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Introduction: As fire pits grow in popularity, so do the associated burn injuries. Our study examines pediatric fire pit burns characteristics to raise awareness and promote safety precautions. Methods: We conducted a retrospective review of pediatric patients (≤21 years) with firepit burns at a tertiary care hospital from 2016 to 2021. Results: Eighty-four patients were identified, of whom 70.2% were male, with a median age of 62 months. The median percent total body surface area burned was 2% (interquartile range (IQR)=1-4). Thirty-five (41.7%) patients were admitted and 7 (8.3%) underwent grafting. Neck and trunk burns had the highest grafting rates (66% and 33%, respectively). The hands (41.7%) and the lower extremities (27.4%) were the most frequently burned body areas. The leading causes of burns were ashes/hot coals (34.5%), flames (31.0%), and direct contact (25.0%), often resulting from falling into the fire (59.5%) or running or playing in activities near it (26.2%). Thirty-five (41.7%) were admitted for inpatient management, while 49 (58.3%) were treated as outpatient. Eleven (13.2%) underwent at least one reconstructive surgery, 7 (8.4%) had at least one rehabilitation visit, and 65 (77.4%) had follow-up clinic visits. The median length of stay was 2 days (IQR=1.0-3.5). The peak months for burns were from August through October (n=40, 46.0%), with an increase observed from 10 cases in 2016 to 20 cases in 2020. Conclusions: Given the significant proportion of firepit burns resulting from unsafe fire behaviors, it is crucial that caretakers are aware of proper firepit safety precautions. Level of evidence: III.
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The temporal control of pH in microreactors such as emulsion droplets plays a vital role in applications including biomineralisation and microparticle synthesis. Typically, pH changes are achieved either by passive diffusion of species into a droplet or by acid/base producing reactions. Here, we exploit an enzyme reaction combined with the properties of a water-oil-water (W/O/W) double emulsion to control the pH-time profile in the droplets. A microfluidic platform was used for production of â¼100-200 µm urease-encapsulated double emulsions with a tuneable mineral oil shell thickness of 10-40 µm. The reaction was initiated on-demand by addition of urea and a pulse in base (ammonia) up to pH 8 was observed in the droplets after a time lag of the order of minutes. The pH-time profile can be manipulated by the diffusion timescale of urea and ammonia through the oil layer, resulting in a steady state pH not observed in bulk reactive solutions. This approach may be used to regulate the formation of pH sensitive materials under mild conditions and, as a proof of concept, the reaction was coupled to calcium phosphate precipitation in the droplets. The oil shell thickness was varied to select for either brushite microplatelets or hydroxyapatite particles, compared to the mixture of different precipitates obtained in bulk.
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Necrotizing enterocolitis (NEC) is the leading cause of morbidity and mortality in premature infants. One of the most devastating complications of NEC is the development of NEC-induced brain injury, which manifests as impaired cognition that persists beyond infancy and which represents a proinflammatory activation of the gut-brain axis. Given that oral administration of the human milk oligosaccharides (HMOs) 2'-fucosyllactose (2'-FL) and 6'-sialyslactose (6'-SL) significantly reduced intestinal inflammation in mice, we hypothesized that oral administration of these HMOs would reduce NEC-induced brain injury and sought to determine the mechanisms involved. We now show that the administration of either 2'-FL or 6'-SL significantly attenuated NEC-induced brain injury, reversed myelin loss in the corpus callosum and midbrain of newborn mice, and prevented the impaired cognition observed in mice with NEC-induced brain injury. In seeking to define the mechanisms involved, 2'-FL or 6'-SL administration resulted in a restoration of the blood-brain barrier in newborn mice and also had a direct anti-inflammatory effect on the brain as revealed through the study of brain organoids. Metabolites of 2'-FL were detected in the infant mouse brain by nuclear magnetic resonance (NMR), whereas intact 2'-FL was not. Strikingly, the beneficial effects of 2'-FL or 6'-SL against NEC-induced brain injury required the release of the neurotrophic factor brain-derived neurotrophic factor (BDNF), as mice lacking BDNF were not protected by these HMOs from the development of NEC-induced brain injury. Taken in aggregate, these findings reveal that the HMOs 2'-FL and 6'-SL interrupt the gut-brain inflammatory axis and reduce the risk of NEC-induced brain injury.NEW & NOTEWORTHY This study reveals that the administration of human milk oligosaccharides, which are present in human breast milk, can interfere with the proinflammatory gut-brain axis and prevent neuroinflammation in the setting of necrotizing enterocolitis, a major intestinal disorder seen in premature infants.
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Lesiones Encefálicas , Disfunción Cognitiva , Enterocolitis Necrotizante , Humanos , Recién Nacido , Lactante , Femenino , Animales , Ratones , Leche Humana/metabolismo , Factor Neurotrófico Derivado del Encéfalo , Enfermedades Neuroinflamatorias , Enterocolitis Necrotizante/etiología , Oligosacáridos/farmacología , Oligosacáridos/uso terapéutico , Oligosacáridos/análisis , Disfunción Cognitiva/prevención & control , Disfunción Cognitiva/complicaciones , Lesiones Encefálicas/complicaciones , Lesiones Encefálicas/metabolismoRESUMEN
Precise metal-protein coordination by design remains a considerable challenge. Polydentate, high-metal-affinity protein modifications, both chemical and recombinant, can enable metal localization. However, these constructs are often bulky, conformationally and stereochemically ill-defined, or coordinately saturated. Here, we expand the biomolecular metal-coordination toolbox with the irreversible attachment to cysteine of bis(1-methylimidazol-2-yl)ethene ("BMIE"), which generates a compact imidazole-based metal-coordinating ligand. Conjugate additions of small-molecule thiols (thiocresol and N-Boc-Cys) with BMIE confirm general thiol reactivity. The BMIE adducts are shown to complex the divalent metal ions Cu++ and Zn++ in bidentate (N2) and tridentate (N2S*) coordination geometries. Cysteine-targeted BMIE modification (>90% yield at pH 8.0) of a model protein, the S203C variant of carboxypeptidase G2 (CPG2), measured with ESI-MS, confirms its utility as a site-selective bioconjugation method. ICP-MS analysis confirms mono-metallation of the BMIE-modified CPG2 protein with Zn++, Cu++, and Co++. EPR characterization of the BMIE-modified CPG2 protein reveals the structural details of the site selective 1:1 BMIE-Cu++ coordination and symmetric tetragonal geometry under physiological conditions and in the presence of various competing and exchangeable ligands (H2O/HO-, tris, and phenanthroline). An X-ray protein crystal structure of BMIE-modified CPG2-S203C demonstrates that the BMIE modification is minimally disruptive to the overall protein structure, including the carboxypeptidase active sites, although Zn++ metalation could not be conclusively discerned at the resolution obtained. The carboxypeptidase catalytic activity of BMIE-modified CPG2-S203C was also assayed and found to be minimally affected. These features, combined with ease of attachment, define the new BMIE-based ligation as a versatile metalloprotein design tool, and enable future catalytic and structural applications.
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Metaloproteínas , Metaloproteínas/química , Cisteína , Zinc/química , Metales , Péptido Hidrolasas , Imidazoles , Compuestos de Sulfhidrilo/química , Cobre/química , Cristalografía por Rayos X , LigandosRESUMEN
The beating of cilia and flagella, which relies on an efficient conversion of energy from ATP-hydrolysis into mechanical work, offers a promising way to propel synthetic cargoes. Recent experimental realizations of such micro-swimmers, in which micron-sized beads are propelled by isolated and demembranated flagella from the green algae Chlamydomonas reinhardtii (C. reinhardtii), revealed a variety of propulsion modes, depending in particular on the calcium concentration. Here, we investigate theoretically and numerically the propulsion of a bead as a function of the flagellar waveform and the attachment geometries between the bead and the flagellum. To this end, we take advantage of the low Reynolds number of the fluid flows generated by the micro-swimmer, which allows us to neglect fluid inertia. By describing the flagellar waveform as a superposition of a static component and a propagating wave, and using resistive-force theory, we show that the asymmetric sideways attachment of the flagellum to the bead makes a contribution to the rotational velocity of the micro-swimmer that is comparable to the contribution caused by the static component of the flagellar waveform. Remarkably, our analysis reveals the existence of a counter-intuitive propulsion regime in which an increase in the size of the cargo, and hence its drag, leads to an increase in some components of the velocity of the bead. Finally, we discuss the relevance of the uncovered mechanisms for the fabrication of synthetic, bio-actuated medical micro-robots for targeted drug delivery.
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Chlamydomonas reinhardtii , Flagelos , Cilios , Fenómenos Mecánicos , Calcio de la DietaRESUMEN
Patients with carcinoid heart disease (CHD) are referred for valve replacement if they have severe symptomatic disease or evidence of right ventricular (RV) failure and an anticipated survival of at least 12 months. Data are lacking, however, on the role of transthoracic echocardiography in predicting outcomes. We carried out a retrospective, single-centre cohort study of patients with a biopsy-confirmed neuroendocrine tumour (NET) and CHD undergoing valve replacement for severe valve disease and symptoms of right heart failure. The aim was to identify factors associated with postoperative mortality, both within one year of surgery and during long-term follow-up. Of 88 patients with NET, 49 were treated surgically (mean age: 64.4 ± 7.6 years; 55% male), of whom 48 had a bioprosthetic tricuspid valve replacement for severe tricuspid regurgitation; 39 patients had a pulmonary valve replacement. Over a median potential follow-up of 96 months (interquartile range: 56-125), there were 37 deaths, with 30-day and one-year mortality of 14% (n = 7) and 39% (n = 19), respectively. A significant relationship between RV size and one-year mortality was observed, with 57% of those with severe RV dilatation dying within a year of surgery, compared to 33% in those with normal RV size (p = 0.039). This difference remained significant in the time-to-event analysis of long-term survival (p = 0.008). RV size was found to reduce significantly with surgery (p < 0.001). Those with persisting RV dilatation (p = 0.007) or worse RV function (p = 0.001) on postoperative echocardiography had significantly shorter long-term survival. In this single-centre retrospective study of patients undergoing surgery for CHD, increasingly severe RV dilatation on preoperative echocardiography predicted adverse outcomes, yielding a doubling of the one-year mortality rate relative to normal RV size. These data support the possibility that early surgery might deliver greater long-term benefits in this patient cohort.
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Necrotizing enterocolitis (NEC) is the leading cause of death and disability from gastrointestinal disease in premature infants. The mortality of patients with NEC is approximately 30%, a figure that has not changed in many decades, reflecting the need for a greater understanding of its pathogenesis. Progress towards understanding the cellular and molecular mechanisms underlying NEC requires the study of highly translational animal models. Such animal models must mimic the biology and physiology of premature infants, while still allowing for safe experimental manipulation of environmental and microbial factors thought to be associated with the risk and severity of NEC. Findings from animal models have yielded insights into the interactions between the host, the colonizing microbes, and the innate immune receptor Toll-like Receptor 4 (TLR4) in driving disease development. This review discusses the relative strengths and weaknesses of available in vivo, in vitro, and NEC-in-a-dish models of this disease. We also highlight the unique contributions that each model has made to our understanding of the complex interactions between enterocytes, microbiota, and immune cells in the pathogenesis of NEC. The overall purpose of this review is to provide a menu of options regarding currently available animal models of NEC, while in parallel hopefully reducing the potential uncertainty and confusion regarding NEC models to assist those who wish to enter this field from other disciplines.
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Enterocolitis Necrotizante , Enfermedades Fetales , Enfermedades del Recién Nacido , Microbiota , Animales , Femenino , Recién Nacido , Humanos , Recien Nacido Prematuro , Modelos Animales , Modelos Animales de EnfermedadRESUMEN
The decline of CD8+ T cell functions contributes to deteriorating health with aging, but the mechanisms that underlie this phenomenon are not well understood. We use single-cell RNA sequencing with both cross-sectional and longitudinal samples to assess how human CD8+ T cell heterogeneity and transcriptomes change over nine decades of life. Eleven subpopulations of CD8+ T cells and their dynamic changes with age are identified. Age-related changes in gene expression result from changes in the percentage of cells expressing a given transcript, quantitative changes in the transcript level, or a combination of these two. We develop a machine learning model capable of predicting the age of individual cells based on their transcriptomic features, which are closely associated with their differentiation and mutation burden. Finally, we validate this model in two separate contexts of CD8+ T cell aging: HIV infection and CAR T cell expansion in vivo.
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Linfocitos T CD8-positivos , Infecciones por VIH , Envejecimiento/genética , Linfocitos T CD8-positivos/metabolismo , Estudios Transversales , Infecciones por VIH/genética , Infecciones por VIH/metabolismo , Humanos , TranscriptomaRESUMEN
Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare malignancy with a low malignant potential and strong female preponderance. Diagnosis during pregnancy is extraordinary, and management must consider the risks to the mother and foetus of tumour growth and rupture. A large 35-cm SPN was identified on magnetic resonance imaging (MRI) in a 24-year-old woman at 6 weeks of gestation following presentation with an abdominal mass. Surgery was delayed to allow the foetus to reach as close to term as possible because surveillance MRIs showed incremental mass growth. Emergency c-section was undertaken at 35 weeks of gestation due to persistent tachycardia and suspected haemorrhage into the tumour. A Hb of 70 g/l post-delivery despite four units of RBCs and an albumin of 11 g/l necessitated urgent multivisceral surgery. Surgical resection is the mainstay of treatment for SPN. However, the strategy of choice during pregnancy remains undetermined, with more recent reports delaying surgery until post-partum.
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Necrotizing enterocolitis (NEC) is the leading cause of death from gastrointestinal disease in premature infants and is steadily rising in frequency. Patients who develop NEC have a very high mortality, illustrating the importance of developing novel prevention or treatment approaches. We and others have shown that NEC arises in part from exaggerated signaling via the bacterial receptor, Toll-like receptor 4 (TLR4) on the intestinal epithelium, leading to widespread intestinal inflammation and intestinal ischemia. Strategies that limit the extent of TLR4 signaling, including the administration of amniotic fluid, can reduce NEC development in mouse and piglet models. We now seek to test the hypothesis that a secretome derived from amnion-derived cells can prevent or treat NEC in preclinical models of this disease via a process involving TLR4 inhibition. In support of this hypothesis, we show that the administration of this secretome, named ST266, to mice or piglets can prevent and treat experimental NEC. The protective effects of ST266 occurred in the presence of marked TLR4 inhibition in the intestinal epithelium of cultured epithelial cells, intestinal organoids, and human intestinal samples ex vivo, independent of epidermal growth factor. Strikingly, RNA-seq analysis of the intestinal epithelium in mice reveals that the ST266 upregulates critical genes associated with gut remodeling, intestinal immunity, gut differentiation. and energy metabolism. These findings show that the amnion-derived secretome ST266 can prevent and treat NEC, suggesting the possibility of novel therapeutic approaches for patients with this devastating disease.NEW & NOTEWORTHY This work provides hope for children who develop NEC, a devastating disease of premature infants that is often fatal, by revealing that the secreted product of amniotic progenitor cells (called ST266) can prevent or treat NEC in mice, piglet, and "NEC-in-a-dish" models of this disease. Mechanistically, ST266 prevented bacterial signaling, and a detailed transcriptomic analysis revealed effects on gut differentiation, immunity, and metabolism. Thus, an amniotic secretome may offer novel approaches for NEC.
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Enterocolitis Necrotizante , Células Madre Multipotentes , Secretoma , Amnios/citología , Animales , Modelos Animales de Enfermedad , Enterocolitis Necrotizante/prevención & control , Mucosa Intestinal/metabolismo , Ratones , Células Madre Multipotentes/metabolismo , Porcinos , Receptor Toll-Like 4/metabolismoRESUMEN
Bio-hybrid micro-swimmers, composed of biological entities integrated with synthetic constructs, actively transport cargo by converting chemical energy into mechanical work. Here, using isolated and demembranated flagella from green algae Chlamydomonas reinhardtii (C. reinhardtii), we build efficient axonemally-driven micro-swimmers that consume ATP to propel micron-sized beads. Depending on the calcium concentration, we observed two main classes of motion: whereas beads move along curved trajectories at calcium concentrations below 0.03 mM, they are propelled along straight paths when the calcium concentration increases. In this regime, they reached velocities of approximately 20 µm s-1, comparable to human sperm velocity in vivo. We relate this transition to the properties of beating axonemes, in particular the reduced static curvature with increasing calcium concentration. Our designed system has potential applications in the fabrication of synthetic micro-swimmers, and in particular, bio-actuated medical micro-robots for targeted drug delivery.
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Calcio , Chlamydomonas reinhardtii , Flagelos , Humanos , Masculino , Semillas , EspermatozoidesRESUMEN
BACKGROUND: Sigmoid volvulus is a common cause of emergency surgical admission. Those patients are often treated conservatively with a high rate of recurrence. We wondered if a more aggressive management might be indicated. METHODS: We have reviewed data of patients diagnosed with acute sigmoid volvulus over a 2-year period. The primary endpoint was patient survival. RESULTS: We analysed 332 admissions of 78 patients. 39.7% underwent resection. Survival was 54.9 ± 8.8 months from the first hospitalization, irrespective of the treatment. Long-term survival was positively influenced by being female, having a low "social score", a younger age and surgery. Multivariate analysis showed that only being female and surgery were independently associated with better survival. CONCLUSION: Early surgery may be the best approach in patients with recurrent sigmoid volvulus, as it ensures longer survival with a better quality of life, regardless of the patient's social and functional condition.
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Vólvulo Intestinal , Enfermedades del Sigmoide , Femenino , Humanos , Vólvulo Intestinal/diagnóstico , Vólvulo Intestinal/cirugía , Pronóstico , Calidad de Vida , Estudios Retrospectivos , Enfermedades del Sigmoide/diagnóstico , Enfermedades del Sigmoide/cirugíaRESUMEN
Lysine specific methyltransferase 2D (Kmt2d) catalyzes the mono-methylation of histone 3 lysine 4 (H3K4me1) and plays a critical role in regulatory T cell generation via modulating Foxp3 gene expression. Here we report a role of Kmt2d in naïve CD8+ T cell generation and survival. In the absence of Kmt2d, the number of CD8+ T cells, particularly naïve CD8+ T cells (CD62Lhi/CD44lo), in spleen was greatly decreased and in vitro activation-related death significantly increased from Kmt2d fl/flCD4cre+ (KO) compared to Kmt2d fl/flCD4cre- (WT) mice. Furthermore, analyses by ChIPseq, RNAseq, and scRNAseq showed reduced H3K4me1 levels in enhancers and reduced expression of apoptosis-related genes in activated naïve CD8+ T cells in the absence of Kmt2d. Finally, we confirmed the activation-induced death of antigen-specific naïve CD8+ T cells in vivo in Kmt2d KO mice upon challenge with Listeria monocytogenes infection. These findings reveal that Kmt2d regulates activation-induced naïve CD8+ T cell survival via modulating H3K4me1 levels in enhancer regions of apoptosis and immune function-related genes.
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Linfocitos T CD8-positivos , N-Metiltransferasa de Histona-Lisina , Lisina , Animales , Ratones , Biomarcadores , Linfocitos T CD8-positivos/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , N-Metiltransferasa de Histona-Lisina/metabolismo , Histonas/metabolismo , Factores de Transcripción/metabolismoRESUMEN
The finding of a pigmented lesion within another distinct lesion is rare but not unheard of. Here, we describe the presence of an atypical fibroxanthoma within a melanoma in a 72-year-old female referred to the plastics surgery department with a pigmented lesion on her left knee. It was excised in view of clinical suspicion of melanoma. The histopathology report documented a single lesion with two distinct components, namely a melanoma of superficial spreading type with a Breslow thickness of 3.0mm, and a central nodule of atypical fibroxanthoma.
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BACKGROUND: Tubulysins, linear tetrapeptides show extraordinary cytotoxicity against various cancer cells, with IC50 values in nano or picomolar range. Due to their extremely vigorous anti-proliferative and antiangiogenic characteristics, tubulysins exhibit captivating prospects in the development of anticancer drugs. This review focuses on diverse routes for the total synthesis of natural and synthetic tubulysins as well as their fragments. OBJECTIVE: The purpose of this review is to present the synthetic strategies for the development of antitumor agents, tubulysins. CONCLUSION: A range of synthetic pathways adopted for the total synthesis of tubulysins and their fragments have been described in this review. Synthesis of fragments, Tuv, Tup, and Tut can be accomplished by adopting appropriate strategies such as Manganese-mediated synthesis, Ireland-Claisen rearrangement, Mukaiyama aldol reaction, and Mannich process etc. Tubulysin B, D, U, V, and N14-desacetoxytubulysin H have been prepared through Mitsunobu reaction, tert-butanesulfinamide method, Tandem reaction, aza-Barbier reaction, Evans aldol reaction, and C-H activation strategies etc. The remarkable anticancer potential of tubulysins toward a substantiate target make them prominent leads for developing novel drugs against multidrug-resistant cancers.
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Cadmium is an environmental pollutant and significant health hazard that is similar to the physiological metal zinc. In Caenorhabditis elegans, high zinc homeostasis is regulated by the high zinc activated nuclear receptor (HIZR-1) transcription factor. To define relationships between the responses to high zinc and cadmium, we analyzed transcription. Many genes were activated by both high zinc and cadmium, and hizr-1 was necessary for activation of a subset of these genes; in addition, many genes activated by cadmium did not require hizr-1, indicating there are at least two mechanisms of cadmium-regulated transcription. Cadmium directly bound HIZR-1, promoted nuclear accumulation of HIZR-1 in intestinal cells, and activated HIZR-1-mediated transcription via the high zinc activation (HZA) enhancer. Thus, cadmium binding promotes HIZR-1 activity, indicating that cadmium acts as a zinc mimetic to hijack the high zinc response. To elucidate the relationships between high zinc and cadmium detoxification, we analyzed genes that function in three pathways: the pcs-1/phytochelatin pathway strongly promoted cadmium resistance but not high zinc resistance, the hizr-1/HZA pathway strongly promoted high zinc resistance but not cadmium resistance, and the mek-1/sek-1/kinase signaling pathway promoted resistance to high zinc and cadmium. These studies identify resistance pathways that are specific for high zinc and cadmium, as well as a shared pathway.
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Cadmio/farmacología , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/efectos de los fármacos , Receptores Citoplasmáticos y Nucleares/metabolismo , Zinc/metabolismo , Animales , Caenorhabditis elegans/metabolismo , Homeostasis , Ligandos , Metalotioneína/metabolismo , Unión ProteicaRESUMEN
Importance: Total thyroidectomy is associated with risks related to temporary hypocalcemia and vocal quality dysfunction. Dexamethasone has been proposed to have a physiological effect on hypocalcemia and voice quality. Objective: To assess the effect of preoperative dexamethasone used to improve hypocalcemia and postthyroidectomy voice dysfunction. Design, Setting, and Participants: This double-blind, parallel-group, placebo-controlled randomized clinical trial was conducted from January 15, 2014, to December 31, 2019, at the Department of Surgery, Holy Family Hospital in Rawalpindi, Pakistan. All patients with a benign thyroid condition and no preoperative corrected hypocalcemia and voice or vocal quality dysfunction were included. Patients were excluded if they had previous thyroid or neck surgery, known vocal cord dysfunction on laryngoscopy, hearing or voice problems, a history of gastroesophageal reflux, stomach ulcer disease, or contraindications to steroid use. Interventions: Corrected serum calcium levels and Voice Analog Score defined and measured preoperatively. The dexamethasone group received a 2-mL intravenous dose of 8 mg of dexamethasone 60 minutes before the induction of anesthesia. In contrast, the placebo group received 2 mL of intravenous normal saline (0.9%) 60 minutes before the induction of anesthesia. Main Outcomes and Measures: Evidence of hypocalcemia and voice dysfunction. Voice dysfunction was defined as a subjective score of less than 50 on a Voice Analog Score scale of 0 to 100 points. Results: A total of 192 patients (mean [SD] age, 38.9 [12.4] years; 156 women [81.2%]) were included in the study, with 96 patients randomized to each study group (dexamethasone group, mean [SD] age, 39.2 [12.1] years; 75 women [78.1%]; placebo group, mean [SD] age, 38.5 [12.9] years; 81 women [84.5%]). In the first 24 hours after undergoing thyroidectomy, 47 patients (24.4%) developed hypocalcemia and 18 (9.4%) were symptomatic. At 3 days postthyroidectomy, 4 of 96 patients (4.2%) in the placebo group had hypocalcemia compared with no patients in the dexamethasone group. At 24 hours postthyroidectomy, 8 of 96 patients (8.3%) in the dexamethasone group had voice dysfunction compared with 32 of 96 patients (33.3%) in the placebo group. A total of 40 patients (20.8%) reported voice dysfunction. The absolute reduction in the rate of hypocalcemia at 24 hours was 24% (95% CI, 11.9%-35.2%) and at 3 days was 4.2% (-0.44% to 10.0%). The rate of symptomatic hypocalcemia was 19% lower in the dexamethasone group than in the placebo group (95% CI, 11.1%-27.7%). The rate of voice dysfunction was 25% lower in the dexamethasone group than in the placebo group (95% CI, 13.7%-35.7%). Conclusions and Relevance: In this randomized clinical trial, a single preoperative dose of dexamethasone was safe and effective in reducing postoperative hypocalcemia and voice dysfunction rates in patients undergoing thyroidectomy. Trial Registration: ClinicalTrials.gov identifier: NCT04752852.
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Dexametasona/uso terapéutico , Hipocalcemia/prevención & control , Complicaciones Posoperatorias/prevención & control , Esteroides/uso terapéutico , Tiroidectomía , Trastornos de la Voz/prevención & control , Adulto , Método Doble Ciego , Femenino , Humanos , Masculino , Pakistán , Calidad de la VozRESUMEN
Artificial systems capable of self-sustained movement with self-sufficient energy are of high interest with respect to the development of many challenging applications, including medical treatments, but also technical applications. The bottom-up assembly of such systems in the context of synthetic biology is still a challenging task. In this work, we demonstrate the biocompatibility and efficiency of an artificial light-driven energy module and a motility functional unit by integrating light-switchable photosynthetic vesicles with demembranated flagella. The flagellar propulsion is coupled to the beating frequency, and dynamic ATP synthesis in response to illumination allows us to control beating frequency of flagella in a light-dependent manner. In addition, we verified the functionality of light-powered synthetic vesicles in in vitro motility assays by encapsulating microtubules assembled with force-generating kinesin-1 motors and the energy module to investigate the dynamics of a contractile filamentous network in cell-like compartments by optical stimulation. Integration of this photosynthetic system with various biological building blocks such as cytoskeletal filaments and molecular motors may contribute to the bottom-up synthesis of artificial cells that are able to undergo motor-driven morphological deformations and exhibit directional motion in a light-controllable fashion.
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Células Artificiales , Axonema/efectos de la radiación , Ingeniería Celular/métodos , Chlamydomonas reinhardtii/citología , Flagelos/efectos de la radiación , Luz , Adenosina Trifosfato/metabolismo , Axonema/metabolismo , Movimiento Celular/efectos de la radiación , Cilios/efectos de la radiación , Dineínas/metabolismo , Metabolismo Energético/efectos de la radiación , Flagelos/metabolismo , Cinesinas/metabolismo , Liposomas/metabolismo , Liposomas/efectos de la radiación , Fotosíntesis/efectos de la radiación , Transducción de Señal/efectos de la radiaciónRESUMEN
Introduction The laparoscopic approach, as compared to open cholecystectomy, is still considered the gold standard, despite a higher incidence of micro insults. The most common approach to treat spilled biliary contents and lost stones in laparoscopic cholecystectomy is the retrieval of the stone through an open approach, or laparoscopically, ending with a peritoneal wash and aspiration. Material and methods We conducted a double-blinded randomized controlled trial. In the study group, patients with bile spillage during cholecystectomy underwent suction of all spilled bile and evacuation of all visible stones followed by dry mopping of the gallbladder fossa with gauze swab through an epigastric port. In the control group, after suction of all bile and visible stones, the gallbladder fossa was washed with 250 ml of saline, and fluid was aspirated through the epigastric port. Results Sixty patients were included (30 patients in each group), 71.6% were female and the rest were male. There was a statistically significant difference in pain scores between the two groups (p=0.001). The dry mopping group had lower pain scores as compared to the other group postoperatively. The incidence of the intraabdominal collection in both groups are statistically insignificant, however, port site infection and intraabdominal collection are higher in the control group (irrigation group). Conclusion Although there is not much literature on the best approach to biliary spillage in laparoscopic cholecystectomy. We believe that dry mopping had better postoperative patient outcome as compared to the saline wash.