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An energetic γ-ray burst (GRB), GRB 211211A, was observed on 11 December 20211,2. Despite its long duration, typically associated with bursts produced by the collapse of massive stars, the observation of an optical-infrared kilonova points to a compact binary merger origin3. Here we report observations of a significant (more than five sigma) transient-like emission in the high-energy γ-rays of GRB 211211A (more than 0.1 gigaelectronvolts) starting 103 seconds after the burst. After an initial phase with a roughly constant flux (about 5 × 10-10 erg per second per square centimetre) lasting about 2 × 104 seconds, the flux started decreasing and soon went undetected. Our detailed modelling of public and dedicated multi-wavelength observations demonstrates that gigaelectronvolt emission from GRB 211211A is in excess with respect to the flux predicted by the state-of-the-art afterglow model at such late time. We explore the possibility that the gigaelectronvolt excess is inverse Compton emission owing to the interaction of a late-time, low-power jet with an external source of photons, and find that kilonova emission can provide the seed photons. Our results open perspectives for observing binary neutron star mergers.
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BACKGROUND AND OBJECTIVE: Biomedical research in regenerative medicine prompts researchers to formulate cost-effective therapeutics for wound healing. The present study was conducted to characterize the ascorbate based formulation vis-a-vis investigating the molecular dynamics of the formulation. MATERIALS AND METHODS: To characterize the formulation, particle size, zeta potential, thermal stability, compatibility, anti-oxidant, and permeation prospective were measured using standard protocols. The in-vitro healing potential and safety formulae were evaluated using the L929 cell line. For molecular unravelling of the pharmacodynamics of formulation, an excision wound model was used, and 54 mice were randomly and equally divided into three groups, i.e., untreated, betadine-treated, and formulation-treated, to ascertain the interplay between cytokines and chemokines and their culminative role in the release of growth factors. RESULTS: The ascorbate formulae were found to be amorphous, biocompatible, safe, and long-lasting, with particle sizes and zeta potentials of 389.7 ± 0.69 nm and -38.1 ± 0.65 mV, respectively, and anti-oxidative potential. An in-vitro study revealed that the formulation has a significant (p<0.05) migration potential and is non-toxic. Expression profiling of TGF-ß, FGF-2, VEGF, and collagen III & I showed significant (p<0.05) up-regulation, whereas significant (p<0.05) down-regulation of pro-inflammatory genes like IL-1α, IL-1ß, TNF-α, IL-6, and temporal change in CCR-5 was observed in formulae-treated animals as compared to other groups. CONCLUSION: By up-regulating angiogenic and collagen-promoting growth factor gene expression while down-regulating pro-inflammatory gene expression, ascorbate formulation promotes wound healing via extracellular matrix and granulation tissue deposition with significant improvement in tensile strength.
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Citocinas , Cicatrización de Heridas , Ratones , Animales , Estudios Prospectivos , Cicatrización de Heridas/fisiología , Colágeno , Modelos Animales de Enfermedad , Colágeno Tipo I/genética , AntiinflamatoriosRESUMEN
PURPOSE: Hyporeactivity to vasopressors leading to multiple organ failure is a serious clinical implication in sepsis. Though the regulatory role of purinoceptors in inflammation is reported, their involvement in sepsis-induced vasoplegia is still unknown. Thus we investigated the effect of sepsis on vascular AT1 and P2Y6 receptors. MATERIALS AND METHODS: Polymicrobial sepsis was induced by cecal ligation and puncture in mice. Vascular reactivity was assessed by organ bath study and aortic mRNA expression of AT1 and P2Y6 was quantified by qRT-PCR. RESULTS: Both angiotensin-II and UDP produced higher contractions in the absence of endothelium as well as following inhibition of nitric oxide synthase. Angiotensin-II mediated aortic contraction was antagonized by losartan (AT1 antagonist), but not by PD123319 (AT2 antagonist) whereas UDP-induced aortic contraction was significantly inhibited by MRS2578 (P2Y6 antagonist). In addition, MRS2578 significantly inhibited the contractile response of Ang-II. Compared to SO mice, angiotensin-II and UDP-induced maximum contraction were found to be significantly attenuated in sepsis. Accordingly, aortic mRNA expression of AT1a receptors was significantly down-regulated while that of P2Y6 receptors was significantly increased in sepsis. 1400 W (a selective iNOS inhibitor) significantly reversed angiotensin-II-induced vascular hyporeactivity in sepsis without affecting UDP-induced hypo-reactivity. CONCLUSION: Sepsis-induced vascular hyporeactivity to angiotensin-II is mediated by enhanced expression of iNOS. Moreover, AT1R-P2Y6 cross talk/heterodimerization could be a novel target for regulating vascular dysfunction in sepsis.
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Angiotensina II , Sepsis , Ratones , Animales , Angiotensina II/farmacología , Sepsis/complicaciones , Sepsis/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Uridina DifosfatoRESUMEN
A complete characterization of the burn wound based on cutaneous architectural changes and inflammatory response is extremely important to provide evidence for progressive changes in the burn wound. Burn wounds are highly susceptible to conversion into deeper wounds, which need special care and attention; thereby, the complete characterization of burn wound type and their subsequent inflammatory status in the cutaneous system at the earliest is of paramount importance. Inflammatory markers at different degrees will help clinicians devise better and more specific treatment strategies for each burn type. The present study is carried out to profile pro-inflammatory gene expression along with immune cell quantification, vascular perfusion, and histopathological assessment in the cutaneous system of murine models. The study revealed that burn injury caused an immediate increase in vascular perfusion in superficial and partial-thickness burns, whereas there was a decrease in vascular perfusion in full-thickness burns. An influx of lymphocytes at the edges of burn wounds in each type of burn injury was well-orchestrated with the event of vascular perfusion. Further, pro-inflammatory gene expression profiling revealed significant upregulation vis-à-vis upregulation of TNF-α and MCP-1 genes, with an increase in the number of neutrophils following 72 h of injury that evidently cemented the conversion of superficial burn into partial-thickness burn. The molecular findings were profoundly supported by the histopathological changes. Thus, our foundational studies show distinct characteristic cutaneous changes correlated with the expression of key pro-inflammatory genes in three different types of burn injuries. Characterization of these cutaneous inflammatory responses provides a promising future for medical interventions involved with different degrees of burn injury, and it will also help in the pre-clinical testing of therapies for burn injury.
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Quemaduras , Traumatismos de los Tejidos Blandos , Humanos , Ratones , Animales , Piel/patología , Factor de Necrosis Tumoral alfa , Neutrófilos , Quemaduras/complicaciones , Quemaduras/terapiaRESUMEN
Present study was conducted to undermine the wound healing potential of mangiferin vis a vis its molecular dynamics in immunocompromised excisional rat model. 120 rats were randomly and equally divided into five groups viz. group I (Healthy control), group II (Immunocompromised control), group III (Immunocompromised group treated with silver sulphadiazine), group IV (Immunocompromised group treated with 2.5 %Mangiferin) and group V (Immunocompromised group treated with 5 %Mangiferin). Immuno compromised state was achieved following intramuscular injection of Hydrocortisone @ 80 mg/kg body weight. Study was conducted for a period of 28 days. Six animals from each group were humanely sacrificed at weekly interval till day 28th of study. Planimetric analysis, biochemical studies viz. hydroxyproline assay, total protein and DNA content, antioxidative potential through LPO assay was done along with molecular studies involving expression profiling of IL1ß, TNFα and COX-2 and Immunohistochemistry of angiogenic marker i.e. VEGF was performed to undermine the pharmacodynamics of mangiferin. Histopathological studies including H&E and Masson's Trichome was also performed to study histoarchitectural changes in wound healing and reparative process following application of mangiferin ointment. Study revealed significant (P ≤ 0.05) reduction in wound area measurement and significant (P ≤ 0.05) increase in wound contraction (%) following mangiferin administration in immunocompromised rats. Hydroxyproline, DNA and total protein showed significant (P ≤ 0.05) increase in skin tissues of mangiferin treated immunocompromised rats. LPO assay revealed significant (P ≤ 0.05) reduction in mangiferin treated animals. Histopathological studies of skin tissues revealed complete restoration advocating grade III of healing in 2.5% mangiferin treated group. Higher expression and strong signal intensity of VEGF was noticed in 2.5% mangiferin treatment group along with significant (P ≤ 0.05) upregulation IL1ß and TNFα on day 7 in 2.5% mangiferin treatment group with significant (P ≤ 0.05) down regulation of COX-2 in mangiferin treatment group as compared to other groups i.e. group II and III. It is concluded from our study that mangiferin facilitates wound healing through improved wound closure, organized deposition of collagen deposition and granulation matrix formation.
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Xantonas , Animales , Ciclooxigenasa 2/metabolismo , Glucósidos/farmacología , Hidroxiprolina/metabolismo , Hidroxiprolina/farmacología , Interleucina-1beta/metabolismo , Pomadas/metabolismo , Pomadas/farmacología , Ratas , Piel/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Xantonas/metabolismo , Xantonas/farmacologíaRESUMEN
AIM: Cell-based therapy has emerged as promising strategy for chronic and impaired wounds treatment. Current research is focused on developing biomaterial systems that act as a niche for mesenchymal stem cells (MSCs) to promote wound healing through paracrine molecular cascading. This study was aimed to evaluate the wound healing potential of Velgraft, a ready-to-use biodegradable artificial skin substitute, on excision wound in goats. MATERIALS AND METHODS: Twelve male goats were randomized divided in to three groups of four animals each. After infliction of surgical wound, Velgraft and Soframycin were applied on wounds of the animals of Groups II and III while Group I (sham operated) served as control. Wound diameters were measured at pre-defined time-points for determination of progressive wound healing up to 28 days. Skin sections were stained using Hematoxylin and eosin (H&E) for examining the histoarchitectural changes, Masson trichome staining for ascertaining collagen synthesis and immunohistochemistry for expression of CD31, VEGF and TGF-ß1 proteins to determine post-treatment angiogenesis in the inflicted wounds. RESULTS: Velgraft application appreciably enhanced wound closure by day 21 which was confirmed through restoration of the normal skin architecture as evident based on histopathological examination and characterized by complete regeneration of epidermal layers, collagen fibers, blood capillaries and hair follicular formation. Stimulation of angiogenesis markers was also observed at different time-points post-Velgraft application; which is suggestive of the improved angiogenesis and vasculogenesis. CONCLUSION: Velgraft facilitates wound healing by augmenting early wound closure, enhancing collagen synthesis and deposition, trichosis development and promoting revascularization and epidermal layers restoration.
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Biopolímeros/farmacología , Quitosano/farmacología , Gelatina/farmacología , Células Madre Mesenquimatosas/metabolismo , Cicatrización de Heridas/efectos de los fármacos , Análisis de Varianza , Animales , Biopolímeros/uso terapéutico , Quitosano/metabolismo , Quitosano/uso terapéutico , Modelos Animales de Enfermedad , Gelatina/metabolismo , Gelatina/uso terapéutico , Cabras , Masculino , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/análisis , Factor de Crecimiento Transformador beta1/análisis , Factor A de Crecimiento Endotelial Vascular/análisisRESUMEN
In recent years there has been a tremendous increase in use of Wi-Fi devices along with mobile phones, globally. Wi-Fi devices make use of 2.4GHz frequency. The present study evaluated the impact of 2.45GHz radiation exposure for 4h/day for 45days on behavioral and oxidative stress parameters in female Sprague Dawley rats. Behavioral tests of anxiety, learning and memory were started from day 38. Oxidative stress parameters were estimated in brain homogenates after sacrificing the rats on day 45. In morris water maze, elevated plus maze and light dark box test, the 2.45GHz radiation exposed rats elicited memory decline and anxiety behavior. Exposure decreased activities of super oxide dismutase, catalase and reduced glutathione levels whereas increased levels of brain lipid peroxidation was encountered in the radiation exposed rats, showing compromised anti-oxidant defense. Expression of caspase 3 gene in brain samples were quantified which unraveled notable increase in the apoptotic marker caspase 3 in 2.45GHz radiation exposed group as compared to sham exposed group. No significant changes were observed in histopathological examinations and brain levels of TNF-α. Analysis of dendritic arborization of neurons showcased reduction in number of dendritic branching and intersections which corresponds to alteration in dendritic structure of neurons, affecting neuronal signaling. The study clearly indicates that exposure of rats to microwave radiation of 2.45GHz leads to detrimental changes in brain leading to lowering of learning and memory and expression of anxiety behavior in rats along with fall in brain antioxidant enzyme systems.
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The objective of this study was to estimate the annual resource use and costs before and after COPD diagnosis and compare it across stages of airflow obstruction and levels of dyspnoea in the UK primary care setting. A retrospective cohort of newly diagnosed COPD patients (1/1/2008-31/12/2009) was identified in the UK Clinical Practice Research Datalink (CPRD). Resource use did not include medication costs and comprised of exacerbations, all cause GP interactions, and non-COPD hospitalisations, which were estimated for up to 12 months before and 24 months after COPD diagnosis. It was further stratified using baseline characteristics, Medical Research Council (MRC) dyspnoea score, and stages of airflow limitation. COPD costs were estimated using NHS reference costs. The analysis included 7881 newly diagnosed COPD patients (mean age, 67.2 years; 45% females). In the 2 years follow-up, the cohort experienced moderate and severe exacerbations, non-COPD hospitalisations, and GP surgery visits at an annual rate of 0.51, 0.13, 0.47, and 12.85, respectively. All resource components showed an upward trend with increase airflow limitation and dyspnoea. GP interactions accounted for 58.5% of annual per patient COPD management costs, estimated to be £ 2047 during the observation period. The annual costs doubled from patients with low levels of dyspnoea (MRC = 1; £ 1473) to those with high levels of dyspnoea (MRC = 5; £ 3243). COPD management costs in the primary care setting continued to remain high up to 2 years following initial diagnosis. The cost burden increased with high levels of dyspnoea and airflow obstruction, suggesting that both measures can identify patients requiring increased monitoring.
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Progresión de la Enfermedad , Atención Primaria de Salud/economía , Atención Primaria de Salud/estadística & datos numéricos , Enfermedad Pulmonar Obstructiva Crónica/economía , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Anciano , Estudios de Cohortes , Disnea/epidemiología , Femenino , Estudios de Seguimiento , Hospitalización/economía , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Visita a Consultorio Médico/economía , Visita a Consultorio Médico/estadística & datos numéricos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Estudios Retrospectivos , Medicina Estatal/economía , Reino Unido/epidemiologíaRESUMEN
This retrospective cohort study aimed to analyze the prescribing practices of general practitioners treating patients with newly diagnosed chronic obstructive pulmonary disease (COPD), and to assess characteristics associated with initial pharmacotherapy. Patients were identified in the General Practice Research Database, a population-based UK electronic medical record (EMR) with data from January 1, 2008 to December 31, 2009. Patient characteristics, prescribed COPD pharmacotherapies (≤12 months before diagnosis and within 3 months following diagnosis), co-morbidities, hospitalizations, and events indicative of a possible COPD exacerbation (≤12 months before diagnosis) were analyzed in 7881 patients with newly diagnosed COPD. Most patients (64.4%) were prescribed COPD pharmacotherapy in the 12 months before diagnosis. Following diagnosis, COPD pharmacotherapy was prescribed within 3 months in 85.0% of patients. Short-acting bronchodilators alone (22.9%) or inhaled corticosteroids + long-acting beta-2 agonists (ICS+LABA, 22.1%) were prescribed most frequently. Compared with other pharmacotherapies, the prevalence of severe airflow limitation was highest in patients prescribed ICS+LABA+long-acting muscarinic antagonists (LAMA). Moderate-to-severe dyspnea was identified most frequently in patients prescribed a LAMA-containing regimen. Patients prescribed an ICS-containing regimen had a higher prevalence of asthma or possible exacerbations recorded in the EMR than those not prescribed ICS. In conclusion, pharmacotherapy prescribed at initial COPD diagnosis varied by disease severity indicators as assessed by airflow limitation, dyspnea, history of asthma, and possible exacerbations. Frequent prescription of COPD pharmacotherapies before the first-recorded COPD diagnosis indicates a delay between obstructive lung disease presentation in primary care practice and assignment of a medical diagnosis.
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Corticoesteroides/uso terapéutico , Agonistas de Receptores Adrenérgicos beta 2/uso terapéutico , Broncodilatadores/uso terapéutico , Antagonistas Muscarínicos/uso terapéutico , Pautas de la Práctica en Medicina , Atención Primaria de Salud , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Administración por Inhalación , Anciano , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Reino UnidoRESUMEN
Recent advancements in Artificial Intelligence (AI), particularly in generative language models and algorithms, have led to significant impacts across diverse domains. AI capabilities to address prompts are growing beyond human capability but we expect AI to perform well also as a prompt engineer. Additionally, AI can serve as a guardian for ethical, security, and other predefined issues related to generated content. We postulate that enforcing dialogues among AI-as-prompt-engineer, AI-as-prompt-responder, and AI-as-Compliance-Guardian can lead to high-quality and responsible solutions. This paper introduces a novel AI collaboration paradigm emphasizing responsible autonomy, with implications for addressing real-world challenges. The paradigm of responsible AI-AI conversation establishes structured interaction patterns, guaranteeing decision-making autonomy. Key implications include enhanced understanding of AI dialogue flow, compliance with rules and regulations, and decision-making scenarios exemplifying responsible autonomy. Real-world applications envision AI systems autonomously addressing complex challenges. We have made preliminary testing of such a paradigm involving instances of ChatGPT autonomously playing various roles in a set of experimental AI-AI conversations and observed evident added value of such a framework.
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Osteochondral tissue (OC) repair remains a significant challenge in the field of musculoskeletal tissue engineering. OC tissue displays a gradient structure characterized by variations in both cell types and extracellular matrix components, from cartilage to the subchondral bone. These functional gradients observed in the native tissue have been replicated to engineer OC tissuein vitro. While diverse fabrication methods have been employed to create these microenvironments, emulating the natural gradients and effective regeneration of the tissue continues to present a significant challenge. In this study, we present the design and development of CMC-silk interpenetrating (IPN) hydrogel with opposing dual biochemical gradients similar to native tissue with the aim to regenerate the complete OC unit. The gradients of biochemical cues were generated using an in-house-built extrusion system. Firstly, we fabricated a hydrogel that exhibits a smooth transition of sulfated carboxymethyl cellulose (sCMC) and TGF-ß1 (SCT gradient hydrogel) from the upper to the lower region of the IPN hydrogel to regenerate the cartilage layer. Secondly, a hydrogel with a hydroxyapatite (HAp) gradient (HAp gradient hydrogel) from the lower to the upper region was fabricated to facilitate the regeneration of the subchondral bone layer. Subsequently, we developed a dual biochemical gradient hydrogel with a smooth transition of sCMC + TGF-ß1 and HAp gradients in opposing directions, along with a blend of both biochemical cues in the middle. The results showed that the dual biochemical gradient hydrogels with biochemical cues corresponding to the three zones (i.e. cartilage, interface and bone) of the OC tissue led to differentiation of bone-marrow-derived mesenchymal stem cells to zone-specific lineages, thereby demonstrating their efficacy in directing the fate of progenitor cells. In summary, our study provided a simple and innovative method for incorporating gradients of biochemical cues into hydrogels. The gradients of biochemical cues spatially guided the differentiation of stem cells and facilitated tissue growth, which would eventually lead to the regeneration of the entire OC tissue with a smooth transition from cartilage (soft) to bone (hard) tissues. This promising approach is translatable and has the potential to generate numerous biochemical and biophysical gradients for regeneration of other interface tissues, such as tendon-to-muscle and ligament-to-bone.
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Hidrogeles , Ingeniería de Tejidos , Hidrogeles/química , Animales , Andamios del Tejido/química , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Condrogénesis/efectos de los fármacos , Cartílago/citología , Cartílago/fisiología , Diferenciación Celular/efectos de los fármacos , Huesos/citología , Durapatita/química , Durapatita/farmacologíaRESUMEN
The transition to the third dimension enables the creation of spintronic nanodevices with significantly enhanced functionality compared to traditional 2D magnetic applications. In this study, we extend common two-dimensional magnetic vortex configurations, which are known for their efficient dynamical response to external stimuli without a bias magnetic field, into the third dimension. This extension results in a substantial increase in vortex frequency, reaching up to 5 GHz, compared to the typical sub-GHz range observed in planar vortex oscillators. A systematic study reveals a complex pattern of vortex excitation modes, explaining the decrease in the lowest gyrotropic mode frequency, the inversion of vortex mode intensities, and the nontrivial spatial distribution of vortex dynamical magnetization noted in previous research. These phenomena enable the optimization of both oscillation frequency and frequency reproducibility, minimizing the impact of uncontrolled size variations in those magnetic nanodevices.
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With the spread of the deadly coronavirus disease throughout the geographies of the globe, expertise from every field has been sought to fight the impact of the virus. The use of Artificial Intelligence (AI), especially, has been the center of attention due to its capability to produce trustworthy results in a reasonable time. As a result, AI centric based research on coronavirus (or COVID-19) has been receiving growing attention from different domains ranging from medicine, virology, and psychiatry etc. We present this comprehensive study that closely monitors the impact of the pandemic on global research activities related exclusively to AI. In this article, we produce highly informative insights pertaining to publications, such as the best articles, research areas, most productive and influential journals, authors, and institutions. Studies are made on top 50 most cited articles to identify the most influential AI subcategories. We also study the outcome of research from different geographic areas while identifying the research collaborations that have had an impact. This study also compares the outcome of research from the different countries around the globe and produces insights on the same.
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Background and objective The Clinical Frailty Scale (CFS) is a rapid assessment tool to identify vulnerable and frail patients. We sought to evaluate the association between preoperative CFS scores and outcomes following emergency laparotomy in a dense, rural, and healthcare-deprived region of the UK inhabited by a multi-comorbid population. Methods We retrospectively reviewed regional National Emergency Laparotomy Audit (NELA) data across United Lincolnshire Hospitals NHS trust to identify all patients aged 65 years and above who underwent emergency laparotomy between December 2018 and March 2021. We also conducted a comprehensive multi-database literature search of Medline, Embase, and Cochrane to synthesise contemporaneous topical evidence. Results A total of 191 patients were assessed using the CFS before they underwent emergency laparotomy. Among 90 (47.1%) individuals categorised as vulnerable or frail (CFS score ≥4), there was no significant difference in age, gender, or length of stay related to the procedure compared with fit patients. However, vulnerable and frail patients were significantly more likely to die (84.8% vs. 39.2%, p<0.0001). Regression analysis identified a vulnerable or frail score to be a significant predictor of 30-day all-cause mortality (OR: 9.327; 95% CI: 3.101-28.054; p<0.0001). A total of six relevant papers were identified in the literature, all indicating a significant association between mortality as well as prolonged length and stay with clinical vulnerability and frailty. Conclusions The CFS is a practical and effective tool for assessing preoperative vulnerability and frailty among patients undergoing emergency laparotomy and can be used to predict mortality and morbidity after surgery.
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Inhibition of Notch signaling in macrophages is known to reduce inflammation, however, its role in regulating vascular hyporeactivity in sepsis is unknown. Thus we aimed to evaluate the effect of sepsis on vascular Notch signaling. Polymicrobial sepsis was induced by caecal ligation and puncture (CLP) in mice. mRNA expressions of Notch receptors (Notch1,3) and ligands (Jag1, Dll4), and downstream effector genes (Hey1, MLCK, MYPT1) were assessed by RT-qPCR. Protein level of activated Notch (NICD) was assessed by Western blot and immuno-histochemistry. Isometric tension in isolated aortic rings was measured by wire myography.CLP down-regulated aortic expression of Notch3, Jag1 and Dll4 as compared to control mice. Additionally, the protein level of NICD was found to be lesser in aortic tissue sections from CLP mice. Expression of Hey1 and MLCK were attenuated whereas MYPT1 expression was increased in septic mouse aorta. DAPT pretreatment did not improve CLP-induced vascular hyporeactivity to NA, CaCl2 and high K+ (80 mM), rather significantly attenuated the aortic response to these vasoconstrictors in control mice. Treatment with 1400 W reversed attenuated Notch3 (but not Jag1 and MLCK) expression in septic mouse aorta. In conclusion, sepsis significantly attenuated the Notch (especially Notch3) signaling in mouse aorta along with reduction in contractile gene expression and vasoconstriction response. Further, iNOS/NO pathway was involved in sepsis-induced down-regulation of Notch3 receptor. Thus systemic inhibition of Notch signaling during sepsis may have serious impact on sepsis-induced vascular hyporeactivity.
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Aorta/metabolismo , Presión Arterial/genética , Presión Arterial/fisiología , Regulación hacia Abajo/genética , Receptor Notch3/metabolismo , Sepsis/genética , Sepsis/metabolismo , Transducción de Señal/genética , Transducción de Señal/fisiología , Vasoconstricción/genética , Vasoconstricción/fisiología , Animales , Aorta/fisiopatología , Ratones , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Sepsis/fisiopatologíaRESUMEN
Broca's aphasia results due to lesions involving the anterior perisylvian speech area. Patients have intact comprehension and writing but have labored, nonfluent speech with decreased linguistic output. We hereby present a case of a 47-year-old female who was operated on for left ventricular trigonal meningioma by a modified middle temporal gyrus approach and developed motor aphasia as a complication. She had intact comprehension and writing but had decreased linguistic, labored output. It could not be labeled as subcortical aphasia as she had no repetition. Eventually, her aphasia improved completely. Our case is the first of its kind and hence we propose that the posterior middle temporal gyrus area has speech output function, the lesion of which could cause motor aphasia.
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This paper reports an approach for the fabrication of highly aligned soft elastic fibrous scaffolds using touch spinning of thermoplastic polycaprolactone-polyurethane elastomers and demonstrates their potential for the engineering of muscle tissue. A family of polyester-polyurethane soft copolymers based on polycaprolactone with different molecular weights and three different chain extenders such as 1,4-butanediol and polyethylene glycols with different molecular weight was synthesized. By varying the molar ratio and molecular weights between the segments of the copolymer, different physicochemical and mechanical properties were obtained. The polymers possess elastic modulus in the range of a few megapascals and good reversibility of deformation after stretching. The combination of the selected materials and fabrication methods allows several essential advantages such as biocompatibility, biodegradability, suitable mechanical properties (elasticity and softness of the fibers), high recovery ratio, and high resilience mimicking properties of the extracellular matrix of muscle tissue. Myoblasts demonstrate high viability in contact with aligned fibrous scaffolds, where they align along the fibers, allowing efficient cell patterning on top of the structures. Altogether, the importance of this approach is the fabrication of highly oriented fiber constructs that can support the proliferation and alignment of muscle cells for muscle tissue engineering applications.
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Poliuretanos , Ingeniería de Tejidos , Músculo Esquelético , Polímeros/química , Poliuretanos/química , Andamios del Tejido/químicaRESUMEN
BACKGROUND AND AIM: Selection and dissemination of plasmid-encoded extended-spectrum ß-lactamase (ESBL) among Enterobacteriaceae confers resistance to beta-lactam antibiotics. The purpose of this study was to determine the prevalence and molecular characteristics of ESBL-producing organisms isolated from dairy cattle with a uterine infection. MATERIALS AND METHODS: Bacterial isolates (n=62) were characterized by biochemical test for genus and species determination. Antimicrobial susceptibility tests were performed by Kirby-Bauer disk diffusion method using panel of antibiotics for initial screening of ESBL organism. Phenotypic confirmation of ESBL-suspected strains was done by combination disk method and double-disk method. Multiplex polymerase chain reaction (PCR) was carried out for phylogrouping of Escherichia coli isolates as well as for genotyping ESBL genes. Enterobacterial repetitive intergenic consensus-PCR method was used for genotypic characterization of isolates. RESULTS: Antibiotic susceptibility profile of E. coli (n=40) isolates showed high rates of resistance for ampicillin (95.0%), cefpodoxime (97.5%), cefotaxime (87.5%), and ceftriaxone (70%). However, low rates of resistance were observed for cefoxitin (25%), amoxicillin/clavulanic acid (20%), ceftazidime (17.5%), gentamicin (10%), and ertapenem (7.5%). A total of 39/40 E. coli isolates were confirmed as ESBL with Epsilometer test as well as the genotypic method and 28 (70%) of them were multidrug-resistant. Genotype blaCTX-M was observed as a predominant beta-lactamase type with the preponderance of CTX-M Group 1. The following combinations were observed: blaTEM + blaCTX-M in 15 (36.2%) isolates, blaTEM /blaSHV in 8 (5.2%) isolates, and blaCTX-M /blaSHV in 6 (5.2%) isolates. The phylogenetic grouping of E. coli strains revealed the highest prevalence for B1 (22.0%) followed by A (20%). CONCLUSION: This report shows a high frequency of ESBL E. coli from cattle with postpartum uterine infections. These isolates showed reduced susceptibility to common antibiotics used for the treatment of uterine infections greater affecting the therapeutic outcome.
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This paper reports an approach for the fabrication of shape-changing bilayered scaffolds, which allow the growth of aligned skeletal muscle cells, using a combination of 3D printing of hyaluronic acid hydrogel, melt electrowriting of thermoplastic polycaprolactone-polyurethane elastomer, and shape transformation. The combination of the selected materials and fabrication methods allows a number of important advantages such as biocompatibility, biodegradability, and suitable mechanical properties (elasticity and softness of the fibers) similar to those of important components of extracellular matrix (ECM), which allow proper cell alignment and shape transformation. Myoblasts demonstrate excellent viability on the surface of the shape-changing bilayer, where they occupy space between fibers and align along them, allowing efficient cell patterning inside folded structures. The bilayer scaffold is able to undergo a controlled shape transformation and form multilayer scroll-like structures with cells encapsulated inside. Overall, the importance of this approach is the fabrication of tubular constructs with a patterned interior that can support the proliferation and alignment of muscle cells for muscle tissue regeneration.
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Materiales Biocompatibles/química , Elastómeros/química , Hidrogeles/química , Fibras Musculares Esqueléticas/química , Impresión Tridimensional , Ingeniería de Tejidos , Animales , Materiales Biocompatibles/farmacología , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Elastómeros/farmacología , Matriz Extracelular/química , Hidrogeles/farmacología , Ensayo de Materiales , Ratones , Andamios del Tejido/químicaRESUMEN
The spread of COVID-19 worldwide continues despite multidimensional efforts to curtail its spread and provide treatment. Efforts to contain the COVID-19 pandemic have triggered partial or full lockdowns across the globe. This paper presents a novel framework that intelligently combines machine learning models and the Internet of Things (IoT) technology specifically to combat COVID-19 in smart cities. The purpose of the study is to promote the interoperability of machine learning algorithms with IoT technology by interacting with a population and its environment to curtail the COVID-19 pandemic. Furthermore, the study also investigates and discusses some solution frameworks, which can generate, capture, store, and analyze data using machine learning algorithms. These algorithms can detect, prevent, and trace the spread of COVID-19 and provide a better understanding of the disease in smart cities. Similarly, the study outlined case studies on the application of machine learning to help fight against COVID-19 in hospitals worldwide. The framework proposed in the study is a comprehensive presentation on the major components needed to integrate the machine learning approach with other AI-based solutions. Finally, the machine learning framework presented in this study has the potential to help national healthcare systems in curtailing the COVID-19 pandemic in smart cities. In addition, the proposed framework is poised as a pointer for generating research interests that would yield outcomes capable of been integrated to form an improved framework.