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Abstract Background Chronic musculoskeletal pain is common and has been increasingly managed by opioid medications, of which the long-term efficacy is unknown. Furthermore, there is evidence that long-term use of opioids is associated with reduced pain control, declining physical function and quality of life, and could hinder the goals of integrated pain management. Electroacupuncture (EA) has been shown to be effective in reducing postoperative opioid consumption. Limited evidence suggests that acupuncture could assist patients with chronic pain to reduce their requirements for opioids. The proposed research aims to assess if EA is an effective adjunct therapy to standard pain and medication management in reducing opioids use by patients with chronic musculoskeletal pain. Methods In this multicentre, randomised, sham-acupuncture controlled, three-arm clinical trial, 316 patients regularly taking opioids for pain control and meeting the defined selection criteria will be recruited from pain management centres and clinics of primary care providers in Victoria, Australia. After a four-week run-in period, the participants are randomly assigned to one of three treatment groups to receive EA, sham EA or no-EA with a ratio of 2:1:1. All participants receive routine pain medication management delivered and supervised by the trial medical doctors. Twelve sessions of semi-structured EA or sham EA treatment are delivered over 10 weeks. Upon completion of the acupuncture treatment period, there is a 12-week follow-up. In total, participants are involved in the trial for 26 weeks. Outcome measures of opioid and non-opioid medication consumption, pain scores and opioid-related adverse events are documented throughout the study. Quality of life, depression, function, and attitude to pain medications are also assessed. Discussion This randomised controlled trial will determine whether EA is of significant clinical value in assisting the management of debilitating chronic pain by reducing opioids consumption and their associated adverse events, as well as improving the quality of life for those with chronic pain. Such an outcome will provide the rationale for including EA into multidisciplinary programmes for effective management of chronic musculoskeletal pain. Trial registration Australian New Zealand Clinical Trial Registry (ACTRN12609000676213) http://www.anzctr.org.au/trial_view.aspx?ID=308008

Abstract Scientists use otoliths to trace fish life history, especially fish migrations. Otoliths incorporate signatures of individual growth and environmental use. For many species, distinct increment patterns in the otolith are difficult to discern; thus, questions remain about crucial life history information. To unravel the history of such species, we use synchrotron-based scanning X-ray fluorescence. It allows the mapping of elements on the entire otolith at a high spatial resolution. It gives access to precise fish migration history by tagging landmark signature for environmental transition and it also characterises localised growth processes at a mineral level. Freshwater pipefish, which are of conservation concern, have otoliths that are small and fragile. Growth increments are impossible to identify and count; therefore, there is a major lack of knowledge about their life history. We confirm for the first time, by mapping strontium that the two tropical pipefish species studied are diadromous (transition freshwater/marine/freshwater). Mapping of other elements uncovered the existence of different migratory routes during the marine phase. Another major breakthrough is that we can chemically count growth increments solely based on sulphur signal as it is implicated in biomineralization processes. This novel method circumvents reader bias issues and enables age estimation even for otoliths with seemingly untraceable increments. The high spatial resolution elemental mapping methods push back limits of studies on life traits or stock characterisation.

Abstract Background Recent reports suggested a different predictive value for TyG index compared to HOMA-IR in coronary artery calcification (CAC) and other atherosclerotic outcomes, despite that both indices are proposed as surrogate markers of insulin resistance. We hypothesized a key role for liver pathology as an explanation and therefore assessed the relationship among the two indices and the intrahepatic lipid content stratified by PNPLA3 rs738409 genotypes as a known non-alcoholic fatty liver disease (NAFLD) genetic risk. Methods Thirty-nine women from a prior GDM-genetic study were recalled with PNPLA3 rs738409 CC and GG genotypes for metabolic phenotyping and to assess hepatic triglyceride content (HTGC). 75 g OGTT was performed, fasting lipid, glucose, insulin levels and calculated insulin resistance indices (TyG and HOMA2-IR) were used. HTGC was measured by MR based methods. Mann–Whitney-U, χ2 and for the correlation analysis Spearman rank order tests were applied. Results The PNPLA3 rs738409 genotype had a significant effect on the direct correlation between the HOMA2-IR and TyG index: the correlation (R = 0.52, p = 0.0054) found in the CC group was completely abolished in those with the GG (NAFLD) risk genotype. In addition, the HOMA2-IR correlated with HTGC in the entire study population (R = 0.69, p

Abstract Background Hypoxia inducible factor-1 alpha (HIF-1α) is a transcription factor that plays an important role in neo-vascularisation, embryonic pancreas beta-cell mass development, and beta cell protection. Recently a non synonymous single nucleotide polymorphism (g.C45035T SNP, rs11549465) of HIF-1α gene, resulting in the p.P582S amino acid change has been shown to be associated with type 2 diabetes (T2DM) in a Japanese population. Our aim was to replicate these findings on a Caucasian (Hungarian) population, as well as to study whether this genetic effect is restricted to T2DM or can be expanded to diabetes in general. Methods A large Caucasian sample (N = 890) was recruited including 370 T2DM, 166 T1DM and 354 healthy subjects. Genotyping was validated by two independent methods: a restriction fragment analysis (RFLP) and a real time PCR using TaqMan probes. An overestimation of heterozygotes by RFLP was observed as a consequence of a nearby SNP (rs34005929). Therefore genotyping results of the justified TaqMan system were accepted. The measured genotype distribution corresponded to Hardy-Weinberg equilibrium (P = 0.740) Results As the TT genotype was extremely rare in the population (0.6% in clinical sample and 2.5% in controls), the genotypes were grouped as T absent (CC) and T present (CT and TT). Genotype-wise analysis showed a significant increase of T present group in controls (24.0%) as compared to patients (16.8%, P = 0.008). This genetic effect was demonstrated in the separated samples of type 1 (15.1%, P = 0.020), and also in type 2 (17.6%, P = 0.032) diabetes. Allele-wise analysis gave identical results showing a higher frequency of the T allele in the control sample (13.3%) than in the clinical sample (8.7%, P = 0.002) with similar results in type 1 (7.8%, P = 0.010) and type 2 (9.1%, P = 0.011) diabetes. The odds ratio for diabetes (either type 1 or 2) was 1.56 in the presence of the C allele. Conclusion We confirmed the protective effect of a rare genetic variant of HIF-1α gene against type 2 diabetes in a Caucasian sample. Moreover we demonstrated a genetic contribution of the same polymorphism in type 1 diabetes as well, supporting a possible overlap in pathomechanism for T2DM and a T1DM.

To understand the function of cortical circuits, it is necessary to catalog their cellular diversity. Past attempts to do so using anatomical, physiological or molecular features of cortical cells have not resulted in a unified taxonomy of neuronal or glial cell types, partly due to limited data. Single-cell transcriptomics is enabling, for the first time, systematic high-throughput measurements of cortical cells and generation of datasets that hold the promise of being complete, accurate and permanent. Statistical analyses of these data reveal clusters that often correspond to cell types previously defined by morphological or physiological criteria and that appear conserved across cortical areas and species. To capitalize on these new methods, we propose the adoption of a transcriptome-based taxonomy of cell types for mammalian neocortex. This classification should be hierarchical and use a standardized nomenclature. It should be based on a probabilistic definition of a cell type and incorporate data from different approaches, developmental stages and species. A community-based classification and data aggregation model, such as a knowledge graph, could provide a common foundation for the study of cortical circuits. This community-based classification, nomenclature and data aggregation could serve as an example for cell type atlases in other parts of the body.

The global spread of antimicrobial resistance has become a prominent issue in both veterinary and public health in the 21st century. The extensive use of amoxicillin, a beta-lactam antibiotic, and consequent resistance development are particularly alarming in food-producing animals, with a focus on the swine and poultry sectors. Another beta-lactam, cefotaxime, is widely utilized in human medicine, where the escalating resistance to third- and fourth-generation cephalosporins is a major concern. The aim of this study was to simulate the development of phenotypic and genotypic resistance to beta-lactam antibiotics, focusing on amoxicillin and cefotaxime. The investigation of the minimal inhibitory concentrations (MIC) of antibiotics was performed at 1×, 10×, 100×, and 1000× concentrations using the modified microbial evolution and growth arena (MEGA-plate) method. Our results indicate that amoxicillin significantly increased the MIC values of several tested antibiotics, except for oxytetracycline and florfenicol. In the case of cefotaxime, this increase was observed in all classes. A total of 44 antimicrobial resistance genes were identified in all samples. Chromosomal point mutations, particularly concerning cefotaxime, revealed numerous complex mutations, deletions, insertions, and single nucleotide polymorphisms (SNPs) that were not experienced in the case of amoxicillin. The findings suggest that, regarding amoxicillin, the point mutation of the acrB gene could explain the observed MIC value increases due to the heightened activity of the acrAB-tolC efflux pump system. However, under the influence of cefotaxime, more intricate processes occurred, including complex amino acid substitutions in the ampC gene promoter region, increased enzyme production induced by amino acid substitutions and SNPs, as well as mutations in the acrR and robA repressor genes that heightened the activity of the acrAB-tolC efflux pump system. These changes may contribute to the significant MIC increases observed for all tested antibiotics. The results underscore the importance of understanding cross-resistance development between individual drugs when choosing clinical alternative drugs. The point mutations in the mdtB and emrR genes may also contribute to the increased activity of the mdtABC-tolC and emrAB-tolC pump systems against all tested antibiotics. The exceptionally high mutation rate induced by cephalosporins justifies further investigations to clarify the exact mechanism behind.

Due to the growing concerns about pharmaceutical contamination and its devastating impact on the economy and the health of humans and the environment, developing efficient approaches for removing such contaminants has become essential. Adsorption is a cost-effective technique for removing pollutants. Thus, in this work, banana peels as agro-industrial waste were utilized for synthesizing activated carbon for removing pharmaceuticals, namely amoxicillin and carbamazepine from different water matrices. The chemically activated carbon by phosphoric acid (H3PO4) was carbonized at temperatures 350 °C, 450 °C and 550 °C. The material was characterized by several techniques such as scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDS), Fourier transform infrared spectroscopy (FTIR), Boehm titration, point of zero charge (pHPZC), BET surface area (SBET), the proximate and ultimate analyses, X-ray powder diffraction (XRD), and thermos-gravimetric analysis (TGA). The SEM of banana peel activated carbon (BPAC) depicted a semi-regular and heterogeneous morphology, characterized by an abundance of pores with diverse forms and sizes. Boehm titration revealed an increase in the amounts of acidic groups by 0.711 mmol/g due to activation by H3PO4. FTIR recorded different peaks suggesting significant modifications in the spectroscopic characteristics of the BPAC surface due to the successful activation and adsorption of the pollutant molecules. The pHpzc of BPAC was calculated to be 5.005. The SBET surface area dramatically increased to 911.59 m2/g after the activation. The optimum conditions were 25 °C, a materials dosage of 1.2 g/L, a saturation time of 120 min, a pollutants mixture of 25 mg/L, and a pH of 5. Langmuir exhibits a slightly better fit than Freundlich with a low value of the residual sum of squares (SSE) and the data were better fitted to the pseudo-second-order kinetic. Furthermore, the efficacy of BPAC in eliminating pharmaceuticals from Milli Q water, lake water, and wastewater was successfully investigated over the seven cycles. The results of the present work highlighted a potential usage of agro-industrial waste in eliminating organic micropollutants while exhibiting sustainable management of this waste.

Background: Respiratory parameters in experimental animals are often characterised under general anaesthesia. However, anaesthesia regimes may alter the functional and mechanical properties of the respiratory system. While most anaesthesia regimes have been shown to affect the respiratory system, the effects of general anaesthesia protocols commonly used in animal models on lung function have not been systematically compared.Methods: The present study comprised 40 male Sprague-Dawley rats divided into five groups (N = 8 in each) according to anaesthesia regime applied: intravenous (iv) Na-pentobarbital, intraperitoneal (ip) ketamine-xylazine, iv propofol-fentanyl, inhaled sevoflurane, and ip urethane. All drugs were administered at commonly used doses. End-expiratory lung volume (EELV), airway resistance (Raw) and tissue mechanics were measured in addition to arterial blood gas parameters during mechanical ventilation while maintaining positive end-expiratory pressure (PEEP) values of 0, 3, and 6 cm H2O. Respiratory mechanics were also measured during iv methacholine (MCh) challenges to assess bronchial responsiveness.Results: While PEEP influenced baseline respiratory mechanics, EELV and blood gas parameters (p < 0.001), no between-group differences were observed (p > 0.10). Conversely, significantly lower doses of MCh were required to achieve the same elevation in Raw under ketamine-xylazine anaesthesia compared to the other groups.Conclusion: In the most frequent rodent model of respiratory disorders, no differences in baseline respiratory mechanics or function were observed between commonly used anaesthesia regimes. Bronchial hyperresponsiveness in response to ketamine-xylazine anaesthesia should be considered when designing experiments using this regime. The findings of the present study indicate commonly used anaesthetic regimes allow fair comparison of respiratory mechanics in experimental animals undergoing any of the examined anaesthesia protocols.

We compute the next-to-leading-order (NLO) QCD corrections to the Higgs pT distribution in Higgs production in association with a jet via gluon fusion at the LHC, with exact dependence on the mass of the quark circulating in the heavy-quark loops. The NLO corrections are presented including the top-quark mass, and for the first time, the bottom-quark mass as well. Further, besides the on-shell mass scheme, we consider for the first time a running mass renormalisation scheme. The computation is based on amplitudes which are valid for arbitrary heavy-quark masses.

Measuring circularity is necessary to prove the feasibility of transforming linear technologies into circular ones. However, most of the circular economic researches consider water only as a medium. Food industry processes are excellent examples of systems that are hard to break free from linearity, albeit not impossible. This paper explores solutions to include water in circularity calculations using a Hungarian poultry processing plant as a case study. Two circular economic indicators, the questionnaire-type Circular Economy Indicator Prototype (CEIP) and the product-centric Material Circularity Indicator (MCI and MCI’) and the Water Footprint were examined in detail and modified to fit the needs of assessing circularity with water included as raw material. The calculations were supported by Life Cycle Assessment (LCA). The impact on circularity and the environment were quantified by considering different reuse scenarios. As the results of CEIP show, including water reuse in the technology or recycling for irrigation could increase the indicator values from low to medium-high level of circularity. However, the level of improvement highly depends on the amount of water used. LCA highlighted the significant environmental effects of packaging (