ABSTRACT
After spinal cord injury (SCI), infiltrating macrophages undergo excessive phagocytosis of myelin and cellular debris, forming lipid-laden foamy macrophages. To understand their role in the cellular pathology of SCI, investigation of the foamy macrophage phenotype in vitro revealed a pro-inflammatory profile, increased reactive oxygen species (ROS) production, and mitochondrial dysfunction. Bioinformatic analysis identified PI3K as a regulator of inflammation in foamy macrophages, and inhibition of this pathway decreased their lipid content, inflammatory cytokines, and ROS production. Macrophage-specific inhibition of PI3K using liposomes significantly decreased foamy macrophages at the injury site after a mid-thoracic contusive SCI in mice. RNA sequencing and in vitro analysis of foamy macrophages revealed increased autophagy and decreased phagocytosis after PI3K inhibition as potential mechanisms for reduced lipid accumulation. Together, our data suggest that the formation of pro-inflammatory foamy macrophages after SCI is due to the activation of PI3K signaling, which increases phagocytosis and decreases autophagy.
Subject(s)
Phosphatidylinositol 3-Kinases , Spinal Cord Injuries , Mice , Animals , Phosphatidylinositol 3-Kinases/metabolism , Reactive Oxygen Species/metabolism , Macrophages/metabolism , Spinal Cord Injuries/metabolism , Lipids , Spinal Cord/pathologyABSTRACT
Background: A wide variety of electrocardiogram (ECG) changes can manifest with antidepressant drugs, occurring at both therapeutic doses and toxic levels. Notably, ECG abnormalities like wide QRS and QT prolongation may be observed in poisoned patients with tricyclic antidepressants (TCAs), indicating severe conditions that necessitate the implementation of cardiac monitoring systems. This study aimed to investigate ECG Abnormality in poisoned patients with tricyclic antidepressants. Methods: This retrospective patient record study was conducted at Razi Hospital in Ahvaz, Iran, from 2006 to 2009. Patient information was extracted from hospital medical records after the established protocol. The chi-square test was employed for initial analysis; subsequently, logistic regression was applied to identify risk factors associated with abnormal ECG findings. We analyzed the data using SPSS (Version 19; IBM) statistical software. P < 0.05 was defined as statistically significant. Results: Among the 210 poisoned patients, comprising 88 men (41.9%) and 122 women (58.1%), the majority fell within the age range of 15 to 25 years. In our study, the most commonly ingested drugs by poisoned patients were amitriptyline in 134 patients (63.8%) and nortriptyline in 42 patients (20%). A significant portion of 137 patients (65.2%) exhibited poisoning symptoms within Ë 6 hours, while 73 patients (34.8%) showed symptoms between 6 and 24 hours. Our findings indicated that the initial symptoms in poisoned patients included a decreased level of consciousness in 168 patients (80%), nausea and vomiting in 20 patients (9.5%), and various other symptoms. Notably, our results revealed ECG changes in 70 patients, with 32 patients (15.2%) showing a QRS widening (> 0.1sec), 5 patients (2.4%) displaying a tall R wave in aVR, 5 patients (2.4%) exhibiting right axis deviation, and other observed changes. Conclusion: QRS widening in poisoned patients with tricyclic antidepressants is more frequently observed in symptomatic patients, highlighting the importance of ECG screening in these patients.
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PURPOSE OF REVIEW: This review delves into the potential of artificial intelligence (AI), particularly machine learning (ML), in enhancing graft-versus-host disease (GVHD) risk assessment, diagnosis, and personalized treatment. RECENT FINDINGS: Recent studies have demonstrated the superiority of ML algorithms over traditional multivariate statistical models in donor selection for allogeneic hematopoietic stem cell transplantation. ML has recently enabled dynamic risk assessment by modeling time-series data, an upgrade from the static, "snapshot" assessment of patients that conventional statistical models and older ML algorithms offer. Regarding diagnosis, a deep learning model, a subset of ML, can accurately identify skin segments affected with chronic GVHD with satisfactory results. ML methods such as Q-learning and deep reinforcement learning have been utilized to develop adaptive treatment strategies (ATS) for the personalized prevention and treatment of acute and chronic GVHD. SUMMARY: To capitalize on these promising advancements, there is a need for large-scale, multicenter collaborations to develop generalizable ML models. Furthermore, addressing pertinent issues such as the implementation of stringent ethical guidelines is crucial before the widespread introduction of AI into GVHD care.
Subject(s)
Bronchiolitis Obliterans Syndrome , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Artificial Intelligence , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Graft vs Host Disease/therapy , Graft vs Host Disease/prevention & control , Machine Learning , Multicenter Studies as TopicABSTRACT
In brief: Ovarian tissue cryopreservation and culture provide an option for fertility preservation without tissue grafting, but need optimization. This study reveals that vitrified bovine ovarian tissue can be cultured on agarose gel and maintain follicle morphology, low activation, and low apoptosis. Abstract: Ovarian tissue preservation is hitherto a promising fertility insurance option for precious animals. Ovarian tissue vitrification and culture combined approach would eliminate the need of transplanting ovarian tissue to obtain mature oocytes. We aimed at optimizing vitrification and in vitro culture conditions for improved bovine ovarian tissue viability. Ovaries obtained from the slaughterhouse were punched into fragments and divided into three groups. Group 1 (fresh) was divided into two and immediately placed in two-culture systems (culture inserts and agarose inserts). Group 2 was vitrified, warmed, and placed in the two-culture systems, while group 3 was only equilibrated and then placed in the two-culture systems. All cultures were maintained for 6 days and spent media were collected on alternate days for cytokine (interleukin 1ß and interleukin 6) evaluation. Fragments were fixed for morphology assessment and immunohistochemistry. Higher percentages (P < 0.05) of grade 1 (morphologically intact) follicles were observed in fragments on agarose compared to those on culture inserts on days 2 and 4 of the culture. Conversely, we found higher (P < 0.05) shifts of primordial follicles to transitional follicles in fragments on culture inserts vis-à-vis agarose inserts which was consistent with a higher proportion of Ki-67 and MCM-7 and activated caspase-3-positive follicles. In conclusion, in vitro culture of bovine ovarian tissue on agarose inserts maintained follicle morphology, low follicle activation, and low apoptosis compared to culture inserts.
Subject(s)
Cryopreservation , Ovarian Follicle , Female , Animals , Cattle , Sepharose , Cryopreservation/veterinary , Ovary , VitrificationABSTRACT
Persistent inflammation contributes to various inflammatory conditions. Inflammation-related diseases may be treated by inhibiting pro-inflammatory mediators and cytokines. Curcumin and coumarin derivatives can target signalling pathways and cellular factors to address immune-related and inflammatory ailments. This study involved designing and synthesising three series of coumarin-based analogs that incorporated curcumin and other heterocycles. These analogs were evaluated for their potential as anti-inflammatory agents in LPS-induced macrophages. Among the fourteen synthesised coumarin derivatives, compound 14b, which contained 3,4-dimethoxybenzylidene hydrazinyl, demonstrated the highest anti-inflammatory activity with an EC50 value of 5.32 µM. The anti-inflammatory effects of 14b were achieved by modulating signalling pathways like AKT/mTOR and Nrf2/HO-1, and downregulating NF-kß, resulting in reduced production of pro-inflammatory cytokines such as IL-6, IL-1ß, and TNF-α. The modelling studies revealed that 14b and dexamethasone bind to the same TNF-α pocket, suggesting that 14b has potential as a therapeutic agent superior to dexamethasone for TNF-α.
Three series of curcumin-based analogs, incorporating other heterocycles, were synthesised with the intention of exploring their potential as anti-inflammatory agents.Subsequently, these analogs underwent biological assessment in macrophages induced by LPS to determine their anti-inflammatory efficacy.Among the fourteen coumarin derivatives synthesised, the most potent anti-inflammatory activity was observed in the coumarin compound 14b, which featured a 3,4-dimethoxybenzylidene hydrazinyl moiety, with an EC50 value of 5.32 µM.The anti-inflammatory effects of compound 14b were achieved through the modulation of signalling pathways such as AKT/mTOR and Nrf2/HO-1, as well as the downregulation of NF-kß, resulting in decreased production of pro-inflammatory cytokines including IL-6, IL-1ß, and TNF-α.Molecular modelling studies revealed that both compound 14b and dexamethasone bind to the same binding site on TNF-α, suggesting that 14b has the potential to serve as a therapeutic agent for TNF-α and other pro-inflammatory cytokines that surpasses that of dexamethasone.
Subject(s)
Anti-Inflammatory Agents , Coumarins , Curcumin , NF-kappa B , Humans , Anti-Inflammatory Agents/pharmacology , Coumarins/pharmacology , Curcumin/pharmacology , Cytokines/metabolism , Dexamethasone/pharmacology , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/metabolism , Lipopolysaccharides , Macrophages , NF-E2-Related Factor 2/metabolism , NF-kappa B/metabolism , Proto-Oncogene Proteins c-akt/metabolism , TOR Serine-Threonine Kinases/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Axon injury is a hallmark of many neurodegenerative diseases, often resulting in neuronal cell death and functional impairment. Dual leucine zipper kinase (DLK) has emerged as a key mediator of this process. However, while DLK inhibition is robustly protective in a wide range of neurodegenerative disease models, it also inhibits axonal regeneration. Indeed, there are no genetic perturbations that are known to both improve long-term survival and promote regeneration. To identify such a neuroprotective target, we conducted a set of complementary high-throughput screens using a protein kinase inhibitor library in human stem cell-derived retinal ganglion cells (hRGCs). Overlapping compounds that promoted both neuroprotection and neurite outgrowth were bioinformatically deconvoluted to identify specific kinases that regulated neuronal death and axon regeneration. This work identified the role of germinal cell kinase four (GCK-IV) kinases in cell death and additionally revealed their unexpected activity in suppressing axon regeneration. Using an adeno-associated virus (AAV) approach, coupled with genome editing, we validated that GCK-IV kinase knockout improves neuronal survival, comparable to that of DLK knockout, while simultaneously promoting axon regeneration. Finally, we also found that GCK-IV kinase inhibition also prevented the attrition of RGCs in developing retinal organoid cultures without compromising axon outgrowth, addressing a major issue in the field of stem cell-derived retinas. Together, these results demonstrate a role for the GCK-IV kinases in dissociating the cell death and axonal outgrowth in neurons and their druggability provides for therapeutic options for neurodegenerative diseases.
Subject(s)
Axons/enzymology , Axons/pathology , Central Nervous System/pathology , Germinal Center Kinases/metabolism , Nerve Regeneration , Animals , Base Sequence , CRISPR-Cas Systems/genetics , Cell Death/drug effects , Cell Survival/drug effects , Dependovirus/metabolism , Disease Models, Animal , Humans , Mice, Inbred C57BL , Nerve Regeneration/drug effects , Neuronal Outgrowth/drug effects , Optic Nerve Injuries/metabolism , Optic Nerve Injuries/pathology , Organoids/metabolism , Protein Kinase Inhibitors/pharmacology , Retinal Ganglion Cells/drug effects , Retinal Ganglion Cells/metabolism , Signal Transduction/drug effectsABSTRACT
Due to the recent advances in the domain of smart agriculture as a result of integrating traditional agriculture and the latest information technologies including the Internet of Things (IoT), cloud computing, and artificial intelligence (AI), there is an urgent need to address the information security-related issues and challenges in this field. In this article, we propose the integration of lightweight cryptography techniques into the IoT ecosystem for smart agriculture to meet the requirements of resource-constrained IoT devices. Moreover, we investigate the adoption of a lightweight encryption protocol, namely, the Expeditious Cipher (X-cipher), to create a secure channel between the sensing layer and the broker in the Message Queue Telemetry Transport (MQTT) protocol as well as a secure channel between the broker and its subscribers. Our case study focuses on smart irrigation systems, and the MQTT protocol is deployed as the application messaging protocol in these systems. Smart irrigation strives to decrease the misuse of natural resources by enhancing the efficiency of agricultural irrigation. This secure channel is utilized to eliminate the main security threat in precision agriculture by protecting sensors' published data from eavesdropping and theft, as well as from unauthorized changes to sensitive data that can negatively impact crops' development. In addition, the secure channel protects the irrigation decisions made by the data analytics (DA) entity regarding the irrigation time and the quantity of water that is returned to actuators from any alteration. Performance evaluation of our chosen lightweight encryption protocol revealed an improvement in terms of power consumption, execution time, and required memory usage when compared with the Advanced Encryption Standard (AES). Moreover, the selected lightweight encryption protocol outperforms the PRESENT lightweight encryption protocol in terms of throughput and memory usage.
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Software Defect Prediction (SDP) is an integral aspect of the Software Development Life-Cycle (SDLC). As the prevalence of software systems increases and becomes more integrated into our daily lives, so the complexity of these systems increases the risks of widespread defects. With reliance on these systems increasing, the ability to accurately identify a defective model using Machine Learning (ML) has been overlooked and less addressed. Thus, this article contributes an investigation of various ML techniques for SDP. An investigation, comparative analysis and recommendation of appropriate Feature Extraction (FE) techniques, Principal Component Analysis (PCA), Partial Least Squares Regression (PLS), Feature Selection (FS) techniques, Fisher score, Recursive Feature Elimination (RFE), and Elastic Net are presented. Validation of the following techniques, both separately and in combination with ML algorithms, is performed: Support Vector Machine (SVM), Logistic Regression (LR), Naïve Bayes (NB), K-Nearest Neighbour (KNN), Multilayer Perceptron (MLP), Decision Tree (DT), and ensemble learning methods Bootstrap Aggregation (Bagging), Adaptive Boosting (AdaBoost), Extreme Gradient Boosting (XGBoost), Random Forest(RF), and Generalized Stacking (Stacking). Extensive experimental setup was built and the results of the experiments revealed that FE and FS can both positively and negatively affect performance over the base model or Baseline. PLS, both separately and in combination with FS techniques, provides impressive, and the most consistent, improvements, while PCA, in combination with Elastic-Net, shows acceptable improvement.
Subject(s)
Algorithms , Software , Bayes Theorem , Machine Learning , Neural Networks, Computer , Support Vector MachineABSTRACT
The rapid technological advancements in the current modern world bring the attention of researchers to fast and real-time healthcare and monitoring systems. Smart healthcare is one of the best choices for this purpose, in which different on-body and off-body sensors and devices monitor and share patient data with healthcare personnel and hospitals for quick and real-time decisions about patients' health. Cognitive radio (CR) can be very useful for effective and smart healthcare systems to send and receive patient's health data by exploiting the primary user's (PU) spectrum. In this paper, tree-based algorithms (TBAs) of machine learning (ML) are investigated to evaluate spectrum sensing in CR-based smart healthcare systems. The required data sets for TBAs are created based on the probability of detection (Pd) and probability of false alarm (Pf). These data sets are used to train and test the system by using fine tree, coarse tree, ensemble boosted tree, medium tree, ensemble bagged tree, ensemble RUSBoosted tree, and optimizable tree. Training and testing accuracies of all TBAs are calculated for both simulated and theoretical data sets. The comparison of training and testing accuracies of all classifiers is presented for the different numbers of received signal samples. Results depict that optimizable tree gives the best accuracy results to evaluate the spectrum sensing with minimum classification error (MCE).
Subject(s)
Algorithms , Health Personnel , Humans , Hospitals , Machine Learning , ProbabilityABSTRACT
Smart healthcare is altering the delivery of healthcare by combining the benefits of IoT, mobile, and cloud computing. Cloud computing has tremendously helped the health industry connect healthcare facilities, caregivers, and patients for information sharing. The main drivers for implementing effective healthcare systems are low latency and faster response times. Thus, quick responses among healthcare organizations are important in general, but in an emergency, significant latency at different stakeholders might result in disastrous situations. Thus, cutting-edge approaches like edge computing and artificial intelligence (AI) can deal with such problems. A packet cannot be sent from one location to another unless the "quality of service" (QoS) specifications are met. The term QoS refers to how well a service works for users. QoS parameters like throughput, bandwidth, transmission delay, availability, jitter, latency, and packet loss are crucial in this regard. Our focus is on the individual devices present at different levels of the smart healthcare infrastructure and the QoS requirements of the healthcare system as a whole. The contribution of this paper is five-fold: first, a novel pre-SLR method for comprehensive keyword research on subject-related themes for mining pertinent research papers for quality SLR; second, SLR on QoS improvement in smart healthcare apps; third a review of several QoS techniques used in current smart healthcare apps; fourth, the examination of the most important QoS measures in contemporary smart healthcare apps; fifth, offering solutions to the problems encountered in delivering QoS in smart healthcare IoT applications to improve healthcare services.
Subject(s)
Artificial Intelligence , Disasters , Humans , Cloud Computing , Industry , Delivery of Health CareABSTRACT
Age and sex differences in Takotsubo syndrome (TTS) are still a matter of debate. The present study aimed to evaluate the difference in cardiovascular (CV) risk factors, CV disease, in-hospital complications, and death within different sex-age groups. Using the National Inpatient Sample database between 2012 and 2016, 32,474 patients older than 18 years of age hospitalized with the primary diagnosis of TTS were identified. A total of 32,474 patients were enrolled; 27,611 (85.04%) were female. CV risk factors were higher in females, while CV diseases and in-hospital complications were significantly higher in males. The mortality in males was twice as high as that of female patients (9.83% versus 4.58%, p<0.01), and in the logistic regression model after adjustment for confounders, the odds ratio (OR) was 1.79, the confidence interval was 1.60-2.02, and p<0.01. After dividing the group based on age, in-hospital complications were inversely related to age in both sexes, and the length of in-hospital stay was double in the youngest group compared to the oldest one. Mortality increased progressively with age in both groups but was constantly higher in males for each age group. Multiple logistic regression analysis for mortality was performed for the two sexes separately and for the three age groups, considering the youngest one as the reference group. In females, the OR was 1.59 and 2.88, respectively, for groups 2 and 3; for males, the OR was 1.92 and 3.15, all of them statistically significant (p<0.01). In-hospital complications were more common in younger patients with TTS, particularly in males. Mortality was positively correlated with age for both sexes, but mortality was higher in males compared to females in all age groups.
Subject(s)
Inpatients , Takotsubo Cardiomyopathy , Humans , Male , Female , Takotsubo Cardiomyopathy/diagnosis , Length of Stay , Hospital Mortality , HospitalsABSTRACT
BACKGROUND: Respectful maternity care (RMC) emphasizes the social and relational elements of maternity care and is a crucial part of initiatives to improve service accessibility and quality. Women's perceptions have influenced much of what we know about RMC and contempt in the labor ward. In order to understand midwives' perspectives of RMC, this meta-synthesis focused on them. METHOD: For this inquiry, the databases PubMed/Medline, Embase, Web of Science, and Scopus were searched to find studies on midwives' perceptions of RMC written between 2011 and April 20th 2023. The included articles were to English language restriction. The results of the included research were examined using thematic analysis. Using the inclusion criteria, 84 potentially relevant articles were carefully reviewed, and only 22 were ultimately selected for synthesis. The quality of the qualitative study was assessed using the CASP, a tool for quality evaluation and PRISMA guidelines were followed. Using the MAXQDA program, the cited quotes and the original authors' interpretations were combined. RESULT: There were 22 studies total, thematic synthesis was determined to be appropriate for a total of 22 research studies. Following are the topics which we summarized our analysis: in six major themes: Midwives' conceptualizations of RMC, Midwives commitment to woman's rights, The value and impact of RMC to midwives, Midwife's perception of disrespectful care, Challenges in providing respectful maternity care, and Midwives' recommendations for optimal RMC practice. CONCLUSION: In addition to specific focus on promoting cooperation, policies to enhance health systems and strategic consideration of the midwifery profession's future are required.
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The objective of this research is to assess the impact of radon concentration on workers at certain construction material industries in Erbil, Kurdistan Region of Iraq. The CR-39 solid-state track detector was used in this experiment to monitor radon levels and their daughters. For this purpose, as a case study group, 70 workers were divided into seven subgroups (gypsum, cement plant, lightweight block, marble, red brick 1, crusher stone, and concrete block 2), and 20 healthy volunteers were selected as a control group. The findings demonstrate that the mean concentrations of radon, radium, uranium, and radon daughters deposited on the detector face (POS) and chamber walls (POW) for the case study group were 9.61 ± 1.52 Bq/m3, 0.33 ± 0.05 Bq/Kg, 5.39 ± 0.86 mBq/Kg, 4 ± 0.63, and 16.62 ± 2.64 mBq/m3, whereas for the control group, they were 3.39 ± 0.58 Bq/m3, 0.117 ± 0.03 Bq/Kg, 1.91 ± 0.32 mBq/Kg, 1.41 ± 0.24, and 5.88 ± 1 mBq/m3, respectively. The statistical analysis revealed that radon, radium, uranium, and POW and POS concentrations were statistically significant (p ≤ 0.001) in the samples for the case study groups of cement, lightweight block, red brick 1, marble, and crusher stone factories in comparison to the control group; however, the results for gypsum and concrete block 2 factories were not statistically significant in comparison to the control group. Intriguingly, the radon levels in every blood sample examined were far lower than the 200 Bq/m3 limit established by the International Atomic Energy Agency. Hence, it may be argued that the blood is devoid of contaminants. These results are crucial for determining whether or not an individual is exposed to substantial quantities of radiation and for demonstrating a link between radon, its daughter, uranium, and the prevalence of cancer among workers in the Kurdish region of Iraq.
Subject(s)
Air Pollutants, Radioactive , Radiation Monitoring , Radium , Radon , Uranium , Humans , Radium/analysis , Uranium/analysis , Calcium Sulfate/analysis , Environmental Monitoring , Radon/analysis , Air Pollutants, Radioactive/analysis , Construction Materials/analysis , Calcium Carbonate/analysis , Radiation Monitoring/methodsABSTRACT
Vegetables are industrial crops endowed with both nutritional and medicinal values. The overwhelming contributions of vegetables to human living in the form of nutrients and medicine cannot be under emphasised. Thus, this study examined the recoveries of phenolic compounds and antioxidants from Corchorus olitorius leaves using a microwave-enhanced extraction technique. Furthermore, the phenolic compounds in the leaf extract of C. olitorius were comprehensively identified using liquid chromatography-mass spectrometry quadrupole of flight (LC-QToF-MS). At the optimized conditions of microwave-enhanced extraction (extraction time of 131 s, microwave power 305 W, solvent/sample ratio of 12 mL/g, and ethanol concentration of 50%), total phenolic content (TPC) of 343.098 ± 3.05 mg GAE/10 g d.b., IC50 values of 68.89 ± 1.08 and 29.76 ± 1.00 µg/mL for 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6'-sulfonic acid) (ABTS) assays, respectively, were achieved. Furthermore, an aggregate of fourteen phenolic compounds that include 1-galloyl-glucose, 1,3,5-O-tricaffeoylquinic acid, procyanidin C-1, 4,4',5,6-tetrahydroxystilbene, 3,4,5-O-tricaffeoylquinic acid, 5-desgalloylstachyurin, sanguiin H-4, corilagin_1, 1-O-galloylpedunculagin, laevigatin A, pedunculagin, 2,4,6-tri-O-galloyl-ß-D-glucose, 1,3,6-trigalloyl-ß-D-glucose, and 1,2,3,6-tetra-O-galloyl-ß-D-glucose was tentatively identified in the leaf extract of C. olitorius. In general, this study has established C. olitorius leaves as sources of phenolic compounds and natural antioxidants. Thus, the intake can continue to be promoted as a way forward in solving the problem of food insecurity. Supplementary Information: The online version contains supplementary material available at 10.1007/s11696-023-02771-x.
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Advances in the understanding of lipid droplet biology have revealed essential roles for these organelles in mediating proper cellular homeostasis and stress response. Lipid droplets were initially thought to play a passive role in energy storage. However, recent studies demonstrate that they have substantially broader functions, including protection from reactive oxygen species, endoplasmic reticulum stress, and lipotoxicity. Dysregulation of lipid droplet homeostasis is associated with various pathologies spanning neurological, metabolic, cardiovascular, oncological, and renal diseases. This review provides an overview of the current understanding of lipid droplet biology in both health and disease.
Subject(s)
Lipid Droplets , Lipid Metabolism , Endoplasmic Reticulum Stress , Homeostasis , Lipid Droplets/metabolism , Lipid Metabolism/physiologyABSTRACT
Tissue damage after spinal cord injury (SCI) elicits a robust inflammatory cascade that fails to resolve in a timely manner, resulting in impaired wound healing and cellular regeneration. This inflammatory response is partly mediated by infiltrating immune cells, including macrophages. As professional phagocytes, macrophages initially play an important role in debris clearance at the injury site, which would be necessary for proper tissue regeneration. After SCI, most macrophages become filled with lipid droplets due to excessive uptake of lipid debris, assuming a "foamy" phenotype that is associated with a proinflammatory state. Myelin has been assumed to be the main source of lipid that induces foamy macrophage formation after injury given its abundance in the spinal cord. This assumption has led to the widespread use of purified myelin treatment to model foamy macrophage formation in vitro. However, the assumption that myelin is necessary for foamy macrophage formation remains untested. To this end, we developed a novel foamy macrophage assay utilizing total spinal cord homogenate to include all sources of lipid present at the injury site. Using the myelin basic protein knockout (MBP KO, i.e., Shiverer) mice that lack myelin, we investigated lipid accumulation in foamy macrophages. Primary macrophages treated with myelin-deficient spinal cord homogenate still formed large lipid droplets typically observed in foamy macrophages, although to a lesser degree than cells treated with normal homogenate. Similarly, MBP KO mice subjected to contusive spinal cord injury also formed foamy macrophages that exhibited reduced lipid content and associated with improved histological outcomes and reduced immune cell infiltration. Therefore, the absence of myelin does not preclude foamy macrophage formation, indicating that myelin is not the only major source of lipid that contributes this pathology, even though myelin may alter certain aspects of its inflammatory profile.
Subject(s)
Macrophages/pathology , Myelin Sheath/pathology , Spinal Cord Injuries/pathology , Spinal Cord/pathology , Animals , Cytokines/metabolism , Disease Models, Animal , Female , Inflammation/metabolism , Inflammation/pathology , Lipids , Macrophage Activation/physiology , Macrophages/metabolism , Male , Mice , Myelin Sheath/metabolism , Spinal Cord/metabolism , Spinal Cord Injuries/metabolismABSTRACT
Multiple parameters need to be monitored to analyze the kinetics of biological progresses. Surface plasmon polariton resonance sensors offer a non-invasive approach to continuously detect the local change of refractive index of molecules with high sensitivity. However, the fabrication of miniaturized, compact, and low-cost sensors is still challenging. In this paper, we propose and demonstrate a grating-coupled SPR sensor platform featuring dual mode operation for simultaneous sensing of pressure and refractive index, which can be fabricated using a highly-efficient low-cost method, allowing large-scale production. Both sensing functionalities are realized by optical means via monitoring the spectral positions of a surface plasmon polariton mode (for refractive index sensing) and Fabry-Perot or metal-insulator-metal modes (for pressure sensing), which are supported by the structure. Simultaneous measurement of refractive index with the sensitivity of 494 nm/RIU and pressure was demonstrated experimentally. The proposed platform is promising for biomonitoring that requires both high refractive index sensitivity and local pressure detection.
Subject(s)
Refractometry , Surface Plasmon Resonance , Surface Plasmon Resonance/methodsABSTRACT
BACKGROUND: Adherence to standard guidelines is imperative when question comes to disease management. The present study aimed to evaluate the administration of adjunctive vitamin D therapy in various diseases, its adherence to standard guideline and the effect of socioeconomic status on the consumption of vitamin D in children. METHODS: Cross sectional observational study was conducted among 400 ambulatory pediatric patients at Children's Hospital, Pakistan Institute of Medical Sciences Islamabad, from November 2017 to June 2018. Data were collected by a self-designed structured questionnaire from the patient's medical chart. Adjunctive vitamin D therapy adherence was evaluated by the U. S endocrinology clinical practice guideline of vitamin D deficiency. The association between socioeconomic status and consumption of vitamin D was examined by chi-square. Alpha value (p ≤ 0.005) was considered statistically significant. Statistical analysis was done by SPSS version 25. RESULTS: In 400 patients, 9 diseases and 21 comorbid conditions were identified, in which adjunctive vitamin D therapy was prescribed. Adherence to vitamin D testing in high-risk vitamin D deficiency diseases as; seizures (3.8%), bone deformities (13.3%), steroid-resistant nephrotic syndrome (0.0%), cerebral palsy (5.9%) and meningitis (14.3%). Adherence to prescribed vitamin D dose was in (41.3%) patients in various diseases. Significant association (p < 0.05) was found between socioeconomic status and consumption of vitamin D in children and mothers. CONCLUSIONS: It was found that adjunctive vitamin D was being prescribed in various diseases and comorbidities. Overall poor adherence to the standard guideline was observed in disease management in children. Low socioeconomic status affects vitamin D supplementation consumption in children.
Subject(s)
Vitamin D Deficiency , Vitamin D , Child , Cross-Sectional Studies , Dietary Supplements , Humans , Vitamin D/therapeutic use , Vitamin D Deficiency/drug therapy , Vitamins/therapeutic useABSTRACT
OBJECTIVE(S): This study was designed to evaluate the efficacy and safety of serratus anterior plane block (SAPB) as an analgesic technique for thoracotomies in pediatric patients. DESIGN: Double-blinded randomized controlled trial. SETTING: A single-center study at Aboelrish Pediatric Hospital, one tertiary hospital of Cairo University Hospitals. PARTICIPANTS: Seventy pediatric patients aged six months-to-three years scheduled for thoracotomies. INTERVENTIONS: Patients were randomized into two groups, group SF and group F. Group SF received an ultrasound-guided SAPB (n = 35), whereas group F (n = 35) did not. All groups received an intraoperative fentanyl infusion (at 0.5 µg/kg /h). MEASUREMENTS: The primary outcome was the total dose of postoperatively administrated fentanyl in the first 24 hours. The secondary outcomes included the total dose of intraoperative additional fentanyl boluses; time of the first postoperative rescue analgesia; and postoperative Face, Legs, Activity, Cry, Consolability scale (FLACC) score values. MAIN RESULTS: The main results of this study showed that the administrated fentanyl in the 24 hours postoperatively was significantly lower in SF group than in F group (p value Ë 0.001). In addition, significant decreases of the postoperative FLACC pain score (p value Ë 0.001), reduction of intraoperative fentanyl consumption (p value Ë 0.001), and delay of the first rescue analgesia (p value Ë 0.001) were recorded in SF group in relation to F group without significant complications in both groups. CONCLUSIONS: Serratus anterior plane block can provide a safe, effective, and easy-to-perform regional technique for children undergoing thoracotomies.
Subject(s)
Analgesia , Nerve Block , Analgesia/methods , Child , Fentanyl , Humans , Nerve Block/methods , Pain, Postoperative/etiology , Pain, Postoperative/prevention & control , Ultrasonography, Interventional/methodsABSTRACT
BACKGROUND: Diagnostic error is a major source of patient suffering. Researchshows that physicians experience frequent interruptions while being engaged with patients and indicate that diagnostic accuracy may be impaired as a result. Since most studies in the field are observational, there is as yet no evidence suggesting a direct causal link between being interrupted and diagnostic error. Theexperiments reported in this article were intended to assess this hypothesis. METHODS: Three experiments were conducted to test the hypothesis that interruptions hurt diagnostic reasoning and increase time on task. In the first experiment (N = 42), internal medicine residents, while diagnosing vignettes of actual clinical cases were interrupted halfway with a task unrelated to medicine, solving word-spotting puzzles and anagrams. In the second experiment (N = 78), the interruptions were medically relevant ones. In the third experiment (N = 30), we put additional time pressure on the participants. In all these experiments, a control group diagnosed the cases without interruption. Dependent variables were diagnostic accuracy and amount of time spent on the vignettes. RESULTS: In none of the experiments interruptions were demonstrated to influence diagnostic accuracy. In Experiment 1: Mean of interrupted group was 0.88 (SD = 0.37) versus non- interrupted group 0.91 (SD = 0.32). In Experiment 2: Mean of interrupted group was 0.95 (SD = 0.32) versus non-interrupted group 0.94 (SD = 0.38). In Experiment 3: Mean of interrupted group was 0.42 (SD = 0.12) versus non-interrupted group 0.37 (SD = 0.08). Although interrupted residents in all experiments needed more time to complete the diagnostic task, only in Experiment 2, this effect was statistically significant. CONCLUSIONS: These three experiments, taken together, failed to demonstrate negative effects of interruptions on diagnostic reasoning. Perhaps physicians who are interrupted may still have sufficient cognitive resources available to recover from it most of the time.