible health workforce planning and recruitment policy to manage the patient load and disease burden. WISN should, thus, be incorporated as a planning tool for health managers. There should be a regular review of health workforce management decisions, and these should be amended based on periodic reviews.

The ARRIVE guidelines 2.0: updated guidelines for reporting animal research.

Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour and reproduce the methods and results. Despite considerable levels of endorsement by funders and journals over the years, adherence to the guidelines has been inconsistent, and the anticipated improvements in the quality of reporting in animal research publications have not been achieved. Here, we introduce ARRIVE 2.0. The guidelines have been updated and information reorganised to facilitate their use in practice. We used a Delphi exercise to prioritise and divide the items of the guidelines into two sets, the 'ARRIVE Essential 10', which constitutes the minimum requirement, and the 'Recommended Set', which describes the research context. This division facilitates improved reporting of animal research by supporting a stepwise approach to implementation. This helps journal editors and reviewers verify that the most important items are being reported in manuscripts. We have also developed the accompanying Explanation and Elaboration document, which serves (1) to explain the rationale behind each item in the guidelines, (2) to clarify key concepts and (3) to provide illustrative examples. We aim, through these changes, to help ensure that researchers, reviewers and journal editors are better equipped to improve the rigour and transparency of the scientific process and thus reproducibility.

The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research.

Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and reproduce the methods and results. Despite considerable levels of endorsement by funders and journals over the years, adherence to the guidelines has been inconsistent, and the anticipated improvements in the quality of reporting in animal research publications have not been achieved. Here, we introduce ARRIVE 2.0. The guidelines have been updated and information reorganised to facilitate their use in practice. We used a Delphi exercise to prioritise and divide the items of the guidelines into 2 sets, the "ARRIVE Essential 10," which constitutes the minimum requirement, and the "Recommended Set," which describes the research context. This division facilitates improved reporting of animal research by supporting a stepwise approach to implementation. This helps journal editors and reviewers verify that the most important items are being reported in manuscripts. We have also developed the accompanying Explanation and Elaboration (E&E) document, which serves (1) to explain the rationale behind each item in the guidelines, (2) to clarify key concepts, and (3) to provide illustrative examples. We aim, through these changes, to help ensure that researchers, reviewers, and journal editors are better equipped to improve the rigour and transparency of the scientific process and thus reproducibility.

The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research.

Reproducible science requires transparent reporting. The ARRIVE guidelines (Animal Research: Reporting of In Vivo Experiments) were originally developed in 2010 to improve the reporting of animal research. They consist of a checklist of information to include in publications describing in vivo experiments to enable others to scrutinise the work adequately, evaluate its methodological rigour, and reproduce the methods and results. Despite considerable levels of endorsement by funders and journals over the years, adherence to the guidelines has been inconsistent, and the anticipated improvements in the quality of reporting in animal research publications have not been achieved. Here, we introduce ARRIVE 2.0. The guidelines have been updated and information reorganised to facilitate their use in practice. We used a Delphi exercise to prioritise and divide the items of the guidelines into 2 sets, the "ARRIVE Essential 10," which constitutes the minimum requirement, and the "Recommended Set," which describes the research context. This division facilitates improved reporting of animal research by supporting a stepwise approach to implementation. This helps journal editors and reviewers verify that the most important items are being reported in manuscripts. We have also developed the accompanying Explanation and Elaboration document, which serves (1) to explain the rationale behind each item in the guidelines, (2) to clarify key concepts, and (3) to provide illustrative examples. We aim, through these changes, to help ensure that researchers, reviewers, and journal editors are better equipped to improve the rigour and transparency of the scientific process and thus reproducibility.

Revision of the ARRIVE guidelines: rationale and scope.

In 2010, the NC3Rs published the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines to improve the reporting of animal research. Despite considerable levels of support from the scientific community, the impact on the quality of reporting in animal research publications has been limited. This position paper highlights the strategy of an expert working group established to revise the guidelines and facilitate their uptake. The group's initial work will focus on three main areas: prioritisation of the ARRIVE items into a tiered system, development of an explanation and elaboration document, and revision of specific items.

Human peripheral blood mononuclear cells express GABAA receptor subunits.

The polymerase chain reaction was used to screen human peripheral blood mononuclear cells (PBMC) and Jurkat cells for the presence of GABAA receptor subunit mRNAs. Positive signals were detected for the alpha1, alpha3, beta2, beta3, delta and epsilon subunit mRNAs in both cell populations, with the Jurkat cells giving a positive signal for some additional species. Real-time PCR was used to confirm that PBMC, lymphocytes and monocytes contained significant levels of the alpha1 subunit mRNA and that PBMC and lymphocytes contained low levels of beta2 mRNA. The alpha1 subunit was detected in PBMC and fractionated T-cell populations, as well as Jurkat and HL-60 cell lines, by Western blotting and immunofluorescence using a specific antibody. The application of 1mM GABA reduced the specific increase in intracellular PBMC Ca2+ levels produced by addition of 1 nM fMLP: this effect was mimicked by muscimol, but not glycine, and was blocked by bicuculline. The inhibitory effect of GABA was limited to a subset of PBMC. We conclude that cells within the human PBMC population, including lymphocytes, express functional GABAA receptors and these receptors may modulate immune responses.