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Autoimmune diseases are typically characterized by aberrant activation of immune system that leads to excessive inflammatory reactions and tissue damage. Nevertheless, precise targeted and efficient therapies are limited. Thus, studies into novel therapeutic targets for the management of autoimmune diseases are urgently needed. Radical S-adenosyl methionine domain-containing 2 (RSAD2) is an interferon-stimulated gene (ISG) renowned for the antiviral properties of the protein it encodes, named viperin. An increasing number of studies have underscored the new roles of RSAD2/viperin in immunomodulation and mitochondrial metabolism. Previous studies have shown that there is a complex interplay between RSAD2/vipeirn and mitochondria and that binding of the iron-sulfur (Fe-S) cluster is necessary for the involvement of viperin in mitochondrial metabolism. Viperin influences the proliferation and development of immune cells as well as inflammation via different signaling pathways. However, the function of RSAD2/viperin varies in different studies and a comprehensive overview of this emerging theme is lacking. This review will describe the characteristics of RSAD2/viperin, decipher its function in immunometabolic processes, and clarify the crosstalk between RSAD2/viperin and mitochondria. Furthermore, we emphasize the crucial roles of RSAD2 in autoimmune diseases and its potential application value.
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Accurate detection, identification, and subsequent confirmation of pathogens causing foodborne illness are essential for the prevention and investigation of foodborne outbreaks. This is particularly true when the causative agent is an enteric virus that has a very low infectious dose and is likely to be present at or near the limit of detection. In this study, whole-genome sequencing (WGS) was combined with either of two non-targeted pre-amplification methods (SPIA and SISPA) to investigate their utility as a confirmatory method for RT-qPCR positive results of foods contaminated with enteric viruses. Frozen berries (raspberries, strawberries, and blackberries) were chosen as the food matrix of interest due to their association with numerous outbreaks of foodborne illness. The hepatitis A virus (HAV) and human norovirus (HuNoV) were used as the contaminating agents. The non-targeted WGS strategy employed in this study could detect and confirm HuNoV and HAV at genomic copy numbers in the single digit range, and in a few cases, identified viruses present in samples that had been found negative by RT-qPCR analyses. However, some RT-qPCR-positive samples could not be confirmed using the WGS method, and in cases with very high Ct values, only a few viral reads and short sequences were recovered from the samples. WGS techniques show great potential for confirmation and identification of virally contaminated food items. The approaches described here should be further optimized for routine application to confirm the viral contamination in berries.
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Contaminación de Alimentos , Enfermedades Transmitidas por los Alimentos , Fragaria , Frutas , Reacción en Cadena en Tiempo Real de la Polimerasa , Rubus , Secuenciación Completa del Genoma , Frutas/virología , Secuenciación Completa del Genoma/métodos , Contaminación de Alimentos/análisis , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Fragaria/virología , Humanos , Rubus/virología , Enfermedades Transmitidas por los Alimentos/virología , Genoma Viral/genética , Virus de la Hepatitis A/genética , Virus de la Hepatitis A/aislamiento & purificación , Virus de la Hepatitis A/clasificación , Alimentos Congelados/virología , Norovirus/genética , Norovirus/aislamiento & purificación , Norovirus/clasificaciónRESUMEN
Cerebral neural electronics play a crucial role in neuroscience research with increasing translational applications such as brain-computer interfaces for sensory input and motor output restoration. While widely utilized for decades, the understanding of the cellular mechanisms underlying this technology remains limited. Although two-photon microscopy (TPM) has shown great promise in imaging superficial neural electrodes, its application to deep-penetrating electrodes is technically difficult. Here, a novel device integrating transparent microelectrode arrays with glass microprisms, enabling electrophysiology recording and stimulation alongside TPM imaging across all cortical layers in a vertical plane, is introduced. Tested in Thy1-GCaMP6 mice for over 4 months, the integrated device demonstrates the capability for multisite electrophysiological recording/stimulation and simultaneous TPM calcium imaging. As a proof of concept, the impact of microstimulation amplitude, frequency, and depth on neural activation patterns is investigated using the setup. With future improvements in material stability and single unit yield, this multimodal tool greatly expands integrated electrophysiology and optical imaging from the superficial brain to the entire cortical column, opening new avenues for neuroscience research and neurotechnology development.
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Cerebral microbleeds (CMBs) are associated with higher risk for various neurological diseases including stroke, dementia, and Alzheimer's disease. However, the understanding of cellular pathology of CMBs, particularly in deep brain regions, remains limited. Utilizing two-photon microscopy and microprism implantation, we longitudinally imaged the impact of CMBs on neuronal and microglial activities across cortical depths in awake mice. A temporary decline in spontaneous neuronal activity occurred throughout cortical layers, followed by recovery within a week. However, significant changes of neuron-neuron activity correlations persisted for weeks. Moreover, microglial contact with neuron soma significantly increased post-microbleeds, indicating an important modulatory role of microglia. Notably, microglial contact, negatively correlated with neuronal firing rate in normal conditions, became uncorrelated after microbleeds, suggesting a decreased neuron-microglia inhibition. These findings reveal chronic alterations in cortical neuronal networks and microglial-neuronal interactions across cortical depths, shedding light on the pathology of CMBs.
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In this work, we report an environmentally friendly renewable nanocomposite magnetic lignin-based palladium nanoparticles (Fe3O4-lignin@Pd-NPs) for efficient wastewater treatment by decorating palladium nanoparticles without using any toxic reducing agents on the magnetic lignin abstracted from Poplar. The structure of composite Fe3O4-lignin@Pd-NPs was unambiguously confirmed by XRD, SEM, TEM, EDS, FTIR, and Zeta potential. After systematic evaluation of the use and efficiency of the composite to remove toxic organic dyes in wastewater, some promising results were observed as follows: Fe3O4-lignin@Pd-NPs exhibits highly active and efficient performance in the removal of toxic methylene blue (MB) (up to 99.8 %) wastewater in 2 min at different concentrations of MB and different pH values. Moreover, except for toxic MB, the other organic dyes including Rhodamine B (RhB), Rhodamine 6G (Rh6G), and Methyl Orange (MO) can also be removed efficiently by the composite. Finally, the easily recovered composite Fe3O4-lignin@Pd-NPs exhibits well stability and reusability, and catalytic efficiency is maintained well after ten cycles. In conclusion, the lignin-based magnetism Pd composite exhibits powerful potential practical application in industrial wastewater treatment.
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Nanopartículas del Metal , Nanocompuestos , Purificación del Agua , Lignina , Nanopartículas del Metal/química , Paladio/química , Aguas Residuales , ColorantesRESUMEN
Chinese and American children aged 5-11 years (total N = 144) heard two child informants make conflicting empirical claims about each of 4 scenarios. For example, one informant claimed that a ball would float when dropped in water whereas the other informant claimed that it would sink. Children were asked to judge whether each informant could be right, and to justify their overall judgment. In both samples, there was a change with age. Older children often said that each informant could be right whereas younger children, especially in China, were more likely to say that only one informant could be right. Nevertheless, in the wake of decisive empirical evidence (e.g., the ball was shown to sink when dropped in water), almost all children, irrespective of age, drew appropriate conclusions about which of the two informants had been right. Thus, with increasing age, children differ in their prospective - but not in their retrospective - appraisal of empirical disagreement. Absent decisive evidence, older children are more likely than younger children to suspend judgment by acknowledging that either of two conflicting claims could be right. We argue that children's tendency to suspend judgment is linked to their developing awareness of empirical uncertainty, as expressed both in the justifications they give when judging the disagreement and in their own beliefs about the scenarios. Implications for children's understanding of disagreement are discussed.
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Formación de Concepto , Juicio , Humanos , Niño , Estados Unidos , Adolescente , Preescolar , Estudios Prospectivos , Estudios Retrospectivos , Incertidumbre , AguaRESUMEN
Purpose: Thyroid nodules classified as indeterminate in previous fine-needle aspiration cytology often necessitate additional evaluation to determine their histology, while shear wave elastography (SWE) offers an alternative option in this regard. The objective of this study was to assess the diagnostic effectiveness of SWE in evaluating indeterminate nodules. Methods: The PubMed, EMBASE, and Web of Science databases were searched from 1st January 1970 to 1st March 2023. The studies were reviewed and the data was extracted by two separate reviewers. A Bayesian bivariate model was utilized to quantitatively synthesize the diagnostic accuracy and yield of the studies in R. Results: A total of seven studies, involving indeterminate thyroid nodules undergoing SWE were included, and the overall malignancy rate was 34.1% (307/900). The summarized estimates of sensitivity and specificity were 0.792 (95% credible interval [CI], 0.727-0.850) and 0.845 (95% CI, 0.797-0.887), respectively. The summarized estimate for the diagnostic odds ratio (DOR) was 17.8 (95% CI, 14.0-22.6). Summarized receiver operating characteristic (SROC) plots indicated a trade-off between sensitivity and specificity, and the estimate of AUC was 0.866 (95% CI, 0.834-0.895). The summary estimates for positive and negative likelihood ratios were 4.67 (95% CI, 3.98-5.85) and 0.26 (95% CI, 0.23-0.28), respectively. Conclusions: The overall accuracy of SWE remains satisfactory in indeterminate thyroid nodules. However, it should be noted that the available data are still extremely limited, and more studies or guidelines are required to provide further insights.
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The combination of electric heating and thermal energy storage (TES) with phase change material (PCM) can achieve load shifting for air conditioning energy saving in building sectors. Their non-flammability, relatively good mechanical properties, and low cost make inorganic PCMs attractive in construction engineering. However, PCMs often show poor thermal conductivity, low heat transfer efficiency, leakage risk, etc., in applications. Moreover, the practical thermal performance of PCM-TES sometimes fails to meet demand variations during charge and discharge cycles. Therefore, in this study, a novel integrated electric PCM wall panel module is proposed with quick dynamic thermal response in space heating suitable for both retrofitting of existing buildings and new construction. Sodium-urea PCM composites are chosen as PCM wall components for energy storage. Based on the enthalpy-porosity method, a mathematical heat transfer model is established, and numerical simulation studies on the charge-discharge characteristics of the module are conducted using ANSYS software. Preliminary results show that the melting temperature decreases from 50 °C to approximately 30 °C with a 30% urea mixing ratio, approaching the desired indoor thermal comfort zone for space heating. With declining PCM layer thickness, the melting time drops, and released heat capacity rises during the charge process. For a 20 mm thick PCM layer, 150 W/m2 can maintain the average surface temperature within a comfort range for 12.1 h, about half the time of a 24 h charge-discharge cycling periodicity. Furthermore, placing the heating film in the unit center is preferable for improving overall heat efficiency and shortening the time to reach the thermal comfort temperature range. This work can provide guidance for practical thermal design optimization of building envelopes integrated with PCM for thermal insulation and energy storage.
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Cutaneous pili migrans is a rare condition caused by embedded hair shafts or fragments which presents as a mobile black linear rash and is easily confused with cutaneous larva migrans. "Ingrowing hair", in which the hair shaft grows inside the skin and burrows into the uppermost dermis rather than exiting the skin, is much rarer, and only 8 cases have been reported thus far, all in Asian men. We report a case of a 22-year-old Chinese male with a 4 cm-long black linear rash that migrated from the anterior abdomen to the left lower abdomen. The black lines represented hair shafts with follicular structures. The lesion disappeared immediately after hair removal. No recurrence occurred in 4 weeks of follow-up. To our knowledge, this is the first description of ingrowing hair occurring in the abdomen.
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Severe cutaneous adverse drug reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are challenging to be early diagnosed and evaluate their prognoses. This investigation aimed to analyse the expression profiles of SJS/TEN in peripheral blood mononuclear cells (PBMC) and assess the correlation between circular RNA (circRNA) and disease severity. Sixteen SJS/TEN patients and sixteen controls were enrolled and serum samples of both groups were obtained. CircRNA expression profiles in three SJS/TEN patients and three controls were detected by RNA sequencing and bioinformatic analyses were then performed. The differentially expressed circRNAs were verified by quantitative polymerase chain reaction (qPCR). Then, analysing the correlation of circRNAs with the toxic epidermal necrolysis-specific severity of illness score (SCORTEN) and the epidermal detachment area. A total of 134 circRNAs were differentially expressed in the PBMCs of SJS/TEN individuals, according to our results. The qPCR showed that three circRNAs (hsa_circ_0000711, hsa_circ_0083619 and hsa_circ_0005615) were down-regulated, and one circRNA (hsa_circ_0003028) was up-regulated, which were compatible with the sequencing findings. The concentration of hsa_circ_0083619 was closely associated with the SCORTEN scale (r = -0.581, p = 0.037) and the epidermal detachment area (r = -0.576, p = 0.039). The circRNA-miRNA-mRNA prediction network was used to construct the hsa_circ_0083619/miR-18a-5p/BCL2L10 axis. The hsa_circ_0083619 could serve as a disease severity indicator for SJS/TEN. Through bioinformatics analysis, we speculated that hsa_circ_0083619/miR-18a-5p/BCL2L10 axis might play a role in SJS/TEN pathogenesis.
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MicroARNs , Síndrome de Stevens-Johnson , Humanos , ARN Circular/genética , Síndrome de Stevens-Johnson/genética , Leucocitos Mononucleares/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
The cavitation dynamics of a two-bubble system in viscoelastic media excited by dual-frequency ultrasound is studied numerically with a focus on the effects of inter-bubble interactions. Compared to the isolated bubble cases, the enhancement or suppression effects can be exerted on the amplitude and nonlinearity of the bubble oscillations to different degrees. Moreover, the interaction effects are found to be highly sensitive to multiple paramount parameters related to the two-bubble system, the dual-frequency ultrasound and the medium viscoelasticity. Specifically, the larger bubble of a two-bubble system shows a stronger effect on the smaller one, and this effect becomes more pronounced when the larger bubble undergoes harmonic and/or subharmonic resonances as well as the two bubbles get closer (e.g., d0 < 100 µm). For the influences of the dual-frequency excitation, the results show that the bubbles can achieve enhanced harmonic and/or subharmonic oscillations as the frequency combinations with small frequency differences (e.g., Δf < 0.2 MHz) close to the corresponding resonance frequencies of bubbles, and the interaction effects are consequently intensified. Similarly, the bubble oscillations and the interaction effects can also be enhanced as the acoustic pressure amplitude of each frequency component is equal and the pressure amplitude pA increases. Above a pressure threshold (pA = 215 kPa), a larger bubble undergoes period 2 (P2) oscillations, which can force a smaller bubble to change its oscillation pattern from period 1 (P1) into P2 oscillations. In addition, it is found that the medium viscosity dampens the bubble oscillations while the medium elasticity affects the bubble resonances, accordingly exhibiting stronger interaction effects at smaller viscosities (e.g., µ < 4 mPa·s) or certain elasticities (approximately G = 70-120 kPa, G = 160-200 kPa and G = 640-780 kPa) at which the bubble resonances occur. The study can contribute to a better understanding of the complex dynamic behaviors of interacting cavitation bubbles in viscoelastic tissues for high efficient cavitation-mediated biomedical applications using dual-frequency ultrasound.
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Research has documented the critical role played by the early home environment in children's mathematical development in Western contexts. Yet little is known about how Chinese parents support their preschoolers' development of math skills. The Chinese context is of particular interest because Chinese children outperform their Western counterparts in math, even early in development. The current study sought to fill this gap by examining a sample of 90 families of 4- and 5-year-olds from mainland China. Parental support-as measured by the frequency of parent-child engagement in home activities as well as parent number talk-and parents' role in children's numeracy skills were investigated. Results indicate wide variation among parents in both types of support. Frequency of engagement in formal numeracy activities, including counting objects and reading number story books, was related to children's knowledge of cardinality. A principal components analysis did not identify informal numeracy activities as a distinct home activity component, likely due to the infrequent occurrences of game-like numeracy activities among the Chinese families. Instead, a structured activity component emerged (e.g., playing musical instruments) and was positively related to children's arithmetic skills. Diversity, but not quantity, of parent number talk was related to children's symbolic magnitude understanding. The distinctive relationships between specific parental measures and child outcomes speak to the need for nuanced identification of home environment factors that are beneficial to particular math competencies. The findings also suggest cultural variations in the mechanisms that support children's mathematical development, highlighting the merits of investigating this topic in non-Western contexts.
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Relaciones Padres-Hijo , Lectura , Humanos , Preescolar , Matemática , Padres , ChinaRESUMEN
BACKGROUND: Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel was recommended as the secondary prevention of minor ischemic stroke or transient ischaemic attack (TIA). However, genetic polymorphisms of CYP2C19 had been identified as the major cause of poor responsiveness to clopidogrel. Ticagrelor, unlike clopidogrel, did not depend on metabolic activation, but it remained unclear whether ticagrelor was superior to clopidogrel in ischemic stroke. We performed a network meta-analysis to compare the efficacy and safety of ticagrelor, clopidogrel, and aspirin in the minor ischemic stroke and TIA populations. METHODS: Databases of Cochrane Library, ClinicalTrials.gov, and PubMed were searched up to June 19, 2023. Randomized controlled trials (RCTs) assessing antiplatelet drugs for minor stroke or TIA were included. Statistical processing was conducted by using multivariate meta-analysis routines of STATA. RESULTS: Seven RCTs were included involving 41,745 participants. There was no significant difference between the two DAPTs in preventing stroke recurrence (OR, 1.16; 95% CI, 0.93-1.44), ischemic stroke recurrence (OR, 1.16; 95% CI, 0.93-1.45), and major hemorrhage (OR, 1.22; 95% CI, 0.62,2.39). Compared with aspirin alone, the two DAPT regimen reduced the risk of stroke recurrence (clopidogrel: OR, 0.69; 95% CI, 0.60-0.80, ticagrelor: OR, 0.66; 95% CI, 0.49-0.87) and ischemic stroke recurrence, but increased the incidence of major hemorrhage (clopidogrel: OR, 2.05; 95% CI, 1.22- 3.77; ticagrelor: OR, 2.55; 95% CI, 1.25-4.99). Despite being associated with a higher risk of any bleeding, ticagrelor did not impact the composite of vascular events or mortality. While ticagrelor and aspirin reduced the risk of ischemic stroke recurrence (OR, 0.77; 95% CI, 0.63- 0.92) without increasing the risk of major bleeding (OR 0.94; 95% CI 0.45-1.95) in the Asian population mainly Chinese. CONCLUSIONS: DAPT was superior to aspirin in stroke prevention, but little difference existed between the two DAPT regimens. Asian population mainly Chinese may benefit from DAPT with aspirin and ticagrelor. But further head-to-head RCTs are needed to validate the study results.
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Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Aspirina/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ataque Isquémico Transitorio/tratamiento farmacológico , Ataque Isquémico Transitorio/prevención & control , Ticagrelor/uso terapéutico , Clopidogrel/uso terapéutico , Metaanálisis en Red , Quimioterapia Combinada , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/prevención & control , Hemorragia/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/prevención & controlRESUMEN
Healing of the cutaneous wound requires macrophage recruitment at the sites of injury, where chemotactic migration of macrophages toward the wound is regulated by local inflammation. Recent studies suggest a positive contribution of DNA methyltransferase 1 (Dnmt1) to macrophage pro-informatory responses; however, its role in regulating macrophage motility remains unknown. In this study, myeloid-specific depletion of Dnmt1 in mice promoted cutaneous wound healing and de-suppressed the lipopolysaccharides (LPS)-inhibited macrophage motility. Dnmt1 inhibition in macrophages eliminated the LPS-stimulated changes in cellular mechanical properties in terms of elasticity and viscoelasticity. LPS increased the cellular accumulation of cholesterol in a Dnmt1-depedent manner; cholesterol content determined cellular stiffness and motility. Lipidomic analysis indicated that Dnmt1 inhibition altered the cellular lipid homeostasis, probably through down-regulating the expression of cluster of differentiation 36 CD36 (facilitating lipid influx) and up-regulating the expression of ATP-binding cassette transporter ABCA1 (mediating lipid efflux) and sterol O-acyltransferase 1 SOAT1 (also named ACAT1, catalyzing the esterification of cholesterol). Our study revealed a Dnmt1-dependent epigenetic mechanism in the control of macrophage mechanical properties and the related chemotactic motility, indicating Dnmt1 as both a marker of diseases and a potential target of therapeutic intervention for wound healing.
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Testicular torsion (TT) is a medical emergency that requires immediate diagnostic evaluation. Photoacoustic imaging (PAI) has the potential to provide spatially resolved oxygen saturation (sO2), which can serve as a valuable marker in TT diagnosis. We investigated the potential of PAI as an alternative method for TT diagnosis and testicular injury assessment. We measured sO2 levels in different degrees of TT models using PAI at various time points. Based on histopathological results, we found that the averaged sO2 per pixel (sO2®) and reduction of sO2® (rsO2) in twisted testicles had significant correlations with hypoxic conditions. Both sO2® and rsO2 exhibited excellent diagnostic abilities in detecting TT and identifying ischemia/hypoxia injury following TT. Furthermore, PAI-measured sO2 demonstrated favorable diagnostic capabilities in discriminating if the testicle had suffered irreversible injury. In summary, PAI presents a potentially promising novel approach in evaluating TT and warrants further clinical investigation.
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Disturbed blood flow induces endothelial pro-inflammatory responses that promote atherogenesis. Nanoparticle-based therapeutics aimed at treating endothelial inflammation in vasculature where disturbed flow occurs may provide a promising avenue to prevent atherosclerosis. By using a vertical-step flow apparatus and a microfluidic chip of vascular stenosis, herein, it is found that the disk-shaped versus the spherical nanoparticles exhibit preferential margination (localization and adhesion) to the regions with the pro-atherogenic disturbed flow. By employing a mouse model of carotid partial ligation, superior targeting and higher accumulation of the disk-shaped particles are also demonstrated within disturbed flow areas than that of the spherical particles. In hyperlipidemia mice, administration of disk-shaped particles loaded with hypomethylating agent decitabine (DAC) displays greater anti-inflammatory and anti-atherosclerotic effects compared with that of the spherical counterparts and exhibits reduced toxicity than "naked" DAC. The findings suggest that shaping nanoparticles to disk is an effective strategy for promoting their delivery to atheroprone endothelia.
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Aterosclerosis , Nanopartículas , Animales , Ratones , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/prevención & control , Arterias CarótidasRESUMEN
Objective: To evaluate the incidence and risk factors for complications following volar locking plate (VLP) fixation of unstable distal radius fracture (DRF). Methods: This retrospective study identified patients who underwent VLP fixation of unstable DRF between 2017 and 2020 with a minimum 12-month follow-up assessments. By reviewing electronic medical records and follow-up notes, patients were categorized complication or noncomplication group. Differences in variables were detected by using univariate analyses, and independent factors were identified using multivariate logistic regression analysis. Results: During this study period, 423 patients were included, and 63 (rate, 14.9%) complications in 58 patients were documented. Wound infection (17, 4.0%) was most common, followed in decreasing frequency by carpal tunnel syndrome (13, 3.1%), tendon rupture/irritation (10, 2.4%), complex regional pain syndrome (8, 1.9%), and plate/screw-related complications (5, 1.7%). In the univariate analyses, 18 variables were found to be significantly different (p < 0.05). Logistic regression analysis identified 5 independent factors, including being male (OR, 3.5; p = 0.014), type C fracture (vs. type A, OR: 2.7, and p = 0.035), general anesthesia (vs. regional, OR: 2.4, and p = 0.045), bone grafting (OR, 6.3; p < 0.001), and surgery performed by less experienced surgeons (OR, 3.1; p = 0.003). The goodness-of-fit of the final model was acceptable. Conclusions: These factors will help surgeons individualize and stratify the risk of complications and help patients for risk counselling; especially, an informed clinical decision targeting those modifiable factors (anesthesia mode, bone grafting, and surgeon experience) can be considered, when indicated.
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Fracturas de la Muñeca , Humanos , Masculino , Femenino , Estudios Retrospectivos , Proyectos de Investigación , Factores de RiesgoRESUMEN
Neural electrode insertion trauma impedes the recording and stimulation capabilities of numerous diagnostic and treatment avenues. Implantation leads to the activation of inflammatory markers and cell types, which is detrimental to neural tissue health and recording capabilities. Oxidative stress and inflammation at the implant site have been shown to decrease with chronic administration of antioxidant melatonin at week 16, but its effects on the acute landscape have not been studied. To assess the effect of melatonin administration in the acute phase, specifically the first week post-implantation, we utilized histological and q-PCR methods to quantify cellular and molecular indicators of inflammation and oxidative stress in the tissue surrounding implanted probes in C57BL/6 mice as well as two-photon microscopy to track the microglial responses to the probes in real-time in transgenic mice expressing GFP with CX3CR1 promotor. Histological results indicate that melatonin effectively maintained neuron density surrounding the electrode, inhibited accumulation and activation of microglia and astrocytes, and reduced oxidative tissue damage. The expression of the pro-inflammatory cytokines, TNF-α and IL-6, were significantly reduced in melatonin-treated animals. Additionally, microglial encapsulation of the implant surface was inhibited by melatonin as compared to control animals following implantation. Our results combined with previous research suggest that melatonin is a particularly suitable drug for modulating inflammatory activity around neural electrode implants both acutely and chronically, translating to more stable and reliable interfaces.
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Chronic microstimulation is faced with challenges that require an additional understanding of stability and safety. We implanted silicon arrays coated with poly(3,4-ethylenedioxythiophene) (PEDOT)/Carbon Nanotubes (CNT), or PCand IrOx into the cortex of GCaMP6s mice and electrically stimulated them for up to 12 weeks. We quantified neuronal responses to stimulation using two-photon imaging and mesoscale fluorescence microscopy and characterized electrode performance over time. We observed dynamic changes in stimulation stability over time and a significant advantage in energy efficiency using PC coated electrodes over IrOx coated electrodes. In a subset of mice, we observed abnormal ictal cortical responses or cortical spreading depression using stimulation parameters commonly used in intracortical stimulation applications, suggesting the need to investigate the potential neuronal damage and redefine the stimulation safety limit. This study not only revealed the dynamic changes in stimulation efficiency after implantation but also reiterates the potential for PC as a high-efficiency material in chronic neuromodulation.
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PURPOSE: This study aimed to assess the diagnostic performance of supersonic impulse (SSI) elastography in differentiating malignant and benign cervical lymph nodes. METHODS: The Medline, Embase, and Cochrane Central databases were searched until December 1, 2020. Two different reviewers checked the studies and extracted the data. The diagnostic yields were quantitatively synthesized using a Bayesian bivariate model with an integrated nested Laplace approximation in R. RESULTS: In total, 590 patients with 892 cervical lymph nodes who underwent SSI elastography were included. The total prevalence of malignancy was 33.7% (301/892), and the four elastic modulus values (mean, maximum, minimum, and standard deviation) were significantly different between malignant and benign lymph nodes. For the mean elastic modulus, the summary estimates for sensitivity and specificity were 0.720 (95% credible interval [CrI], 0.592 to 0.824) and 0.877 (95% CrI, 0.727 to 0.969), respectively. The estimated area under the curve (AUC) was 0.845 (95% CrI, 0.672 to 0.914). For the maximum elastic modulus, the sensitivity and specificity were estimated to be 0.809 (95% CrI, 0.698 to 0.899) and 0.816 (95% CrI, 0.643 to 0.924), respectively. The estimated AUC was 0.834 (95% CrI, 0.579 to 0.938). The minimum and standard deviation of the elastic modulus and the outcomes of the positive and negative likelihood ratio, diagnostic odds ratio, and risk difference were also calculated. CONCLUSION: SSI elastography is an acceptable imaging technique for diagnosing malignant cervical lymph nodes, and it can play a complementary role today. Both maximum and mean elastic modulus values should be taken into consideration to make a clinical judgment.