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A sequential approach of alkali enzymatic extraction of dietary fiber from rice bran: Effects on structural, thermal, crystalline properties, and food application
Shaikh JR, Chakraborty S, Odaneth A and Annapure US
Rice bran is abundant in dietary fiber and is often referred to as the seventh nutrient, recognized for its numerous health benefits. The objective of the current study is to investigate the extraction of both soluble and insoluble dietary fiber from defatted rice bran (DRB) using an alkali-enzymatic treatment through response surface methodology. The independent variables like substrate percentage (5-30 %), enzyme concentration (1-50 µL/g), and treatment time (2-12 h) and dependent variables were the yield of soluble and insoluble DF. The highest extraction yield was observed with alkali enzyme concentration (50 µL/g) treatment, resulting in 2 % SDF and 59.5 % IDF at 24 h of extraction. The results indicate that cellulase-AC enzyme aids in the hydrolysis of higher polysaccharides, leading to structural alterations in DRB and an increase in DF yield. Furthermore, the disruption of intra-molecular hydrogen bonding between oligosaccharides and the starch matrix helps to increase in DF yield, was also confirmed through FTIR and SEM. The extracted DF soluble and insoluble was then used to develop rice porridge. Sensory evaluation using fuzzy logic analysis reported the highest scores for samples containing 0.5 % insoluble DF and 1.25 % soluble DF.
Mild alkalinity preheating treatment regulates the heat and ionic strength co-tolerance of whey protein aggregates
Zhang R, Zhang J, Zou B, Ren C, Na X, Xu X, Du M, Zhu B and Wu C
A major obstacle to the use of whey protein in protein-enriched sports beverages is the heat-induced gelation of the protein in the presence of salt. In this study, whey protein soluble aggregates (WPSAs) with high tolerance to NaCl and heat were successfully generated by preheating whey protein isolate (WPI) at a low concentration (1 % w/v) and pH 8.5. The suspension of WPSAs (5 % w/v) with 100 mM NaCl maintained clarity, transparency, and good flowability even after 30 min of heating at 100 °C. However, suspensions prepared by untreated WPI turned into milky white gels. WPSAs had a reduced Zeta potential at pH 7 compared to WPI, making them more resistant to the electrostatic screening caused by NaCl. Additionally, WPSAs exhibited reduced sensitivity to heat treatment due to a more compact structure achieved through preheating modification. In light of these findings, a straightforward and effective method was presented for regulating the heat and ionic strength tolerance of whey protein aggregates.
Circular RNAs mediate the regulation of maternal placental nutrient transport and fetal development by sugar-sweetened beverages
He T, Yuan Z, Chen Q, Luo J, Mao J, Yang Y, Cao K and Yang Z
Epidemiological and experimental studies have demonstrated a strong association between maternal diet and fetal birth weight, obesity, and metabolic syndrome. We investigated the pathways and modes of action of circular RNAs (circRNAs) that mediate the regulation of maternal reproductive performance and fetal development by sugar-sweetened beverages (20 % sucrose water, SSBs) using C57BL/6J mice as a model. Results showed that SSBs significantly increased the reproductive performance (P<0.05), body weight (P<0.01), fetal birth weight (P<0.05), placental weight (P<0.01), and the expression of nutrient transporter genes in the placenta and fetal liver (P<0.05), mainly by accelerating the maternal energy metabolism during pregnancy. However, maternal serum biochemical indices, antioxidant indices, and pathological damage to the liver and placenta predicted that the mother would be at greater health risks during this period. Moreover, transcriptomics results indicated that the differentially expressed (DE) circRNAs in the placenta regulate the maternal multiple metabolic pathways and the placental nutrient transport efficiency by sponging miRNAs and forming growth factors and proteins, ultimately improving the maternal reproductive performance. In addition, we verified the reliability of the sequencing results using reverse transcription polymerase chain reaction and identified the possibility of DE circRNAs binding to nutrient transporter genes using targeting relationship prediction. Finally, we constructed a correlation network that regulates maternal placental nutrient transport based on DE circRNAs, targeted miRNAs and nutrient transport-related genes. This study will provide scientific dietary guidance for pregnant women and new research ideas for preventing and treating pregnancy complications.
Oxygen and air cold plasma for the inactivation of Bacillus cereus in low-water activity soy powder
Teresa Fernández-Felipe M, Inés Valdez-Narváez M, Martinez A and Rodrigo D
Cold plasma (CP) technology is a promising alternative to thermal treatments for the microbial decontamination of foods with low-water activity. The aim of this work is study the application of low-pressure CP (0.35 mbar) for the inactivation of Bacillus cereus in a soybean powder matrix using O₂ and synthetic air as ionizing gases. The parameters tested were an input power of 100, 200 and 300 W and an exposure time of 10 to 30 min. The excited reactive species formed were monitored by optical emission spectroscopy, and survival data were analyzed using the Weibull mathematical model. Treatments with both gases were effective in inactivating B. cereus. Air plasma resulted in a maximum 3.71-log reduction in bacterial counts at 300 W and 30 min, while O plasma showed the strongest inactivation ability, achieving levels higher than 5 log cycles at 300 W and > 25 min. This is likely due to the strong antimicrobial activity of oxygen-derived radicals together with carbon monoxide as an oxidation by-product. In addition, the Weibull distribution function accurately modeled the inactivation of B. cereus. Cold plasma technology is a promising approach for the decontamination of bacteria in low-water activity foods.
Tracking the changes and bioaccessibility of phenolic compounds of sorghum grains (Sorghum bicolor (L.) Moench) upon germination and seedling growth by UHPLC-QTOF-MS/MS
D'Almeida CTDS, Abdelbost L, Mameri H and Ferreira MSL
In this study, phenolic profile/content was analyzed by high-resolution untargeted metabolomics after short germination (72 h) and seedling growth (144 h), using three sorghum genotypes varying in tannin content (IS 29569, Macia and IS 30400). In vitro antioxidant capacity and phenolic bioaccessibility were determined by microplate-based and INFOGEST methods, respectively. A total of 58 % annotated compounds were found in all genotypes; and phenolic acids and flavonoids represent more than 80 % of sorghum total abundance. PCA analysis showed higher phenolic variability in germination times (72 %) than genotypes (51 %). Germination reduced total ion abundance (-7 %) and free:bound phenolic compounds ratio (2.4-1.1), but antioxidant capacity remained constant. These results indicate the cell matrix-phenolic decomplexation, with the free compounds were quickly consumed after radicle emergence. Germination increased phenolic bioaccessibility (mainly in oral phase) but reduces flavonoids contents in gastric/intestinal digestion steps. This work can stimulate seed germination as a viable option for sorghum-based foods development, with improved nutritional and bioactive properties.
Global analysis of spatio-temporal variation in mineral nutritional quality of pepper (Capsicum spp.) fruit and its regulatory variables: A meta-analysis
Zhou CX, Zhang W, Yu BG, Yang HF, Zhao QY, Wang Y, Sun K, Lakshmanan P, Chen XP and Zou CQ
Pepper (Capsicum spp.) is an important fruit vegetable worldwide, and it is a rich dietary source of minerals for human being. Yet, the spatio-temporal distribution of pepper fruit mineral composition and the factors influencing such variations at global scale remain unknown. A global meta-analysis of 140 publications providing 649, 562, 690, 811 datapoints was conducted to quantify and evaluate the nutritional quality, comprising potassium (K), magnesium (Mg), iron (Fe) and zinc (Zn), of pepper fruits and its influencing variables. The analysis showed that the global average of K, Mg, Fe and Zn content in pepper fruits was 20-25 g kg, 1-1.5 g kg, 80-100 mg kg, and 20-40 mg kg, respectively. There had been a downward trend in pepper fruit nutritional quality over the last decade, especially for Fe and Zn. And, the concentration of all these four nutrients were at lower levels in less developed regions, especially in Africa. Our results showed that the vegetable "green pepper" contains more K, Mg, Fe and Zn than the "hot pepper" used as spice. The concentration of K, Mg, Fe and Zn were increased with fruit yield but that of Fe and Zn were decreased with increase in single fruit weight. Nutritional quality was optimal at mean annual temperature of 10 ℃ - 20 ℃, and was adversely affected when mean annual precipitation was < 500 mm. Pepper fruits produced at pH 6.5-7.5 had higher fruit K concentration while acidic soils (pH<6.5) favored higher Fe and Zn concentrations. The higher soil organic matter (SOM) generally improved the nutritional quality of the pepper. Our results suggest that systematic selection of superior varieties and soil amelioration (adjusting pH and SOM) of the soil-crop system are needed to achieve higher nutritional quality of pepper fruit.
Multiscale modeling of solid starch-based foods digestion in the intestinal tract for dietary property-based glycemic prediction
Qin Y, Xiao J, Yu A and Dong Chen X
The digestion of starch-based foods in the intestinal tract is important for human health. Modeling the details enhances fundamental understanding and glycemic prediction accuracy. It is, however, a challenge to take granular properties into account. A multiscale digestion model has been proposed to characterize mass transfer and hydrolysis reaction at both the intestine and particle scales, seamlessly integrating inter-scale mass exchange. A specific grid scheme was formulated for the shrinkage and transport of the particle computational domain. By incorporating additional glycemic-related processes, e.g., intestinal absorption, a dietary property-based glycemic prediction system has been developed. Its effectiveness was validated based on a human tolerance experiment of cooked rice particles. The model-based investigation comprehensively reveals the impact of initial size on digestion behavior, specifically in terms of enzyme distribution and particle evolution. This work also demonstrates the significance of modeling both particle-scale diffusion and intestine-scale transport, a combination not previously explored. The results indicate that ignoring the former mechanism leads to an overestimation of the glycemic peak by at least 50.8%, while ignoring the latter results in an underestimation of 16.3%.
Pore shape matters - In-situ investigation of freeze-drying kinetics by 4D XCT methods
Gruber S, Greiner J, Eppink A, Thomik M, Coppens F, Vorhauer-Huget N, Tsotsas E and Foerst P
Freeze-drying is a commonly employed method in the food industry to extend shelf life of products. However, this process remains time and energy consuming. While higher shelf temperatures accelerate the process, they also pose the risk of product damage. The microstructure of the product, influencing heat and mass transport, is a critical factor. This study aims to understand the impact of 3-dimensional (3D) structural parameters (pore size, shape and orientation) on local primary freeze-drying kinetics. Freeze-drying experiments were conducted with maltodextrin solutions (c = 0.05, c = 0.15 and c = 0.3 w/w) at different shelf temperatures (T = -11, T = -15 and T = -33 °C) with the use of a freeze-drying stage that allows in-situ visualization of the process inside a 4D-X-Ray computed tomography (XCT). The findings show the importance of understanding the microstructure in detail to optimize the sublimation time during the freeze-drying process. It is shown that for longitudinal pores, the orientation is a crucial parameter.
Evaluating intestinal absorption of peptide Met-Lys-Pro in casein hydrolysate using Caco-2 and human iPS cell-derived small intestinal epithelial cells
Yago T, Yuda N, Tanaka M, Iwao T and Matsunaga T
High blood pressure is a major risk factor for cardiovascular disease. Our previous study confirmed that daily intake of casein hydrolysate that contained Met-Lys-Pro (MKP) can safely lower mildly elevated blood pressure. The present study aimed to evaluate the intestinal absorption differences between peptide MKP as a casein hydrolysate and synthetic MKP alone using Caco-2 cells and human iPS cell-derived small intestinal epithelial cells (hiSIECs). MKP was transported intact through Caco-2 cells and hiSIECs with permeability coefficient (P) values of 0.57 ± 0.14 × 10 and 1.03 ± 0.44 × 10 cm/s, respectively. This difference in P suggests differences in the tight junction strength and peptidase activity of each cell. Moreover, the transepithelial transport and residual ratio of intact MKP after adding casein hydrolysate containing MKP was significantly higher than that after adding synthetic MKP alone, suggesting that other peptides in casein hydrolysate suppressed MKP degradation and increased its transport. These findings suggest that hiSIECs could be useful for predicting the human intestinal absorption of bioactive peptides; ingesting MKP as a casein hydrolysate may also improve MKP bioavailability.
Insight into the changes in active metabolite profiles of noni (Morinda citrifolia L.) fruit subjected to different drying treatments
Su C, Kang J, Zhang L, Liu S and Li C
Noni fruit is renowned for its abundance of bioactive compounds. Drying is an important method for processing functional products derived from noni. However, limited information exists on how drying methods affect the active metabolite profiles of noni fruit. This study investigated the impact of four common drying methods, including hot-air drying (HAD), vacuum freeze drying (VFD), microwave drying (MWD), and far infrared drying (FID), on the physicochemical indexes, bioactive components, and functional properties of dried noni fruit slices using targeted and untargeted metabonomics analysis. The results showed significant variations in appearance, water migration, and microstructure of dried noni fruit slices subjected to the four drying methods. VFD treatment yielded better dried noni fruit products when compared to other drying methods. The superiority of VFD treatment was due to its uniform stratification, reduced collapse, better retention of bioactive components and antioxidants, and higher enzyme inhibitory rates. These findings suggest that VFD method is ideal for obtaining premium bioactive profiles and maintaining the biological activity of noni fruit.
Exploring volatile compounds and microbial dynamics: Kluyveromyces marxianus and Hanseniaspora opuntiae reduce Forastero cocoa fermentation time
Coria-Hinojosa LM, Velásquez-Reyes D, Alcázar-Valle M, Kirchmayr MR, Calva-Estrada S, Gschaedler A, Mojica L and Lugo E
Traditional cocoa bean fermentation is a spontaneous process and can result in heterogeneous sensory quality. For this reason, yeast-integrated starter cultures may be an option for creating consistent organoleptic profiles. This study proposes the mixture of Hanseniaspora opuntiae and Kluyveromyces marxianus (from non-cocoa fermentation) as starter culture candidates. The microorganisms and volatile compounds were analyzed during the cocoa fermentation process, and the most abundant were correlated with predominant microorganisms. Results showed that Kluyveromyces marxianus, isolated from mezcal fermentation, was identified as the dominant yeast by high-throughput DNA sequencing. A total of 63 volatile compounds identified by HS-SPME-GC-MS were correlated with the more abundant bacteria and yeast using Principal Component Analysis and Agglomerative Hierarchical Clustering. This study demonstrates that yeasts from other fermentative processes can be used as starter cultures in cocoa fermentation and lead to the formation of more aromatic esters, decrease the acetic acid content.
Three-dimensional mass transfer modeling and phenolic chemistry exploration for ultrasound-assisted and microwave drying of goji berry
Zhu R, Ma X, Li D, Han Y, Manickam S, Jiao Y, Flores EMM and Tao Y
Herein, goji berries were pretreated with sodium carbonate (NaCO) and then dried via ultrasound-assisted air drying or microwave drying. Water migration and phenolic chemistry of goji berries were studied under drying. A three-dimensional ellipsoid water transport model, accounting for porosity and temperature fluctuations, was established to explore the intricacies of the drying mechanism. Generally, microwave drying promoted interior water transport compared to ultrasound drying. Among all the drying methods, microwave drying at 240 W (MW-240 W) exhibited the highest D (from 7.34 × 10 to 9.61 × 10 m/s) and k (6.78 × 10 m/s) values. The goji berries received a considerably high water content gradient between its surface and center within the first 2 s of all the drying treatments. Microwave drying diminished the water content gradient earlier than air drying and ultrasound-assisted air drying treatments. Furthermore, most correlations observed among phenolics, oxidase activity, and cell wall pectin did not align with the established theories, highlighting the highly nonlinear nature of phenolic chemistry during goji berry drying. This study provides a three-dimensional model to study the mass transfer mechanism of goji berries and analyzes the evolution of polyphenols during the drying process.
Optimal Brassicaceae family microgreens from a phytochemical and sensory perspective
Bafumo RF, Alloggia FP, Ramirez DA, Maza MA, Fontana A, Moreno DA and Camargo AB
Microgreens, also called superfoods, emerge because of their high levels of nutrients, diverse flavour profiles, and sustainable cultivation methods, which make them culinary delights and valuable to a healthy and flavorful diet. The present study investigated Brassicaceae family microgreens, proposing a novel system (quality indices) that allows scoring among them. Fourteen Brassica microgreen species were morphological, phytochemical, and sensorial investigated. The morphological assessment revealed that radish microgreens exhibited the highest leaf area (p < 0.05), while red mizuna demonstrated superior yield. Cauliflower microgreens contained the highest concentrations of ascorbic acid (HPLC-DAD) and total phenolic content (p < 0.05). Phytochemical analysis using HPLC-MS/MS identified over 18 glucosinolates and phenolic compounds. Red mustard and red cabbage showed the highest glucosinolate content (p < 0.05). Watercress exhibited the highest phenolic compound content (p < 0.05), primarily flavonoids, while broccoli and radish contained the highest isothiocyanate levels. Cauliflower microgreens resulted in the most consumer-accepted variety. Appling quality indices scoring system identified radish, cauliflower, and broccoli microgreens as the most promising species. This study underscores the potential of Brassica microgreens as an excellent source of health-promoting phytochemicals with favorable market acceptance, providing valuable insights for both nutritional research and commercial applications.
"That Looks Like My Kitchen!" - Personalized context by usage frequency and familiarity influences consumer perception and liking of chicken nuggets in VR
Man K, Patterson JA and Simons CT
Restoring relevant context during consumer sensory testing using virtual reality (VR) technologies may facilitate evaluations reflective of real-world experiences, enabling reliable data collection to better predict product success. Prior research has applied the same consumption scenario to all participants without accounting for variations in individual consumption habits. Thus, a consumption scenario of low personal relevance can lead to misleading conclusions. This study aimed to investigate how personal relevance (usage frequency and similarity) of a consumption environment influences consumer perception and acceptance during product evaluations. Using a VR system, 63 consumers evaluated four commercial frozen chicken nuggets in three virtual environments one week apart: sensory booth, high-relevance kitchen, and low-relevance kitchen. Participants assessed the products virtually on overall liking, Check-All-That-Apply (CATA) on 20 attributes, and purchase intent. They also completed a virtual presence and engagement questionnaire after testing. Results found better product discrimination in both kitchen environments compared to the booth as demonstrated in more post-hoc statistical subgroups (p's < 0.05) on liking and purchase intent. Additionally, more significant product differences were found among CATA attributes in the kitchens. CATA penalty-lift analyses indicated that sensory attributes had more pronounced positive and negative impacts on liking in the high relevance kitchen, followed by the low relevance kitchen, and lastly the booth. Consumers were equally present and engaged during testing across conditions (p's > 0.05). Results suggest providing a personally relevant consumption environment via VR technologies for consumer testing generated more discriminating data that can improve the quality of consumer insights.
Research progress on detection of foodborne pathogens: The more rapid and accurate answer to food safety
Gao R, Liu X, Xiong Z, Wang G and Ai L
In recent years, foodborne diseases have posed a serious threat to human health, and rapid detection of foodborne pathogens is particularly crucial for the prevention and control of such diseases. This article offers a detailed overview of the development of detection techniques for foodborne pathogens, transitioning from traditional microbiological culture methods to the current array of techniques, including immunological, molecular biological, and biosensor-based methods. It summarizes the technical principles, advantages, disadvantages, and research progress of these diverse methods. Furthermore, the article demonstrates that the combination of different methods enhances the efficiency and accuracy of pathogens detection. Specifically, the article focuses on the application and advantages of combining CRISPR/Cas systems with other detection methods in the detection of foodborne pathogens. CRISPR/Cas systems, with their high specificity, sensitivity, and ease of operation, show great potential in the field of foodborne pathogens detection. When integrated with other detection techniques such as immunological detection techniques, molecular biology detection techniques, and biosensors, the accuracy and efficiency of detection can be further improved. By fully utilizing these tools, early detection and control of foodborne diseases can be achieved, enhancing public health and preventing disease outbreaks. This article serves as a valuable reference for exploring more convenient, accurate, and sensitive field detection methods for foodborne pathogens, promoting the application of rapid detection techniques, and ensuring food safety and human health.
Investigating biological mechanisms of colour changes in sustainable food systems: The role of Starmerella bacillaris in white wine colouration using a combination of genomic and biostatistics strategies
da Silva Duarte V, Treu L, Campanaro S, Fioravante Guerra A, Giacomini A, Mas A, Corich V and Lemos Junior WJF
This study explores the biological mechanisms behind colour changes in white wine fermentation using different strains of Starmerella bacillaris. We combined food engineering, genomics, machine learning, and physicochemical analyses to examine interactions between S. bacillaris and Saccharomyces cerevisiae. Significant differences in total polyphenol content were observed, with S. bacillaris fermentation yielding 6 % higher polyphenol content compared to S. cerevisiae EC1118. Genomic analysis identified 12 genes in S. bacillaris with high variant counts that could impact phenotypic properties related to wine color. Notably, SNP analysis revealed numerous missense and synonymous variants, as well as stop-gained and start-lost variants between PAS13 and FRI751, suggesting changes in metabolic pathways affecting pigment production. Besides that, high upstream gene variants in SSK1 and HIP1R indicated potential regulatory changes influencing gene expression. Fermentation trials revealed FRI751 consistently showed high antioxidant activity and polyphenol content (Total Polyphenol: 299.33 ± 3.51 mg GAE/L, DPPH: 1.09 ± 0.01 mmol TE/L, FRAP: 0.95 ± 0.02 mmol TE/L). PAS13 exhibited a balanced profile, while EC1118 had lower values, indicating moderate antioxidant activity. The Weibull model effectively captured nitrogen consumption dynamics, with EC1118 serving as a reliable benchmark. The scale parameter delta for EC1118 was 23.04 ± 2.63, indicating moderate variability in event times. These findings highlight S. bacillaris as a valuable component in sustainable winemaking, offering an alternative to chemical additives for maintaining wine quality and enhancing colours profiles. This study provides insights into the biotechnological and fermented food systems applications of yeast strains in improving food sustainability and supply chain, opening new avenues in food engineering and microbiology.
Electric fields as effective strategies for enhancing quality attributes of meat in cold chain logistics: A review
Lin H, Wu G, Hu X, Chisoro P, Yang C, Li Q, Blecker C, Li X and Zhang C
Meat quality (MQ) is unstable during cold chain logistics (CCL). Different technologies have been developed to enhance MQ during the CCL process, while most of them cannot cover all the links of the cold chain because of complex environment (especially transportation and distribution), compatibility issues, and their single effect. Electric fields (EFs) have been explored as a novel treatment for different food processing. The effects and potential advantages of EFs for biological cryopreservation have been reported in many publications and some commercial applications in CCL have been realized. However, there is still a lack of a systematic review on the effects of EFs on their quality attributes in meat and its applications in CCL. In this review, the potential mechanisms of EFs on meat physicochemical properties (heat and mass transfer and ice formation and melting) and MQ attributes during different CCL links (freezing, thawing, and refrigeration processes) were summarized. The current applications and limitations of EFs for cryopreserving meat were also discussed. Although high intensity EFs have some detrimental effects on the quality attributes in meat due to electroporation and electro-breakdown effect, EFs present good applicability opportunities in most CCL scenes that have been realized in some commercial applications. Future studies should focus on the biochemical reactions of meat to the different EFs parameters, and break the limitations on equipment, so as to make EFs techniques closer to usability in the production environment and realize cost-effective large-scale application of EFs on CCL.
Impact of heat treatment on the flavor stability of Longjing green tea beverages: Metabolomic insights and sensory correlations
Wang JQ, Tang BM, Gao Y, Chen JX, Wang F, Yin JF, Zeng L, Zhou WB and Xu YQ
The flavor stability of tea beverages during storage has long been a concern. The study aimed to explore the flavor stability of Longjing green tea beverage using accelerated heat treatment trials, addressing the shortage of lengthy storage trials. Sensory evaluations revealed changes in bitterness, umami, overall harmonization, astringency, and ripeness as treatment duration increased. Accompanied by a decrease in L-values, ΔE and an increase in a and b-values. Seventeen non-volatile metabolites and three volatile metabolites were identified differential among samples by metabolomics, with subsequent correlation analysis indicating associations between sensory attributes and specific metabolites. Umami was linked to epigallocatechin 3,5-digallate and alpha-D-glucopyranose, astringency was correlated with ellagic acid and 1-ethyl-1H-pyrrole. Ripeness showed associations with ellagic acid, 6,7-dihydroxycoumarin, heptanal, and benzaldehyde, and overall harmonization was linked to 6,7-dihydroxycoumarin, β-myrcene, α-terpineol, and heptanal. A series of verification tests confirmed the feasibility of accelerated heat treatment trials to replace traditional storage trials. These results offer valuable insights into unraveling the complex relationship between sensory and chemical profiles of green tea beverages.
Dynamics of microbiome and resistome in a poultry burger processing line
Merino N, Pagán E, Berdejo D, Worby CJ, Young M, Manson AL, Pagán R, Earl AM and García-Gonzalo D
Traditionally, surveillance programs for food products and food processing environments have focused on targeted pathogens and resistance genes. Recent advances in high throughput sequencing allow for more comprehensive and untargeted monitoring. This study assessed the microbiome and resistome in a poultry burger processing line using culturing techniques and whole metagenomic sequencing (WMS). Samples included meat, burgers, and expired burgers, and different work surfaces. Microbiome analysis revealed spoilage microorganisms as the main microbiota, with substantial shifts observed during the shelf-life period. Core microbiota of meat and burgers included Pseudomonas spp., Psychrobacter spp., Shewanella spp. and Brochothrix spp., while expired burgers were dominated by Latilactobacillus spp. and Leuconostoc spp. Cleaning and disinfection (C&D) procedures altered the microbial composition of work surfaces, which still harbored Hafnia spp. and Acinetobacter spp. after C&D. Resistome analysis showed a low overall abundance of resistance genes, suggesting that effective interventions during processing may mitigate their transmission. However, biocide resistance genes were frequently found, indicating potential biofilm formation or inefficient C&D protocols. This study demonstrates the utility of combining culturing techniques and WMS for comprehensive of the microbiome and resistome characterization in food processing lines.
Enzyme-esterified grape seed proanthocyanidin derivatives as novel lipid-lowering agents
Chen M, Ye S, Deng M, Zhang L and Yu S
Grape seed proanthocyanidin (GSP), as a natural antioxidant, has great potential to be developed into a lipid-lowering agent, but its low lipophilicity and stability greatly limit its application. In this study, an enzymatic esterification strategy was developed to introduce fatty acid chains into GSP, resulting in the successful synthesis of a series of new GSP derivatives. The results showed that up to 85% conversion of GSP and 35% TAG inhibition rate of GSP derivatives were achieved. The structures of GSP derivatives were identified by UPLC-MS/MS, and seven derivatives were confirmed as catechin-3'-O-laurate, epicatechin-3'-O-laurate, epicatechin gallate-3″,5″-di-O-laurate, epicatechin gallate-3',3″,5″-tri-O-laurate, procyanidin B1-3',3″-di-O-laurate, procyanidin B2-3',3″-di-O-laurate and procyanidin C1-3',3″,3‴-tri-O-laurate by NMR. GSP derivatives exhibited higher inhibitory effects on lipid accumulation, intracellular TAG and TC than parent GSP. These results indicate that GSP derivatives have potential as lipid-lowering agents for utilization in the food industry.
Exploration of the mechanism of temperature influence on bitter taste of theacrine by activating human bitter taste receptor hTAS2R14
Xie J, Wen H, Shi Y, Wei F, Jiang J, Luo L and Zeng L
Theacrine, a purine alkaloid derived from Camellia assamica var. kucha, has a distinct bitter taste. Our previous study found the lower recognition threshold of theacrine at 25 °C than 45 °C. This study aims to investigate the bitterness characterizations of theacrine at aforementioned temperatures and its taste perception mechanism. Sensory analysis exhibited higher bitterness intensity for theacrine at 25 °C than 45 °C. Subsequently, flow cytometry was performed to verify the above characterization at the cellular level. It revealed that theacrine could activated the bitter receptor hTAS2R14 and the calcium signal at 25 °C was higher than 45 °C. Ultimately, the interaction mechanism was studied by molecular dynamics simulations, indicating that the conformation of theacrine-hTAS2R14 had a higher binding capacity and better stability at 25 °C. Overall, temperature affected the binding of theacrine to the bitter receptor hTAS2R14, resulting in the stronger bitterness intensity of theacrine at 25 °C than 45 °C.
Mechanical pain sensitivity is associated with hippocampal structural integrity
Ayoub LJ, Honigman L, Barnett AJ, McAndrews MP and Moayedi M
Rodents and human studies indicate that the hippocampus, a brain region necessary for memory processing, responds to noxious stimuli. However, the hippocampus has yet to be considered a key brain region directly involved in the human pain experience. One approach to answer this question is to perform quantitative sensory testing on patients with hippocampal damage-ie, medial temporal lobe epilepsy. Some case studies and case series have performed such tests in a handful of patients with various types of epilepsy and have reported mixed results. Here, we aimed to determine whether mechanical pain sensitivity was altered in patients diagnosed with temporal lobe epilepsy. We first investigated whether mechanical pain sensitivity in patients with temporal lobe epilepsy differs from that of healthy individuals. Next, in patients with temporal lobe epilepsy, we evaluated whether the degree of pain sensitivity is associated with the degree of hippocampal integrity. Structural integrity was based on hippocampal volume, and functional integrity was based on verbal and visuospatial memory scores. Our findings show that patients with temporal lobe epilepsy have lower mechanical pain sensitivity than healthy individuals. Only left hippocampal volume was positively associated with mechanical pain sensitivity-the greater the hippocampal damage, the lower the sensitivity to mechanical pain. Hippocampal measures of functional integrity were not significantly associated with mechanical pain sensitivity, suggesting that the mechanisms of hippocampal pain processing may be different than its memory functions. Future studies are necessary to determine the mechanisms of pain processing in the hippocampus.
Psychiatrists' experiences of involuntary care in South Africa: dilemmas for practice in challenging contexts
Freeman AM, Asmal L and Swartz L
Providing for people with psychosocial conditions in crisis is a complex and controversial endeavour that has gained significant attention over the past decade. This increased focus is driven by global calls to reduce coercion, including by the United Nations Committee on the Rights of Persons with Disabilities, who interpret Article 12 of the United Nations Convention on the Rights of Persons with Disabilities in General Comment 1 to advocate for the replacement of substituted decision-making with supported decision-making. Psychiatrists occupy a central role in determining how to care for and respond to individuals with psychosocial conditions in crisis in the midst of these debates. They must protect the rights of people with psychosocial conditions in crisis and provide appropriate support within challenging and dynamic contexts. This responsibility includes promoting the autonomy of people with psychosocial condition while ensuring their long-term health, safety and well-being.In this study, we conducted a phenomenological analysis with a sample of nine psychiatrists in South Africa to explore their experiences with involuntary care and the complex dilemmas they face in delivering healthcare to individuals with mental health conditions. Our findings indicate that psychiatrists encounter significant challenges in preserving patient autonomy, particularly within the resource-limited context of South Africa. Pervasive stigma and insufficient support infrastructure complicate efforts to prioritise autonomy. At the same time, professionals must address the critical need to ensure the long-term safety and well-being of their patients. The absence of involuntary care can exacerbate a person's vulnerability to community stigma and inadequate community support, posing severe risks to their welfare. Balancing between protecting a person's autonomy and addressing the limitations of support structures creates a complex predicament for mental health professionals, often resulting in feelings of isolation and moral distress among psychiatrists.
Care coordination models for transition and long-term follow-up among childhood cancer survivors: a scoping review
Wong CL, Chan CWH, Zhang M, Cheung YT, Chow KM, Li CK, Li WHC, Brauer E and Chen Y
Childhood cancer survivors may experience complex health issues during transition and long-term follow-up (LTFU); therefore, high-quality healthcare is warranted. Care coordination is one of the essential concepts in advanced healthcare. Care coordination models vary among childhood cancer survivors in transition and LTFU. This study aimed to identify care coordination models for childhood cancer survivors in transition and LTFU and synthesise essential components of the models.
Automated explainable wavelet-based sleep scoring system for a population suspected with insomnia, apnea and periodic leg movement
Ingle M, Sharma M, Verma S, Sharma N, Bhurane A and Rajendra Acharya U
Sleep is an integral and vital component of human life, contributing significantly to overall health and well-being, but a considerable number of people worldwide experience sleep disorders. Sleep disorder diagnosis heavily depends on accurately classifying sleep stages. Traditionally, this classification has been performed manually by trained sleep technologists that visually inspect polysomnography records. However, in order to mitigate the labor-intensive nature of this process, automated approaches have been developed. These automated methods aim to streamline and facilitate sleep stage classification. This study aims to classify sleep stages in a dataset comprising subjects with insomnia, PLM, and sleep apnea. The dataset consists of PSG recordings from the multi-ethnic study of atherosclerosis (MESA) cohort of the national sleep research resource (NSRR), including 2056 subjects. Among these subjects, 130 have insomnia, 39 suffer from PLM, 156 have sleep apnea, and the remaining 1731 are classified as good sleepers. This study proposes an automated computerized technique to classify sleep stages, developing a machine-learning model with explainable artificial intelligence (XAI) capabilities using wavelet-based Hjorth parameters. An optimal biorthogonal wavelet filter bank (BOWFB) has been employed to extract subbands (SBs) from 30 seconds of electroencephalogram (EEG) epochs. Three EEG channels, namely: Fz_Cz, Cz_Oz, and C4_M1, are employed to yield an optimum outcome. The Hjorth parameters extracted from SBs were then fed to different machine learning algorithms. To gain an understanding of the model, in this study, we used SHAP (Shapley Additive explanations) method. For subjects suffering from the aforementioned diseases, the model utilized features derived from all channels and employed an ensembled bagged trees (EnBT) classifier. The highest accuracy of 86.8%, 87.3%, 85.0%, 84.5%, and 83.8% is obtained for the insomniac, PLM, apniac, good sleepers and complete datasets, respectively. Using these techniques and datasets, the study aims to enhance sleep stage classification accuracy and improve understanding of sleep disorders such as insomnia, PLM, and sleep apnea.
Accuracy tradeoffs between individual bone and joint-level statistical shape models of knee morphology
Fugit WJ, Aram LJ, Bayoglu R and Laz PJ
Statistical shape models (SSMs) are useful tools in evaluating variation in bony anatomy to assess pathology, plan surgical interventions, and inform the design of orthopaedic implants and instrumentation. Recently, by considering multiple bones spanning a joint or the whole lower extremity, SSMs can support studies investigating articular conformity and joint mechanics. The objective of this study was to assess tradeoffs in accuracy between SSMs of the femur or tibia individually versus a combined joint-level model. Three statistical shape models were developed (femur-only, tibia-only, and joint-level) for a training set of 179 total knee arthroplasty (TKA) patients with osteoarthritis representing both genders and several ethnicities. Bone geometries were segmented from preoperative CT scans, meshed with triangular elements, and registered to a template for each SSM. Principal component analysis was performed to determine modes of variation. The statistical shape models were compared using measures of compactness, accuracy, generalization, and specificity. The generalization evaluation, assessing the ability to describe an unseen instance in a leave-one-out analysis, showed that errors were consistently smaller for the individual femur and tibia SSMs than for the joint-level model. However, when additional modes were included in the joint-level model, the errors were comparable to the individual bone results, with minimal additional computational expense. When developing more complex SSMs at the joint, lower limb, or whole-body level, the use of an error threshold to inform the number of included modes, instead of 95 % of the variation explained, can help to ensure accurate representations of anatomy.
Cross-sectional study of determinants of undernutrition among children aged 6-36 months in Kabul, Afghanistan
Rezaee MT, Zakki SA, Haq IU, Rahimi N and Fayaz M
The current study aimed to find the distribution and factors associated with undernutrition among children aged 6-36 months in Kabul.
Geometric accuracy of low-dose CT scans for use in shoulder musculoskeletal research applications
Lawrence RL, Nicholson L, Lee ECS, Napier K, Zmistowski B and Rainbow MJ
Computed tomography (CT) imaging is frequently employed in a variety of musculoskeletal research applications. Although research studies often use imaging protocols developed for clinical applications, lower dose protocols are likely possible when the goal is to reconstruct 3D bone models. Our purpose was to describe the dose-accuracy trade-off between incrementally lower-dose CT scans and the geometric reconstruction accuracy of the humerus, scapula, and clavicle. Six shoulder specimens were acquired and scanned using 5 helical CT protocols: 1) 120 kVp, 450 mA (full-dose); 2) 120 kVp, 120 mA; 3) 120 kVp, 100 mA; 4) 100 kVp, 100 mA; 5) 80 kVp, 80 mA. Scans were segmented and reconstructed into 3D surface meshes. Geometric error was assessed by comparing the surfaces of the low-dose meshes to the full-dose (gold standard) mesh and was described using mean absolute error, bias, precision, and worst-case error. All low-dose protocols resulted in a >70 % reduction in the effective dose. Lower dose scans resulted in higher geometric errors; however, error magnitudes were generally <0.5 mm. These data suggest that the effective dose associated with CT imaging can be substantially reduced without a significant loss of geometric reconstruction accuracy.
Appendicolith classification: physical and chemical properties of appendicoliths in patients with CT diagnosed acute appendicitis - a prospective cohort study
Vanhatalo S, Mäkilä E, Hakanen AJ, Munukka E, Salonen J, Saarinen T, Grönroos J, Sippola S and Salminen P
Appendicoliths are associated with a more complicated course of acute appendicitis and failure of non-operative treatment. We aimed to update the appendicolith classification originally described in 1966 and to assess the association of appendicolith characteristics with appendicitis severity.
Transition from rehabilitation hospital to the National Disability Insurance Scheme (NDIS) for people with brain injury and spinal cord injury: a data linkage protocol
Guthrie SAJ, Alexander T, Tickle L, Winkler D and Walsh JE
Traumatic brain injury (TBI) and spinal cord injury (SCI) are both major contributors to permanent disability globally, with an estimated 27 million new cases of TBI and 0.93 million new cases of SCI globally in 2016. In Australia, the National Disability Insurance Scheme (NDIS) provides support to people with disability. Reports from the NDIS suggest that the cost of support for people with TBI and SCI has been increasing dramatically, and there is a lack of independent analysis of the drivers of these increases. This data linkage seeks to better understand the participant transition between rehabilitation hospitals and the NDIS and the correlation between functional independence in rehabilitation and resource allocation in the NDIS.
'': a qualitative study exploring the intersectional experiences of BAME LGBTQ+ medical students in the UK
Ly D and Chakrabarti R
The positive formation of professional identity is considered crucial in how medical students begin to feel and act as clinicians. Although, awareness of how Professional Identity Formation (PIF) may be affected among minoritised groups is increasing, understanding from an intersectional lens remains limited. The aim of this study was to explore the experiences of Black, Asian, Minoritised Ethnic (BAME) and Lesbian, Gay, Bisexual, Transgender, Queer (LGBTQ+) medical students in the undergraduate Bachelor of Medicine, Bachelor of Science programme.
Carpal tunnel syndrome and occupational hand exposures: a Danish nationwide cohort study
Tabatabaeifar S and Dalbøge A
The aim was to examine exposure-response relations between occupational hand exposures and carpal tunnel syndrome (CTS) and to compare the relation between surgery-treated and non-surgery-treated CTS. The secondary aim was to study sex-specific differences in exposure-response relations.
Application of smartphone-based infrared thermography devices for ocular surface thermal imaging
Zadorozhnyy O, Kustryn T, Nasinnyk I, Nevska A, Guzun O, Korol A and Pasyechnikova N
Infrared thermography (IRT) is a well-known imaging technique that provides a non-invasive displaying of the ocular surface temperature distribution. Currently, compact smartphone-based IRT devices, as well as special software for processing thermal images, have become available. The study aimed to determine the possible use of smartphone-based IRT devices for real-time ocular surface thermal imaging. This study involved 32 healthy individuals (64 eyes); 10 patients (10 eyes) with proliferative diabetic retinopathy (PDR) and absolute glaucoma; 10 patients (10 eyes) with PDR, who underwent vitreoretinal surgery. In all cases, simultaneous ocular surface IRT of both eyes was performed. In healthy individuals, the ocular surface temperature (OST) averaged 34.6 ± 0.8 °C and did not differ substantially between the paired eyes, in different age groups, and after pupil dilation. In our study, high intraocular pressure was accompanied by a decrease in OST in all cases. After vitreoretinal surgery in cases with confirmed subclinical inflammation, the OST was higher than the baseline and differed from that of the paired eye by more than 1.0 °C. These results highlight that smartphone-based IRT imaging could be useful for the non-invasive detection of OST asymmetry between paired eyes due to increased intraocular pressure or subclinical inflammation.
Combining robotics and functional electrical stimulation for assist-as-needed support of leg movements in stroke patients: A feasibility study
Rikhof CJH, Leerskov KS, Prange-Lasonder GB, Prinsen EC, Spaich EG, Dosen S, Struijk LNSA, Buurke JH and Rietman JS
Rehabilitation technology can be used to provide intensive training in the early phases after stroke. The current study aims to assess the feasibility of combining robotics and functional electrical stimulation (FES), with an assist-as-needed approach to support actively-initiated leg movements in (sub-)acute stroke patients.
Treating iron deficiency in patients with heart failure: what, why, when, how, where and who
Graham FJ, Guha K, Cleland JG and Kalra PR
For patients with heart failure and reduced or mildly reduced left ventricular ejection fraction, iron deficiency is common and associated with more severe symptoms, worse quality of life and an increased risk of hospitalisations and death. Iron deficiency can be swiftly, effectively and safely treated by administering intravenous iron, either as ferric carboxymaltose or ferric derisomaltose, which improves patient well-being and reduces the risk of hospitalisations including those for heart failure. However, the current definition of iron deficiency in heart failure has serious flaws. A serum ferritin <100 µg/L does not identify patients more likely to respond to intravenous iron. In contrast, patients with transferrin saturations <20%, most of whom are also anaemic, are more likely to have a beneficial response to intravenous iron. In this review, we summarise the available evidence for use of intravenous iron in heart failure and provide recommendations for targeted future research and practical considerations for the general cardiologist.
Low levels and determinants of appropriate complementary feeding practices among children aged 6-23 months from Tigray, Ethiopia: a community-based cross-sectional study
Mulugeta A, Abebe HT, Redae G, Gebremariam M, Abay M, Gebreyohannes D and Bazzano AN
Complementary feeding is considered appropriate when introduced timely at 6 months of age, and where it fulfils the minimum meal frequency, minimum dietary diversity and minimum acceptable diet. Sufficient evidence is available on the different individual indicators of appropriate complementary feeding.
Core outcome sets for trials of interventions to prevent and to treat multimorbidity in adults in low and middle-income countries: the COSMOS study
Vidyasagaran AL, Ayesha R, Boehnke JR, Kirkham J, Rose L, Hurst JR, Miranda JJ, Rana RZ, Vedanthan R, Faisal MR, Afaq S, Agarwal G, Aguilar-Salinas CA, Akinroye K, Akinyemi RO, Ali SR, Aman R, Anza-Ramirez C, Appuhamy KK, Baldew SS, Barbui C, Batista SRR, Caamaño MDC, Chowdhury AH, de Siqueira-Filha NT, Del Castillo Fernández D, Downey L, Flores-Flores O, García OP, García-Ulloa AC, Holt RI, Huque R, Kabukye JK, Kanan S, Khalid H, Koly KN, Kwashie JS, Levitt NS, Lopez-Jaramillo P, Mohan S, Muliyala KP, Naz Q, Odili AN, Oyeyemi AL, Pacheco-Barrios NV, Praveen D, Purgato M, Ronquillo D, Siddiqi K, Singh R, Tran PB, Tufail P, Uphoff EP, van Olmen J, Verhey R, Wright JM, Zafra-Tanaka JH, Zavala GA, Zhao YW, Siddiqi N and
The burden of multimorbidity is recognised increasingly in low- and middle-income countries (LMICs), creating a strong emphasis on the need for effective evidence-based interventions. Core outcome sets (COS) appropriate for the study of multimorbidity in LMICs do not presently exist. These are required to standardise reporting and contribute to a consistent and cohesive evidence-base to inform policy and practice. We describe the development of two COS for intervention trials aimed at preventing and treating multimorbidity in adults in LMICs.
Exploring the efficacy and safety of acupuncture versus sham acupuncture for diminished ovarian reserve: study protocol for a multicentre randomised controlled trial
Xiao Q, Wu Y, Su C, Yang J, Wang J, Pei L, Wang Y, Hu J, Chen L, Yang L, Li J, Li W, Gou M, Feng Y, Xu H and Fang Y
The therapeutic needs of women with diminished ovarian reserve (DOR), coupled with the increasing application of acupuncture in improving ovarian function, have highlighted the need to verify the efficacy and safety of acupuncture for DOR. This study aims to provide high-quality evidence by evaluating both ovarian reserve and in vitro fertilisation (IVF) outcomes.
Clinical relevance of aortic conduit and reservoir function
Assadi H, Sawh C, Spohr H, Nelthorpe F, Nair S, Hughes M, Ashman D, Ryding A, Matthews G, Li R, Grafton-Clarke C, Mehmood Z, Al-Mohammad A, Kasmai B, Vassiliou VS and Garg P
Aortic conduit and reservoir functions can be directly measured by four-dimensional flow (4D flow) cardiovascular magnetic resonance (CMR).
Childhood Health and Educational outcomes afteR perinatal Brain injury (CHERuB): protocol for a population-matched cohort study
Rees P, Gale C, Battersby C, Williams C, Purkayastha M, Zylbersztejn A, Carter B and Sutcliffe A
Over 3000 infants suffer a brain injury around the time of birth every year in England. Although these injuries can have important implications for children and their families, our understanding of how these injuries affect children's lives is limited.
Prognostic value of cardiopulmonary exercise test in children with congenital heart defects
Terol C, Hagen J, Rammeloo L, Kuipers IM, Blom NA and Ten Harkel AD
Cardiopulmonary exercise testing (CPET) has an important prognostic value in adults with different congenital heart defects (CHDs) and is a useful tool for risk stratification and clinical decision-making. In this retrospective study, we studied the prognostic value of CPET in paediatric patients with CHD.
Assessment of the understanding and awareness of bioethics among healthcare professionals in all public and private hospitals of Haripur district, Pakistan: a multicentre cross-sectional study
Ateeb M, Haq IU, Zakki SA, Altaf E, Junaid M, Ali M, Rehman AU, Wajid D, Fareed A and Mehmood A
To assess the level of bioethics awareness among healthcare professionals in Pakistan, focusing on the associations with sociodemographic characteristics, training and teaching of ethics, medical ethics practice and specific ethical issues.
Sensitivity of classification criteria from time of diagnosis in an incident systemic lupus erythematosus cohort: a population-based study from Norway
Haukeland H, Moe SR, Brunborg C, Botea A, Damjanic N, Wivestad GÅ, Øvreås HK, Bøe TB, Orre A, Torhild G, Sanner H, Lerang K and Molberg Ø
To compare the sensitivity of 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology (EULAR/ACR) classification criteria against 1997 ACR criteria for systemic lupus erythematosus (SLE), for incident SLE cases in the presumably complete population-based Nor-SLE cohort from Southeast Norway (2.9 million inhabitants).
Biomechanical validation of novel polyurethane-resin synthetic osteoporotic femoral bones in axial compression, four-point bending and torsion
Hollensteiner M, Sandriesser S, Libert J, Spitzer-Vanech L, Baumeister D, Greinwald M, Mühling M and Augat P
In addition to human donor bones, bone models made of synthetic materials are the gold standard substitutes for biomechanical testing of osteosyntheses. However, commercially available artificial bone models are not able to adequately reproduce the mechanical properties of human bone, especially not human osteoporotic bone. To overcome this issue, new types of polyurethane-based synthetic osteoporotic bone models have been developed. Its base materials for the cancellous bone portion and for the cortical portion have already been morphologically and mechanically validated against human bone. Thus, the aim of this study was to combine the two validated base materials for the two bone components to produce femur models with real human geometry, one with a hollow intramedullary canal and one with an intramedullary canal filled with synthetic cancellous bone, and mechanically validate them in comparison to fresh frozen human bone. These custom-made synthetic bone models were fabricated from a computer-tomography data set in a 2-step casting process to achieve not only the real geometry but also realistic cortical thicknesses of the femur. The synthetic bones were tested for axial compression, four-point bending in two planes, and torsion and validated against human osteoporotic bone. The results showed that the mechanical properties of the polyurethane-based synthetic bone models with hollow intramedullary canals are in the range of those of the human osteoporotic femur. Both, the femur models with the hollow and spongy-bone-filled intramedullary canal, showed no substantial differences in bending stiffness and axial compression stiffness compared to human osteoporotic bone. Torsional stiffnesses were slightly higher but within the range of human osteoporotic femurs. Concluding, this study shows that the innovative polyurethane-based femur models are comparable to human bones in terms of bending, axial compression, and torsional stiffness.
'Gout was like the boss'. A qualitative study exploring the impact of gout on employment
Diaz-Torne C, Pou MA, Horne A, Gasteiger C and Dalbeth N
Previous research has identified that gout impacts various domains of daily life. However, there have been no qualitative studies focusing on employment. This study aimed to understand the impact of gout on employment.
Automatic diagnosis of epileptic seizures using entropy-based features and multimodel deep learning approaches
Al-Qazzaz NK, Alrahhal M, Jaafer SH, Ali SHBM and Ahmad SA
Epilepsy is one of the most common brain diseases, characterised by repeated seizures that occur on a regular basis. During a seizure, a patient's muscles flex uncontrollably, causing a loss of mobility and balance, which can be harmful or even fatal. Developing an automatic approach for warning patients of oncoming seizures necessitates substantial research. Analyzing the electroencephalogram (EEG) output from the human brain's scalp region can help predict seizures. EEG data were analyzed to extract time domain features such as Hurst exponent (Hur), Tsallis entropy (TsEn), enhanced permutation entropy (impe), and amplitude-aware permutation entropy (AAPE). In order to automatically diagnose epileptic seizure in children from normal children, this study conducted two sessions. In the first session, the extracted features from the EEG dataset were classified using three machine learning (ML)-based models, including support vector machine (SVM), K nearest neighbor (KNN), or decision tree (DT), and in the second session, the dataset was classified using three deep learning (DL)-based recurrent neural network (RNN) classifiers in The EEG dataset was obtained from the Neurology Clinic of the Ibn Rushd Training Hospital. In this regard, extensive explanations and research from the time domain and entropy characteristics demonstrate that employing GRU, LSTM, and BiLSTM RNN deep learning classifiers on the All-time-entropy fusion feature improves the final classification results.
Understanding how traumatic brain injury-related changes in fluid biomarkers affect quality of life outcomes in veterans: a prospective observational trial protocol (UNTANGLE)
Metry Y, McMullan C, Upthegrove R, Belli A, Gomes RSM, Blanch RJ and Ahmed Z
Traumatic brain injury (TBI) is a major cause of disability, with annual global incidence estimated as 69 million people. Survivors can experience long-term visual changes, altered mental state, neurological deficits and long-term effects that may be associated with mental illness. TBI is prevalent in military personnel due to gunshot wounds, and blast injury. This study aims to evaluate the relationship between evolving visual, biochemical and mental health changes in both military veterans and civilians, suffering from TBI, and detect preliminary indicators of prognosis for TBI recovery, and quality-of-life outcomes.
Feature evaluation for myoelectric pattern recognition of multiple nearby reaching targets
Davarinia F and Maleki A
Intention detection of the reaching movement is considerable for myoelectric human and machine collaboration applications. A comprehensive set of handcrafted features was mined from windows of electromyogram (EMG) of the upper-limb muscles while reaching nine nearby targets like activities of daily living. The feature selection-based scoring method, neighborhood component analysis (NCA), selected the relevant feature subset. Finally, the target was recognized by the support vector machine (SVM) model. The classification performance was generalized by a nested cross-validation structure that selected the optimal feature subset in the inner loop. According to the low spatial resolution of the target location on display and following the slight discrimination of signals between targets, the best classification accuracy of 77.11 % was achieved for concatenating the features of two segments with a length of 2 and 0.25 s. Due to the lack of subtle variation in EMG, while reaching different targets, a wide range of features was applied to consider additional aspects of the knowledge contained in EMG signals. Furthermore, since NCA selected features that provided more discriminant power, it became achievable to employ various combinations of features and even concatenated features extracted from different movement parts to improve classification performance.
Digital training for self-injectable contraceptives: a feasibility and acceptability pilot study
Mills R, Krong R, Kithinji F and Baraitser P
Self-injectable contraceptives, namely subcutaneous depot medroxyprogesterone acetate 104 mg micronised formulation delivered via uniject system, reduce the need to travel to a facility for contraceptive access, but the initial, in-person, training may be a barrier to starting this method. This article reports on a small, exploratory pilot in Kenya to test the feasibility and acceptability of digital self-injection training.
Characterising and differentiating cognitive and motor speed in older adults: structural equation modelling on a UK longitudinal birth cohort
Bundil I, Baltruschat S and Zhang J
Information processing speed (IPS) has been proposed to be a key component in healthy ageing and cognitive functioning. Yet, current studies lack a consistent definition and specific influential characteristics. This study aimed to investigate IPS as a multifaceted concept by differentiating cognitive and motor IPS.
Motion reconstruction and finite element analysis of the temporomandibular joint during swallowing in healthy adults
Teng H, Shu J, Ma H, Shao B and Liu Z
There is a close physiological connection between swallowing and the temporomandibular joint (TMJ). However, a shortage of quantitative research on the biomechanical behavior of the TMJ during swallowing exists. The purpose of this study was to reconstruct the movement of the temporomandibular joint (TMJ) based on in vivo experiment and analyze the biomechanical responses during swallowing in healthy adults to investigate the role of the TMJ in swallowing. Motion capture of swallowing, computed tomography (CT), and magnet resonance images (MRI) were performed on six healthy subjects. The movements of the TMJ during swallowing were reconstructed from the motion capture data. The three-dimensional finite element model was constructed. The dynamic finite element analysis of the swallowing process was performed based on the motion data. The range of condylar displacement was within 1 mm in all subjects. The left and right condyle movements were asymmetrical in two-thirds of the subjects. The peak stresses of the discs were relatively low, with a maximum of 0.11 MPa. During swallowing, the condylar displacement showed two trends: slow retraction and slow extension. The tendency to extend could lead to a gradual increase in stress on the disc.
Using machine learning to automatically measure kyphotic and lordotic angle measurements on radiographs for children with adolescent idiopathic scoliosis
Wong J, Reformat M, Parent E and Lou E
Measuring the kyphotic angle (KA) and lordotic angle (LA) on lateral radiographs is important to truly diagnose children with adolescent idiopathic scoliosis. However, it is a time-consuming process to measure the KA because the endplate of the upper thoracic vertebra is normally difficult to identify. To save time and improve measurement accuracy, a machine learning algorithm was developed to automatically extract the KA and LA. The accuracy and reliability of the T1-T12 KA, T5-T12 KA, and L1-L5 LA were reported. A convolutional neural network was trained using 100 radiographs with data augmentation to segment the T1-L5 vertebrae. Sixty radiographs were used to test the method. Accuracy and reliability were reported using the percentage of measurements within clinical acceptance (≤9°), standard error of measurement (SEM), and inter-method intraclass correlation coefficient (ICC). The automatic method detected 95 % (57/60), 100 %, and 100 % for T1-T12 KA, T5-T12 KA, and L1-L5 LA, respectively. The clinical acceptance rate, SEM, and ICC for T1-T12 KA, T5-T12 KA, and L1-L5 LA were (98 %, 0.80°, 0.91), (75 %, 4.08°, 0.60), and (97 %, 1.38°, 0.88), respectively. The automatic method measured quickly with an average of 4 ± 2 s per radiograph and illustrated how measurements were made on the image, allowing verifications by clinicians.
PEER CONNECT: a pragmatic feasibility randomised controlled trial of peer coaching for adults with long-term conditions
Dennett R, Thompson T, Clyne W, Straukiene A, Davies-Cox H, Hosking J, Bones K and Elston J
To test the feasibility of a targeted peer coaching intervention on the health and well-being of people with long-term health conditions and low activation attending outpatient clinics at a UK National Health Service (NHS) Trust.
From imaging to personalized 3D printed molds in cranioplasty
Geroski T, Kovačević V, Nikolić D and Filipović N
Cranioplasty is the surgical repair of a bone defect in the skull resulting from a previous operation or injury, which involves lifting the scalp and restoring the contour of the skull with a graft made from material that is reconstructed from scans of the patient's own skull. The paper introduces a 3D printing technology in creating molds, which are filled with polymethyl methacrylate (PMMA) to reconstruct the missing bone part of the skull. The procedure included several steps to create a 3D model in an STL format, conversion into a G-code which is further used to produce the mold itself using a 3D printer. The paper presents our initial experience with 5 patients who undergone cranioplasty utilizing 3D printed molds. Making a patient-specific model is a very complex process and consists of several steps. The creation of a patient-specific 3D model loading of DICOM images obtained by CT scanning, followed by thresholding-based segmentation and generation of a precise 3D model of part of the patient's skull. Next step is creating the G-code models for 3D printing, after which the actual models are printed using Fused Deposition Modeling printer and PLA material. All surgeries showed good match of the missing bone part and part created using 3D printed mold, without additional steps in refinement. In such a way, 3D printing technology helps in creating personalized and visually appealing bone replacements, at a low cost of the final product.
An efficient channel recurrent Criss-cross attention network for epileptic seizure prediction
Zhu L, Wang W, Huang A, Ying N, Xu P and Zhang J
Epilepsy is a chronic disease caused by repeated abnormal discharge of neurons in the brain. Accurately predicting the onset of epilepsy can effectively improve the quality of life for patients with the condition. While there are many methods for detecting epilepsy, EEG is currently considered one of the most effective analytical tools due to the abundant information it provides about brain activity. The aim of this study is to explore potential time-frequency and channel features from multi-channel epileptic EEG signals and to develop a patient-specific seizure prediction network. In this paper, an epilepsy EEG signal classification algorithm called Channel Recurrent Criss-cross Attention Network (CRCANet) is proposed. Firstly, the spectrograms processed by the short-time fourier transform is input into a Convolutional Neural Network (CNN). Then, the spectrogram feature map obtained in the previous step is input into the channel attention module to establish correlations between channels. Subsequently, the feature diagram containing channel attention characteristics is input into the recurrent criss-cross attention module to enhance the information content of each pixel. Finally, two fully connected layers are used for classification. We validated the method on 13 patients in the public CHB-MIT scalp EEG dataset, achieving an average accuracy of 93.8 %, sensitivity of 94.3 %, and specificity of 93.5 %. The experimental results indicate that CRCANet can effectively capture the time-frequency and channel characteristics of EEG signals while improving training efficiency.
Selecting appropriate excipients for paediatric dosage form - Paediatric excipients risk assessment (PERA) framework - Part 1
Salunke S, Agrawal A, Walsh J, Nunn A, Hughes K, Kuehl P, Caivano G, Clapham D, Thompson K, Rumondor A, Enright B and Sherratt P
Excipients are often the major component of the formulation that critically affect the dosage form, manufacturing process, product performance, stability and safety. They exert different roles and functions in a dosage form. Selecting excipients with appropriate safety and tolerability is a major hurdle in paediatric formulation development. The suitability of a particular excipient will be dependent on the context of its use with regard to the paediatric age range, acute versus chronic use, and clinical risk-benefit of the disease, active and excipient. Scientists are encouraged to apply the principle of risk-benefit to assess the suitability of excipients to the specific paediatric population. Indicative list of parameters that should be taken into consideration and hierarchy of information sources when assessing the excipients risks is provided by regulatory agencies. However, the approach to be taken and details of how the risk evaluation should be undertaken are lacking. There is a need for a systematic approach to selection of excipients and assessment of the risk of excipient exposure. The Paediatric Excipients Risk Assessment (PERA) framework developed and proposed in this paper provides a structured, systematic decision-making framework via customizable tools and processes that can help to improve the transparency and communications on the selection and justification of use of excipients in a paediatric formulation.
Ten-year progression of obesity-related complications in a population with overweight and obesity in the UK: A retrospective open cohort study
Pearson-Stuttard J, Holloway S, Sommer Matthiessen K, Thompson A and Capucci S
To assess the prevalence of individual obesity-related complications (ORCs) and multimorbidity (≥ 1, ≥ 2 and ≥ 3 ORCs), and multimorbidity-associated healthcare costs, over 10 years.
Landscape analysis of the Kenyan policy on the treatment and prevention of diarrheal disease among under-5 children
Mberu B, Simiyu S, Gutema FD, Sewell D, Busienei PJ, Tumwebaze IK and Baker KK
Diarrhoea remains a leading cause of morbidity and death among under-5 children in Kenya, despite multipronged policy and programme initiatives to increase access to treatment. This study interrogates the comprehensiveness and adequacy of Kenya's policies, frameworks and action plans for diarrheal management and prevention. The study seeks to identify policy and practice gaps that need to be filled to strengthen diarrhoea treatment and prevention among under-5 children in Kenya.
Empowerment of parent carers is a fallacy when healthcare doesn't listen
Wright R
Doctors in India launch nationwide strike after trainee is raped and murdered
Mahase E
Why I . . . am a football referee
Oxtoby K
Haemophagocytic lymphohistiocytosis (HLH) secondary to disseminated histoplasmosis infection in a patient with HIV
Zimmerman JT, Hanson C and Iardino A
A male in his 30s who was recently diagnosed with HIV arrived at the emergency department exhibiting an altered mental state and acute respiratory distress. Initial laboratory tests revealed a high anion gap metabolic acidosis, elevated liver enzyme levels and bicytopenia. A CT scan identified a miliary pattern. Bronchoscopy with bronchoalveolar lavage displayed epithelial and inflammatory cells. However, subsequent tests ruled out the presence of fungi, Pneumocystis organisms, malignancies, granulomas and viral inclusions. Broad-spectrum antibiotics with emphasis on and antifungal treatments were administered. The regimen was adjusted after a positive urine test for the Histoplasma antigen.The patient later manifested signs and symptoms, including increased ferritin level, fever, splenomegaly, diminished natural killer cell function and heightened interleukin-2 receptor levels, confirming haemophagocytic lymphohistiocytosis. Given the patient's gravely decompensated state, the treatment incorporated dexamethasone, and the patient's vasopressor-resistant septic shock was addressed with methylene blue.
Yellow nail syndrome in anti-SSA and anti-SSB positive primary Sjögren's syndrome
D'Adamo LJ, Oh Y and Young L
Yellow nail syndrome (YNS) is a rare, acquired condition, characterised by at least two of the three clinical criteria: nail changes, respiratory tract disease and lymphoedema. Currently, the aetiology of YNS remains unknown; however, it is believed to be caused by impaired lymphatic drainage. Currently, there remain no definitive treatment options available and no prospective trials evaluating this. Management includes supportive care and symptomatic treatment. The presence of YNS has been described alongside various conditions, including autoimmune diseases, malignancies and drug exposures. To strengthen the literature on this topic, we present the case of a female patient with a history of anti-SSA and anti-SSB positive primary Sjögren's syndrome, who developed YNS in the immediate postpartum period.
Transient fourth nerve palsy preceding cervical myelopathy due to carotid-cavernous fistula
Viola V, Faini C, Bortolotti C, Guarino M, Cirillo L and Rinaldi R
Carotid-cavernous fistulas (CCFs) are rare intracranial vascular malformations. Among the various classifications available, the most recently proposed highlights the strong correlation between venous drainage pattern and clinical presentation. We present the case of a woman in her 70s with a history of transient palsy of the fourth cranial nerve who presented with subacute cervical myelopathy, which was caused by a CCF with venous drainage into the peribulbar and perimedullary plexus.Given this atypical presentation of CCF and the diagnostic challenges it poses, we conducted a comprehensive PubMed search looking for CCFs presenting with cervical myelopathy and our results confirmed their rarity and allowed us to identify clinical elements that may help clinicians diagnose and manage this potentially treatable condition.
Retrieval of refluxed Onyx cast during a paediatric AVM embolisation
Kishore K and van Adel B
Endovascular embolisation of arteriovenous malformations (AVM) has been greatly facilitated by liquid embolic agents. While advancements in catheter technology and techniques of creating a proximal plug minimise the risk of inadvertent proximal reflux of the embolysate, this remains one of the main complications associated with use of liquid embolics.We report a case of paediatric AVM embolisation which was complicated by parent vessel occlusion due to inadvertent proximal reflux of the embolysate in pericallosal artery. This was safely and effectively rescued using a stent retriever manoeuvre, following similar principles and tenets as in endovascular thrombectomy in stroke. This is the first case report of using a newer smaller 3 mm stentriever in a paediatric medium vessel occlusion, although for a different aetiology but with the same goal.Bail-out or rescue strategy as presented here is an important addition to neurointerventionalists' armamentarium to salvage a non-targeted migration of liquid embolic agent.
Protein-losing enteropathy as a result of colon polyposis and colon cancer: a multidisciplinary approach to diagnosis and treatment
Kuipers H, van Westreenen HL, Moll FCP and de Vos Tot Nederveen Cappel WH
A man in his 60s presented to our emergency department with severe peripheral pitting oedema, weight gain, dyspnoea and diarrhoea. Blood tests showed a hypoalbuminaemia of 15 g/L. A suspicion of protein-losing enteropathy arose after the exclusion of albuminuria, cardiac failure, protein deficiency and liver cirrhosis. An abdominal CT scan revealed a wall thickening of the colon, and a subsequent colonoscopy identified multiple large obstructive polyps in the ascending colon. The patient underwent a right hemicolectomy which revealed the presence of tubulovillous polyps and a pT2N0 colon carcinoma. Following surgery, the patient experienced clinical improvement with normalisation of serum albumin and resolution of the oedema.Protein-losing enteropathy should be considered an underlying syndrome in patients with peripheral oedema and hypoalbuminaemia in the absence of cardiac failure, proteinuria, malnutrition and hepatic disease. This diagnostic process requires a multidisciplinary approach. For adequate treatment, the primary cause of protein-losing enteropathy needs to be investigated.
Right putamen and claustrum infarction mimicking normal pressure hydrocephalus
Chunga N, Curtis K, Tomcik CB and Lizarraga KJ
A woman in her 70s presented with approximately 2 years of sudden-onset gait and cognitive problems. She had been diagnosed with normal pressure hydrocephalus (NPH) and underwent ventriculoperitoneal shunt (VPS) placement 1 year prior. Before VPS placement, brain imaging showed ventriculomegaly and chronic infarction of the right putamen and claustrum. A lumbar drain trial resulted in modest improvement of gait dysfunction. She underwent VPS placement for suspected NPH, but her symptoms remained unchanged. Examination revealed mild cognitive impairment, left-sided and lower body predominant parkinsonism, as well as disproportionately prominent postural instability. Gait analysis showed increased gait variability, reduced velocity and shortened step length bilaterally. Motor and gait abnormalities did not change after administration of levodopa. Her symptoms have remained stable for up to 52 months since symptom onset. We postulate that the infarction affecting the right putamen and claustrum could have led to a higher-level gait disorder mimicking NPH.
Extraconal orbital craniopharyngioma
Koyya SS, Gupta RK, Sharma A and Pati S
A female, in her 60s, presented with pain and swelling of the right eye for 3 years. The radiological work-up revealed an extraconal solid-cystic orbital tumour suggestive of an epidermoid cyst. The patient underwent supraorbital craniotomy with a gross total excision of the tumour. An intraoperative diagnosis was sought, which on both squash smear and frozen section showed features of craniopharyngioma (CP), later confirmed on paraffin sections and immunohistochemistry. The orbit is a very rare site for ectopic CP, with only two cases reported in the literature. Many theories have been proposed to explain the occurrence of CP at ectopic sites. This report aims to provide insight into the different hypotheses of the pathogenesis of ectopic CP through a review of the literature.
Unveiling collodion baby: confronting ectropion and respiratory drama in neonatal care
Srivastava U, Singh KA, Sahu A and Dalai R
A neonate presented to us with respiratory distress with diffuse involvement of skin with thickening, cracking and peeling since birth with severe ectropion and eclabium. The hospital course was complicated by polymicrobial sepsis requiring prolonged antibiotics and antifungals. The skin lesions were treated with acitretin, humidification and topical emollients. With the improvement of pneumonia and clearing of nasal debris, the neonate could be gradually weaned off respiratory support. Despite a stormy course, there was marked improvement in all skin lesions including ectropion and eclabium at discharge. This case highlights and discusses the challenges in diagnosis and underscores the need for multidisciplinary involvement of neonatology, dermatology and ophthalmology for a neonate with collodion baby syndrome.
Tears of blood: an unusual case of haemolacria due to conjunctival vascular malformation successfully managed by embolisation
Kiran A, Nagesh C, Jhalaksreemol KRV and Jayadev C
A boy in his mid-teens presented with progressively increasing bleeding from the right eye and nostril intermittently over a period of 6 weeks. A complete ophthalmic examination revealed nothing significant. His otorhinological examination and haematological investigations were within normal limits. The patient came a month later with frank bleeding from the right eye. Ophthalmic examination revealed hyperaemia and maceration of the right lower palpebral conjunctiva. A histopathological examination of conjunctival scrapings from the site showed abnormal dilated blood vessels suggestive of a vascular malformation. Digital subtraction angiography confirmed the presence of a conjunctival micro arteriovenous malformation supplied by the external carotid and ophthalmic artery branches. He underwent successful transarterial Onyx embolisation resulting in complete resolution of the haemolacria.
Sarcoidosis with laryngeal and tracheal involvement
King RB, Nassereddin AT, Chheda NN and Robinson MD
A woman in her early 30s presented to her primary care physician's office with hoarseness, joint pain and facial swelling. The objective evaluation revealed elevated inflammatory markers and angiotensin-1-converting enzyme, a chest radiograph with bilateral hilar prominence and a maxillofacial CT scan with diffuse inflammation in the upper airway. Otolaryngology evaluation revealed exophytic lesions diffusely within the nasal cavity, base of tongue, supraglottis, glottis and trachea. A biopsy confirmed the diagnosis of sarcoidosis. She was treated with corticosteroids with improvement in upper and lower airway symptoms. She continued to experience other extrapulmonary manifestations of sarcoidosis requiring alternative immunosuppressant therapy. At 30 months from symptom onset, her disease was noted to be in remission.
Rapidly progressive cystic lung disease in a patient with a scalp lesion
Majumdar U, Sameed M, Mukhopadhyay S, Ghosh S, Stoller JK and Chaisson N
We describe an elderly patient presenting with pneumothorax, cystic lung disease and a scalp lesion. The pneumothorax resolved after placing a chest tube and suction but recurred within a week. Progression of cystic features was also seen, and biopsies of the lung and scalp lesions were performed. Immunohistochemistry was positive for markers of endothelial cells (CD31 and ERG) and negative for markers expected to be positive in alveolar cells (keratin AE1/AE3 and TTF-1), supporting the diagnosis of metastatic angiosarcoma. Palliative chemotherapy did not prevent progression and the patient expired soon after. In describing the clinico-radiological correlation of metastatic angiosarcoma, we also briefly describe the approach to cystic lung disease. Understanding the pathophysiology of cyst formation in metastatic angiosarcoma may help clinicians to better appreciate and manage the full spectrum of cystic lung disease, especially with atypical features.
US says that first negotiated drug prices for older people will save $6bn
Tanne JH
Utilization of a Clark electrode device as a respirometer for small insects: A convincing test on ants allowing to detect discontinuous respiration
Kervella M, Cansell C, Criscuolo F and Bouillaud F
Respirometry provides a direct measure of an organism's O consumption rate (VO), which is a significant component of its metabolic rate (energy expenditure). Amongst ants, variations in lifespan between different social castes (such as workers and queens) can be substantial, varying depending to the species. As metabolic rate is higher in short-living species, we aimed to determine how VO and longevity may have coevolved within ant casts. Measuring VO in such tiny animal models can be challenging, and as a first methodological step, we validate the use of a Clark electrode, initially designed for measuring mitochondrial respiration control pathways, for assessing VO in ants within a sealed chamber. This was done by comparing it with stop-flow VO and CO production, using a traditional indirect calorimetry device. The global aim is to provide a reliable protocol to conduct accurate comparisons of metabolic rates within and among ant species. As expected, using Clark electrode entails high time resolution and revealed that queens and workers exhibited discontinuous respiration, with episodes of apnea lasting up to 20 min.
Variations in healthcare costs by body mass index and obesity-related complications in a UK population: A retrospective open cohort study
Pearson-Stuttard J, Holloway S, Sommer Matthiessen K, Thompson A and Capucci S
To estimate healthcare resource utilization (HCRU) and healthcare costs by body mass index (BMI) in a UK cohort and to explore how this varied by defined BMI strata.
Trends in Performance of Thrombectomy for Acute Ischemic Stroke Patients in Teaching and Non-teaching Hospitals
Qureshi AI, Bhatti IA, Gomez CR, Hanley DF, Ford DE, Hassan AE, Nguyen TN, Spiotta AM and Kwok CS
The value of thrombectomy in patients with acute ischemic stroke cannot be understated. As such, whether these patients get access to this treatment can significantly impact their disease outcomes. We analyzed the trends in thrombectomy adoption between teaching and non-teaching hospitals in the United States, and their impact on overall patient care.
Mitochondrial elongation confers protection against doxorubicin-induced cardiotoxicity
He W, He W, Chen X, Zeng L, Zeng L, Liu Y, He P and Sun Z
Doxorubicin (DOX)-induced cardiac damage remains a leading cause of death amongst cancer survivors. DOX-induced cardiotoxicity (DIC) is mediated by disturbed mitochondrial dynamics, but it remains debated that the mechanisms by which DOX disrupted equilibrium between mitochondrial fission and fusion. In the present study, we observed DOX induced mitochondrial elongation in multiple cardiovascular cell lines. Mechanically, DOX not only downregulated the mitochondrial fusion proteins including Mitofusin 1/2 (MFN1/2) and Optic atrophy 1 (OPA1), but also induced lower motility of dynamin-related protein 1(Drp1) and its phosphorylation on 637 serine, which could inhibit mitochondrial fission. Interestingly, DOX failed to induce mitochondrial elongation in cardiomyocytes co-treated with protein kinase A (PKA) inhibitor H89 or expressing phosphodeficient Drp1-S637A variants. Besides, carbonyl cyanide 3-chlorophenylhydrazone (CCCP) was able to blocked the mitochondrial elongation induced by DOX treatment, which could be phenocopied by OPA1 knockdown. Therefore, we speculated that DOX inhibited both mitochondrial fission and fusion simultaneously, yet enabled mitochondrial fusion dominate the mitochondrial dynamics, resulting in mitochondrial elongation as the main manifestation. Notably, blocking mitochondrial elongation by inhibiting Drp1-S637 phosphorylation or OPA1 knockdown aggravated DOX-induced cardiomyocytes death. Based on these results, we propose a novel mechanistic model that DOX-induced mitochondrial elongation is attributed to the equilibrium disturbance of mitochondrial dynamics, which serves as an adaptive response and confers protection against DIC.
Gynecological cancer tumor Microenvironment: Unveiling cellular complexity and therapeutic potential
Garg P, Ramisetty S, Raghu Subbalakshmi A, Krishna M, Pareek S, Mohanty A, Kulkarni P, Horne D, Salgia R and Singhal SS
Gynecological cancers, including ovarian, cervical, endometrial, and vulvar cancers, present significant challenges in diagnosis and treatment globally. The tumor microenvironment (TME) plays a pivotal role in cancer progression and therapy response, necessitating a deeper understanding of its composition and dynamics. This review offers a comprehensive overview of the gynecological cancer tumor microenvironment, emphasizing its cellular complexity and therapeutic potential. The diverse cellular components of the TME, including cancer cells, immune cells, stromal cells, and extracellular matrix elements, are explored, elucidating their interplay in shaping tumor behavior and treatment outcomes. Across various stages of cancer progression, the TME exerts profound effects on tumor heterogeneity, immune modulation, angiogenesis, and metabolic reprogramming. The urgency for novel therapeutic strategies is underscored by understanding immune evasion mechanisms within the TME. Emerging approaches such as immunotherapy, stromal-targeting therapies, anti-angiogenic agents, and metabolic inhibitors are discussed, offering promising avenues for improving patient outcomes. Interdisciplinary collaborations and translational research are emphasized, aiming to advance precision oncology and enhance therapeutic efficacy in gynecological cancers.
Micro-electrode array recording of extracellular electrical potentials of liquid static surface fermented Hericium erinaceus
Browner D and Adamatzky A
Hericium erinaceus is a Basidiomycetes fungus with previously uncharacterised extracellular electrophysiology. Here, we present results of recordings of the electrical potentials of fungal biofilms of this species using microelectrode arrays (MEAs). In particular, we focused on modelling the temporal and spatial progression of the low frequency (≤ 1 Hz) potentials. Culture media control studies showed that the electrical potential activity results from the growth and subsequent spiking behaviours of the mycelium extracellular matrices. An antifungal assay using nystatin suspension, 10,000 unit/mL in DPBS, provided evidence for the biological origin of electrical potentials due to targeting of the selective permeability of the cell membrane and subsequent cessation of electrical activity. Conversely, injection of L-glutamic acid increased the combined multi-channel mean firing rate from 0.04 Hz to 0.1 Hz. Analysis of bursting and spatial propagation of the extracellular signals are also presented.
Spatial transcriptomic revealed intratumor heterogeneity and cancer stem cell enrichment in colorectal cancer metastasis
Zhou L, Wen R, Bai C, Li Z, Zheng K, Yu Y, Zhang T, Jia H, Peng Z, Zhu X, Lou Z, Hao L, Yu G, Yang F and Zhang W
Metastasis is the main cause of mortality in colorectal cancer (CRC) patients. Exploring the mechanisms of metastasis is of great importance in both clinical and fundamental CRC research. CRC is a highly heterogeneous disease with variable therapeutic outcomes of treatment. In this study, we applied spatial transcriptomics (ST) to generate a tissue-wide transcriptome from two primary colorectal cancer tissues and their matched liver metastatic tissues. Spatial RNA information showed intratumoral heterogeneity (ITH) of both primary and metastatic tissues. The comparison of gene expressions across tissues revealed an apparent enrichment of cancer stem cells (CSCs) in metastatic tissues and identified FOXD1 as a novel metastatic CSC marker. Trajectory and pseudo-time analyses revealed distinct evolutionary trajectories and a dedifferentiation-differentiation process during metastasis. CellphoneDB analysis suggested a dominant interaction of CD74-MIF with tumor cells in metastatic tissues. Further analysis confirmed FOXD1 as a maker of CSCs and the predictor of patient survival, especially in metastatic diseases. Our study found ITH of primary and metastatic tissues and provides novel insights into the cellular mechanisms underlying liver metastasis of CRC and foundations for therapeutic strategies for CRC metastasis.
"The Association Between HALP Score and Infection in Acute Ischemic Stroke Patients"
Ozturk U, Nergiz S and Ozturk O
Stroke-associated infection (SAI) is related to increased mortality in acute ischemic stroke (AIS) cases. The HALP index is used to evaluate nutrition and inflammation. Our research aimed to assess the relation between HALP scores and infection risk in AIS cases.
Presence and infestation waves of hematophagous arthropod species
Acuña-Zegarra MA, Tocto-Erazo MR, García-Mendoza CC and Olmos-Liceaga D
The invasion of hematophagous arthropod species in human settlements represents a threat, not only to the economy but also to the health system in general. Recent examples of this phenomenon were seen in Paris and Mexico City, evidencing the importance of understanding these dynamics. In this work, we present a reaction-diffusion model to describe the invasion dynamics of hematophagous arthropod species. The proposed model considers a denso-dependent growth rate and parameters related to the control of the invasive species. Our results illustrate the existence of two invasion levels (presence and infestation) within a region, depending on control parameter values. We also prove analytically the existence of the presence and infestation waves and show different theoretical types of invasion waves that result from varying control parameters. In addition, we present a condition threshold that determines whether or not an infestation occurs. Finally, we illustrate some results when considering the case of bedbugs and brown dog ticks as invasion species.
Impact of COVID-19 public health restrictions on fall-related hip fracture hospitalizations: An interrupted time series analysis
Mitsutake S, Lystad RP, Long JC, Braithwaite J and Mitchell R
There is limited evidence regarding the impact of public health restrictions on hip fracture hospitalization by place of fracture occurrence. This study aimed to examine the impact of COVID-19 public health restrictions on fall-related hip fracture hospitalization rates by place of occurrence.
Alginate binding enhances the structural stability and potentiates the lytic activity of bacteriophage endolysin's partially folded conformation
Ghate MM, Gulati K and Poluri KM
Polysaccharide polymers are increasingly being used as chaperon-like macromolecules in assisting protein folding of unfolded protein molecules. They interact with unfolded or partially folded proteins in a charge and conformation specific manner that results in the formation of stable protein-polysaccharide complexes. In most of the cases, the complex formation of protein-polysaccharide is driven via non-covalent interactions that have found to endorse the activity of proteins. T4L (18.7 kDa) and T7L (17 kDa) endolysins belong to the hydrolase and amidase class of peptidoglycan degrading enzymes. Both T4L and T7L exist in partially folded forms and are devoid of lytic activity at low pH conditions. In the current study, we assessed the binding of alginate with T4L and T7L at pH 7 and 3 using variety of biophysical and biochemical techniques. Spectroscopic studies revealed differential structural modulations of partially folded T4L and T7L upon their interaction with alginate. Further, the complex formation of alginate with partially folded T4L/T7L was confirmed by ITC and STEM. Additionally, the formed complexes of alginate with both T4L /T7L PF endolysins were found to be chemically and enzymatically stable. Moreover, such complexes were also marked with differential enhancement in their lytic activities at acidic pH conditions. This implied the potency of alginate as an excellent choice of matrix to preserve the structural and functional integrity of partially folded forms of T4L and T7L at highly acidic conditions.
Digital video analysis reveals gait parameters that predict performance in the jumping test phase of three-day eventing
Johns LT, Smythe MP, Dewberry S, Staiger EA, Allen K and Brooks SA
In international equestrian sport, visual inspections assess gait and lameness to protect the welfare of performance horses during competition. Horses competing internationally in three-day eventing must pass two mandatory inspections (pre-competition and post-cross country) before attempting the final phase: the jumping test (JT). We hypothesized that digitally quantifying objective gait parameters captured during the two mandatory inspections will identify locomotor characteristics that predict success during the jumping test. Utilizing the DeepLabCut (DLC) software package for labeling of anatomical landmarks and a custom analysis pipeline we calculated gait parameters for 194 competition horses at the trot. During the pre-competition inspection, relative trot speed was significantly associated (P = 0.0060, GLMM), and the forelimb travel trended towards significance (P =0.0800, GLMM), with achieving a clear round in the later jumping test. Post-cross country, the forelimb travel significantly predicted JT results (P = 0.0188, GLMM). As our parameters are scaled for body size, these parameters may indicate conformational characteristics for superior jumping ability and overall athletic fitness. Within each competitive effort, comparisons of the post-cross country and pre-competition observations revealed that the change in speed and duty factor were significantly different in the group that accrued jumping faults (P = 0.00376 and P = 0.02430, GLMM), perhaps capturing locomotor signs of exercise fatigue. Further work employing these approaches to better understand competition performance will encourage the use of objective measures to protect sport horse welfare, as well as provide an advantageous tool for gait evaluation in the horse.
LOW CONCENTRATION DIMETHYL SULFOXIDE (DMSO) MODULATES EPILEPTIFORM SYNCHRONIZATION IN THE 4-AMINOPYRIDINE IN VITRO MODEL
Li FR, Gemayel M, Lévesque M, Wang S, Suarez CF and Avoli M
Dimethyl sulfoxide (DMSO) is commonly used to dissolve water-insoluble drugs due to its dipolar and aprotic properties. It also serves as a vehicle in many pharmacological studies. However, it has been reported that DMSO can induce seizures in human patients, lower seizure threshold in vivo, and modulate ion receptors activities in vitro. Therefore, we investigated here the effect of 0.03% and 0.06% DMSO, which are 10 to 50 times lower than what usually employed in previous studies, in the 4-aminopyridine (4AP) model of epileptiform synchronization in male mouse brain slices. We found that 0.03% and 0.06% DMSO increase 4AP-induced ictal discharge rate, while 0.06% DMSO decreases ictal discharge duration. Our results suggest that the effects of DMSO on neuronal excitability deserve further analysis and that investigators need to be aware of its confounding effect as a solvent, even at very low concentrations.
High plasma BNP concentration associates with clinical outcome after mechanical thrombectomy: Post hoc analysis of SKIP
Aoki J, Suzuki K, Sakamoto Y, Matsumaru Y, Takeuchi M, Morimoto M, Kanazawa R, Takayama Y, Kamiya Y, Shigeta K, Okubo S, Hayakawa M, Ishii N, Koguchi Y, Takigawa T, Inoue M, Naito H, Ota T, Hirano T, Kato N, Ueda T, Iguchi Y, Akaji K, Tsuruta W, Miki K, Fujimoto S, Higashida T, Iwasaki M, Kanamaru T, Saito T, Katano T, Kutsuna A, Nishiyama Y, Otsuka T, Kimura K and
Heart failure may result in reduced brain perfusion, limiting the blood flow needed to achieve clinical recovery. We investigated whether plasma levels of brain natriuretic peptide (BNP), a biological marker of heart failure, were related to clinical outcomes after mechanical thrombectomy (MT).
Improved trunk muscle quality in patients with stroke increases improvements in activities of daily living
Sato K, Tanaka S, Masaki K and Ogawa T
This study aimed to determine whether an increased trunk muscle quality index (TMQI) is associated with activities of daily living (ADL) in patients ≥ 65 years of age with cerebral infarction in a convalescent rehabilitation ward.
NLRP3 inflammasome activation contributes to the development of the pro-fibrotic phenotype of lung fibroblasts
Nguyen TH, Nguyen HH, Nguyen TD, Thi-Hong Tran V, Nguyen HA and Pham DV
Idiopathic pulmonary fibrosis (IPF) is an irreversible progressive interstitial lung disease of unknown cause. The poorly understood pathophysiology of IPF poses substantial challenges to the development of effective anti-lung fibrotic drugs. The NLRP3 inflammasome, a key component of the innate immune system, has recently been linked to the pathogenesis of lung fibrosis. However, the specific contributions of NLRP3 inflammasomes to determination of the pro-fibrotic phenotype of lung fibroblasts, which play a central role in the production of extracellular matrix protein, remain to be investigated. Therefore, the present study was performed to elucidate the involvement of NLRP3 inflammasome signalling pathways in modulation of lung fibroblast proliferation and differentiation. We found that activation of NLRP3 inflammasomes increased in lung fibroblasts derived from individuals with pulmonary fibrosis and in normal lung fibroblasts stimulated with transforming growth factor β and platelet-derived growth factor. Importantly, blockage of NLRP3 inflammasome signalling, either by gene silencing of NLRP3 or using pharmacological inhibitors of NLRP3, caspase-1, or IL-1 receptor, inhibited the proliferation, differentiation, and extracellular matrix protein synthesis of activated lung fibroblasts. Moreover, induction of the reactive oxygen species/thioredoxin-interacting protein axis, an upstream signalling pathway of NLRP3 inflammasomes, was essential for maintenance of the pro-fibrotic phenotype of lung fibroblasts. Interestingly, treatments with pharmacological inhibitors of NLRP3 inflammasomes prevented the progression of bleomycin-induced pulmonary fibrosis in mice. Collectively, these findings suggest that aberrant activation of NLRP3 inflammasomes is a critical event in the pathogenesis of IPF and that targeting NLRP3 inflammasomes may serve as a therapeutic strategy for IPF.
Winter indoor air quality in traditional Mongolian yurts, in a Ger district of Ulaanbaatar
Sainnokhoi TA, Kováts N, Pelden B, Tuvshinbayar Y, Bat-Ochir M, Eck-Varanka B, Teke G and Hubai K
In Ulaanbaatar roughly 60% of the population live in traditional Mongolian yurts in the so-called Ger districts of the city. Winter indoor air quality is a serious concern in these districts as about 98% of households consume solid fossil fuel (mainly coal). In our study, indoor air quality was assessed based on PAHs analysis and ecotoxicity testing of 24-hour samples collected in 4 yurts. Three of the selected yurts were equipped with conventional while the fourth one with improved stoves. Analysis of PAHs profiles showed the prevalence of higher molecular weight PAHs in all yurts. Concentrations of the 5-ring benzo(b)fluoranthene and 6-ring benzo(g.h.i)perylene were extremely high in one yurt using conventional stove, 8430µgg and 6320µgg, respectively. Ecotoxicity of the samples was assessed using the kinetic version of the Vibrio fischeri bioluminescence inhibition bioassay. In concordance with PAHs concentrations, ecotoxicity was also the highest in that yurt.
Early treatment with 2-deoxy-d-glucose reduces proliferative proteins in the kidney and slows cyst growth in a hypomorphic Pkd1 mouse model of autosomal dominant polycystic kidney disease (PKD)
Atwood D, He Z, Miyazaki M, Hailu F, Klawitter J and Edelstein CL
In autosomal dominant polycystic kidney disease (ADPKD) there is cyst growth in the kidneys that leads to chronic kidney disease often requiring dialysis or kidney transplantation. There is enhanced aerobic glycolysis (Warburg effect) in the cyst lining epithelial cells that contributes to cyst growth. The glucose mimetic, 2-Deoxy-d-glucose (2-DG) inhibits glycolysis. The effect of early and late administration of 2-DG on cyst growth and kidney function was determined in Pkd1 mice, a hypomorphic PKD model orthologous to human disease. Early administration of 2-DG resulted in decreased kidney weight, cyst index, cyst number and cyst size, but no change in kidney function. 2-DG decreased proliferation. a major mediator of cyst growth, of cells lining the cyst. Late administration of 2-DG did not have an effect on cyst growth or kidney function. To determine mechanisms of decreased proliferation, an array of mTOR and autophagy proteins was measured in the kidney. 2-DG suppressed autophagic flux in Pkd1 kidneys and decreased autophagy proteins, ATG3, ATG5 and ATG12-5. 2-DG had no effect on p-mTOR or p-S6 (mTORC1) and decreased p-AMPK. 2-DG decreased p-4E-BP1, p-c-Myc and p-ERK that are known to promote proliferation and cyst growth in PKD. 2-DG decreased p-AKT, a marker of mTORC2. So the role of mTORC2 in cyst growth was determined. Knockout of Rictor (mTORC2) in Pkd1 knockout mice did not change the PKD phenotype. In summary, 2-DG decreases proliferation in cells lining the cyst and decreases cyst growth by decreasing proteins that are known to promote proliferation. In conclusion, the present study reinforces the therapeutic potential of 2-DG for use in patients with ADPKD.
Update to RIFM fragrance ingredient safety assessment, hexyl acetate, CAS Registry Number 142-92-7
Api AM, Bartlett A, Belsito D, Botelho D, Bruze M, Bryant-Freidrich A, Burton GA, Cancellieri MA, Chon H, Dagli ML, Dekant W, Deodhar C, Farrell K, Fryer AD, Jones L, Joshi K, Lapczynski A, Lavelle M, Lee I, Moustakas H, Muldoon J, Penning TM, Ritacco G, Sadekar N, Schember I, Schultz TW, Siddiqi F, Sipes IG, Sullivan G, Thakkar Y and Tokura Y
Association of Uterine Leiomyoma with Type 2 Diabetes Mellitus in Young Women: A Population-Based Cohort Study
Sung JH, Kim KS, Han K and Park CY
We investigated the association between uterine leiomyoma (UL) and incident type 2 diabetes mellitus (T2DM) in young women.
Exploring the link between inflammatory myopathies and cancer: A comprehensive retrospective analysis in a Colombian cohort
Bolaños JD, Rivera-Londoño R, Hurtado-Bermúdez LJ, Nieto-Aristizábal I, Enriquez KD, Zura-Rodríguez S, Hormaza-Jaramillo A and Aguirre-Valencia D
This study investigates the association between inflammatory myopathies (IM), and their correlation with cancer. There are several potential causes behind the association of cancer and inflammatory myopathies. The positivity of specific antibodies for myositis plays a significant role. Our objective is to describe cancer and inflammatory myopathies in Colombia, focusing on demographics, clinical characteristics, and laboratory data.
Analysis of factors affecting pregnancy outcomes in patients with adenomyosis after high intensity focused ultrasound ablation: a retrospective study
Ma R, Briones DAB, Zou M, Xiong Y, Bai J and Zhang L
To investigate all pregnancies and analyze the factors influencing pregnancy outcomes in patients with adenomyosis after high intensity focused ultrasound (HIFU).
Can we predict the risk factors for switching due to ineffectiveness in the first year of therapy with bDMARD in patients with rheumatoid arthritis?
Martins A, Pimenta S, Oliveira D, Nicolau R, Bernardo A, Martins Rocha T, Costa L and Bernardes M
Biological disease-modifying antirheumatic drugs (bDMARD) have improved the clinical course and quality of life of patients with rheumatoid arthritis (RA). However, some patients failed to respond or have an insufficient response to bDMARD early in the course of the treatment.
Can microvascular damage predict disease severity in patients with systemic sclerosis?
Martins A, Pimenta S, Oliveira D, Miriam Ferreira R, Bernardes M, Costa L and Terroso G
Systemic sclerosis (SSc) is characterized by progressive fibrosis of the skin and internal organs, microvascular damage and cellular and humoral immunity abnormalities. Microvascular damage can be easily detected through nailfold videocapillaroscopy (NVC).
Treatment Options for Signet Ring Cell Carcinoma of the Urinary Bladder: A Population-Based Study
Xie Y, Zhang Y, Du Z, Liu D, Yan W, Liu Y and Ping H
Signet ring cell carcinoma (SRCC) of the urinary bladder is a rare and highly aggressive form of bladder cancer, with no widely agreed-upon treatment strategy. The aim of this study was to identify important factors influencing patient prognosis and to assess how various treatment approaches affect survival outcomes.
Interaction between angiotensin-converting enzyme gene rs4343 polymorphism, environment factors, and angiotensin II level on susceptibility to knee osteoarthritis
Elnaggar BMMA, Abd Elbaky NM, Albeltagy ES and El Zomor HM
Osteoarthritis (OA) is a complex multifactorial disease. The association of knee OA risk with ACE gene rs4343 polymorphism, gene environment synergistic effect, and angiotensin II serum level has not been previously examined. Therefore, we investigate the ACE gene rs4343 polymorphism in knee OA, and its association with severity of knee OA, and angiotensin II serum level.
How do gene mutation diversity and disease severity scoring affect physical capacity and quality of life in children/adolescents with Familial Mediterranean Fever?
Kabul EG, Bali M, Calik BB, Tekin ZE, Yener GO and Yuksel S
The aim of this study is to examine how gene mutation diversity and disease severity affect physical capacity and quality of life in children/adolescents with Familial Mediterranean Fever (FMF).
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