Malnutrition in total joint arthroplasty: what should the orthopaedic surgeon consider?

Total joint arthroplasty (TJA) is rising globally, with an associated increase in associated complications, necessitating increased efforts in prevention of these complications with pre-operative optimisation. Malnutrition has been highlighted as one of the most important pre-operative modifiable risk factors to be addressed in TJA, with the term malnutrition in orthopaedic surgery having a broad definition that encompasses a wide range of nutritional abnormalities from undernutrition to overnutrition contributing to the outcomes of TJA. Complications associated with malnutrition include periprosthetic joint infection (PJI), periprosthetic fracture, dislocations, aseptic loosening, anaemia, prolonged length of stay (LOS), increased mortality, and raised health care costs. Standardised nutritional scoring tools, anthropometric measurements, and serological markers are all options available in pre-operative nutritional assessment in TJA, but there is no consensus yet regarding the standardisation of what parameters to assess and how to assess them. Abnormal parameters identified using any of the assessment methods results in the diagnosis of malnutrition, and correction of these parameters of overnutrition or undernutrition have shown to improve outcomes in TJA. With the multiple nutritional parameters contributing to the success of total joint arthroplasty, it is imperative that orthopaedic surgeon has a thorough knowledge regarding nutritional peri-operative optimisation in TJA.

Collaborative discussions between pharmacists and general practitioners to optimise patient medication: a qualitative study within a clinical trial.

BACKGROUND: There has been significant investment in pharmacists working in UK general practice to improve the effective and safe use of medicines. However, evidence of how to optimise collaboration between GPs and pharmacists in the context of polypharmacy (multiple medication) is lacking. AIM: To explore GP and pharmacist views and experiences of in-person, inter-professional collaborative discussions (IPCDs) as part of a complex intervention to optimise medication use for patients with polypharmacy in general practice. DESIGN AND SETTING: A mixed-method process evaluation embedded within the Improving Medicines use in People with Polypharmacy in Primary Care (IMPPP) trial conducted in Bristol and the West Midlands. METHOD: Audio-recordings of IPCDs between GPs and pharmacists, and individual semi-structured interviews exploring their reflections on these discussions. All recordings were transcribed verbatim and analysed thematically. RESULTS: Fourteen practices took part in the process evaluation (Feb 2021- Sept 2023). Seventeen IPCD meetings were audio recorded discussing 30 patients (range of 1-6 patients per meeting). Six GPs and 13 pharmacists were interviewed. The IPCD was highly valued by GPs and pharmacists who described benefits including: strengthening their working relationship; learning from each other; and gaining in confidence to manage more complex patients. It was often challenging, however, to find time for the IPCDs. CONCLUSION: The model of IPCD studied provided protected time for GPs and pharmacists to work together to deliver whole-patient care, with both professions finding this beneficial. Protected time for inter-professional liaison and collaboration, and structured interventions may facilitate improved patient care.

Optimisation of a Microwave Synthesis of Silver Nanoparticles by a Quality by Design Approach to Improve SERS Analytical Performances.

A major limitation preventing the use of surface-enhanced Raman scattering (SERS) in routine analyses is the signal variability due to the heterogeneity of metallic nanoparticles used as SERS substrates. This study aimed to robustly optimise a synthesis process of silver nanoparticles to improve the measured SERS signal repeatability and the protocol synthesis repeatability. The process is inspired by a chemical reduction method associated with microwave irradiation to guarantee better controlled and uniform heating. The innovative Quality by Design strategy was implemented to optimise the different parameters of the process. A preliminary investigation design was firstly carried out to evaluate the influence of four parameters selected by means of an Ishikawa diagram. The critical quality attributes were to maximise the intensity of the SERS response and minimise its variance. The reaction time, temperature and stirring speed are critical process parameters. These were optimised using an I-optimal design. A robust operating zone covering the optimal reaction conditions (3.36 min-130 °C-600 rpm) associated with a probability of success was modelled. Validation of this point confirmed the prediction with intra- and inter-batch variabilities of less than 15%. In conclusion, this study successfully optimised silver nanoparticles by a rapid, low cost and simple technique enhancing the quantitative perspectives of SERS.

Sustainability assessment of machining Al 6061-T6 using Taguchi-grey relation integrated approach.

Modern machining requires reduction in energy usage, surface roughness, and burr width to produce finished or near-finished parts. To ensure high surface quality in machining processes, it is crucial to minimize surface finish and minimize burr width, which are considered as significant parameters as specific cutting energy. The objective of this study was to identify the optimal machining parameters for milling in order to minimize surface roughness, burr width, and specific cutting energy. To achieve this, the research investigated the impact of feed per tooth, cutting speed, depth of cut, and number of inserts on the responses across three intervals using Taguchi L9 array. Observing the responses by varying these parameters, underlined the need for multi objective optimisation. Machining conditions of 0.14 mm/tooth f z , 350 m/min V c and 2 mm ap using 1 cutting insert (exp no 9) was identified as the best machining run using grey relational analysis owing to its highest grey relational grade of 0.936. ANOVA examination identified cutting speed as the leading factor impacting the grey relational grade with 31.07 % contribution ratio, with the number of inserts, depth of cut, and feed per tooth also making notable contributions. Conclusively, machining parameters identified through response surface optimisation resulted in 21.69 % improvement in surface finish, 11.39 % reduction in specific energy consumption, and 6.2 % decrease in burr width on the down milling side albeit with an increase of 9 % in burr width on the up-milling side.

Increasing cost-effectiveness of AEDs using algorithms to optimise location.

OBJECTIVES: Volunteer responder systems (VRSs) aim to decrease time to defibrillation by dispatching trained volunteers to automated external defibrillators (AEDs) and out-of-hospital cardiac arrest (OHCA) victims. AEDs are often underutilized due to poor placement. This study provides a cost-effectiveness analysis of adding AEDs at strategic locations to maximize quality-adjusted life years (QALYs). METHODS: We simulated combined volunteer, police, firefighter, and emergency medical service response scenarios to OHCAs, and applied our methods to a case study of Amsterdam, the Netherlands. We compared the competing strategies of placing additional AEDs, using steps of 40 extra AEDs (0, 40, …, 1480), in addition to the existing 369 AEDs. Incremental cost-effectiveness ratios (ICERs) were calculated for each increase in additional AEDs, from a societal perspective. The effect of AED connection and time to connection on survival to hospital admission and neurological outcome at discharge was estimated using logistic regression, using OHCA data from Amsterdam from 2006 to 2018. Other model inputs were obtained from literature. RESULTS: Purchasing up to 1120 additional AEDs (ICER €75,669/QALY) was cost-effective at a willingness-to-pay threshold of €80,000/QALY, when positioned strategically. Compared to current practice, adding 1120 AEDs resulted in a gain of 0.111 QALYs (95% CI 0.110-0.112) at an increased cost of €3792 per OHCA (95% CI €3778-€3807). Health benefits per AED diminished as more AEDs were added. CONCLUSIONS: Our study identified cost-effective strategies to position AEDs at strategic locations in a VRS. The case study findings advocate for a substantial increase in the number of AEDs in Amsterdam.

Evaluation of postoperative results after a presurgical optimisation programme.

BACKGROUND: Presurgical optimisation programmes decrease the risk of postoperative complications, reduce hospital stays and speed up patient recovery. They usually involve a multidisciplinary team addressing physical, nutritional and psychosocial issues. The objective of this study was to assess the results of implementing a presurgical optimisation programme led by a liaison nurse in patients undergoing major surgery in a primary general hospital. METHODS: An observational, retrospective, descriptive, cross-sectional, comparative study based on the revision of patients' health records undergoing major surgery between January 2019 and December 2022. Patients entering the presurgical optimisation programme (intervention group) were compared with patients receiving usual medical care (control group). The presurgical optimisation programme consisted of oral nutritional supplementation, physical exercise, strengthening of lung capacity and psychological and emotional support. Frequency (%) of surgery complications and use of healthcare resources (duration of hospitalisation, time spent in the intensive care unit (ICU), and readmission) at day 30 were recorded. Descriptive statistics were applied. RESULTS: Two hundred eleven patients (58.5% men, mean age: 65.76 years (SD 11.5), 75.2%. non-smokers; mean body mass index (BMI): 28.32 (SD 5.38); mean Nutritional Risk Score (NRS) 3.71 (SD 1.35; oncology diagnosis: 88.6%) were included: 135 in the intervention group, and 76 in the control group. The average duration of the presurgical optimisation programme was 20 days (SD 5). Frequency of postoperative complications was 25% (n = 33) in the intervention group and 52.6% (n = 40) in the control group (p < 0.001) [odds ratio (OR) = 3.4; 95% confidence interval (CI) (1.8; 6.2)]. 14.5% (n = 19) of patients in the intervention group and 34.2% (n = 26) in the control group had remote postoperative complications [OR = 3.1; 95% CI (1.6; 6.2)]. Patients in the intervention group spent fewer days in the hospital [mean 8.34 (SD 6.70) vs 11.63 (SD 10.63)], and there were fewer readmissions at 30 days (7.6% vs 19.7%) compared with the control group. CONCLUSIONS: A presurgical optimisation programme led by a liaison nurse decreases the rate of immediate and late surgical complications and reduces hospital stays and readmissions in patients undergoing major surgery.

Optimising a digitally delivered behavioural weight loss programme: study protocol for a factorial cluster randomised controlled trial.

BACKGROUND: Digitally delivered weight loss programmes can provide a convenient, potentially cheaper, and scalable treatment option for people who may need to lose weight. However, outcomes are often inferior to in-person interventions in the long-term. This trial will use principles from the Multiphase Optimisation Strategy (MOST) framework to test whether it can enhance the effectiveness of a commercial digital behavioural weight loss programme. This trial aims to identify an optimised combination of four intervention components to enhance weight loss over a 24-week period. We will also explore which components contribute to improvements in participant retention and engagement with the programme. METHODS: Approximately 1400 adults with a BMI > 21 kg/m2 will be enrolled and randomised to one of 16 experimental conditions in a 24 factorial cluster design. The trial will test four intervention components: an introductory video call with the health coach, drop-in webchat sessions with the health coach, goal setting statements, and food diary review and feedback. All participants will receive the core digital behavioural weight loss programme and up to four new intervention components. Participation in the trial will last for 24 weeks. The primary outcome will be weight change at 16 weeks. Other outcomes, measured at 4, 16, and 24 weeks, include programme drop-out and engagement (number of interactions with the three main app functions). Fidelity and acceptability will be assessed using data on component adherence and self-report questionnaires. Decision-making for the enhanced programme will be based on components that contribute to at least a minimal improvement in weight loss, defined as ≥ 0.75kg, alone or in combination with other components. DISCUSSION: The factorial design is an efficient way to test the efficacy of behavioural components alone, or in combination, to improve the effectiveness of digital weight loss programmes. This trial will test the implementation of the MOST framework in an industry setting, using routinely collected data, which may provide a better way to refine and evaluate these types of interventions in a model of continuous service improvement. TRIAL REGISTRATION: Trial registration: ISRCTN, ISRCTN14407868. Registered 5 January 2024, 10.1186/ISRCTN14407868.

A quantitative study on the impact of a community falls pharmacist role, on medicines optimisation in older people at risk of falls.

BACKGROUND: The World Falls guidance includes medication review as part of its recommended multifactorial risk assessment for those at high risk of falling. Use of Falls Risk Increasing Drugs (FRIDs) along with polypharmacy and anticholinergic burden (ACB) are known to increase the risk of falls in older people. METHOD: The impact of a community falls pharmacist within a hospital Trust, working as part of a multi-professional community falls prevention service, was evaluated in 92 people aged 65 years or older, by analysing data before and after pharmacist review, namely: number and type of FRIDs prescribed; anticholinergic burden score using ACBcalc®; appropriateness of medicines prescribed; bone health review using an approved too; significance of clinical intervention; cost avoidance, drug cost savings and environmental impact. RESULTS: Following pharmacist review, there was a reduction in polypharmacy (mean number of medicines prescribed per patient reduced by 8%; p < 0.05) and anticholinergic burden score (average score per patient reduced by 33%; p < 0.05). Medicines appropriateness improved (Medicines Appropriateness Index score decreased by 56%; p < 0.05). There were 317 clinically significant interventions by the community falls pharmacist. One hundred and one FRIDs were deprescribed. Annual cost avoidance and drug cost savings were £40,689-£82,642 and avoidable carbon dioxide (CO2) emissions from reducing inappropriate prescribing amounted to 941 kg CO2. CONCLUSION: The community falls pharmacist role increases prescribing appropriateness in the older population at risk of falls, and is an effective and cost-efficient means to optimise medicines in this population, as well as having a positive impact on the environment.

Strength Optimisation of Hybrid Bolted/Bonded Composite Joints Based on Finite Element Analysis.

A finite element analysis (FEA) was conducted to examine the behaviour of single-lap quasi-isotropic (QI) and cross-ply (CP) hybrid bolted/bonded (HBB) configurations subjected to tensile shear loading. Several critical design factors influencing the composite joint strength, failure conditions, and load-sharing mechanisms that would optimise the joining performance were assessed. The study of the stress concentration around the holes and along the adhesive layer highlights the fact that the HBB joints benefit from significantly lower stresses compared to only bolted joints, especially for CP configurations. The simulation results confirmed the redundancy of the middle bolt in a three-bolt HBB joint. The stiffness and plastic behaviour of the adhesive were found to be important factors that define the transition of the behaviour of the joint from a bolted type, where load sharing is predominant, to a bonded joint. The load-sharing potential, known as an indicator of the joint's performance, is improved by reducing the overlap length, using a low-stiffness, high-plasticity adhesive, and using thicker laminates in the QI layup configuration. Enhancing both the ratio of the edge distance to the hole diameter and washer size proves advantageous in reducing stresses within the adhesive layer, thereby improving the joint strength.

How to design optimal brain stimulation to modulate phase-amplitude coupling?

Objective.Phase-amplitude coupling (PAC), the coupling of the amplitude of a faster brain rhythm to the phase of a slower brain rhythm, plays a significant role in brain activity and has been implicated in various neurological disorders. For example, in Parkinson's disease, PAC between the beta (13-30 Hz) and gamma (30-100 Hz) rhythms in the motor cortex is exaggerated, while in Alzheimer's disease, PAC between the theta (4-8 Hz) and gamma rhythms is diminished. Modulating PAC (i.e. reducing or enhancing PAC) using brain stimulation could therefore open new therapeutic avenues. However, while it has been previously reported that phase-locked stimulation can increase PAC, it is unclear what the optimal stimulation strategy to modulate PAC might be. Here, we provide a theoretical framework to narrow down the experimental optimisation of stimulation aimed at modulating PAC, which would otherwise rely on trial and error.Approach.We make analytical predictions using a Stuart-Landau model, and confirm these predictions in a more realistic model of coupled neural populations.Main results.Our framework specifies the critical Fourier coefficients of the stimulation waveform which should be tuned to optimally modulate PAC. Depending on the characteristics of the amplitude response curve of the fast population, these components may include the slow frequency, the fast frequency, combinations of these, as well as their harmonics. We also show that the optimal balance of energy between these Fourier components depends on the relative strength of the endogenous slow and fast rhythms, and that the alignment of fast components with the fast rhythm should change throughout the slow cycle. Furthermore, we identify the conditions requiring to phase-lock stimulation to the fast and/or slow rhythms.Significance.Together, our theoretical framework lays the foundation for guiding the development of innovative and more effective brain stimulation aimed at modulating PAC for therapeutic benefit.

Two-dimensional oxygen-diffusion modelling for FLASH proton therapy with pencil beam scanning-Impact of diffusive tissue properties, dose, dose rate and scan patterns.

Objective.Oxygen depletion is generally believed to play an important role in the FLASH effect-a differential reduction of the radiosensitivity of healthy tissues, relative to that of the tumour under ultra-high dose-rate (UHDR) irradiation conditions. In proton therapy (PT) with pencil-beam scanning (PBS), the deposition of dose, and, hence, the degree of (radiolytic) oxygen depletion varies both spatially and temporally. Therefore, the resulting oxygen concentration and the healthy-tissue sparing effect through radiation-induced hypoxia varies both spatially and temporally as well.Approach.We propose and numerically solve a physical oxygen diffusion model to study these effects and their dependence on tissue parameters and the scan pattern in pencil-beam delivery. Since current clinical FLASH PT (FLASH-PT) is based on 250 MeV shoot-through (transmission) beams, for which dose and dose rate (DR) hardly vary with depth compared to the variation transverse to the beam axis, we focus on the two-dimensional case. We numerically integrate the model to obtain the oxygen concentration in each voxel as a function of time and extract voxel-based and spatially and temporarily integrated metrics for oxygen (FLASH) enhanced dose. Furthermore, we evaluate the impact on oxygen enhancement of standard pencil-beam delivery patterns and patterns that were optimised on dose-rate. Our model can contribute to the identification of tissue properties and pencil-beam delivery parameters that are critical for FLASH-PT and it may be used for the optimisation of FLASH-PT treatment plans and their delivery.Main results.(i) the diffusive properties of oxygen are critical for the steady state concentration and therefore the FLASH effect, even more so in two dimensions when compared to one dimension. (ii) The FLASH effect through oxygen depletion depends primarily on dose and less on other parameters. (iii) At a fixed fraction dose there is a slight dependence on DR. (iv) Scan patterns optimised on DR slightly increase the oxygen induced FLASH effect.Significance.To our best knowledge, this is the first study assessing the impact of scan-pattern optimization (SPO) in FLASH-PT with PBS on a biological FLASH model. While the observed impact of SPO is relatively small, a larger effect is expected for larger target volumes. A better understanding of the FLASH effect and the role of oxygen (depletion) therein is essential for the further development of FLASH-PT with PBS, and SPO.

Empirical Model Variability: Developing a new global optimisation approach to populate compression and compaction mixture rules.

This study systematically evaluated the predictive accuracy of common empirical models for pharmaceutical powder compaction. A dataset of nine placebo and twelve active pharmaceutical ingredient (API) loaded blend formulations (four APIs at three drug loadings) was fitted to the widely used empirical tablet compression (Gurnham, Heckel, and Kawakita) and compaction (Ryshkewitch-Duckworth and Leuenberger) models. At low API loadings (<20w/w%), all models achieved R2 above 90 % and RRMSE (relative root mean squared error) below 0.1. However, as API loads increased, overall model performance decreased, notably in the Heckel model. A parameter variability analysis identified multiple parameter pairs achieving acceptable fits. Consequently, a novel global optimization approach was developed populating arithmetic, geometric, and harmonic mixture rules for empirical tuning parameters. This method outperformed the traditional line of best fit approach. A cross validation study revealed that this method is capable of predicting tuning parameters which achieve an acceptable Goodness of Fit for new blends. Finally, with the restriction of maintaining consistent parameters for the placebo blend, the proposed method could substantially reduce the experimental requirements and API consumption for the exploration of new blends.

Optimised Formulation of a New Sweet Apricot Kernel-Enriched Yoghurt: Assessment of Physicochemical, Sensory and Antioxidant Properties.

Research background: The addition of sweet apricot kernel powder, a by-product of apricot processing, to yoghurt appears to be particularly interesting option for the innovation of new food products. This study focuses on the formulation of a novel yoghurt enriched with sweet apricot kernel powder, sugar and milk powder. Experimental approach: Different yoghurts were prepared by mixing sweet apricot kernel powder, sugar and milk powder as ingredients based on the simplex-centroid mixture design. The optimisation process took into account the physicochemical, antioxidant and sensory properties of the yoghurt. Results and conclusions: The results showed that the optimum values of sugar, milk powder and apricot kernel powder were 3.07, 2.16 and 2.77 %, respectively. The physicochemical assays showed that the addition of apricot kernel powder led to a significant increase in total phenolic content, antioxidant activity, syneresis, viscosity and acidity. The addition of sugar and milk powder also had a significant effect on the taste, texture and consistency of the yoghurt. Moreover, the enrichment of the product with apricot kernel powder significantly influenced the colour, odour, taste, texture and consistency. In conclusion, the optimised yoghurt enriched with apricot kernel had an interesting phenolic content and antioxidant properties with sensory acceptability, while reducing the amount of sugar and milk powder. This confirms the potential of using sweet apricot kernels as an ingredient in yoghurt production. Novelty and scientific contribution: The use of a simplex-centroid mixture design to optimise a new yoghurt formulation enriched with sweet apricot kernels shows significant improvements in total phenolic content, antioxidant activity and sensory acceptability. In addition, less sugar and milk powder is needed. The addition of sweet apricot kernels to yoghurt is therefore a new approach to improving its nutritional value and sensory appeal.

In Silico, In Vitro and Ex Vivo Evaluation of the Antihyperglycaemic, Antioxidant and Cytotoxic Properties of Coccinia grandis L. Leaf Extract.

Research background: Coccinia grandis L. is traditionally used for the treatment of diabetes mellitus. Since the scientific evidence and mechanism of action have not yet been extensively investigated, this study aims to evaluate the antidiabetic and cytotoxic effects together with the optimisation and development of a scale-up process design for higher yields of bioactive phytocompounds from C. grandis. Experimental approach: The in silico study was conducted to predict the binding affinity of phytocompounds of C. grandis for α-amylase and α-glucosidase enzymes involved in the pathophysiology of diabetes with pharmacokinetic assessment. Response surface methodology was used to determine the optimum total phenolic content (TPC), total flavonoid content (TFC), total tannin content (TTC) and antioxidant activities (DPPH and FRAP) in 17 different experimental runs in which the parameters of microwave-assisted extraction such as temperature (50-70 °C), power (400-1000 W) and time (15-45 min) were varied. The phytocompounds were purified and identified using column chromatography, thin-layer chromatography (TLC), UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR) and liquid chromatography-mass spectrometry (LC-MS). The in vitro antidiabetic activity was determined by α-amylase and α-glucosidase enzymatic inhibitory assays, while cytotoxic investigations were done by measuring haemolytic activity, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and chorioallantoic membrane (CAM) assays. Results and conclusions: The reported major bioactive compounds have shown an excellent binding affinity for α-amylase and α-glucosidase enzymes in the range of -14.28 to -36.12 kJ/mol with good pharmacokinetic properties and toxicities ranging from low to medium. The bioactive constituents such as total phenols, total flavonoids, total tannins and antioxidant activities such as DPPH and FRAP were found to be high and dependent on the optimised microwave-assisted extraction parameters such as temperature, time and power: 55 °C, 45 min and 763 W, respectively. Sixteen compounds were identified by FTIR and LC-MS spectra in the plant sample after preliminary identification, purification and TLC. The percentage of enzyme inhibition depended on the concentration of the extract (7.8-125.0 µg/mL) and was higher than that of acarbose. The haemolytic activity was in accordance with ISO standards and low toxicity was observed in the MTT and CAM assays in the range of 7.8-125.0 µg/mL, suggesting its potential use as an antidiabetic drug and for functional food development. Novelty and scientific contribution: The results of the study open up new opportunities for researchers, scientists and entrepreneurs in the food and pharmaceutical sectors to develop antidiabetic foods and medicines that help diabetics to better control their condition and maintain overall health.

Towards pharmacokinetic boosting of phenoxymethylpenicillin (penicillin-V) using probenecid for the treatment of bacterial infections.

In the face of increasing antimicrobial tolerance and resistance there is a global obligation to optimise oral antimicrobial dosing strategies including narrow spectrum penicillins, such as penicillin-V. We conducted a randomised, crossover study in healthy volunteers to characterise the influence of probenecid on penicillin-V pharmacokinetics and estimate the pharmacodynamics against Streptococcus pneumoniae. Twenty participants took six doses of penicillin-V (250 mg, 500 mg or 750 mg four times daily) with and without probenecid. Total and free concentrations of penicillin-V and probenecid were measured at two timepoints. A pharmacokinetic model was developed, and the probability of target attainment (PTA) calculated. The mean difference (95% CI) between penicillin-V alone and in combination with probenecid for serum total and free penicillin-V concentrations was significantly different at both timepoints (total: 45 min 4.32 (3.20-5.32) mg/L p < 0.001, 180 min 2.2 (1.58-3.25) mg/L p < 0.001; free: 45 min 1.15 (0.88-1.42) mg/L p < 0.001, 180 min 0.5 (0.35-0.76) mg/L p < 0.001). There was no difference between the timepoints in probenecid concentrations. PTA analysis shows probenecid allows a fourfold increase in MIC cover. Addition of probenecid was safe and well tolerated. The data support further research into improved dosing structures for complex outpatient therapy and might also be used to address penicillin supply shortages.

Metabolomics analysis based on UHPLC-QTOF-MS/MS to explore the synthesis mechanism and culture conditions optimization of Penicillium EF-2 exopolysaccharide.

Penicillium exopolysaccharide (EPS) inhibits galactose lectins and enhances immunity. However, EPS production is low and its synthesis mechanism remains unclear. Penicillium EF-2 strains with high EPS production were selected for this study, and Penicillium fermentation conditions were subsequently improved. The optimal culture conditions were 30 g/L lactose, 6 g/L yeast extract powder, 4 d seed age, 10 % inoculation amount, 3 d of secondary fermentation time, and the final EPS yield was 3.97 g/L. UHPLC-Q-TOF-MS/MS was used to explore the mechanism of EPS synthesis at the metabolic level. Optimal carbon source: lactose and optimal nitrogen source: yeast extract can provide precursors for EPS synthesis through related metabolic pathways. Moreover, regulating the energy, vitamin, and lipid metabolic pathways created favourable conditions for EPS synthesis and secretion. These findings explain the mechanism of EPS synthesis at the metabolic level and provide a theoretical basis for optimising and industrialising EPS production.

An optimisation approach for planning preventive drought management measures.

While drought impacts are widespread across the globe, climate change projections indicate more frequent and severe droughts. This underscores the pressing need to increase resistance and resilience to drought. The strategic application of Preventive Drought Management Measures (PDMMs) is a suitable avenue to reduce the likelihood of drought and ameliorate associated damages. In this study, we use an optimisation approach with a multicriteria decision-making method to allocate PDMMs for reducing the severity of agricultural and hydrological droughts. The results indicate that implementing PDMMs can reduce the severity of agricultural and hydrological droughts, and the obtained management scenarios (solutions) highlight the utility of multi-objective optimisation for PDMMs planning. However, examined management scenarios also illustrate the trade-off between managing agricultural and hydrological droughts. PDMMs can alleviate the severity of agricultural droughts while producing opposite effects for hydrological droughts (or vice versa). Furthermore, the impact of PDMMs displays temporal and spatial variabilities. For instance, PDMMs implementation within a specific subbasin may mitigate the severity of one type of drought in a given month yet exacerbate drought conditions in preceding or subsequent months. In the case of hydrological droughts, the PDMMs may intensify streamflow deficits in the intervened subbasins while alleviating the hydrological drought severity downstream (or vice versa). These complexities emphasise a customised implementation of PDMMs, considering the basin characteristics (e.g., rainfall distribution over the year, soil properties, land use, and topography) and the quantification of PDMMs' effect on the severity of each type of drought.

Adjustments of iodinated contrast media using lean body weight for abdominopelvic computed tomography: A systematic review and meta-analysis.

PURPOSE: This systematic review aimed to compare the effect of contrast media (CM) dose adjustment based on lean body weight (LBW) method versus other calculation protocols for abdominopelvic CT examinations. METHOD: Studies published from 2002 onwards were systematically searched in June 2024 across Medline, Embase, CINAHL, Cochrane CENTRAL, Web of Science, Google Scholar and four other grey literature sources, with no language limit. Randomised controlled trials (RCT) and quasi-RCT of abdominopelvic or abdominal CT examinations in adults with contrast media injection for oncological and acute diseases were included. The comparators were other contrast dose calculation methods such as total body weight (TBW), fixed volume (FV), body surface area (BSA), and blood volume. The main outcomes considered were liver and aortic enhancement. Titles, abstracts and full texts were independently screened by two reviewers. RESULTS: Eight studies were included from a total of 2029 articles identified. Liver parenchyma and aorta contrast enhancement did not significantly differ between LBW and TBW protocols (p = 0.07, p = 0.06, respectively). However, the meta-analysis revealed significantly lower contrast volume injected with LBW protocol when compared to TBW protocol (p = 0.003). No statistical differences were found for contrast enhancement and contrast volume between LBW and the other strategies. CONCLUSION: Calculation of the CM dosage based on LBW allows a reduction in the injected volume for abdominopelvic CT examination, ensuring the same image quality in terms of contrast enhancement.

A comparison of fixation and immunofluorescence protocols for successful reproducibility and improved signal in human left ventricle cardiac tissue.

Immunohistochemistry (IHC) and immunofluorescence (IF) are crucial techniques for studying cardiac physiology and disease. The accuracy of these techniques is dependent on various aspects of sample preparation and processing. However, standardised protocols for sample preparation of tissues, particularly for fresh-frozen human left ventricle (LV) tissue, have yet to be established and could potentially lead to differences in staining and interpretation. Thus, this study aimed to optimise the reproducibility and quality of IF staining in fresh-frozen human LV tissue by systematically investigating crucial aspects of the sample preparation process. To achieve this, we subjected fresh-frozen human LV tissue to different fixation protocols, primary antibody incubation temperatures, antibody penetration reagents, and fluorescent probes. We found that neutral buffered formalin fixation reduced image artefacts and improved antibody specificity compared to both methanol and acetone fixation. Additionally, incubating primary antibodies at 37°C for 3 h improved fluorescence intensity compared to the commonly practised 4°C overnight incubation. Furthermore, we found that DeepLabel, an antibody penetration reagent, and smaller probes, such as fragmented antibodies and Affimers, improved the visualisation depth of cardiac structures. DeepLabel also improved antibody penetration in CUBIC cleared thick LV tissue fragments. Thus, our data underscores the importance of standardised protocols in IF staining and provides various means of improving staining quality. In addition to contributing to cardiac research by providing methodologies for IF, the findings and processes presented herein also establish a framework by which staining of other tissues may be optimised.