Displaying publications 1 - 20 of 41 in total

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  1. Borman AM, Szekely A, Johnson EM
    Med Mycol, 2017 Jul 01;55(5):563-567.
    PMID: 28204557 DOI: 10.1093/mmy/myw147
    Candida auris has recently emerged as a serious nosocomial health risk, with widespread outbreaks in numerous hospitals worldwide and the existence of geographic region-specific discrete clonal lineages. Here we have compared the rDNA sequences of 24 isolates of Candida auris from 14 different hospital centers in the United Kingdom with those of strains from different international origins present in the public sequence databases. Here we show that UK isolates of C. auris fall into three well-supported clades corresponding to lineages that have previously been reported from India, Malaysia and Kuwait, Japan and Korea, and South Africa, respectively.
  2. Lan MF, Lane AM, Roy J, Hanin NA
    J Sports Sci Med, 2012;11(1):131-5.
    PMID: 24149128
    The aim of the present study was to investigate the factorial validity of the Brunel Mood Scale for use with Malaysian athletes. Athletes (N = 1485 athletes) competing at the Malaysian Games completed the Brunel of Mood Scale (BRUMS). Confirmatory Factor Analysis (CFA) results indicated a Confirmatory Fit Index (CFI) of .90 and Root Mean Squared Error of Approximation (RMSEA) was 0.05. The CFI was below the 0.95 criterion for acceptability and the RMSEA value was within the limits for acceptability suggested by Hu and Bentler, 1999. We suggest that results provide some support for validity of the BRUMS for use with Malaysian athletes. Given the large sample size used in the present study, descriptive statistics could be used as normative data for Malaysian athletes. Key pointsFindings from the present study lend support to the validity of the BRUMS for use with Malaysian athletes.Given the size of the sample used in the present study, we suggest descriptive data be used as the normative data for researchers using the scale with Malaysian athletes.It is suggested that future research investigate the effects of cultural differences on emotional states experienced by athletes before, during and post-competition.
  3. Kamal H, Le CF, Salter AM, Ali A
    Compr Rev Food Sci Food Saf, 2021 05;20(3):2455-2475.
    PMID: 33819382 DOI: 10.1111/1541-4337.12739
    The chief intent of this review is to explain the different extraction techniques and efficiencies for the recovery of protein from food waste (FW) sources. Although FW is not a new concept, increasing concerns about chronic hunger, nutritional deficiency, food security, and sustainability have intensified attention on alternative and sustainable sources of protein for food and feed. Initiatives to extract and utilize protein from FW on a commercial scale have been undertaken, mainly in the developed countries, but they remain largely underutilized and generally suited for low-quality products. The current analysis reveals the extraction of protein from FW is a many-sided (complex) issue, and that identifies for a stronger and extensive integration of diverse extraction perspectives, focusing on nutritional quality, yield, and functionality of the isolated protein as a valued recycled ingredient.
  4. Belton JL, Slater H, Ravindran TKS, Briggs AM
    J Orthop Sports Phys Ther, 2023 Apr;53(4):1-10.
    PMID: 36507691 DOI: 10.2519/jospt.2022.11427
    BACKGROUND: Despite the rising burden of musculoskeletal (MSK) problems (MSK conditions, MSK pain, and MSK injury and trauma) in most countries, actions to improve (strengthen) systems for supporting MSK health are often low on the priority list, relative to other noncommunicable diseases. Delivering effective, person-centered and equitable MSK health care requires strengthening systems for health, for example, through policy, financing, service delivery, and workforce initiatives. A critical, but often overlooked component is genuine integration of lived experience perspectives to cocreate care and systems that are responsive to people's needs and contexts. CLINICAL QUESTION: How can cocreation approaches support effective, person-centered and equitable MSK health care? What principles can stakeholders adopt to build responsive health systems? KEY RESULTS: Lived experience perspectives are not systematically integrated in initiatives to strengthen health systems. However, such integration is critical to creating equitable and person-centered health systems that provide care and support healthy populations. Cocreation principles and frameworks can guide processes to strengthen health systems, which must include historically marginalized groups and consider social and environmental contexts as they relate to health. CLINICAL APPLICATION: Clinicians, educators, and policy-makers play a critical role in creating equitable health systems and environments, and driving system reform with people who have lived experience. Genuine cocreation approaches capture diverse economic development (in particular, low-resource settings where health inequities are more prevalent), span the life course and diagnostic categories, are appropriate and/or adapted for the context and setting, and reflect evolving standards and opportunities for MSK health. J Orthop Sports Phys Ther 2023;53(4):1-10. Epub: 12 December 2022. doi:10.2519/jospt.2022.11427.
  5. Braun BJ, Grimm B, Hanflik AM, Marmor MT, Richter PH, Sands AK, et al.
    EFORT Open Rev, 2020 Jul;5(7):408-420.
    PMID: 32818068 DOI: 10.1302/2058-5241.5.200021
    There are many digital solutions which assist the orthopaedic trauma surgeon. This already broad field is rapidly expanding, making a complete overview of the existing solutions difficult.The AO Foundation has established a task force to address the need for an overview of digital solutions in the field of orthopaedic trauma surgery.Areas of new technology which will help the surgeon gain a greater understanding of these possible solutions are reviewed.We propose a categorization of the current needs in orthopaedic trauma surgery matched with available or potential digital solutions, and provide a narrative overview of this broad topic, including the needs, solutions and basic rules to ensure adequate use in orthopaedic trauma surgery. We seek to make this field more accessible, allowing for technological solutions to be clearly matched to trauma surgeons' needs. Cite this article: EFORT Open Rev 2020;5:408-420. DOI: 10.1302/2058-5241.5.200021.
  6. Karageorghis CI, Mouchlianitis E, Payre W, Kuan G, Howard LW, Reed N, et al.
    Appl Ergon, 2021 Oct;96:103436.
    PMID: 34087703 DOI: 10.1016/j.apergo.2021.103436
    We investigated the effect of participant-selected (PSel) and researcher-selected (RSel) music on urban driving behaviour in young men (N = 27; Mage = 20.6 years, SD = 1.9 years). A counterbalanced, within-subjects design was used with four simulated driving conditions: PSel fast-tempo music, PSel slow-tempo music, RSel music and an urban traffic-noise control. The between-subjects variable of personality (introverts vs. extroverts) was explored. The presence of PSel slow-tempo music and RSel music optimised affective valence and arousal for urban driving. NASA Task Load Index scores indicated that the urban traffic-noise control increased mental demand compared to PSel slow-tempo music. In the PSel slow-tempo condition, less use was made of the brake pedal. When compared to extroverts, introverts recorded lower mean speed and attracted lower risk ratings under PSel slow-tempo music. The utility of PSel slow-tempo and RSel music was demonstrated in terms of optimising affective state for simulated urban driving.
  7. Gibbs S, Hundt PJ, Nelson A, Egan JP, Tongnunui P, Simons AM
    Zootaxa, 2018 Jan 03;4369(2):270-280.
    PMID: 29689891 DOI: 10.11646/zootaxa.4369.2.7
    The combtooth blenny (Blenniidae) genus Omobranchus contains small, cryptobenthic fishes common to nearshore habitats throughout the Indo-West Pacific. Recent molecular systematic studies have resolved Omobranchus as monophyletic but little research has been done to resolve species-level relationships. Herein, phylogenetic analyses of one mitochondrial (CO1) and four nuclear (ENC1, myh6, sreb2, and tbr1) genes provide evidence for the monophyly of Omobranchus and support for the elongatus and banditus species group. Sampling of multiple individuals from widespread species (O. ferox, O. punctatus, and O. elongatus) suggested that the Thai-Malay Peninsula is a phylogeographic break that may be a historic barrier to gene flow. Additionally, common meristics and other morphological characters are used to describe an early life history stage of O. ferox and O. punctatus.
  8. Karageorghis CI, Kuan G, Mouchlianitis E, Payre W, Howard LW, Reed N, et al.
    Ergonomics, 2022 Jan 17.
    PMID: 34779716 DOI: 10.1080/00140139.2021.2003872
    We examined the interactive effects of task load and music tempo on cognition, affect, cardiac response, and safety-relevant behaviour during simulated driving. Using a counterbalanced, within-subjects design, participants (N = 46) were exposed to fast-, slow-, and no-music conditions at high and low loads in a high-grade simulator. Task load had the most salient effect across a broad swath of variables. For core affect, the Load × Music Condition interaction showed that, under high load, affective arousal scores were higher in the fast-tempo condition vs. slow. A main effect of tempo emerged for the HRV index of SDNN, with fast-tempo music eliciting lower scores than both slow- and no-music conditions. Behavioural data showed a main effect of tempo for risk ratings, with fast-tempo music eliciting the highest scores for a traffic-light trigger. Our findings indicate that drivers in high-load, urban environments should exercise caution in their use of fast-tempo music. Practitioner summary: We examined the interactive effects of task load and music tempo in simulated driving (urban and highway). Cognition, mood, cardiac response, and driving behaviour were assessed. Participants exhibited more risky behaviours in response to fast-tempo music. Drivers should exercise caution in their use of up-tempo music in urban settings.
  9. Gedi MA, Briars R, Yuseli F, Zainol N, Darwish R, Salter AM, et al.
    J Food Sci Technol, 2017 Aug;54(9):2746-2757.
    PMID: 28928514 DOI: 10.1007/s13197-017-2711-8
    A study of the literature indicates that chloroplasts synthesise a range of molecules, many of which have nutritional value for humans, but the nutritional credentials of chloroplasts recovered from plant cells are not established. Chloroplast-rich-fractions (CRFs) were prepared from green plant species and the macro- and micro-nutrient composition compared with the whole leaf materials (WLMs). The results indicated that, on a dry weight basis, CRF material from a range of green biomass was enriched in lipids and proteins, and in a range of micronutrients compared with the WLM. Vitamins E, pro-vitamin A, and lutein were all greater in CRF preparations. Of the minerals, iron was most notably concentrated in CRF. Spinach CRFs possessed the highest α-tocopherol [62 mg 100 g-1, dry weight (DW)], β-carotene (336 mg 100 g-1 DW) and lutein (341 mg 100 g-1 DW) contents, whilst grass CRFs had the highest concentration of alpha-linolenic acid (ALA) (69.5 mg g-1). The higher concentrations of α-tocopherol, β-carotene, lutein, ALA and trace minerals (Fe and Mn) in CRFs suggested their potential use as concentrated ingredients in food formulations deficient in these nutrients.
  10. Marmor MT, Grimm B, Hanflik AM, Richter PH, Sivananthan S, Yarboro SR, et al.
    Indian J Orthop, 2022 Jul;56(7):1112-1122.
    PMID: 35813536 DOI: 10.1007/s43465-022-00629-0
    BACKGROUND: Patient-Reported Outcome Measures (PROMs) are widely used for measurement of functional outcomes after orthopaedic trauma. However, PROMs rely on patient collaboration and suffer from various types of bias. Wearable Activity Monitors (WAMs) are increasingly used to objectify functional assessment. The objectives of this systematic review were to identify and characterise the WAMs technology and metrics currently used for orthopaedic trauma research.

    METHODS: PubMed and Embase biomedical literature search engines were queried. Eligibility criteria included: Human clinical studies published in the English language between 2010 and 2019 involving fracture management and WAMs. Variables collected from each article included: Technology used, vendor/product, WAM body location, metrics measured, measurement time period, year of publication, study geographic location, phase of treatment studied, fractures studied, number of patients studied, sex and age of the study subjects, and study level of evidence. Six investigators reviewed the resulting papers. Descriptive statistics of variables of interest were used to analyse the data.

    RESULTS: One hundred and thirty-six papers were available for analysis, showing an increasing trend of publications per year. Accelerometry followed by plantar pressure insoles were the most commonly employed technologies. The most common location for WAM placement was insoles, followed by the waist. The most commonly studied fracture type was hip fractures followed by fragility fractures in general, ankle, "lower extremity", and tibial fractures. The rehabilitation phase following surgery was the most commonly studied period. Sleep duration, activity time or step counts were the most commonly reported WAM metrics. A preferred, clinically validated WAM metric was not identified.

    CONCLUSIONS: WAMs have an increasing presence in the orthopaedic trauma literature. The optimal implementation of this technology and its use to understand patients' pre-injury and post-injury functions is currently insufficiently explored and represents an area that will benefit from future study.

    SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO ID:210344.

    SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43465-022-00629-0.

  11. Ott A, Quintela-Baluja M, Zealand AM, O'Donnell G, Haniffah MRM, Graham DW
    Environ Microbiome, 2021 Nov 18;16(1):21.
    PMID: 34794510 DOI: 10.1186/s40793-021-00391-0
    BACKGROUND: Understanding environmental microbiomes and antibiotic resistance (AR) is hindered by over reliance on relative abundance data from next-generation sequencing. Relative data limits our ability to quantify changes in microbiomes and resistomes over space and time because sequencing depth is not considered and makes data less suitable for Quantitative Microbial Risk Assessments (QMRA), critical in quantifying environmental AR exposure and transmission risks.

    RESULTS: Here we combine quantitative microbiome profiling (QMP; parallelization of amplicon sequencing and 16S rRNA qPCR to estimate cell counts) and absolute resistome profiling (based on high-throughput qPCR) to quantify AR along an anthropogenically impacted river. We show QMP overcomes biases caused by relative taxa abundance data and show the benefits of using unified Hill number diversities to describe environmental microbial communities. Our approach overcomes weaknesses in previous methods and shows Hill numbers are better for QMP in diversity characterisation.

    CONCLUSIONS: Methods here can be adapted for any microbiome and resistome research question, but especially providing more quantitative data for QMRA and other environmental applications.

  12. Storr SJ, Safuan S, Ahmad N, El-Refaee M, Jackson AM, Martin SG
    Cancer Immunol Immunother, 2017 Oct;66(10):1287-1294.
    PMID: 28551814 DOI: 10.1007/s00262-017-2020-0
    Lymphovascular invasion (LVI), encompassing blood and lymphatic vessel invasion, is an important event in tumourigenesis. Macrophages within the tumour microenvironment are linked to the presence of LVI and angiogenesis. This study investigates the role of macrophage-derived, caspase-1-dependent interleukin-1beta (IL-1β) in an in vitro model of LVI. IL-1β significantly augmented the adhesion and transmigration of breast cancer cell lines MCF7 and MDA-MB-231 across endothelial cell barriers. MDA-MB-231 and MCF7 showed a higher percentage of adhesion to lymphatic endothelial cells than blood endothelial cells following endothelial cell IL-1β stimulation (P 
  13. Shen X, Howard DM, Adams MJ, Hill WD, Clarke TK, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, et al.
    Nat Commun, 2020 05 08;11(1):2301.
    PMID: 32385265 DOI: 10.1038/s41467-020-16022-0
    Depression is a leading cause of worldwide disability but there remains considerable uncertainty regarding its neural and behavioural associations. Here, using non-overlapping Psychiatric Genomics Consortium (PGC) datasets as a reference, we estimate polygenic risk scores for depression (depression-PRS) in a discovery (N = 10,674) and replication (N = 11,214) imaging sample from UK Biobank. We report 77 traits that are significantly associated with depression-PRS, in both discovery and replication analyses. Mendelian Randomisation analysis supports a potential causal effect of liability to depression on brain white matter microstructure (β: 0.125 to 0.868, pFDR 
  14. Wang X, Walker A, Revez JA, Ni G, Adams MJ, McIntosh AM, et al.
    Am J Hum Genet, 2023 Jul 06;110(7):1207-1215.
    PMID: 37379836 DOI: 10.1016/j.ajhg.2023.06.006
    In polygenic score (PGS) analysis, the coefficient of determination (R2) is a key statistic to evaluate efficacy. R2 is the proportion of phenotypic variance explained by the PGS, calculated in a cohort that is independent of the genome-wide association study (GWAS) that provided estimates of allelic effect sizes. The SNP-based heritability (hSNP2, the proportion of total phenotypic variances attributable to all common SNPs) is the theoretical upper limit of the out-of-sample prediction R2. However, in real data analyses R2 has been reported to exceed hSNP2, which occurs in parallel with the observation that hSNP2 estimates tend to decline as the number of cohorts being meta-analyzed increases. Here, we quantify why and when these observations are expected. Using theory and simulation, we show that if heterogeneities in cohort-specific hSNP2 exist, or if genetic correlations between cohorts are less than one, hSNP2 estimates can decrease as the number of cohorts being meta-analyzed increases. We derive conditions when the out-of-sample prediction R2 will be greater than hSNP2 and show the validity of our derivations with real data from a binary trait (major depression) and a continuous trait (educational attainment). Our research calls for a better approach to integrating information from multiple cohorts to address issues of between-cohort heterogeneity.
  15. Ott A, O'Donnell G, Tran NH, Mohd Haniffah MR, Su JQ, Zealand AM, et al.
    Environ Sci Technol, 2021 06 01;55(11):7466-7478.
    PMID: 34000189 DOI: 10.1021/acs.est.1c00939
    Pinpointing environmental antibiotic resistance (AR) hot spots in low-and middle-income countries (LMICs) is hindered by a lack of available and comparable AR monitoring data relevant to such settings. Addressing this problem, we performed a comprehensive spatial and seasonal assessment of water quality and AR conditions in a Malaysian river catchment to identify potential "simple" surrogates that mirror elevated AR. We screened for resistant coliforms, 22 antibiotics, 287 AR genes and integrons, and routine water quality parameters, covering absolute concentrations and mass loadings. To understand relationships, we introduced standardized "effect sizes" (Cohen's D) for AR monitoring to improve comparability of field studies. Overall, water quality generally declined and environmental AR levels increased as one moved down the catchment without major seasonal variations, except total antibiotic concentrations that were higher in the dry season (Cohen's D > 0.8, P < 0.05). Among simple surrogates, dissolved oxygen (DO) most strongly correlated (inversely) with total AR gene concentrations (Spearman's ρ 0.81, P < 0.05). We suspect this results from minimally treated sewage inputs, which also contain AR bacteria and genes, depleting DO in the most impacted reaches. Thus, although DO is not a measure of AR, lower DO levels reflect wastewater inputs, flagging possible AR hot spots. DO measurement is inexpensive, already monitored in many catchments, and exists in many numerical water quality models (e.g., oxygen sag curves). Therefore, we propose combining DO data and prospective modeling to guide local interventions, especially in LMIC rivers with limited data.
  16. Braun BJ, Histing T, Menger MM, Platte J, Grimm B, Hanflik AM, et al.
    Medicina (Kaunas), 2023 Feb 19;59(2).
    PMID: 36837604 DOI: 10.3390/medicina59020403
    Background and Objectives: Outcome data from wearable devices are increasingly used in both research and clinics. Traditionally, a dedicated device is chosen for a given study or clinical application to collect outcome data as soon as the patient is included in a study or undergoes a procedure. The current study introduces a new measurement strategy, whereby patients' own devices are utilized, allowing for both a pre-injury baseline measure and ability to show achievable results. Materials and Methods: Patients with a pre-existing musculoskeletal injury of the upper and lower extremity were included in this exploratory, proof-of-concept study. They were followed up for a minimum of 6 weeks after injury, and their wearable outcome data (from a smartphone and/or a body-worn sensor) were continuously acquired during this period. A descriptive analysis of the screening characteristics and the observed and achievable outcome patterns was performed. Results: A total of 432 patients was continuously screened for the study, and their screening was analyzed. The highest success rate for successful inclusion was in younger patients. Forty-eight patients were included in the analysis. The most prevalent outcome was step count. Three distinctive activity data patterns were observed: patients recovering, patients with slow or no recovery, and patients needing additional measures to determine treatment outcomes. Conclusions: Measuring outcomes in trauma patients with the Bring Your Own Device (BYOD) strategy is feasible. With this approach, patients were able to provide continuous activity data without any dedicated equipment given to them. The measurement technique is especially suited to particular patient groups. Our study's screening log and inclusion characteristics can help inform future studies wishing to employ the BYOD design.
  17. Barbu MC, Zeng Y, Shen X, Cox SR, Clarke TK, Gibson J, et al.
    PMID: 30197049 DOI: 10.1016/j.bpsc.2018.07.006
    BACKGROUND: Major depressive disorder is a clinically heterogeneous psychiatric disorder with a polygenic architecture. Genome-wide association studies have identified a number of risk-associated variants across the genome and have reported growing evidence of NETRIN1 pathway involvement. Stratifying disease risk by genetic variation within the NETRIN1 pathway may provide important routes for identification of disease mechanisms by focusing on a specific process, excluding heterogeneous risk-associated variation in other pathways. Here, we sought to investigate whether major depressive disorder polygenic risk scores derived from the NETRIN1 signaling pathway (NETRIN1-PRSs) and the whole genome, excluding NETRIN1 pathway genes (genomic-PRSs), were associated with white matter microstructure.

    METHODS: We used two diffusion tensor imaging measures, fractional anisotropy (FA) and mean diffusivity (MD), in the most up-to-date UK Biobank neuroimaging data release (FA: n = 6401; MD: n = 6390).

    RESULTS: We found significantly lower FA in the superior longitudinal fasciculus (β = -.035, pcorrected = .029) and significantly higher MD in a global measure of thalamic radiations (β = .029, pcorrected = .021), as well as higher MD in the superior (β = .034, pcorrected = .039) and inferior (β = .029, pcorrected = .043) longitudinal fasciculus and in the anterior (β = .025, pcorrected = .046) and superior (β = .027, pcorrected = .043) thalamic radiation associated with NETRIN1-PRS. Genomic-PRS was also associated with lower FA and higher MD in several tracts.

    CONCLUSIONS: Our findings indicate that variation in the NETRIN1 signaling pathway may confer risk for major depressive disorder through effects on a number of white matter tracts.

  18. Li T, Heenan TMM, Rabuni MF, Wang B, Farandos NM, Kelsall GH, et al.
    Nat Commun, 2019 04 02;10(1):1497.
    PMID: 30940801 DOI: 10.1038/s41467-019-09427-z
    Ceramic fuel cells offer a clean and efficient means of producing electricity through a variety of fuels. However, miniaturization of cell dimensions for portable device application remains a challenge, as volumetric power densities generated by readily-available planar/tubular ceramic cells are limited. Here, we demonstrate a concept of 'micro-monolithic' ceramic cell design. The mechanical robustness and structural integrity of this design is thoroughly investigated with real-time, synchrotron X-ray diffraction computed tomography, suggesting excellent thermal cycling stability. The successful miniaturization results in an exceptional power density of 1.27 W cm-2 at 800 °C, which is among the highest reported. This holistic design incorporates both mechanical integrity and electrochemical performance, leading to mechanical property enhancement and representing an important step toward commercial development of portable ceramic devices with high volumetric power (>10 W cm-3), fast thermal cycling and marked mechanical reliability.
  19. Briggs AM, Jordan JE, Sharma S, Young JJ, Chua J, Foster HE, et al.
    Health Policy Plan, 2023 Feb 13;38(2):129-149.
    PMID: 35876078 DOI: 10.1093/heapol/czac061
    Musculoskeletal (MSK) health impairments contribute substantially to the pain and disability burden in low- and middle-income countries (LMICs), yet health systems strengthening (HSS) responses are nascent in these settings. We aimed to explore the contemporary context, framed as challenges and opportunities, for improving population-level prevention and management of MSK health in LMICs using secondary qualitative data from a previous study exploring HSS priorities for MSK health globally and (2) to contextualize these findings through a primary analysis of health policies for integrated management of non-communicable diseases (NCDs) in select LMICs. Part 1: 12 transcripts of interviews with LMIC-based key informants (KIs) were inductively analysed. Part 2: systematic content analysis of health policies for integrated care of NCDs where KIs were resident (Argentina, Bangladesh, Brazil, Ethiopia, India, Kenya, Malaysia, Philippines and South Africa). A thematic framework of LMIC-relevant challenges and opportunities was empirically derived and organized around five meta-themes: (1) MSK health is a low priority; (2) social determinants adversely affect MSK health; (3) healthcare system issues de-prioritize MSK health; (4) economic constraints restrict system capacity to direct and mobilize resources to MSK health; and (5) build research capacity. Twelve policy documents were included, describing explicit foci on cardiovascular disease (100%), diabetes (100%), respiratory conditions (100%) and cancer (89%); none explicitly focused on MSK health. Policy strategies were coded into three categories: (1) general principles for people-centred NCD care, (2) service delivery and (3) system strengthening. Four policies described strategies to address MSK health in some way, mostly related to injury care. Priorities and opportunities for HSS for MSK health identified by KIs aligned with broader strategies targeting NCDs identified in the policies. MSK health is not currently prioritized in NCD health policies among selected LMICs. However, opportunities to address the MSK-attributed disability burden exist through integrating MSK-specific HSS initiatives with initiatives targeting NCDs generally and injury and trauma care.
  20. Davis OC, Dickie AC, Mustapa MB, Boyle KA, Browne TJ, Gradwell MA, et al.
    Sci Rep, 2023 Jul 18;13(1):11561.
    PMID: 37464016 DOI: 10.1038/s41598-023-38605-9
    Unmyelinated non-peptidergic nociceptors (NP afferents) arborise in lamina II of the spinal cord and receive GABAergic axoaxonic synapses, which mediate presynaptic inhibition. However, until now the source of this axoaxonic synaptic input was not known. Here we provide evidence that it originates from a population of inhibitory calretinin-expressing interneurons (iCRs), which correspond to lamina II islet cells. The NP afferents can be assigned to 3 functionally distinct classes (NP1-3). NP1 afferents have been implicated in pathological pain states, while NP2 and NP3 afferents also function as pruritoceptors. Our findings suggest that all 3 of these afferent types innervate iCRs and receive axoaxonic synapses from them, providing feedback inhibition of NP input. The iCRs also form axodendritic synapses, and their targets include cells that are themselves innervated by the NP afferents, thus allowing for feedforward inhibition. The iCRs are therefore ideally placed to control the input from non-peptidergic nociceptors and pruritoceptors to other dorsal horn neurons, and thus represent a potential therapeutic target for the treatment of chronic pain and itch.
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