Development of a Methodology Based on Optical Interferometry for Measuring Fibrinolytic Activity.

Fibrinolytic activity assay is particularly important for the detection, diagnosis, and treatment of cardiovascular disease and the development of fibrinolytic drugs. A novel efficacious strategy for real-time and label-free dynamic detection of fibrinolytic activity based on ordered porous layer interferometry (OPLI) was developed. Fibrin or a mixture of fibrin and plasminogen (Plg) was loaded into the highly ordered silica colloidal crystal (SCC) film scaffold to construct a fibrinolytic response interference layer to measure fibrinolytic activity with different mechanisms of action. Fibrinolytic enzyme-triggered fibrinolysis led to the migration of interference fringes in the interferogram, which could be represented by optical thickness changes (ΔOT) tracked in real time by the OPLI system. The morphology and optical property of the fibrinolytic response interference layer were characterized, and the Plg content in the fibrinolytic response interference layer and experimental parameters of the system were optimized. The method showed adequate sensitivity for the fibrinolytic activity of lumbrokinase and streptokinase, with wide linear ranges of 12-6000 and 10-2000 U/mL, respectively. Compared with the traditional fibrin plate method, it has a lower detection limit and higher linearity. The whole kinetic process of fibrinolysis by these two fibrinolytic drug models was recorded in real time, and the Michaelis constant and apparent kinetic parameters were calculated. Importantly, some other blood proteins were less interfering with this system, and it showed reliability in fibrin activity detection in real whole blood samples. This study established a better and more targeted research method of in vitro fibrinolysis and provided dynamic monitoring data for the analysis of fibrinolytic activity of whole blood.

Structural optimization using a genetic algorithm aiming for the minimum mass of vertical axis wind turbines using composite materials.

A wind turbine comprises multiple components constructed from diverse materials. This complexity introduces challenges in designing the blade structure. In this study, we developed a structural optimization framework for Vertical Axis Wind Turbines (VAWT). This framework integrates a parametric Finite Element Analysis (FEA) model, which simulates the structure's global behavior, with a Genetic Algorithm (GA) optimization technique that navigates the design domain to identify optimal parameters. The goal is to minimize the mass of VAWT structures while adhering to a suite of complex constraints. This framework quantifies the mass reduction impact attributable to material selection and structural designs. The optimization cases indicate that blades made from Carbon Fiber Reinforced Plastics (CFRP) materials are 47.1 % lighter than those made from Glass Fiber Reinforced Plastics (GFRP), while the structural parts are 44.8 % lighter. This work also provides further recommendations regarding the scale and design of the structures. With the materials and structural design established, future studies can expand to include more load cases and detailed designs of specific components.

Technology-Based Strategy to Improve Medication Compliance Among Patients With Schizophrenia Spectrum Disorders.

INTRODUCTION:  Non-compliance to medications remains a challenging problem in schizophrenia. Newer strategies with high feasibility and acceptability are always being researched. This study aimed to assess the effectiveness of technology-based intervention in improving medication compliance in individuals with schizophrenia. METHOD: This was a prospective intervention study where participants were required to use the SuperMD smartphone application (Digital-Health Technologies Pte Ltd, Kuala Lumpur, Malaysia) for a month. A change in the Medication Adherence Rating Scale-Malay Translation (MARS-M) and Malay Translation of Drug Adherence Inventory-9 (MDAI-9) scores indicated a change in compliance and attitude to medication. Positive and Negative Syndrome Scale (PANSS) was used to assess change in symptoms and insight. Medication compliance was also obtained from the SuperMD application. Paired T-test was used to evaluate the significance of changes in mean scores of research variables over the study period. Wilcoxon signed-rank test was used to analyze the subscale of MDAI-9 and the change in PANSS score. The Kruskal-Wallis test was used to determine the effect of the change of insight on the level of compliance with medication. RESULTS: There were 36 participants in this study. The results showed statistically significant improvement in compliance (0.65, p ≤ 0.01) but not in attitude towards medication (0.78, p = 0.065). There was also an improvement in PANNS score (-2.58, P ≤ 0.01). There was no significant change in insight (χ2(2) = 3.802, p = 0.15).  Conclusion:The use of technology-based strategies like SuperMD is effective in improving medication compliance for individuals with schizophrenia.

Epstein-barr virus (EBV)-positive inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDCS) presenting as thrombocytopenia: A case report and literature review.

Background: Follicular dendritic cell sarcoma (FDCS) represents an exceedingly rare malignant neoplasm. Inflammatory pseudotumor-like follicular dendritic cell sarcoma (IPT-like FDCS) is recognized as a variant manifestation of FDCS. The clinical incidence of this particular disease is remarkably low, resulting in the absence of established standardized clinical protocols for its management and treatment. Methods: Presented here is a case of primary Epstein-Barr virus (EBV)-positive splenic IPT-like FDCS, noteworthy for manifesting thrombocytopenia as its initial symptom. Our study analyzed the clinicopathologic characteristics of this case and 29 previously reported cases identified in the literature. Also, we conducted a comprehensive review of pertinent literature. Results: We administered splenectomy to this patient and verified the diagnosis of EBV-positive IPT-like FDCS through immunohistochemical examination. Postoperatively, the patient underwent a one-year follow-up period, demonstrating no signs of recurrence. Analyzing a total of 30 cases revealed that this disease is more prevalent in female patients (F:M = 1.14:1), with a median age of 62 years. Fifteen patients were asymptomatic, and nine patients presented with abdominal discomfort or pain. All patients underwent surgical treatment. Among the cases, histopathological and immunohistochemical information was unavailable for five; however, in the remaining 25 cases, histopathology revealed a distinct inflammatory cell infiltration and spindle tumor cells arranged in sheets or fascicles. These tumor cells had vesicular chromatin and distinct nucleoli and they expressed conventional FDC markers. In situ hybridization analysis of Epstein-Barr virus-encoded small RNA (EBER) showed that all 30 cases were EBV-positive. Follow-up information showed that no patients relapsed and one (3.8 %) patient died. Conclusion: The clinical diagnosis of EBV-positive IPT-like FDCS poses considerable challenges, necessitating a conclusive diagnosis through pathological immunohistochemical examination. EBER in situ hybridization holds significance for the definitive diagnosis of the disease. We advocate for splenectomy as the treatment of choice for limited splenic IPT-like FDCS.

[Non-targeted renal metabolomics reveals multi-target effects of Dahuang Zhechong Pills on renal aging in rats].

This study aims to observe the effects of the traditional Chinese medicine prescription Dahuang Zhechong Pills(DHZCP on renal aging and explore its potential multi-target effects. Rats were assigned into the normal, model, DHZCP, and vitamin E(VE)groups. Firstly, the rat model of D-galactose(D-gal)-induced renal aging was established. During the modeling period, the rats in the 4 groups were administrated with double distilled water, double distilled water, DHZCP suspension, and VE suspension, respectively,by gavage every day. On day 60 of intervention, the indicators of renal aging and injury in rats were measured, including the function,histopathological characteristics, senescence-associated ß-galactosidase( SA-ß-gal) staining, and expression levels of Klotho and proteins associated with cell cycle arrest and senescence-associated secretory phenotype(SASP) in the renal tissue. Moreover, nontargeted metabolomic analysis of the renal tissue was performed for the 4 groups of rats to screen out the potential biomarkers and metabolic pathways. Finally, the signaling pathways of key targets were preliminarily validated. The results showed that DHZCP and VE significantly improved the renal function, histopathological features of renal tubular/interstitial tissue, and degree of SA-ß-gal staining, up-regulated the expression level of Klotho, and down-regulated the expression levels of proteins associated with cell cycle arrest and SASP in the renal tissue of the aging rats. In addition, DHZCP and VE regulated the metabolites in the renal tissue of the aging rats. There were 21 common differential metabolites. Among them, 5 differential metabolites were significantly increased in the aging rats and recovered after DHZCP or VE treatment, and they were involved in the lipid metabolism and energy metabolism pathways. The areas under the curves of the groups in comparison varied within the range of 0. 88-1. DHZCP regulated multiple signaling pathways, such as the adenosine monophosphate-activated protein kinase(AMPK), cyclic guanosine monophosphate-protein kinase G( c GMP-PKG), cyclic adenylic acid( c AMP), phosphatidylinositol-3-kinase-protein kinase B( PI3K-Akt), mammalian target of rapamycin(mTOR), and autophagy signaling pathways. In addition, it affected the multiple metabolic pathways, such as renin secretion, longevity regulation pathway, diabetic cardiomyopathy, and niacin and nicotinamide metabolism. DHZCP and VE significantly up-regulated the expression level of the key proteins in the AMPK signaling pathway in the renal tissue of the aging rats. In all, DHZCP and VE could mitigate renal aging and injury. DHZCP exerted multi-target effects via multiple signaling pathways and metabolic pathways in the kidney, in which the AMPK signaling pathway may be one of the key targets for action.

Association between asthma and COVID-19 severity during Omicron epidemic: a retrospective cohort study using real-world data.

BACKGROUND: The available evidence presented inconsistencies and inconclusive findings regarding the associations between co-existing asthma and mortality among COVID-19 patients. The objective of the current study is to investigate the relationship between asthma and severe outcomes after SARS-CoV-2 Omicron infection in an infection-naïve population. METHODS: A retrospective cohort study using propensity score matching was conducted. The COVID-19 patients requiring hospitalisation in Hong Kong from January 1, 2022, to November 13, 2022, an Omicron-predominated period, were identified. Severe clinical outcomes were defined as ICU admission and inpatient death after the first positive PCR results as well as a composite outcome of both. RESULTS: Of the 74,396 hospitalised COVID-19 patients admitted, 1,290 asthma patients and 18,641 non-asthma patients were included in the matched cohort. The rates of death and the composite outcome were 15·3% and 17·2%, respectively, among the non-asthma patients,12·2% and 13·6%, respectively, among the asthma patients, with adjusted hazard ratios equal to 0·775 (95% CI: 0·660-0·909) and 0·770 (95% CI: 0·662-0·895), respectively. The negative association was more apparent in the elderly and female groups. Asthma remained a factor that lowered the risk of disease severity even though the patients were not fully vaccinated with at least two doses. CONCLUSIONS: We used real-world data to demonstrate that asthma was not a risk factor for COVID-19 severity of the infections of Omicron variant, even though the patients were not fully vaccinated.

Two new species of Paraphlomis (Lamiales, Lamiaceae) from limestone karsts in Guangdong Province, China.

Paraphlomisqingyuanensis and P.baiwanensis (Lamiaceae), two new species from the limestone area in Guangdong Province, China, are described. Morphologically, both species belong to P.ser.Subcoriaceae C.Y. Wu & H.W. Li. A close relationship between the two new and P.subcoriacea was revealed by molecular phylogenetic analyses based on ETS and ITS. Further morphological and population genetic evidence indicated that they are distinct species in Paraphlomis. According to the IUCN Red List Categories and Criteria, P.qingyuanensis and P.baiwanensis were assessed as Endangered (EN) and Deficient (DD), respectively.

The effect of nalbuphine on prevention of emergence delirium in children: a systematic review with meta-analysis.

BACKGROUND: Emergence delirium remains a major postoperative concern for children undergoing surgery. Nalbuphine is a synthetic mixed agonist-antagonist opioid, which is believed to reduce the incidence of emergence delirium in children. The primary objective was to examine the effect of nalbuphine on emergence delirium in children undergoing surgery. METHODS: Databases of MEDLINE, EMBASE, and CENTRAL were searched from their starting dates until April 2023. Randomized Clinical Trials (RCT) and observational studies comparing nalbuphine and control in children undergoing surgery were included. RESULTS: Eight studies (n = 1,466 patients) were eligible for inclusion of data analysis. Compared to the control, our pooled data showed that the nalbuphine group was associated with lower incidence of emergence delirium (RR = 0.38, 95% CI [0.30, 0.47], p < 0.001) and reduced postoperative pain scores (MD = -0.98, 95% CI [-1.92, -0.04], p = 0.04). CONCLUSIONS: This review showed the administration of nalbuphine is associated with significant decrease in the incidence of emergence delirium and postoperative pain scores among children undergoing surgery. However, due to limited sample size, high degree of heterogeneity and low level of evidence, future adequately powered trials are warranted to explore the efficacy of nalbuphine on emergence delirium among the pediatric population.

Concomitant epidermal growth factor receptor mutation/c-ros oncogene 1 rearrangement in non-small cell lung cancer: A case report.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutation and c-ros oncogene 1 (ROS1) rearrangement are key genetic alterations and predictive tumor markers for non-small cell lung cancer (NSCLC) and are typically considered to be mutually exclusive. EGFR/ROS1 co-mutation is a rare event, and the standard treatment approach for such cases is still equivocal. CASE SUMMARY: Herein, we report the case of a 64-year-old woman diagnosed with lung adenocarcinoma, with concomitant EGFR L858R mutation and ROS1 rearrangement. The patient received two cycles of chemotherapy after surgery, but the disease progressed. Following 1-month treatment with gefitinib, the disease progressed again. However, after switching to crizotinib, the lesion became stable. Currently, crizotinib has been administered for over 53 months with a remarkable treatment effect. CONCLUSION: The efficacy of EGFR tyrosine kinase inhibitors and crizotinib was vastly different in this NSCLC patient with EGFR/ROS1 co-mutation. This report will aid future treatment of such patients.

Fast Metabolic Glycan Labeling for Click-Labeling and Imaging of Sialoglycans in Living Acute Brain Slices from Mice and Human Patients.

Living acute brain slices provide a practical platform for imaging sialylation in human brain pathology. However, the limited lifespan of acute brain slices has impeded the use of metabolic glycan labeling (MGL), which requires long-term incubation of clickable unnatural sugars such as N-azidoacetylmannosamine (ManNAz) to metabolically incorporate azides into sialoglycans. Here, we report a fast variant of MGL (fMGL), in which ManNAz-6-phosphate enables efficient azidosugar incorporation within 12 h by bypassing the bottleneck step in the sialic acid biosynthesis pathway, followed by click-labeling with fluorophores and imaging of sialoglycans in acute brain slices from mice and human patients. In the clinical samples of ganglioglioma, fMGL-based imaging reveals specific upregulation of sialylation in astrocyte-like but not neuron-like tumor cells. In addition, fMGL is integrated with click-expansion microscopy for high-resolution imaging of sialoglycans in brain slices. The fMGL strategy should find broad applications in the tissue imaging of glycans and surgical pathology.

Effects of perioperative dexmedetomidine on delayed graft function following renal transplant: a systematic review and meta-analysis.

BACKGROUND: Dexmedetomidine, a highly selective alpha-2 adrenoceptor agonist with sedative and analgesic effects, has been suggested in recent studies to possess renoprotective properties. Dexmedetomidine may reduce the incidence of delayed graft function and contribute to effective pain control post-renal transplantation. The primary objective of this systematic review was to assess whether dexmedetomidine decreases the occurrence of delayed graft function in renal transplant patients. METHODS: Databases including MEDLINE, EMBASE, and CENTRAL were comprehensively searched from their inception until March 2023. The inclusion criteria covered all Randomized Clinical Trials (RCTs) and observational studies comparing dexmedetomidine to control in adult patients undergoing renal transplant surgery. Exclusions comprised case series and case reports. RESULTS: Ten RCTs involving a total of 1358 patients met the eligibility criteria for data synthesis. Compared to the control group, the dexmedetomidine group demonstrated a significantly lower incidence of delayed graft function (OR = 0.71, 95% CI 0.52-0.97, p = 0.03, GRADE: Very low, I2 = 0%). Dexmedetomidine also significantly prolonged time to initiation of rescue analgesia (MD = 6.73, 95% CI 2.32-11.14, p = 0.003, GRADE: Very low, I2 = 93%) and reduced overall morphine consumption after renal transplant (MD = -5.43, 95% CI -7.95 to -2.91, p < 0.0001, GRADE: Very low, I2 = 0%). The dexmedetomidine group exhibited a significant decrease in heart rate (MD = -8.15, 95% CI -11.45 to -4.86, p < 0.00001, GRADE: Very low, I2 = 84%) and mean arterial pressure compared to the control group (MD = -6.66, 95% CI -11.27 to -2.04, p = 0.005, GRADE: Very low, I2 = 87%). CONCLUSIONS: This meta-analysis suggests that dexmedetomidine may potentially reduce the incidence of delayed graft function and offers a superior analgesia profile as compared to control in adults undergoing renal transplants. However, the high degree of heterogeneity and inadequate sample size underscore the need for future adequately powered trials to confirm these findings.

Akkermansia muciniphila isolated from forest musk deer ameliorates diarrhea in mice via modification of gut microbiota.

BACKGROUND: The forest musk deer, a rare fauna species found in China, is famous for its musk secretion which is used in selected Traditional Chinese medicines. However, over-hunting has led to musk deer becoming an endangered species, and their survival is also greatly challenged by various high incidence and high mortality respiratory and intestinal diseases such as septic pneumonia and enteritis. Accumulating evidence has demonstrated that Akkermannia muciniphila (AKK) is a promising probiotic, and we wondered whether AKK could be used as a food additive in animal breeding programmes to help prevent intestinal diseases. METHODS: We isolated one AKK strain from musk deer feces (AKK-D) using an improved enrichment medium combined with real-time PCR. After confirmation by 16S rRNA gene sequencing, a series of in vitro tests was conducted to evaluate the probiotic effects of AKK-D by assessing its reproductive capability, simulated gastrointestinal fluid tolerance, acid and bile salt resistance, self-aggregation ability, hydrophobicity, antibiotic sensitivity, hemolysis, harmful metabolite production, biofilm formation ability, and bacterial adhesion to gastrointestinal mucosa. RESULTS: The AKK-D strain has a probiotic function similar to that of the standard strain in humans (AKK-H). An in vivo study found that AKK-D significantly ameliorated symptoms in the enterotoxigenic Escherichia coli (ETEC)-induced murine diarrhea model. AKK-D improved organ damage, inhibited inflammatory responses, and improved intestinal barrier permeability. Additionally, AKK-D promoted the reconstitution and maintenance of the homeostasis of gut microflora, as indicated by the fact that AKK-D-treated mice showed a decrease in Bacteroidetes and an increase in the proportion of other beneficial bacteria like Muribaculaceae, Muribaculum, and unclassified f_Lachnospiaceae compared with the diarrhea model mice. CONCLUSION: Taken together, our data show that this novel AKK-D strain might be a potential probiotic for use in musk deer breeding, although further extensive systematic research is still needed.

Validation of the Malay Translation of Drug Attitude Inventory.

INTRODUCTION: The Drug Attitude Inventory 9 (DAI-9) is a nine-item self-rated questionnaire. The questionnaire assessed positive and negative attitudes of patients toward taking medication, presence of medication side effects and perceived autonomy in treatment decision. Aim: This study aimed to validate the psychometric properties of the Malay translation of Drug Attitude Inventory 9 (MDAI-9). METHOD: DAI-9 was translated from English to Malay via forward and backward translation process to produce MDAI-9. MDAI-9 was then validated on patients with psychosis who were attending psychiatry out-patient clinics. Results: There were 54 participants in this study. The subscale (attitude towards psychotropic medications) has a Cronbach's α of 0.93, whereas the subscale that assesses the presence of side effect problems has a Cronbach's α of 0.86. Exploratory factor analysis supported a two-factor model. Kaiser-Meyer-Olkin's measure of sampling adequacy was 0.64 and Bartlett's test of sphericity was significant (​​​​​X2   (36) = 281.8, p <0.001). CONCLUSION: In conclusion, MDAI-9 is reliable and valid.

Macrophage polarization as a novel endpoint for assessing combined risk of phthalate esters.

Combined exposure to phthalate esters (PAEs) has garnered increasing attention due to potential synergistic effects on human health. This study aimed to develop an in vitro model using human macrophages to evaluate the combined toxicity of PAEs and explore the underlying mechanisms. A high-throughput screening system was engineered by expressing a PPRE-eGFP reporter in THP-1 monocytes to monitor macrophage polarization upon PAEs exposure. Individual PAEs exhibited varied inhibitory effects on M2 macrophage polarization, with mono(2-ethylhexyl) phthalate (MEHP) being the most potent. Isobologram analysis revealed additive interactions when MEHP was combined with other PAEs, resulting in more pronounced suppression of M2 markers compared to individual compounds. Mechanistic studies suggested PAEs may exert effects by modulating PPARγ activity to inhibit M2 polarization. Notably, an equimolar mixture of six PAEs showed additive inhibition of M2 markers. In vivo experiments corroborated the combined hepatotoxic effects, with mice exposed to a PAEs mixture exhibiting reduced liver weight, dyslipidemia, and decreased hepatic M2 macrophages compared to DEHP alone. Transcriptome analysis highlighted disruptions in PPAR signaling, and distinct pathway alterations on cholesterol metabolism in the mixture group. Collectively, these findings underscore the importance of evaluating mixture effects and provide a novel approach for hazard assessment of combined PAEs exposure with implications for environmental health risk assessment.

Comparison of blended learning and traditional lecture method on learning outcomes in the evidence-based medicine course: a comparative study.

BACKGROUND: Blended learning comprised with flipped classroom (FC) and "internet plus" is a new learning strategy that reverses the position of teacher and students in class, and provides abundant learning resources before and after class. This study aimed to assess the impact of blended learning on learning outcomes in evidence-based medicine course, and compare with traditional learning method. METHODS: The participants of the two groups were from two difference cohorts in Air force medical university in China. The two groups toke the same pre-test before class and then were given the teaching of same chapters of evidence-based medicine with two different learning strategy. In the blended learning group, the participants were required to create a debriefing slide about their learning outcomes and the answers of questions given in advance after study the learning material sent by teacher a week before class, and the teacher gave a detailed summary based on the common problems, and distributed multimedia resources for review. After the experiment was carried out, learning outcomes including mastering knowledge, learning satisfaction, and self-evaluation were compared. RESULTS: 37 and 39 participants were enrolled to blended learning and traditional learning groups, respectively, and no statistically significant difference were found in baseline information and pre-test grades. Statistically significant differences were found in learning outcomes including post-test score (t = 2.90, p = 0.005), changes of scores between pre-test and post-test (t = 2.49, p = 0.022), learning satisfaction (t = 12.41, p = 0.001), and self-evaluation of the two groups (t = 7.82, p = 0.001). Especially, the changes of scores between pre-test and post-test of blended learning and traditional learning groups were 4.05 (4.26), and 2.00 (2.85), respectively. CONCLUSIONS: This study showed that compared with traditional learning strategy, blended learning can effectively enhanced participants' acquisition of knowledge, learning satisfaction, and self-evaluation in evidence-based medicine. Using blended learning method including "internet plus" and flipped classroom is recommended in the teaching of evidence-based medicine course.

Identification of residues in Lassa virus glycoprotein 1 involved in receptor switch.

Lassa virus (LASV) is an enveloped, negative-sense RNA virus that causes Lassa hemorrhagic fever. Successful entry of LASV requires the viral glycoprotein 1 (GP1) to undergo a receptor switch from its primary receptor alpha-dystroglycan (α-DG) to its endosomal receptor lysosome-associated membrane protein 1 (LAMP1). A conserved histidine triad in LASV GP1 has been reported to be responsible for receptor switch. To test the hypothesis that other non-conserved residues also contribute to receptor switch, we constructed a series of mutant LASV GP1 proteins and tested them for binding to LAMP1. Four residues, L84, K88, L107, and H170, were identified as critical for receptor switch. Substituting any of the four residues with the corresponding lymphocytic choriomeningitis virus (LCMV) residue (L84 â€‹N, K88E, L10F, and H170S) reduced the binding affinity of LASV GP1 for LAMP1. Moreover, all mutations caused decreases in glycoprotein precursor (GPC)-mediated membrane fusion at both pH 4.5 and 5.2. The infectivity of pseudotyped viruses bearing either GPCL84N or GPCK88E decreased sharply in multiple cell types, while L107F and H170S had only mild effects on infectivity. Using biolayer light interferometry assay, we found that all four mutants had decreased binding affinity to LAMP1, in the order of binding affinity being L84 â€‹N â€‹> â€‹L107F â€‹> â€‹K88E â€‹> â€‹H170S. The four amino acid loci identified for the first time in this study have important reference significance for the in-depth investigation of the mechanism of receptor switching and immune escape of LASV occurrence and the development of reserve anti-LASV infection drugs.

The effect of foot orientation modifications on knee joint biomechanics during daily activities in people with and without knee osteoarthritis.

BACKGROUND: Altered gait could influence knee joint moment magnitudes and cumulative damage over time. Gait modifications have been shown to reduce knee loading in people with knee osteoarthritis during walking, although this has not been explored in multiple daily activities. Therefore, this study investigated the effect of different foot orientations on knee loading during multiple daily activities in people with and without knee osteoarthritis. METHODS: Thirty people with knee osteoarthritis and twenty-nine without (control) performed walking, stair ambulation and sit-to-stand across a range of foot progression angles (neutral, toe-in, toe-out and preferred). Peak knee adduction moment, knee adduction moment impulse and knee pain were compared across a continuous range of foot orientations, between activities, and groups. FINDINGS: Increased foot progression angle (more toe-in) reduced 1st peak knee adduction moment across all activities in both knee osteoarthritis and control (P < 0.001). There was a greater reduction in knee adduction moment in the control group during walking and stair ambulation (P ≤ 0.006), where the knee osteoarthritis group already walked preferably less toe-out than the control group. Under preferred condition, stair descent had the greatest knee loading and knee pain compared to other activities. INTERPRETATION: Although increased foot progression angle (toward toe-in) appeared to be more effective in reducing knee loading for all activities, toe-in modification might not benefit stair ambulation. Future gait modification should likely be personalised to each patient considering the individual difference in preferred gait and knee alignment required to shift the loading medially or laterally.

Identification of ∼200 transformation products of polyhalogenated compounds to characterize their transformation pathways in sludges.

Sewage sludge adsorbs a large amount of harmful organic pollutants, particularly the persistent and hydrophobic polyhalogenated compounds (PHCs). PHCs have been subjected to biological and chemical oxidation treatments during wastewater treatment processes; however, the species and concentrations of their transformation products (TPs) in sludge remain unknown, and the transformation pathways are unclear. In this study, 234 TPs of PHCs, including 77 TPs of chlorinated paraffins (CPs-TPs), 102 TPs of organochlorine pesticides (OCPs-TPs), 45 TPs of dechlorane plus (DPs-TPs), and 10 TPs of brominated flame retardants (BFRs-TPs), were identified in sludge through Ph4PCl-enhanced ionization coupled with ultra-performance liquid chromatography-Orbitrap-mass spectrometry. Based on the chemical structures of the identified TPs, we identified three major transformation pathways: dehalogenation-hydroxylation, carbon chain decomposition, and desulfurization. Approximately 97 TPs were newly discovered through the pathways. Carbon chain decomposition products of OCPs and DPs were detected for the first time at relatively high abundances. More hydroxylation products of DPs and hexabromocyclododecane (HBCD) and multi-dehalogenation products of heptachlor, toxaphene, DPs and HBCDs were detected at relative intensities higher than those of the known TPs. The oxidation treatment of sludge achieved up to 13 %-94 % of PHCs to be removed, with dehalogenation-hydroxylation as the main transformation pathway. Advanced treatment technologies are needed for degradation of both PHCs and their TPs.

Analgesic Effects of Intraperitoneal Lidocaine in Adults Undergoing Surgery: A Systematic Review and Meta-Analysis with Trial Sequential Analysis.

OBJECTIVE: The administration of local anaesthesia in intraperitoneal space as part of the multi-modal analgesic regimen has shown to be effective in reducing postoperative pain. Recent studies demonstrated that intraperitoneal lidocaine may provide analgesic effects. Primary objective was to determine the impact of intraperitoneal lidocaine on postoperative pain scores at rest. DESIGN: We carried out a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). METHODS: Databases of MEDLINE, EMBASE, and CENTRAL were searched from their inception date until May 2023. Randomized clinical trials (RCT) comparing intraperitoneal lidocaine and placebo in adults undergoing surgery were included. RESULTS: Our systematic review included 24 RCTs (n = 1,824). The intraperitoneal lidocaine group was significantly associated with lower postoperative pain scores at rest (MD: -0.87, 95% CI: -1.04 to -0.69) and at movement (MD: -0.50, 95% Cl: -0.93 to -0.08) among adult patients after surgery. Its administration also significantly decreased morphine consumption (MD: -6.42 mg, 95% Cl: -11.56 to -1.27), lowered the incidence of needing analgesia (OR: 0.22, 95% Cl: 0.14 to 0.35). Intraperitoneal lidocaine statistically reduced time to resume regular diet (MD: 0.16 days; 95% Cl: -0.31 to -0.01), and lowered postoperative incidence of nausea and vomiting (OR: 0.54, 95% Cl: 0.39 to 0.75). CONCLUSIONS: In this review, our findings should be interpreted with caution. Future studies are warranted to determine the optimal dose of administering intraperitoneal lidocaine among adult patients undergoing surgery.