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SARS-CoV-2 and other sarbecoviruses continue to threaten humanity, highlighting the need to characterize common mechanisms of viral immune evasion for pandemic preparedness. Cytotoxic lymphocytes are vital for antiviral immunity and express NKG2D, an activating receptor conserved among mammals that recognizes infection-induced stress ligands (e.g., MIC-A/B). We found that SARS-CoV-2 evades NKG2D recognition by surface downregulation of MIC-A/B via shedding, observed in human lung tissue and COVID-19 patient serum. Systematic testing of SARS-CoV-2 proteins revealed that ORF6, an accessory protein uniquely conserved among sarbecoviruses, was responsible for MIC-A/B downregulation via shedding. Further investigation demonstrated that natural killer (NK) cells efficiently killed SARS-CoV-2-infected cells and limited viral spread. However, inhibition of MIC-A/B shedding with a monoclonal antibody, 7C6, further enhanced NK-cell activity toward SARS-CoV-2-infected cells. Our findings unveil a strategy employed by SARS-CoV-2 to evade cytotoxic immunity, identify the culprit immunevasin shared among sarbecoviruses, and suggest a potential novel antiviral immunotherapy.
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COVID-19 , Evasão da Resposta Imune , Células Matadoras Naturais , Subfamília K de Receptores Semelhantes a Lectina de Células NK , SARS-CoV-2 , Humanos , SARS-CoV-2/imunologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , COVID-19/imunologia , COVID-19/virologia , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Animais , Citotoxicidade Imunológica , Regulação para Baixo , Pulmão/imunologia , Pulmão/virologia , Pulmão/patologiaRESUMO
Optical frequency combs have revolutionized precision measurement, time-keeping and molecular spectroscopy1-7. A substantial effort has developed around 'microcombs': integrating comb-generating technologies into compact photonic platforms5,7-9. Current approaches for generating these microcombs involve either the electro-optic10 or Kerr mechanisms11. Despite rapid progress, maintaining high efficiency and wide bandwidth remains challenging. Here we introduce a previously unknown class of microcomb-an integrated device that combines electro-optics and parametric amplification to yield a frequency-modulated optical parametric oscillator (FM-OPO). In contrast to the other solutions, it does not form pulses but maintains operational simplicity and highly efficient pump power use with an output resembling a frequency-modulated laser12. We outline the working principles of our device and demonstrate it by fabricating the complete optical system in thin-film lithium niobate. We measure pump-to-comb internal conversion efficiency exceeding 93% (34% out-coupled) over a nearly flat-top spectral distribution spanning about 200 modes (over 1 THz). Compared with an electro-optic comb, the cavity dispersion rather than loss determines the FM-OPO bandwidth, enabling broadband combs with a smaller radio-frequency modulation power. The FM-OPO microcomb offers robust operational dynamics, high efficiency and broad bandwidth, promising compact precision tools for metrology, spectroscopy, telecommunications, sensing and computing.
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The human Solute Carrier (SLC) family member, monocarboxylate transporter 1 (MCT1), transports lactic and pyruvic acid across biological membranes to regulate cellular pH and metabolism. Proper trafficking of MCT1 from the endoplasmic reticulum to the plasma membrane hinges on its interactions with the membrane-bound chaperone protein, CD147. Here, using AlphaFold2 modeling and copurification, we show how a conserved signature motif located in the flexible N-terminus of MCT1 is a crucial region of interaction between MCT1 and the C-terminus of CD147. Mutations to this motif-namely, the thymic cancer linked G19C and the highly conserved W20A-destabilize the MCT1-CD147 complex and lead to a loss of proper membrane localization and cellular substrate flux. Notably, the monomeric stability of MCT1 remains unaffected in mutants, thus supporting the role of CD147 in mediating the trafficking of the heterocomplex. Using the auxiliary chaperone, GP70, we demonstrated that W20A-MCT1 can be trafficked to the plasma membrane, while G19C-MCT1 remains internalized. Overall, our findings underscore the critical role of the MCT1 transmembrane one signature motif for engaging CD147 and identify altered chaperone binding mechanisms between the CD147 and GP70 glycoprotein chaperones.
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Motivos de Aminoácidos , Basigina , Transportadores de Ácidos Monocarboxílicos , Transporte Proteico , Simportadores , Basigina/metabolismo , Basigina/genética , Basigina/química , Transportadores de Ácidos Monocarboxílicos/metabolismo , Transportadores de Ácidos Monocarboxílicos/genética , Transportadores de Ácidos Monocarboxílicos/química , Humanos , Simportadores/metabolismo , Simportadores/química , Simportadores/genética , Membrana Celular/metabolismo , Retículo Endoplasmático/metabolismo , Células HEK293 , Mutação de Sentido IncorretoRESUMO
Gamma-ray bursts (GRBs) are brief flashes of γ-rays and are considered to be the most energetic explosive phenomena in the Universe1. The emission from GRBs comprises a short (typically tens of seconds) and bright prompt emission, followed by a much longer afterglow phase. During the afterglow phase, the shocked outflow-produced by the interaction between the ejected matter and the circumburst medium-slows down, and a gradual decrease in brightness is observed2. GRBs typically emit most of their energy via γ-rays with energies in the kiloelectronvolt-to-megaelectronvolt range, but a few photons with energies of tens of gigaelectronvolts have been detected by space-based instruments3. However, the origins of such high-energy (above one gigaelectronvolt) photons and the presence of very-high-energy (more than 100 gigaelectronvolts) emission have remained elusive4. Here we report observations of very-high-energy emission in the bright GRB 180720B deep in the GRB afterglow-ten hours after the end of the prompt emission phase, when the X-ray flux had already decayed by four orders of magnitude. Two possible explanations exist for the observed radiation: inverse Compton emission and synchrotron emission of ultrarelativistic electrons. Our observations show that the energy fluxes in the X-ray and γ-ray range and their photon indices remain comparable to each other throughout the afterglow. This discovery places distinct constraints on the GRB environment for both emission mechanisms, with the inverse Compton explanation alleviating the particle energy requirements for the emission observed at late times. The late timing of this detection has consequences for the future observations of GRBs at the highest energies.
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Effective gene therapy for gain-of-function or dominant-negative disease mutations may require eliminating expression of the mutant copy together with wildtype replacement. We evaluated such a "knockdown-replace" strategy in a mouse model of DNM1 disease, a debilitating and intractable neurodevelopmental epilepsy. To challenge the approach robustly, we expressed a patient-based variant in GABAergic neurons - which resulted in growth delay and lethal seizures evident by postnatal week three - and delivered to newborn pups an AAV9-based vector encoding a ubiquitously-expressed, Dnm1-specific interfering RNA (RNAi) bivalently in tail-to-tail configuration with a neuron-specific, RNAi-resistant, codon-optimized Dnm1 cDNA. Pups receiving RNAi or cDNA alone fared no better than untreated, whereas the vast majority of mutants receiving modest doses survived with almost full growth recovery. Synaptic recordings of cortical neurons derived from treated pups revealed that significant alterations in transmission from inhibitory to excitatory neurons were rectified by bivalent vector application. To examine the mutant transcriptome and impact of treatment, we used RNAseq and functional annotation clustering. Mutants displayed abnormal expression of >1000 genes in highly significant and relevant functional clusters, clusters that were abrogated by treatment. Together these results suggest knockdown-replace as a potentially effective strategy for treating DNM1 and related genetic neurodevelopmental disease.
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BACKGROUND: H56:IC31 is a candidate vaccine against tuberculosis (TB) with the potential to reduce TB recurrence rate. It is thus important for future clinical trials to demonstrate safety and immunogenicity of H56:IC31 in individuals treated for TB. METHODS: 22 adults confirmed to be Mtb negative (by 2 GeneXpert tests or 2 sputum cultures) after four-five months of TB treatment, and not more than 28 days after completion of TB treatment, were randomized to receive two doses of H56:IC31 (5 mg H56:500 nmol IC31; N=16) or placebo (N=6) 56 days apart. Participants were followed for 420 days for safety and immunogenicity. RESULTS: H56:IC31 vaccination was associated with an acceptable safety profile, consisting mostly of mild self-limited injection site reactions. No serious adverse events, and no vaccine-related severe adverse events, were reported. H56:IC31 induced a CD4+ T-cell response for Ag85B and ESAT-6, with ESAT-6 being immunodominant, which persisted through six months after the last vaccination. There was some evidence of CD8+ T-cell responses for both Ag85B and ESAT-6, but to a lesser extent than CD4+ responses. CONCLUSIONS: H56:IC31 was associated with an acceptable safety profile, and induced a predominant CD4+ T-cell response, in adults recently treated for drug-susceptible, uncomplicated pulmonary TB. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02375698.
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Insulin insensitivity decreases exogenous glucose oxidation and metabolic clearance rate (MCR) during aerobic exercise in unacclimatized lowlanders at high altitude (HA). Whether use of an oral insulin sensitizer before acute HA exposure enhances exogenous glucose oxidation is unclear. This study investigated the impact of pioglitazone (PIO) on exogenous glucose oxidation and glucose turnover compared with placebo (PLA) during aerobic exercise at HA. With the use of a randomized crossover design, native lowlanders (n = 7 males, means ± SD, age: 23 ± 6 yr, body mass: 84 ± 11 kg) consumed 145 g (1.8 g/min) of glucose while performing 80 min of steady-state (1.43 ± 0.16 VÌo2 L/min) treadmill exercise at HA (460 mmHg; [Formula: see text] 96.6 mmHg) following short-term (5 days) use of PIO (15 mg oral dose per day) or PLA (microcrystalline cellulose pill). Substrate oxidation and glucose turnover were determined using indirect calorimetry and stable isotopes ([13C]glucose and 6,6-[2H2]glucose). Exogenous glucose oxidation was not different between PIO (0.31 ± 0.03 g/min) and PLA (0.32 ± 0.09 g/min). Total carbohydrate oxidation (PIO: 1.65 ± 0.22 g/min, PLA: 1.68 ± 0.32 g/min) or fat oxidation (PIO: 0.10 ± 0.0.08 g/min, PLA: 0.09 ± 0.07 g/min) was not different between treatments. There was no treatment effect on glucose rate of appearance (PIO: 2.46 ± 0.27, PLA: 2.43 ± 0.27 mg/kg/min), disappearance (PIO: 2.19 ± 0.17, PLA: 2.20 ± 0.22 mg/kg/min), or MCR (PIO: 1.63 ± 0.37, PLA: 1.73 ± 0.40 mL/kg/min). Results from this study indicate that PIO is not an effective intervention to enhance exogenous glucose oxidation or MCR during acute HA exposure. Lack of effect with PIO suggests that the etiology of glucose metabolism dysregulation during acute HA exposure may not result from insulin resistance in peripheral tissues.NEW & NOTEWORTHY Short-term (5 days) use of the oral insulin sensitizer pioglitazone does not alter circulating glucose or insulin responses to enhance exogenous glucose oxidation during steady-state aerobic exercise in young healthy men under simulated acute (8 h) high-altitude (460 mmHg) conditions. These results indicate that dysregulations in glucose metabolism in native lowlanders sojourning at high altitude may not be due to insulin resistance at peripheral tissue.
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Altitude , Estudos Cross-Over , Exercício Físico , Glucose , Hipoglicemiantes , Oxirredução , Pioglitazona , Humanos , Pioglitazona/administração & dosagem , Pioglitazona/farmacologia , Masculino , Adulto Jovem , Exercício Físico/fisiologia , Adulto , Glucose/metabolismo , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacologia , Hipoglicemiantes/farmacocinética , Taxa de Depuração Metabólica , Glicemia/metabolismo , Glicemia/efeitos dos fármacos , Insulina/sangue , Insulina/metabolismoRESUMO
BACKGROUND: Prebiotic fibers are non-digestible substrates that modulate the gut microbiome by promoting expansion of microbes having the genetic and physiological potential to utilize those molecules. Although several prebiotic substrates have been consistently shown to provide health benefits in human clinical trials, responder and non-responder phenotypes are often reported. These observations had led to interest in identifying, a priori, prebiotic responders and non-responders as a basis for personalized nutrition. In this study, we conducted in vitro fecal enrichments and applied shotgun metagenomics and machine learning tools to identify microbial gene signatures from adult subjects that could be used to predict prebiotic responders and non-responders. RESULTS: Using short chain fatty acids as a targeted response, we identified genetic features, consisting of carbohydrate active enzymes, transcription factors and sugar transporters, from metagenomic sequencing of in vitro fermentations for three prebiotic substrates: xylooligosacharides, fructooligosacharides, and inulin. A machine learning approach was then used to select substrate-specific gene signatures as predictive features. These features were found to be predictive for XOS responders with respect to SCFA production in an in vivo trial. CONCLUSIONS: Our results confirm the bifidogenic effect of commonly used prebiotic substrates along with inter-individual microbial responses towards these substrates. We successfully trained classifiers for the prediction of prebiotic responders towards XOS and inulin with robust accuracy (≥ AUC 0.9) and demonstrated its utility in a human feeding trial. Overall, the findings from this study highlight the practical implementation of pre-intervention targeted profiling of individual microbiomes to stratify responders and non-responders.
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Ácidos Graxos Voláteis , Fezes , Fermentação , Microbioma Gastrointestinal , Prebióticos , Prebióticos/análise , Humanos , Fezes/microbiologia , Microbioma Gastrointestinal/genética , Adulto , Ácidos Graxos Voláteis/metabolismo , Família Multigênica , Aprendizado de Máquina , Metagenômica/métodos , Biomarcadores/metabolismo , Bactérias/genética , Bactérias/metabolismo , Bactérias/classificação , Feminino , Masculino , Inulina/metabolismo , Adulto Jovem , Metabolismo dos CarboidratosRESUMO
In situ tunable photonic filters and memories are important for emerging quantum and classical optics technologies. However, most photonic devices have fixed resonances and bandwidths determined at the time of fabrication. Here we present an in situ tunable optical resonator on thin-film lithium niobate. By leveraging the linear electro-optic effect, we demonstrate widely tunable control over resonator frequency and bandwidth on two different devices. We observe up to â¼50 × tuning in the bandwidth over â¼50 V with linear frequency control of â¼230 MHz/V. We also develop a closed-form model predicting the tuning behavior of the device. This paves the way for rapid phase and amplitude control over light transmitted through our device.
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The development of sustainable routes to organic building blocks is a critical endeavor for reducing the environmental impact of chemical synthesis. Biocatalysts are poised to play an important role in sustainable synthesis, as they perform highly selective reactions under mild conditions. The application of enzymes to organic synthesis requires an approach which is operationally simple, inexpensive to prepare, and reasonably scalable. In this work, we demonstrated the utility of a Type I ring-cleaving dioxygenase CatA (P. putida KT2440) for preparative-scale synthesis of muconic acid derivatives. Muconic acids are important precursors in the synthesis of polymers and commodity chemicals. In this work, we optimized the performance of CatA under millimolar substrate concentrations and characterized the activity of the enzyme with an array of catechol substrates. Furthermore, we developed a scalable platform using cellular lysates to produce diverse muconic acids, generating up to a gram of the desired product. A simple trituration procedure was utilized for the purification of these muconic acids that obviated the need for chromatographic purification and reduced overall solvent waste.
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Emerging evidence suggests that point-of-decision messages may be an effective way to promote healthy food choices. Previous studies show improvements in overall nutritional quality, as well as increases in underconsumed food categories, such as fruits and vegetables, and underconsumed nutrients of public health concern, like dietary fiber. However, there have been multiple approaches used for delivering point-of-decision messages, including very brief messages that remind individuals to consider health during choice, as well as longer messages providing educational information about health benefits. While both approaches have demonstrated positive impacts on outcomes, there is no comparative evidence of the messages' effectiveness. In this study, we examine the impact of four messages on two nutritional attributes of cereals selected in a two-round pre- and post-message breakfast cereal choice exercise with numerous (n = 33) breakfast cereals available. Data were collected via an online survey of adult US residents recruited from the Prolific consumer panel. Three of the messages were simple reminder messages (taste, health, fiber), while there was additionally a longer fiber-focused messaging detailing the health benefits of fiber. Findings show that the simple messages outperformed the longer educational message, though there were some trade-offs between general health and fiber messages. The simple dietary fiber-focused message resulted in significantly higher dietary fiber content in cereals chosen than in any other messaging condition, while the general health message did not result in significantly higher measures of nutritional quality than the simple fiber message. The results of the study suggest that simpler messages may be more effective at increasing the nutritional quality of food choices. Additionally, messages focused on specific nutrients lead to significantly greater increases in the content of those nutrients.
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Fibras na Dieta , Preferências Alimentares , Adulto , Humanos , Escolaridade , Valor Nutritivo , Grão ComestívelRESUMO
BACKGROUND: Rural and low-income pediatric populations are at higher risk for trauma. Craniomaxillofacial (CMF) trauma in this population has not been studied. PURPOSE: This study's purpose was to determine if rural populations or low-income populations are at higher risk for pediatric CMF trauma than urban or high-income populations, respectively, and to determine differences in mechanism of injury (MOI). STUDY DESIGN, SETTING, SAMPLE: A retrospective cohort study of CMF trauma patients younger than 17 years-old, living in the region served by one institution in Tennessee, and requiring oral and maxillofacial surgery consultation between January 2011 and December 2022 was performed. Exclusion criteria were incomplete medical records. PREDICTOR VARIABLE: The primary predictor variable was geographic residence of the patient grouped into two categories: rural or urban defined by the state of Tennessee. Secondary variables were postal code (PC) average median household income (MHI) and PC population density. MAIN OUTCOME VARIABLE(S): The main outcome variable was pediatric CMF injury rate per 100,000 people. MOI is a secondary outcome variable. COVARIATE(S): Covariates included sex, age, and race. ANALYSES: Frequencies and percentages, Fisher's exact test, and Poisson regression models were utilized. Statistical significance was assumed at P-value <.05. RESULTS: Rural or urban county designation was not associated with differing trauma rates (incident risk ratio (IRR) = 0.91; 95% confidence interval (CI) 0.78 to 1.05; P = .18) by itself. One standard deviation increase in MHI decreased CMF trauma rates in rural designation counties by 24% (IRR: 0.76, 95% CI: 0.66, 0.88) and 6% in urban designation counties (IRR: 0.94, 95% CI: 0.87, 1.02). Lower rates of CMF trauma were associated with residence in higher income PCs (IRR = 0.91; 95% (CI) 0.86 to 0.97; P = .004), and higher population density (IRR = 0.87; 95% CI 0.79 to 0.94; P < .001). Dog bites and falls were more common in infancy and early childhood. Interpersonal violence was more common in older patients. CONCLUSIONS AND RELEVANCE: Patients in PCs with lower population density or incomes were at highest risk for CMF injuries. MOI differences by age were similar to findings in other studies. Tennessee's urban/rural county designation has complex interactions with MHI and pediatric CMF trauma rates.
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População Rural , Adolescente , Criança , Pré-Escolar , Humanos , Região dos Apalaches/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Fatores Socioeconômicos , Lactente , Masculino , FemininoRESUMO
The systematic identification of genetic events driving cellular transformation and tumor progression in the absence of a highly recurrent oncogenic driver mutation is a challenge in cutaneous oncology. In cutaneous squamous cell carcinoma (cuSCC), the high UV-induced mutational burden poses a hurdle to achieve a complete molecular landscape of this disease. Here, we utilized the Sleeping Beauty transposon mutagenesis system to statistically define drivers of keratinocyte transformation and cuSCC progression in vivo in the absence of UV-IR, and identified both known tumor suppressor genes and novel oncogenic drivers of cuSCC. Functional analysis confirms an oncogenic role for the ZMIZ genes, and tumor suppressive roles for KMT2C, CREBBP and NCOA2, in the initiation or progression of human cuSCC. Taken together, our in vivo screen demonstrates an extremely heterogeneous genetic landscape of cuSCC initiation and progression, which can be harnessed to better understand skin oncogenic etiology and prioritize therapeutic candidates.
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Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Transformação Celular Neoplásica/genética , Queratinócitos/patologia , Mutagênese Insercional/métodos , Análise de Sequência de DNA/métodos , Neoplasias Cutâneas/genética , Proteína de Ligação a CREB/genética , Carcinoma de Células Escamosas/patologia , Transformação Celular Neoplásica/patologia , Elementos de DNA Transponíveis , Proteínas de Ligação a DNA/genética , Progressão da Doença , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Coativador 2 de Receptor Nuclear/genética , Neoplasias Cutâneas/patologiaRESUMO
Gambling is common in the US, yet nearly one in three players experience gambling-related problems. Using Self-Determination Theory, this study explores how three causality orientations-autonomous, controlled, and impersonal-affect the severity of problem gambling. The study further investigates the mediating roles of nonattachment, dispositional greed, and anhedonia to illuminate how these orientations relate to problem gambling. The data from 675 participants (59% male; Mean age = 40.4 years, SD = 12.9) via Amazon's Mechanical Turk were collected following a screening procedure to identify at-risk players. Findings showed that dispositional greed mediated the impact of a controlled orientation on problem gambling severity, while anhedonia mediated the effect of impersonal orientation. Unexpectedly, nonattachment did not explain the effect of autonomous orientation on problem gambling, though a negative association was still observed. This research enhances understanding of how individual differences and causality orientations contribute to problem gambling behavior. The implications are discussed.
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Three-dimensional (3D) printing has demonstrated efficacy in multiple surgical specialties. As accessibility improves, its use in specific fields deserves further attention. We conducted a systematic review of the implementation and outcomes of 3D printing in pediatric craniofacial surgery, as none has been performed. A systematic review was conducted according to Cochrane and PRISMA guidelines. PubMed, Embase, Cochrane library, and Clinicaltrials.gov were queried with combinations of the terms: "3D printing," "craniofacial," "surgery," and "pediatric." Original human studies containing patients <18 years old implementing 3D printing to aid in craniofacial surgery were included. Study selection, grading, and data extraction were performed independently by multiple authors. After screening 120 articles, 7 (3 case series and 4 case reports) were included, published from 2017 to 2022. All studies addressed patients with different disease processes including craniosynostosis, cleft lip/palate, and mandibular hypoplasia. 3D printing was used to create mock surgical models in 2 studies, intraoperative cutting guides/molds (CGs) in 6 studies, and cranioplasty implants in 2 studies. Two case series determined the accuracy of the CGs was acceptable within historical comparison, while 4 articles included subjective statements on improved accuracy. Five studies noted reduced operating time, 2 noted reduced intraoperative blood loss, and 1 felt the use of 3D printed materials was responsible for shorter hospitalization duration. No adverse events were reported. Despite the limitations of the current literature, all studies concluded that the use of 3D printing in pediatric craniofacial surgery was beneficial. Definitive conclusions cannot be made until further controlled research is performed.
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Comparison of microsurgical reconstructive options after mandible resection is limited in the literature. Fibula free flaps (FFFs) can be costly and have timing limitations, but dental restoration can be performed, with varied reported rates of completion. The radial forearm free flap (RFFF) with mandible plating may be an alternative in select populations. The purpose of this study was to determine if the RFFF has similar outcomes to the FFF for mandible reconstruction in a rural population. A retrospective review of patients who underwent mandibulectomy from 2017 to 2021 at a single tertiary-care academic institution was performed. Those with FFF or RFFF reconstruction were included. Mandible defects were classified using the Jewer-Boyd H-C-L system. Sixty-eight patients were included with 53 undergoing FFF and 15 undergoing RFFF. Immediate reconstruction was significantly more common with RFFF than FFF (100% versus 64.2%; P =0.01). Lateral mandible defects were most common among both groups (52.9% FFF versus 73.3% RFFF; P =0.04). Osseous defect length was similar (9.5 cm FFF versus 7.7 cm RFFF; P =0.07), but soft tissue defect size was significantly larger in the RFFF group (28.6 cm 2 versus 15.3 cm 2 ; P =0.01). Complication rates (47.1% FFF versus 46.7% RFFF; P =0.98) and disease-free status at last follow-up (96.2% FFF versus 80.0% RFFF; P =0.06) were similar. Dental restoration occurred in 21.3% of patients undergoing FFF. Patients undergoing RFFF or FFF reconstruction after mandibulectomy had similar surgical and disease outcomes, with a low rate of completed dental restoration after FFF. Our findings suggest RFFF is a reasonable alternative to FFF for mandible reconstruction in select patients.
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Retalhos de Tecido Biológico , Humanos , Antebraço/cirurgia , Fíbula , População Rural , Estudos Retrospectivos , Mandíbula/cirurgiaRESUMO
BACKGROUND: The relevance of emotion regulation (ER) difficulties to nonsuicidal self-injury (NSSI; the deliberate destruction of one's bodily tissue without suicidal intent) has been repeatedly documented. Recently, specific mindfulness facets (i.e., awareness, nonjudging, describing) have been proposed as mechanisms that explain this relationship. The present study sought to extend this line of inquiry by exploring the mediating role of mindfulness facets in the relation between self-determination theory-based ER styles (i.e., integrative ER, suppressive ER, emotion dysregulation) and indices of positive and negative well-being (i.e., subjective vitality, NSSI difficulties), while controlling for gender, in adults with recent NSSI engagement. METHODS: US adults with a history of more than one occurrence of NSSI within the last year (n = 222) completed online measures of ER styles, mindfulness facets, subjective vitality, and NSSI difficulties. RESULTS: A mediation model indicated that the effects of ER styles on positive and negative well-being were explained by specific mindfulness facets (i.e., awareness, nonjudging, nonreactivity, describing). CONCLUSIONS: The present study provides preliminary evidence that facets of dispositional mindfulness may be mechanisms through which ER styles impact positive and negative indices of well-being in adults with lived experience of NSSI.
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Regulação Emocional , Atenção Plena , Autonomia Pessoal , Comportamento Autodestrutivo , Humanos , Feminino , Masculino , Adulto , Comportamento Autodestrutivo/psicologia , Adulto Jovem , Pessoa de Meia-Idade , Satisfação Pessoal , Adolescente , Teoria PsicológicaRESUMO
Project Extension for Community Healthcare Outcomes (ECHO) enables healthcare providers to share knowledge and best practices via telementoring. The ECHO model builds provider capacity and improves care for patients with a variety of health conditions. This study describes a Canada-wide National ECHO pilot project in the area of geriatric mental health and reports on the program's impact on providers' care practices. A mixed-methods approach was used to analyze surveys completed by participating healthcare providers. Program evaluation measured satisfaction, achievement of learning objectives, awareness of issues related to geriatric mental health, and comfort and self-efficacy working with older adults. The program led to a statistically significant increase in participants' awareness of issues related to support for older adults with mental illness and comfort and self-efficacy in managing these patients in their own practice. The National ECHO pilot project was successful in building healthcare providers' capacity to care for older adults with mental health issues and positively impacting their practice. These findings support using the ECHO model to provide ongoing geriatric mental health education for clinicians from across Canada and beyond.
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Coronavirus interaction with its viral receptor is a primary genetic determinant of host range and tissue tropism. SARS-CoV-2 utilizes ACE2 as the receptor to enter host cell in a species-specific manner. We and others have previously shown that ACE2 orthologs from New World monkey, koala and mouse cannot interact with SARS-CoV-2 to mediate viral entry, and this defect can be restored by humanization of the restrictive residues in New World monkey ACE2. To better understand the genetic determinants behind the ability of ACE2 orthologs to support viral entry, we compared koala and mouse ACE2 sequences with that of human and identified the key residues in koala and mouse ACE2 that restrict viral receptor activity. Humanization of these critical residues rendered both koala and mouse ACE2 capable of binding the spike protein and facilitating viral entry. Our study shed more lights into the genetic determinants of ACE2 as the functional receptor of SARS-CoV-2, which facilitates our understanding of viral entry.
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COVID-19/enzimologia , COVID-19/genética , Peptidil Dipeptidase A/genética , Receptores Virais/genética , SARS-CoV-2/fisiologia , Animais , Sequência de Bases , COVID-19/virologia , Especificidade de Hospedeiro , Humanos , Camundongos/genética , Camundongos/virologia , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/metabolismo , Phascolarctidae/genética , Phascolarctidae/virologia , Receptores Virais/metabolismo , SARS-CoV-2/genética , Alinhamento de Sequência , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Internalização do VírusRESUMO
The objective of this research is to estimate the proportion of consumers who consider nutrients identified in the Dietary Guidelines for Americans 2020-2025 (DGA) as being of public health concern during food choice using a large, population-weighted sample of U.S. residents. A question was included in a bi-monthly survey of consumer scanner panel members, asking whether respondents considered each of eight nutrients in a check-all-that-apply format. Four of these nutrients are under-consumed nutrients, while three are nutrients to avoid. Calories was additionally included, as over-consumption of calories causes weight gain. Weighted mean proportions and 95% confidence intervals were estimated. The survey was administered to a population-weighted sample of 42,018 US consumers participating in a consumer scanner panel in May-June 2021 by an online survey firm that maintains the consumer panel. Over one-quarter of respondents considered none of the nutrients. Each under-consumed nutrient of public health concern was considered by less than 30% of respondents, ranging from a low of 14.5% for potassium (95%CI = 14.3-14.7%) to a high of 28.9% for dietary fiber (95%CI = 28.7-29.1%). Nutrients to be avoided were considered by higher percentages of the sample, ranging from 31.8% for saturated fats (95%CI = 31.6-32.0%) to 46.1% for added sugars (95%CI = 45.8-46.3%). Respondents considered an average of just over 2.4 total nutrients, with a greater focus on nutrients to avoid, including calories (weighted mean = 1.55), than under-consumed nutrients (weighted mean = 0.89). Over one-quarter of consumers considered no nutrients of public health concern. Consumers focused more on nutrients to avoid rather than under-consumed nutrients. Promoting increased awareness of important under-consumed nutrients may improve public health.