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The biogas production technology has improved over the last years for the aim of reducing the costs of the process, increasing the biogas yields, and minimizing the greenhouse gas emissions. To obtain a stable and efficient biogas production, there are several design considerations and operational parameters to be taken into account. Besides, adapting the process to unanticipated conditions can be achieved by adequate monitoring of various operational parameters. This paper reviews the research that has been conducted over the last years. This review paper summarizes the developments in biogas design and operation, while highlighting the main factors that affect the efficiency of the anaerobic digestion process. The study’s outcomes revealed that the optimum operational values of the main parameters may vary from one biogas plant to another. Additionally, the negative conditions that should be avoided while operating a biogas plant were identified.

Abdominal pain is the most disabling symptom of inflammatory bowel diseases, but current treatments are limited, leading patients to seek alternatives such as cannabis. Cannabis contains over 100 cannabinoids which, unlike tetrahydrocannabinol, are biologically active compounds often without psychotropic effects (ie, nonpsychotropic cannabinoids [npCBs]). These npCBs have analgesic and anti-inflammatory properties and may show potentiating effects when administered in combination, referred to as the entourage effect. Here, we investigated the analgesic effects of cannabichromene, cannabidiol (CBD), cannabidivarin, and cannabigerol (CBG), individually and in combination, using the mouse model of dextran sulfate sodium colitis-induced visceral hypersensitivity (VHS). We then explored antinociceptive targets through patch-clamp electrophysiology on dorsal root ganglia neurons and recombinant channels. We found that a single injection of 10 mg/kg of either CBD or CBG reduced both VHS and c-Fos activation in the spinal dorsal horn. Moreover, a combination of npCBs consisting of 5 mg/kg CBD with 1 mg/kg of cannabichromene, cannabidivarin, and CBG-all at subtherapeutic dosages-reduced VHS, without altering colitis. Electrophysiological recordings revealed that the antinociceptive mixture of npCBs acts through voltage-gated sodium and calcium channels, particularly Cav2.2, but not Cav3.2 and Kv channels. These results suggest that CBD, CBG, and a mixture of npCBs given at subtherapeutic doses may be beneficial in managing VHS associated with inflammatory bowel disease. SIGNIFICANCE STATEMENT: Cannabis is increasingly used as an alternative treatment for managing pain associated with chronic conditions. Nonpsychotropic cannabinoids, such as cannabidiol, interact with ionotropic and voltage-gated ion channels. In our study, we demonstrated that cannabidiol, cannabigerol, and a combination of nonpsychotropic cannabinoids, administered at subtherapeutic doses, effectively alleviated visceral hypersensitivity associated with inflammatory bowel disease., Competing Interests: Conflict of interest None of the authors declare any conflicts of interest., (Crown Copyright © 2025. Published by Elsevier Inc. All rights reserved.)

Plastic pollution in aquatic ecosystems has become a critical global environmental challenge, threatening biodiversity, water quality, and human health. This study investigates macroplastics distribution and characterization in the highly polluted Klang River, Malaysia, and proposes a protocol to compute total macroplastic yield in the river basin. A total of 240 macroplastic items were collected over a 20-km stretch from the river mouth inland, with an average of 0.91 ± 0.80 g/item (dry weight). Scanning Electron Microscopy revealed that the macroplastics had weathered slowly in the environment, potentially breaking down into smaller microplastic particles. Biofilms and dead phytoplankton were observed on the plastic surfaces, suggesting that plastic debris may act as vectors for other pollutants. The study used SWAT modelling to simulate physical processes in the Klang River Basin and compute pollutant loads through a loading computation procedure. A macroplastic rating curve was created using river discharge, macroplastic loadings, and associate parameters to estimate plastic loading in the river. The fitted equation models macroplastic loading as a function of river discharge and width, expressed as: log(y) = 1.88216-7.36528log(x) - 4.00491log(x 2 ). Here, log(x) represents the ratio of river discharge to river width, while log(y) denotes macroplastic loading adjusted for sampler width and river width. Results indicated that macroplastic transport in the river system is linked to flow rates and sediment yield, which vary due to topographical factors, with an estimated macroplastics yield in the Klang River Basin of 11,600 kg/day. The findings suggest that a river-specific monitoring programs should be conducted to generate comprehensive datasets, integrating both macroplastics and microplastics abundance, which can be utilized for projecting plastic emissions from Malaysian rivers and comparing data with other river basins in the Southeast Asia., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sabiqah Tuan Anuar reports financial support was provided by National Water Research Institute of Malaysia. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Ltd.)

Recent evidence suggests that the gut microbiota can influence pain sensitivity, highlighting the potential for microbiota-targeted pain interventions. During early life, both the microbiota and nociceptors are fine-tuned and respond to environmental factors, however, little is known about how they interact with each other. Using germ-free and gnotobiotic models, we demonstrate that microbiota colonization controls nociceptor sensitivity, partly by modulating mast cell production of nerve growth factor (NGF). We report that germ-free mice respond less to thermal and capsaicin-induced stimulation, which correlates with reduced trafficking of TRPV1 to the cell membrane of nociceptors. In germ-free mice, mast cells express lower levels of NGF. Hyposensitivity to thermal and capsaicin-induced stimulation, reduced TRPV1 trafficking, and decreased NGF expression are reversed when mice are colonized at birth, but not when colonization occurs after weaning. Inhibition of mast cell degranulation and NGF signaling during the first weeks of life in colonized mice leads to a hyposensitive phenotype in adulthood, demonstrating a role for mast cells and NGF signaling in linking early life colonization with nociceptor sensitivity. These findings implicate the early life microbiota in shaping mast cell NGF production and nociceptor sensitivity later in life. SIGNIFICANCE STATEMENT: Nociceptors are specialized sensory neurons that detect and transduce painful stimuli. During the early postnatal period, nociceptors are influenced by sensory experiences and the environment. Our findings demonstrate that gut microbiota colonization is essential in setting the threshold of nociceptor responses to painful stimuli. We show that early-life bacterial colonization controls the production of nerve growth factor by mast cells, affecting our sensitivity to pain later in life. Our study highlights the potential for developing new pain treatments that target the gut microbiome., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: The frequency of multidrug-resistant Klebsiella pneumoniae (MDRKP) has dramatically increased worldwide in recent decades, posing an urgent threat to public health. The aim of this study was to assess the extent of K. pneumoniae in the Aseer region and explore the corresponding antimicrobial resistance profile over the last ten years. Materials and Methods: A record-based retrospective study was conducted in a tertiary hospital during the period of 2013 to 2022. The study targeted laboratory samples taken from patients admitted to the hospital and sent for K. pneumoniae culturing. We included only samples taken from the patient and confirmed by the lab. Data were extracted using a pre-structured data extraction sheet to avoid data-collection bias and confirm the inter-rater precision. Statistical Package for Social Sciences (SPSS) version 26 was employed for statistical analysis. All relationships were tested using Pearson X 2 test for categorical data or chi-square for linear trend for resistance rate over years. Results : We obtained 3921 samples of isolated K. pneumoniae out of 28,420 bacterial samples. The isolation rate began at 11.3% in 2013, decreased to 6.1% in 2016, and then increased to a peak of 16.3% in 2021, before slightly decreasing to 12.8% in 2022. In total, 23.7% of K. pneumoniae samples were identified in urine samples, 19% in sputum samples, 14% in wound samples, and 11.7% in blood samples. The overall antibiotic resistance rate of K. pneumoniae from 2013 to 2022 showed a significant increase, particularly during 2020 and 2021, before decreasing again in 2022. The resistance rate decreased from 22.2% in 2013 to 18.6% in 2016 and increased to 54.6% and 56.4% during 2020 and 2021, respectively ( p = 0.039) . Conclusions: We observed a significant shift in K. pneumoniae resistance for some antibiotics during the study period, highlighting the urgent need for enhanced antimicrobial stewardship and infection-control measures.

Carmoisine dye, a red azo food colorant commonly utilized to impart a red color to synthetic food products, is the subject of this study. Here, we present a novel reversed flow injection analysis with a chemiluminescence detection (FIA-CL) method employing a newly developed homemade flow cell to determine carmoisine dye. This developed method is based on the inhibition effect of the dye on the chemiluminescence light (CL) emission generated from a luminal-hypochlorite system, whereby the reduction in CL intensity correlates directly with the concentration of carmoisine dye. Investigations into various analytical parameters were conducted to enhance method efficiency and applicability. A linear calibration graph of 4.0 to 100.0 µg mL -1 was established (R² = 0.9993), with a detection limit of LOD = 2.93 µg mL -1 . Subsequent application of the proposed method to analyze gelatine dessert samples yielded results in reasonable agreement with those obtained using the reported HPLC method, as evidenced by student t-test and F-test analyses., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Infections of the lung cause observable sickness thought to be secondary to inflammation. Signs of sickness are crucial to alert others via behavioral-immune responses to limit contact with contagious individuals. Gram-negative bacteria produce exopolysaccharide (EPS) that provides microbial protection; however, the impact of EPS on sickness remains uncertain. Using genome-engineered Pseudomonas aeruginosa (P. aeruginosa) strains, we compared EPS-producers versus non-producers and a virulent Escherichia coli (E. coli) lung infection model in male and female mice. EPS-negative P. aeruginosa and virulent E. coli infection caused severe sickness, behavioral alterations, inflammation, and hypothermia mediated by TLR4 detection of the exposed lipopolysaccharide (LPS) in lung TRPV1 + sensory neurons. However, inflammation did not account for sickness. Stimulation of lung nociceptors induced acute stress responses in the paraventricular hypothalamic nuclei by activating corticotropin-releasing hormone neurons responsible for sickness behavior and hypothermia. Thus, EPS-producing biofilm pathogens evade initiating a lung-brain sensory neuronal response that results in sickness., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Inflammation and pain are intertwined responses to injury, infection, or chronic diseases. While acute inflammation is essential in determining pain resolution and opioid analgesia, maladaptive processes occurring during resolution can lead to the transition to chronic pain. Here we found that inflammation activates the cytosolic DNA-sensing protein stimulator of IFN genes (STING) in dorsal root ganglion nociceptors. Neuronal activation of STING promotes signaling through TANK-binding kinase 1 (TBK1) and triggers an IFN-β response that mediates pain resolution. Notably, we found that mice expressing a nociceptor-specific gain-of-function mutation in STING exhibited an IFN gene signature that reduced nociceptor excitability and inflammatory hyperalgesia through a KChIP1-Kv4.3 regulation. Our findings reveal a role of IFN-regulated genes and KChIP1 downstream of STING in the resolution of inflammatory pain.

Microplastics (MPs) with the size of 1 μm-5 mm are pollutants of great concern ubiquitously found in the environment. Existing efforts have found that most of the MPs present in the seas mainly originated from land via riverine inputs. Asian rivers are known to be among the top in microplastic emissions. However, field data are scarce, especially in Malaysia. This study presents the distribution and characteristics of MPs in the surface water of two major river basins of Malaysia, namely Langat River (West Coast/Straits of Malacca) and Kelantan River (East Coast/South China Sea). Water samples were collected at 21-22 locations in Kelantan and Langat rivers, covering the river, estuary and sea. MPs were physically classified based on sizes, shapes, colours and surface morphology (SEM-EDS). The average of 179.6 items/L and 1464.8 items/L of MPs had been quantified from Kelantan and Langat rivers, respectively. Fibre (91.90%) was highly recorded at Kelantan, compared to Langat whereby both fibre (59.21%) and fragment (38.87%) were prevalence. Anthropogenic activities and urbanised areas contribute to high microplastic abundance, especially in the Langat River. Micro-FTIR analysis identified 14 polymers in Kelantan River, whereas 20 polymers were found in Langat River. Polypropylene, polyethylene, polyethylene terephthalate, nylon, phenoxy resins, poly(methyl acrylate), poly(methyl methacrylate), polystyrene, polytetrafluoroethylene, polyurethane and rayon were discovered in both rivers, although only polyethylene was significant (>1 ppm) when further analysed using pyrolysis-GC/MS. Correlation analysis and multiple linear regression were used to explain the relationship between water quality and MP abundance, suggesting only turbidity was positively significant to the microplastic occurrence. This comprehensive study is first to suggest a full-scale monitoring protocol for MPs in Malaysian riverine system and is significant in understanding MPs abundance in correlation to in-situ environmental factors. Consequently, this will allow the right authorities to develop mitigation strategies to address riverine plastic pollution in major river basins in Malaysia and the South East Asia., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yusof Shuaib Ibrahim reports financial support was provided by National Water Research Institute of Malaysia (NAHRIM)., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Booster vaccination has been shown to reduce transmission and serious infection with COVID-19. This study examined the willingness to receive a COVID-19 booster vaccine and its associated factors among high-risk patients at Klinik Kesihatan Putrajaya Presint 9., Method: A cross-sectional study was conducted among patients aged >18 years attending Klinik Kesihatan Putrajaya Presint 9 with a high risk of contracting COVID-19 recruited via systematic random sampling. Data were collected using a self-administered questionnaire. A multiple logistic regression analysis was performed to identify the associated factors., Results: The response rate for this study was 97.4% (N=489). The median patient age was 55 years. Approximately 51.7% were men, and 90.4% were Malays. Approximately 81.2% were willing to receive a COVID-19 booster vaccine. The patients who perceived COVID-19 as a serious illness (Adjusted Odd Ratio, AOR=2.414), those who perceived COVID-19 booster vaccines as beneficial (AOR=7.796), those who disagreed that COVID-19 booster vaccines have many side effects (AOR=3.266), those who had no doubt about the content of COVID-19 vaccines (AOR=2.649) and those who were employed (AOR=2.559) and retired (AOR=2.937) were more likely to be willing to receive a booster vaccine than those who were unemployed and those who did not have close friends or family members who contracted severe COVID-19 (AOR=2.006)., Conclusion: The majority of the participants were willing to receive a COVID-19 booster vaccine. Healthcare authorities should take initiatives to design targeted public intervention programmes to increase the willingness for COVID-19 booster vaccination., Competing Interests: All authors declare no conflicts of interest., (© Academy of Family Physicians of Malaysia.)

Social media addiction has become a serious public health concern due to its adverse psychological effects. Therefore, the purpose of this study was to assess the prevalence and determinants of social media addiction among medical students in Saudi Arabia. A cross-sectional study was designed. Participants ( n = 326) from King Khalid University in Saudi Arabia completed the sociodemographic information, patient health questionnaire-9 scale, and the generalized anxiety disorder-7 tool to measure explanatory variables. The Bergen social media addiction scale (BSMAS) was used to measure social media addiction. A multiple linear regression model was fitted to investigate the predictors of social media addiction. The prevalence of social media addiction among study participants was 55.2% (mean BSMAS score: 16.6). According to the adjusted linear regression, male students had higher social media addiction scores than their female counterparts (β = 4.52, p < 0.001). Students' academic performance was negatively associated with social media addiction scores. Moreover, students with symptoms of depression (β = 1.85, p = 0.005) or anxiety (β = 2.79, p = 0.003) had a higher BSMAS score compared to their counterparts. Further longitudinal studies are warranted to identify the causal factors of social media addiction, which would assist intervention initiatives by policymakers.

Membrane application is widespread in water filtration to remove natural organic matter (NOM), especially humic acid. However, there is a significant concern in membrane filtration, which is fouling, which will cause a reduction in the membrane life span, a high energy requirement, and a loss in product quality. Therefore, the effect of a TiO 2 /PES mixed matrix membrane on different concentrations of TiO 2 photocatalyst and different durations of UV irradiation was studied in removing humic acid to determine the anti-fouling and self-cleaning effects. The TiO 2 photocatalyst and TiO 2 /PES mixed matrix membrane synthesised were characterised using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy, X-ray powder diffraction (XRD), scanning electron microscope (SEM), contact angle, and porosity. The performances of TiO 2 /PES membranes of 0 wt.%, 1 wt.%, 3 wt.%, and 5 wt.% were evaluated via a cross-flow filtration system regarding anti-fouling and self-cleaning effects. After that, all the membranes were irradiated under UV for either 2, 10, or 20 min. A TiO 2 /PES mixed matrix membrane of 3 wt.% was proved to have the best anti-fouling and self-cleaning effect with improved hydrophilicity. The optimum duration for UV irradiation of the TiO 2 /PES mixed matrix membrane was 20 min. Furthermore, the fouling behaviour of mixed matrix membranes was fitted to the intermediate blocking model. Adding TiO 2 photocatalyst into the PES membrane enhanced the anti-fouling and self-cleaning properties.

Despite the government's policies and objectives, Malaysia lags behind in sustainable waste management techniques, particularly recycling. Bins should be located conveniently to encourage recycling and reduce waste. The current model of bin location-allocation is mostly determined by distance. However, it has been identified that previous studies excluded an important factor: litter pattern identification. Litter pattern is important to identify waste generation hotspots and litter distribution. Thus, we proposed the within cluster pattern identification (WCPI) approach to optimize the recycle point distribution. WCPI gathers the information on litter distribution using geotagged images and analyses the pattern distribution. The optimal location for recycle bin can be identified by incorporating k -means clustering to the pattern distribution. Since k -means faces the non-deterministic polynomial-time-hard challenge of selecting the ideal cluster and cluster centre, WCPI used the total within-cluster sum of square on top of k -means clustering. The proposed location by WCPI is validated in terms of accessibility and suitability. Furthermore, this study provides further analysis of carbon footprint that can be reduced by simulating the data from geotagged images. The results show that 10,323.55 kg of carbon emission can be reduced if the litter is sent for recycling. Thus, we believe that locating bins at an optimal location will embark on consumer motivation to dispose of recycled waste, reduce litter and lessen the carbon footprint. At the same time, these efforts could transform Malaysia into a clean and sustainable nation that aims to achieve Agenda 2030.

Microbial-based fertilizer has been widely used as a healthier and better alternative to agrochemical products. However, the effects of biofertilizers on the rhizospheric microbiota has rarely been investigated. Thus, the aim of this study was to investigate the effects of symbiotic fungus Trichoderma asperellum SL2-based inoculant on the soil bacterial population through next generation sequencing using a metabarcoding approach. The treatment plots were treated with T. asperellum SL2 spore suspension, while the control plots were treated with sterilized distilled water. The results showed similar bacterial microbiome profiles in the soil of control and T. asperellum SL2-treated plots. In conclusion, the application of the T. asperellum SL2 inoculant had not exerted a negative impact towards the bacterial population as similar observation was reflected in control plots. Nonetheless, future research should be conducted to investigate the effects of repeated application of T. asperellum SL2 over a longer period on the rice microbiota communities., (© 2022 The Society for Applied Microbiology.)

Hazardous micropollutants (MPs) such as pharmaceutically active compounds (PhACs), pesticides and personal care products (PCPs) have emerged as a critical concern nowadays for acquiring clean and safe water resources. In the last few decades, innumerable water treatment methods involving biodegradation, adsorption and advanced oxidation process have been utilized for the removal of MPs. Of these methods, membrane technology has proven to be a promising technique for the removal of MPs due to its sustainability, high efficiency and cost-effectiveness. Herein, the aim of this article is to provide a comprehensive review regarding the MPs rejection mechanisms of reverse osmosis (RO) and nanofiltration (NF) membranes after incorporation of nanomaterials and also surface modification atop the PA layer. Size exclusion, adsorption and electrostatic charge interaction mechanisms play important roles in governing the MP removal rate. In addition, this review also discusses the state-of-the-art research on the surface modification of thin film composite (TFC) membrane and nanomaterials-incorporated thin film nanocomposite (TFN) membrane in enhancing MPs removal performance. It is hoped that this review can provide insights in modifying the physicochemical properties of NF and RO membranes to achieve better performance in water treatment process, particularly for the removal of emerging hazardous substances., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This paper presents a comprehensive study of the performance of a newly developed titania nanotube incorporated RO membrane for endocrine-disrupting compound (EDC) removal at a low concentration. EDCs are known as an emerging contaminant, and if these pollutants are not properly removed, they can enter the water cycle and reach the water supply for residential use, causing harm to human health. Reverse osmosis (RO) has been known as a promising technology to remove EDCs. However, there is a lack of consensus on their performance, especially on the feed concentrations of EDC that vary from one source to another. In this study, polyamide thin-film composite (PA TFC) membrane was incorporated with one-dimensional titania nanotube (TNT) to mitigate trade-off between water permeability and solute rejection of EDC. The characterization indicated that the membrane surface hydrophilicity has been greatly increased with the presence of TNT. Using bisphenol A (BPA) and caffeine as model EDC, the removal efficiencies of the pristine TFC and thin-film nanocomposite (TFN) membranes were evaluated. Compared to TFC membrane, the membrane modified with 0.01% of TNT exhibited improved permeability of 50% and 49% for BPA and caffeine, respectively. A satisfactory BPA rejection of 89.05% and a caffeine rejection of 97.89% were achieved by the TNT incorporated TFN membranes. Furthermore, the greater hydrophilicity and smoother surface of 0.01 TFN membrane led to lower membrane fouling tendency under long-term filtration.

Alexithymia is a condition in which a person is unable to explain his/her emotions, bodily sensations, or discuss sentiments. This study aims to determine the prevalence of alexithymia and its relationships with socio-demographics and depression among medical students. A cross-sectional survey was conducted among medical students at King Khalid University (KKU), Saudi Arabia. A stratified random sampling technique was utilized for data collection using the Toronto Alexithymia Scale (TAS-20) and the Patient Health Questionnaire-9 (PHQ-9). A multiple logistic regression model was used to identify the factors associated with alexithymia. A total of 333 students participated in this study, almost two-thirds (64.6%) were from clinical years, and 51.4% were females. The prevalence of alexithymia and depression was 47.4% and 88.9%, respectively. Regression analysis showed females had a doubled risk (OR = 2.09), and students with high-income status showed less probability of having alexithymia (OR = 0.39), whereas people with chronic health problems showed a doubled risk for alexithymia (OR = 2.04). Moreover, depression was significantly associated with alexithymia (OR = 1.91). Our study revealed that the prevalence of alexithymia was high along with depression among studied samples. This raises attention towards finding measures to reduce it for the better performance of students and to avoid psychological problems in the future.

The anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase known for its oncogenic potential that is involved in the development of the peripheral and central nervous system. ALK receptor ligands ALKAL1 and ALKAL2 were recently found to promote neuronal differentiation and survival. Here, we show that inflammation or injury enhanced ALKAL2 expression in a subset of TRPV1+ sensory neurons. Notably, ALKAL2 was particularly enriched in both mouse and human peptidergic nociceptors, yet weakly expressed in nonpeptidergic, large-diameter myelinated neurons or in the brain. Using a coculture expression system, we found that nociceptors exposed to ALKAL2 exhibited heightened excitability and neurite outgrowth. Intraplantar CFA or intrathecal infusion of recombinant ALKAL2 led to ALK phosphorylation in the lumbar dorsal horn of the spinal cord. Finally, depletion of ALKAL2 in dorsal root ganglia or blocking ALK with clinically available compounds crizotinib or lorlatinib reversed thermal hyperalgesia and mechanical allodynia induced by inflammation or nerve injury, respectively. Overall, our work uncovers the ALKAL2/ALK signaling axis as a central regulator of nociceptor-induced sensitization. We propose that clinically approved ALK inhibitors used for non-small cell lung cancer and neuroblastomas could be repurposed to treat persistent pain conditions.

Background & Aims: Chronic abdominal pain is a common symptom of inflammatory bowel diseases (IBDs). Peripheral and central mechanisms contribute to the transition from acute to chronic pain during active disease and clinical remission. Lower mechanical threshold and hyperexcitability of visceral afferents induce gliosis in central pain circuits, leading to persistent visceral hypersensitivity (VHS). In the spinal cord, microglia, the immune sentinels of the central nervous system, undergo activation in multiple models of VHS. Here, we investigated the mechanisms of microglia activation to identify centrally acting analgesics for chronic IBD pain., Methods: Using Designer Receptors Exclusively Activated by Designer Drugs (DREADD) expressed in transient receptor potential vanilloid member 1-expressing visceral neurons that sense colonic inflammation, we tested whether neuronal activity was indispensable to control microglia activation and VHS. We then investigated the neuron-microglia signaling system involved in visceral pain chronification., Results: We found that chemogenetic inhibition of transient receptor potential vanilloid member 1 + visceral afferents prevents microglial activation in the spinal cord and subsequent VHS in colitis mice. In contrast, chemogenetic activation, in the absence of colitis, enhanced microglial activation associated with VHS. We identified a purinergic signaling mechanism mediated by neuronal adenosine triphosphate (ATP) and microglial P2Y12 receptor, triggering VHS in colitis. Inhibition of P2RY12 prevented microglial reactivity and chronic VHS post-colitis., Conclusions: Overall, these data provide novel insights into the central mechanisms of chronic visceral pain and suggest that targeting microglial P2RY12 signaling could be harnessed to relieve pain in patients with IBD who are in remission., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Hospital admissions and surgical operations commonly trigger anxiety in young children. Despite employing numerous support measures in our hospital, such as a pre-operative play room, the encouragement of parental companionship during induction of anaesthesia and distraction therapy, allaying the anxiety of our young surgical patients remains a challenge., Objectives: To evaluate the effectiveness of a Home-Initiated-Programme-to-Prepare-for-Operation (HIPPO) on emotional manifestation and anxiety in children undergoing surgery., Design, Setting and Patients: One hundred and thirty children were randomly assigned to either control or intervention group between February 2018 and April 2019 in a tertiary paediatric hospital in Singapore., Intervention: In addition to our standard pre-operative workflow, the intervention group received an additional home preparation kit consisting of an animated video on preoperative preparation and age-specific preoperative preparation activity sheets., Main Outcome Measures: The primary outcome was the Children's Emotional Manifestation Scale score to evaluate behaviour and emotion in the children before and during induction of anaesthesia. Secondary outcomes evaluated anxiety levels in parents and children, the child's behaviour and degree of co-operation using the State-Trait Anxiety Inventory scores, State-Trait Anxiety Inventory Children scores, the Induction Compliance Checklist scores, the Visual Analogue Scale scores for anxiety and the feedback questionnaire., Results: The difference between the Children's Emotional Manifestation Scale score in control and intervention groups was not statistically significant. A promising difference was however observed in one of the secondary outcomes where the state-State-Trait Anxiety Inventory Children scores of 7 to 10-year olds in the intervention group almost reached significance; P = 0.067., Conclusion: Despite being a child-friendly, easily accessible and affordable tool for patient education, HIPPO did not reduce anxiety experienced by children in the pre-operative waiting area or during induction of anaesthesia., Trial Registration: ClinicalTrials.gov, identifier: NCT04271553., (Copyright © 2020 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Microdialysis is a sampling technique first introduced in the late 1950s. Although this technique was originally designed to study endogenous compounds in animal brain, it is later modified to be used in other organs. Additionally, microdialysis is not only able to collect unbound concentration of compounds from tissue sites; this technique can also be used to deliver exogenous compounds to a designated area. Due to its versatility, microdialysis technique is widely employed in a number of areas, including biomedical research. However, for most in vivo studies, the concentration of substance obtained directly from the microdialysis technique does not accurately describe the concentration of the substance on-site. In order to relate the results collected from microdialysis to the actual in vivo condition, a calibration method is required. To date, various microdialysis calibration methods have been reported, with each method being capable to provide valuable insights of the technique itself and its applications. This paper aims to provide a critical review on various calibration methods used in microdialysis applications, inclusive of a detailed description of the microdialysis technique itself to start with. It is expected that this article shall review in detail, the various calibration methods employed, present examples of work related to each calibration method including clinical efforts, plus the advantages and disadvantages of each of the methods.

CD137 is expressed on activated T cells and NK cells, among others, and is a potent co-stimulator of antitumor immune responses. CD137 ligand (CD137L) is expressed by antigen presenting cells (APC), and CD137L reverse signaling into APC enhances their activity. CD137-CD137L interactions as main driver of type 1, cell-mediated immune responses explains the puzzling observation that CD137 agonists which enhance antitumor immune responses also ameliorate autoimmune diseases. Upon co-stimulation by CD137, Th1 CD4 + T cells together with Tc1 CD8 + T cells and NK cells inhibit other T cell subsets, thereby promoting antitumor responses and mitigating non-type 1 auto-immune diseases.

New experimental evidence shows that hollow fibre membrane bioreactor (HFMB) may be applied to grow bulky bone tissues which may then be implanted into patients to repair skeletal defects. To design effective bone tissue engineering protocols, it is necessary to determine the quantitative relationships between the cell environment and tissue behaviour in HFMBs and their relationship with nutrient supply. It is also necessary to determine under what conditions nutritional limitations may occur and, hence, may cause cell death. These require that the appropriate bioreactor conditions for generating neotissues, and the nutrient transfer behaviour and chemical reaction during cell growth and extracellular matrix formation are studied thoroughly. In this paper, we aim to use an existing mathematical framework to analyse the influence of various relevant parameters on nutrient supply for bone tissue growth in HFMB. We adopt the well-known Krogh cylinder approximation of the HFMB. The model parameters (e.g., cell metabolic rates) and operating conditions for the mathematical model have been obtained from, or correspond to, in-house experiments with the exception of a few variables which have been taken from the literature. The framework is then used to study oxygen and glucose transport behaviour in the HFMB. Influence of a number of important process parameters, e.g., reaction kinetics, cell density, inlet concentration of nutrients, etc, on the nutrient distributions have been systematically analysed. The work presented in this paper provides insights on unfavourable system designs and specifications which may be avoided to prevent mass transfer limitations for growing bone tissues in HFMB.