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Despite advances in defining diverse somatic mutations that cause myeloid malignancies, a significant heritable component for these cancers remains largely unexplained. Here, we perform rare variant association studies in a large population cohort to identify inherited predisposition genes for these blood cancers. CTR9, which encodes a key component of the PAF1 transcription elongation complex, is among the significant genes identified. The risk variants found in the cases cause loss of function and result in a â¼10-fold increased odds of acquiring a myeloid malignancy. Partial CTR9 loss of function expands human hematopoietic stem cells (HSCs) by increased super elongation complex-mediated transcriptional activity, which thereby increases the expression of key regulators of HSC self-renewal. By following up on insights from a human genetic study examining inherited predisposition to the myeloid malignancies, we define a previously unknown antagonistic interaction between the PAF1 and super elongation complexes. These insights could enable targeted approaches for blood cancer prevention.
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Neoplasias Hematológicas , Fosfoproteínas , Elongação da Transcrição Genética , Fatores de Transcrição , Humanos , Neoplasias Hematológicas/genética , Células-Tronco Hematopoéticas/metabolismo , Proteínas Nucleares/metabolismo , Fatores de Transcrição/genética , Fosfoproteínas/genéticaRESUMO
During development, inflammation or tissue injury, macrophages may successively engulf and process multiple apoptotic corpses via efferocytosis to achieve tissue homeostasis1. How macrophages may rapidly adapt their transcription to achieve continuous corpse uptake is incompletely understood. Transcriptional pause/release is an evolutionarily conserved mechanism, in which RNA polymerase (Pol) II initiates transcription for 20-60 nucleotides, is paused for minutes to hours and is then released to make full-length mRNA2. Here we show that macrophages, within minutes of corpse encounter, use transcriptional pause/release to unleash a rapid transcriptional response. For human and mouse macrophages, the Pol II pause/release was required for continuous efferocytosis in vitro and in vivo. Interestingly, blocking Pol II pause/release did not impede Fc receptor-mediated phagocytosis, yeast uptake or bacterial phagocytosis. Integration of data from three genomic approaches-precision nuclear run-on sequencing, RNA sequencing, and assay for transposase-accessible chromatin using sequencing (ATAC-seq)-on efferocytic macrophages at different time points revealed that Pol II pause/release controls expression of select transcription factors and downstream target genes. Mechanistic studies on transcription factor EGR3, prominently regulated by pause/release, uncovered EGR3-related reprogramming of other macrophage genes involved in cytoskeleton and corpse processing. Using lysosomal probes and a new genetic fluorescent reporter, we identify a role for pause/release in phagosome acidification during efferocytosis. Furthermore, microglia from egr3-deficient zebrafish embryos displayed reduced phagocytosis of apoptotic neurons and fewer maturing phagosomes, supporting defective corpse processing. Collectively, these data indicate that macrophages use Pol II pause/release as a mechanism to rapidly alter their transcriptional programs for efficient processing of the ingested apoptotic corpses and for successive efferocytosis.
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Eferocitose , Macrófagos , RNA Polimerase II , Elongação da Transcrição Genética , Animais , Humanos , Masculino , Camundongos , Apoptose , Citoesqueleto/metabolismo , Proteína 3 de Resposta de Crescimento Precoce/deficiência , Proteína 3 de Resposta de Crescimento Precoce/genética , Eferocitose/genética , Concentração de Íons de Hidrogênio , Macrófagos/imunologia , Macrófagos/metabolismo , Neurônios/metabolismo , Fagossomos/metabolismo , RNA Polimerase II/metabolismo , Fatores de Transcrição/genética , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Fatores de TempoRESUMO
The rising interest and success in deploying inherited microorganisms and cytoplasmic incompatibility (CI) for vector control strategies necessitate an explanation of the CI mechanism. Wolbachia-induced CI manifests in the form of embryonic lethality when sperm from Wolbachia-bearing testes fertilize eggs from uninfected females. Embryos from infected females however survive to sustain the maternally inherited symbiont. Previously in Drosophila melanogaster flies, we demonstrated that CI modifies chromatin integrity in developing sperm to bestow the embryonic lethality. Here, we validate these findings using wMel-transinfected Aedes aegypti mosquitoes released to control vector-borne diseases. Once again, the prophage WO CI proteins, CifA and CifB, target male gametic nuclei to modify chromatin integrity via an aberrant histone-to-protamine transition. Cifs are not detected in the embryo, and thus elicit CI via the nucleoprotein modifications established pre-fertilization. The rescue protein CifA in oogenesis localizes to stem cell, nurse cell, and oocyte nuclei, as well as embryonic DNA during embryogenesis. Discovery of the nuclear targeting Cifs and altered histone-to-protamine transition in both Aedes aegypti mosquitoes and D. melanogaster flies affirm the Host Modification Model of CI is conserved across these host species. The study also newly uncovers the cell biology of Cif proteins in the ovaries, CifA localization in the embryos, and an impaired histone-to-protamine transition during spermiogenesis of any mosquito species. Overall, these sperm modification findings may enable future optimization of CI efficacy in vectors or pests that are refractory to Wolbachia transinfections.
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Aedes , Arbovírus , Wolbachia , Animais , Feminino , Masculino , Drosophila melanogaster/genética , Histonas/genética , Mosquitos Vetores , Sêmen , Drosophila/genética , Cromatina , Protaminas/genéticaRESUMO
Human neuroimaging studies of episodic memory retrieval routinely observe the engagement of specific cortical regions beyond the medial temporal lobe. Of these, medial parietal cortex (MPC) is of particular interest given its distinct functional characteristics during different retrieval tasks. Specifically, while recognition and autobiographical recall tasks are both used to probe episodic retrieval, these paradigms consistently drive distinct spatial patterns of response within MPC. However, other studies have emphasized alternate MPC functional dissociations in terms of brain network connectivity profiles or stimulus category selectivity. As the unique contributions of MPC to episodic memory remain unclear, adjudicating between these different accounts can provide better consensus regarding MPC function. Therefore, we used a precision-neuroimaging dataset (7T functional magnetic resonance imaging) to examine how MPC regions are differentially engaged during recognition memory and how these task-related dissociations may also reflect distinct connectivity and stimulus category functional profiles. We observed interleaved, though spatially distinct, subregions of MPC where responses were sensitive to either recognition decisions or the semantic representation of stimuli. In addition, this dissociation was further accentuated by functional subregions displaying distinct profiles of connectivity with the hippocampus during task and rest. Finally, we show that recent observations of dissociable person and place selectivity within the MPC reflect category-specific responses from within identified semantic regions that are sensitive to mnemonic demands. Together, by examining precision functional mapping within individuals, these data suggest that previously distinct observations of functional dissociation within MPC conform to a common principle of organization throughout hippocampal-neocortical memory systems.
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Imageamento por Ressonância Magnética , Lobo Parietal , Reconhecimento Psicológico , Humanos , Lobo Parietal/fisiologia , Lobo Parietal/diagnóstico por imagem , Masculino , Feminino , Reconhecimento Psicológico/fisiologia , Adulto , Adulto Jovem , Memória Episódica , Mapeamento Encefálico , Hipocampo/fisiologia , Hipocampo/diagnóstico por imagem , Rememoração Mental/fisiologiaRESUMO
Intracellular pathogens including Staphylococcus aureus contribute to the non-healing phenotype of chronic wounds. Lactobacilli, well known as beneficial bacteria, are also reported to modulate the immune system, yet their role in cutaneous immunity remains largely unknown. We explored the therapeutic potential of bacteria-free postbiotics, bioactive lysates of lactobacilli, to reduce intracellular S. aureus colonization and promote healing. Fourteen postbiotics derived from various lactobacilli species were screened, and Latilactobacillus curvatus BGMK2-41 was selected for further analysis based on the most efficient ability to reduce intracellular infection by S. aureus diabetic foot ulcer clinical isolate and S. aureus USA300. Treatment of both infected keratinocytes in vitro and infected human skin ex vivo with BGMK2-41 postbiotic cleared S. aureus. Keratinocytes treated in vitro with BGMK2-41 upregulated expression of antimicrobial response genes, of which DEFB4, ANG, and RNASE7 were also found upregulated in treated ex vivo human skin together with CAMP exclusively upregulated ex vivo. Furthermore, BGMK2-41 postbiotic treatment has a multifaceted impact on the wound healing process. Treatment of keratinocytes stimulated cell migration and the expression of tight junction proteins, while in ex vivo human skin BGMK2-41 increased expression of anti-inflammatory cytokine IL-10, promoted re-epithelialization, and restored the epidermal barrier via upregulation of tight junction proteins. Together, this provides a potential therapeutic approach for persistent intracellular S. aureus infections.
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Queratinócitos , Lactobacillus , Staphylococcus aureus , Humanos , Queratinócitos/microbiologia , Queratinócitos/metabolismo , Queratinócitos/efeitos dos fármacos , Pele/microbiologia , Pele/metabolismo , Cicatrização/efeitos dos fármacos , Probióticos/farmacologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/metabolismo , Ribonucleases/metabolismoRESUMO
BACKGROUND: How novel phenotypes originate from conserved genes, processes, and tissues remains a major question in biology. Research that sets out to answer this question often focuses on the conserved genes and processes involved, an approach that explicitly excludes the impact of genetic elements that may be classified as clade-specific, even though many of these genes are known to be important for many novel, or clade-restricted, phenotypes. This is especially true for understudied phyla such as mollusks, where limited genomic and functional biology resources for members of this phylum have long hindered assessments of genetic homology and function. To address this gap, we constructed a chromosome-level genome for the gastropod Berghia stephanieae (Valdés, 2005) to investigate the expression of clade-specific genes across both novel and conserved tissue types in this species. RESULTS: The final assembled and filtered Berghia genome is comparable to other high-quality mollusk genomes in terms of size (1.05 Gb) and number of predicted genes (24,960 genes) and is highly contiguous. The proportion of upregulated, clade-specific genes varied across tissues, but with no clear trend between the proportion of clade-specific genes and the novelty of the tissue. However, more complex tissue like the brain had the highest total number of upregulated, clade-specific genes, though the ratio of upregulated clade-specific genes to the total number of upregulated genes was low. CONCLUSIONS: Our results, when combined with previous research on the impact of novel genes on phenotypic evolution, highlight the fact that the complexity of the novel tissue or behavior, the type of novelty, and the developmental timing of evolutionary modifications will all influence how novel and conserved genes interact to generate diversity.
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Gastrópodes , Animais , Gastrópodes/genética , Filogenia , Evolução Molecular , Moluscos/genética , Cromossomos , Fenótipo , Expressão GênicaRESUMO
BACKGROUND & AIMS: Colonoscopic surveillance is recommended in patients with colonic inflammatory bowel disease (IBD) given their increased risk of colorectal cancer (CRC). We aimed to develop and validate a dynamic prediction model for the occurrence of advanced colorectal neoplasia (aCRN, including high-grade dysplasia and CRC) in IBD. METHODS: We pooled data from 6 existing cohort studies from Canada, The Netherlands, the United Kingdom, and the United States. Patients with IBD and an indication for CRC surveillance were included if they underwent at least 1 follow-up procedure. Exclusion criteria included prior aCRN, prior colectomy, or an unclear indication for surveillance. Predictor variables were selected based on the literature. A dynamic prediction model was developed using a landmarking approach based on Cox proportional hazard modeling. Model performance was assessed with Harrell's concordance-statistic (discrimination) and by calibration curves. Generalizability across surveillance cohorts was evaluated by internal-external cross-validation. RESULTS: The surveillance cohorts comprised 3731 patients, enrolled and followed-up in the time period from 1973 to 2021, with a median follow-up period of 5.7 years (26,336 patient-years of follow-up evaluation); 146 individuals were diagnosed with aCRN. The model contained 8 predictors, with a cross-validation median concordance statistic of 0.74 and 0.75 for a 5- and 10-year prediction window, respectively. Calibration plots showed good calibration. Internal-external cross-validation results showed medium discrimination and reasonable to good calibration. CONCLUSIONS: The new prediction model showed good discrimination and calibration, however, generalizability results varied. Future research should focus on formal external validation and relate predicted aCRN risks to surveillance intervals before clinical application.
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Colonoscopia , Neoplasias Colorretais , Doenças Inflamatórias Intestinais , Humanos , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Masculino , Feminino , Doenças Inflamatórias Intestinais/complicações , Pessoa de Meia-Idade , Adulto , Medição de Risco/métodos , Idoso , Estudos de Coortes , Canadá/epidemiologiaRESUMO
OBJECTIVES: To identify research priorities in the management, epidemiology, outcome, and pathophysiology of sepsis and septic shock. DESIGN: Shortly after publication of the most recent Surviving Sepsis Campaign Guidelines, the Surviving Sepsis Research Committee, a multiprofessional group of 16 international experts representing the European Society of Intensive Care Medicine and the Society of Critical Care Medicine, convened virtually and iteratively developed the article and recommendations, which represents an update from the 2018 Surviving Sepsis Campaign Research Priorities. METHODS: Each task force member submitted five research questions on any sepsis-related subject. Committee members then independently ranked their top three priorities from the list generated. The highest rated clinical and basic science questions were developed into the current article. RESULTS: A total of 81 questions were submitted. After merging similar questions, there were 34 clinical and ten basic science research questions submitted for voting. The five top clinical priorities were as follows: 1) what is the best strategy for screening and identification of patients with sepsis, and can predictive modeling assist in real-time recognition of sepsis? 2) what causes organ injury and dysfunction in sepsis, how should it be defined, and how can it be detected? 3) how should fluid resuscitation be individualized initially and beyond? 4) what is the best vasopressor approach for treating the different phases of septic shock? and 5) can a personalized/precision medicine approach identify optimal therapies to improve patient outcomes? The five top basic science priorities were as follows: 1) How can we improve animal models so that they more closely resemble sepsis in humans? 2) What outcome variables maximize correlations between human sepsis and animal models and are therefore most appropriate to use in both? 3) How does sepsis affect the brain, and how do sepsis-induced brain alterations contribute to organ dysfunction? How does sepsis affect interactions between neural, endocrine, and immune systems? 4) How does the microbiome affect sepsis pathobiology? 5) How do genetics and epigenetics influence the development of sepsis, the course of sepsis and the response to treatments for sepsis? CONCLUSIONS: Knowledge advances in multiple clinical domains have been incorporated in progressive iterations of the Surviving Sepsis Campaign guidelines, allowing for evidence-based recommendations for short- and long-term management of sepsis. However, the strength of existing evidence is modest with significant knowledge gaps and mortality from sepsis remains high. The priorities identified represent a roadmap for research in sepsis and septic shock.
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Sepse , Choque Séptico , Humanos , Choque Séptico/terapia , Choque Séptico/diagnóstico , Sepse/diagnóstico , Ressuscitação , Respiração Artificial , Cuidados CríticosRESUMO
Single-photon avalanche diodes (SPADs) that are sensitive to photons in the Short-wave infrared and extended short-wave infrared (SWIR and eSWIR) spectra are important components for communication, ranging, and low-light level imaging. The high gain, low excess noise factor, and widely tunable bandgap of AlxIn1-xAsySb1-y avalanche photodiodes (APDs) make them a suitable candidate for these applications. In this work, we report single-photon-counting results for a separate absorption, charge, and multiplication (SACM) Geiger-mode SPAD within a gated-quenching circuit. The single-photon avalanche probabilities surpass 80% at 80â K, corresponding with single-photon detection efficiencies of 33% and 12% at 1.55 µm and 2 µm, respectively.
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BACKGROUND: Indoor residual spraying (IRS) is one of the most effective malaria control tools. However, its application has become limited to specific contexts due to the increased costs of IRS products and implementation programmes. Selective spraying-selective spray targeted to particular areas/surfaces of dwellings-has been proposed to maintain the malaria control and resistance-management benefits of IRS while decreasing the costs of the intervention. METHODS: A literature search was conducted to find (1) studies that assessed the resting behaviour of Anopheles mosquitoes and (2) studies that evaluated the impact of selective spraying on entomological and malaria outcomes. Additional articles were identified through hand searches of all references cited in articles identified through the initial search. A cost model was developed from PMI VectorLink IRS country programmes, and comparative cost analysis reports to describe the overall cost benefits of selective IRS. RESULTS: In some studies, there appeared to be a clear resting preference for certain Anopheles species in terms of the height at which they rested. However, for other species, and particularly the major African malaria vectors, a clear resting pattern was not detected. Furthermore, resting behaviour was not measured in a standardized way. For the selective spray studies that were assessed, there was a wide range of spray configurations, which complicates the comparison of methods. Many of these spray techniques were effective and resulted in reported 25-68% cost savings and reduced use of insecticide. The reported cost savings in the literature do not always consider all of the IRS implementation costs. Using the IRS cost model, these savings ranged from 17 to 29% for programs that targeted Anopheles spp. and 18-41% for programmes that targeted Aedes aegypti. CONCLUSIONS: Resting behaviour is generally measured in a simplistic way; noting the resting spot of mosquitoes in the morning. This is likely an oversimplification, and there is a need for better monitoring of resting mosquitoes. This may improve the target surface for selective spray techniques, which could reduce the cost of IRS while maintaining its effectiveness. Reporting of cost savings should be calculated considering the entire implementation costs, and a cost model was provided for future calculations.
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Anopheles , Inseticidas , Malária , Controle de Mosquitos , Controle de Mosquitos/métodos , Controle de Mosquitos/economia , Animais , Malária/prevenção & controle , Anopheles/efeitos dos fármacos , Anopheles/fisiologia , Inseticidas/administração & dosagem , Inseticidas/economia , Humanos , Mosquitos Vetores/efeitos dos fármacosRESUMO
Three different types of reaction products were obtained from the reduction of 2-substituted 3-methylbenzothiazolium salts using Na : Hg (1 wt%). Depending on the 2-substituents, two types of dimeric compounds were obtained: the 2-cyclohexyl-, 2-phenyl-, and 2-(p-tolyl)-substituted species are reduced to the corresponding 2,2'-bibenzo[d]thiazoles, while their 2-((p-OMe)C6H4)- and 2-((p-NMe2)C6H4)-substituted derivatives afford cis-[1,4]benzothiazino[3,2-b][1,4]benzothiazines. Furthermore, in the presence of molecular O2, new disulfide derivatives were obtained from the bibenzo[d]thiazoles. The products were obtained in a moderate to good yield, and the structures were confirmed using single-crystal X-ray diffraction. The electrochemistry and further reactivity towards different oxidants of the dimeric compounds were studied; the 2,2'-bibenzo[d]thiazoles show oxidation potentials similar to that of ferrocene and are converted back to the corresponding benzothiazolium cations by mild oxidants such as TCNQ. In contrast, the benzothiazino-benzothiazines show no oxidations in the solvent window of THF.
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BACKGROUND: Helicobacter pylori infection is prevalent worldwide and can lead to peptic ulcer disease (PUD) and gastric cancer. Effective diagnosis and treatment of H. pylori infection by gastroenterologists and family physicians is crucial. However, there are differing views on optimal diagnosis and treatment. The objective of this study is to understand the impressions of Canadian physicians regarding H. pylori diagnosis and treatment and whether impressions differ between gastroenterologists and family physicians. A second objective is to understand physician perspectives on rising antibiotic resistance and how that guides empiric management. METHODS: A survey facilitated via REDCap was administered to Canadian gastroenterologists and family physicians. A total of 105 participants completed the survey, including 43 gastroenterologists and 62 family physicians. Gastroenterologists were recruited from across the country and family physicians were recruited from Manitoba. RESULTS: For diagnosis of H. pylori, 67% of gastroenterologists reported endoscopic biopsies for histology assessment as most common and 73% of family physicians reported serology as their main diagnostic test. While nearly all gastroenterologists believed antibiotic resistance to be a problem, nearly one quarter of family physicians did not believe it was a problem. CONCLUSIONS: There is variability in practices among both gastroenterologists and family physicians regarding diagnosis of H. pylori infection. There was consensus that local antibiotic resistance patterns should guide management. If known, the degree and patterns of antibiotic resistance could bring a more uniform consensus to H. pylori management. Greater education of physicians, especially family physicians regarding management of H pylori is needed.
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Antibacterianos , Infecções por Helicobacter , Helicobacter pylori , Padrões de Prática Médica , Humanos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/diagnóstico , Canadá , Padrões de Prática Médica/estatística & dados numéricos , Antibacterianos/uso terapêutico , Gastroenterologistas , Masculino , Farmacorresistência Bacteriana , Atitude do Pessoal de Saúde , Feminino , Médicos de Família/estatística & dados numéricos , Inquéritos e Questionários , Pessoa de Meia-Idade , Adulto , Biópsia/estatística & dados numéricosRESUMO
STUDY OBJECTIVE: Clinical decision aids can decrease health care disparities. However, many clinical decision aids contain subjective variables that may introduce clinician bias. The HEART score is a clinical decision aid that estimates emergency department (ED) patients' cardiac risk. We sought to explore patient and clinician gender's influence on HEART scores. METHODS: In this secondary analysis of a prospective observational trial, we examined a convenience sample of adult ED patients at one institution presenting with acute coronary syndrome symptoms. We compared ED clinician-generated HEART scores with researcher-generated HEART scores blinded to patient gender. The primary outcome was agreement between clinician and researcher HEART scores by patient gender overall and stratified by clinician gender. Analyses used difference-in-difference (DiD) for continuous score and prevalence-adjusted, bias-adjusted Kappa (PABAK) for binary (low versus moderate/high risk) score comparison. RESULTS: All 336 clinician-patient pairs from the original study were included. In total, 47% (158/336) of patients were women, and 52% (174/336) were treated by a woman clinician. The DiD between clinician and researcher HEART scores among men versus women patients was 0.24 (95% CI -0.01 to 0.48). Compared with researchers, men clinicians assigned a higher score to men versus women patients (DiD 0.51 [95% CI 0.16 to 0.87]), whereas women clinicians did not (DiD 0.00 [95% CI -0.33 to 0.33]). Agreement was the highest among women clinicians (PABAK 0.72; 95% CI 0.61 to 0.81) and lowest among men clinicians assessing men patients (PABAK 0.47; 95% CI 0.29 to 0.66). CONCLUSION: Patient and clinician gender may influence HEART scores. Researchers should strive to understand these influences in developing and implementing this and other clinical decision aids.
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Síndrome Coronariana Aguda , Adulto , Feminino , Humanos , Masculino , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/complicações , Serviço Hospitalar de Emergência , Estudos Observacionais como Assunto , Estudos ProspectivosRESUMO
PURPOSE: To investigate the benefits of cochlear implantation in adults with single-sided deafness (SSD) and asymmetric hearing loss (AHL). STUDY DESIGN: Prospective within-subjects repeated-measures. SETTING: Two tertiary cochlear implant centers. PATIENTS: Fourteen adults with severe-to-profound sensorineural hearing loss in the worse hearing ear and up to moderate SNHL in the better hearing ear. INTERVENTION: Cochlear implantation in the worse hearing ear. MAIN OUTCOME MEASURES: Consonant-nucleus-consonant (CNC) test, AzBio sentence test in noise, and lateralization testing were conducted preoperatively and at 3-, 6-, and 12-months post-activation. Patient-related outcomes were measured using the Speech, Spatial, and Qualities of Hearing Scale and Glasgow Benefit Inventory. Tinnitus Handicap Inventory was administered to subjects with tinnitus. RESULTS: Mean length of hearing loss in the worse hearing ear was 3.5 years. The mean CNC change scores from baseline were 54.8, 55.9, and 58.9 percentage points at 3-, 6-, and 12-months (p < 0.001). AzBio sentence test in noise demonstrated improved scores in all spatial configurations, although statistically significant in S0N0 (speech front, noise front) only. Lateralization testing showed significant improvement of 22.9, 24.5, and 24.0 percentage points at 3-, 6-, and 12 months post-activation (p = 0.002). All patient-related outcome measures revealed significant improvement. CONCLUSION: This study demonstrates improved speech perception in noise, sound lateralization, quality of life, and reduction in tinnitus perception in adults with SSD/AHL who undergo cochlear implantation. Our results add to the growing body of evidence that cochlear implant should be offered to this population.
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Implante Coclear , Implantes Cocleares , Perda Auditiva Unilateral , Perda Auditiva , Percepção da Fala , Zumbido , Adulto , Humanos , Implante Coclear/métodos , Zumbido/cirurgia , Qualidade de Vida , Estudos Prospectivos , Resultado do Tratamento , Perda Auditiva/cirurgia , Percepção da Fala/fisiologia , Perda Auditiva Unilateral/cirurgia , Perda Auditiva Unilateral/reabilitaçãoRESUMO
BACKGROUND: Velopharyngeal insufficiency (VPI) is a condition characterized by incomplete separation of the oral and nasal cavities during speech production, thereby leading to speech abnormalities and audible nasal emissions. Subsequently, this adversely impacts communication and potentially interpersonal social interactions. Autologous fat grafting (AFG) to the velopharynx, a minimally invasive technique, aims to improve oronasal separation by providing bulk and advancing the posterior pharyngeal wall toward the soft palate. Despite its potential, the relative novelty of AFG in treating VPI has resulted in reporting of inconsistent indications, varied surgical techniques, and mixed outcomes across existing literature. METHODS: This systemic review examined the evidence of AFG for VPI treatment over the past decade (2013-2023). A thorough search across five electronic databases yielded 233 studies, with 20 meeting the inclusion criteria (e.g., utilized fat injection as their selected VPI treatment, conducted study in human subjects, did not perform additional surgical procedure at time of fat injection). Selected studies encompassed patient and surgical intervention characteristics, perceptual speech assessment (PSA) scores, gap sizes, nasalance measurements, and complications. RESULTS: The majority of patients had a prior cleft palate diagnosis (78.2%), in which nasoendoscopy was the prevalent method for visualizing the velopharyngeal port defect. Fat harvesting predominantly occurred from the abdomen (64.3%), with an average injection volume of 6.3 mL across studies. PSA and subjective gap size scores were consistently higher preoperatively than postoperatively. PSA score analysis from seven studies revealed significant and sustained improvements postoperatively. Gap size score analysis from four studies demonstrated similar preoperative and postoperative differences. Complications were reported in 17 studies, yielding a 2.7% summative complication rate among 594 cases. CONCLUSIONS: Autologous fat grafting has emerged as a minimally invasive, safe, and effective treatment for mild to moderate VPI. However, challenges remain because of variability in patient selection criteria, diagnostic modalities, and outcome measurements. This review underscores the need for randomized control trials to directly compare AFG with standard-of-care surgical interventions, providing more conclusive evidence of its clinical efficacy.
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Tecido Adiposo , Transplante Autólogo , Insuficiência Velofaríngea , Insuficiência Velofaríngea/cirurgia , Humanos , Tecido Adiposo/transplante , Resultado do TratamentoRESUMO
Amniotic membrane, derived from the innermost placenta, is widely employed in surgery to help regenerate soft tissue and promote re-epithelialization. The authors detail a case report of a 59-year-old female who presented with a large, full-thickness scalp avulsion injury (13 × 10 cm) after being attacked by her pet pitbull. Innovative application of "snowflake" or fragmented amniotic membrane to her wound bed was used during both stages of scalp reconstruction: irrigation and debridement with Integra biological membrane placement and later split-thickness skin grafting. The patient had an uncomplicated recovery with a satisfactory cosmetic outcome. The authors believe that the "snowflake" application of amniotic membrane played an important role in forming healthy granulation tissue and optimizing the wound bed for definitive coverage. "Snowflake" amniotic membrane may help maximize its mechanical and biological benefits and holds promise to be an important adjunctive treatment for surgical wound healing.
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INTRODUCTION: Exercise is the cornerstone of a healthy lifestyle. It is recognized for enhancing cardiovascular health and bolstering mental well-being. While the fitness industry grows, the incidence of exercise-related injuries continues to rise. This study examines craniofacial injuries resulting from exercise and weightlifting over the past decade. The goal is to uncover trends, demographics, diagnoses, and patient dispositions. METHODS AND MATERIALS: A retrospective review was conducted using the National Electronic Injury Surveillance System database. Emergency department visits for craniofacial injuries associated with exercise and weightlifting between 2013 and 2022 were analyzed. One-sample t-tests and the Mann-Kendall test were used to evaluate injury prevalence and significant trends. RESULTS: Over the past decade, 582,972 craniofacial injuries related to exercise and weightlifting were documented. Men accounted for 55.7% of cases. Annual incidence increased by 32.7% between 2013 and 2022. It was statistically significant. Adolescents aged 15 to 19 displayed the highest injury rate. Head injuries were most common (45%), followed by face (26%), neck (21%), mouth (4%), eye (3%), and ear (1%). Diagnoses included internal injury (25.2%), laceration (24.8%), contusions/abrasions (12.9%), and strain/sprain (11.9%). Hospitalization was required for only 8.5% of patients. DISCUSSION: This study elucidates the need for injury prevention strategies. Vulnerable subgroups such as males, adolescents, and the elderly demand targeted prevention efforts. Future research should explore specific mechanisms of injury to identify high-risk exercise. This study promotes the need for safe exercise practices and increases awareness of craniofacial injury risks associated with physical activity.
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INTRODUCTION: Yard and garden tools are increasingly used by Americans. Despite the growing popularity of gardening as a leisure activity, the rate of injury associated with these tools remains remarkedly high. Previous research has highlighted the risks associated with improper handling of tools and associated potential long-term consequences. This retrospective study aims to provide a comprehensive analysis of the craniofacial injuries caused by yard and garden equipment. The investigation will emphasize the need for improved safety measures and regulations. METHODS AND MATERIALS: Publicly available data from the National Electronic Injury Surveillance System (NEISS) database were utilized to identify craniofacial injuries related to yard and garden tool handling during a 10-year period (2013-2022). Study population included patients aged 1 to 85+ years who visited emergency departments secondary to these injuries. Data analysis involved queries for specific products and diagnostic codes related to craniofacial injuries. RESULTS: Over the study period, a total of 588,384 craniofacial injuries associated with yard and garden tools were recorded, averaging 58,838 injuries annually. Men accounted for a significantly higher proportion of injuries (69.2%) compared to women (30.8%). Elderly population, particularly those aged 60 to 64 years, experienced the highest incidence of craniofacial injuries. Cranium was the most commonly affected anatomical location, comprising 34% of all injuries. Lacerations and contusions were the most frequent injury diagnoses. Greenhouse or gardening supplies and lawnmowers are the most common causative agents, respectively. DISCUSSION: Our study highlights the persistent incidence of craniofacial injuries associated with yard and garden tool handling emphasizing the need for standardized safety regulations and guidelines. Sociological and demographic factors, such as differences in gardening habits and behavioral patterns between genders, contribute to the observed disparities in injury rates. Understanding the underlying factors contributing to these craniofacial injuries is crucial to promoting safer practices and reducing the overall burden associated with yard and garden tools.
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Meralgia paresthetica is a neurological disorder characterized by a symptom complex of numbness, burning, tingling, aching, or stabbing in the anterolateral portion of the upper thigh. Typically, this disorder is seen in patients with diabetes mellitus, obesity, and pregnancy. Also, it may result from a wide array of surgical interventions involving the region of the anterior superior iliac spine. Underlying pathophysiology concentrates on entrapment neuropathy of the lateral femoral cutaneous nerve (LFCN). Due to its location and wide anatomic variation, the LFCN is susceptible to compression, scarring, and injury during surgery. It is important to understand the regional anatomy. In addition, the plastic surgeon must have a working knowledge of the most common variations that can precipitate entrapment and increase susceptibility to injury during surgery. Surgeons lacking a substantial background on the numerous risk factors, origins, and anatomic variations of the LFCN may place patients at an even higher risk of damage to the nerve. An extensive knowledge of the anatomy and careful technique may be utilized by surgeons to prevent iatrogenic neuropathy of the LFCN.
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Sports-related craniofacial injuries account for 10% to 42% of facial fractures in the US pediatric population, with the incidence of injury peaking at ages 6 to 7 and 12 to 14. The National Survey of Children's Health reported ~5.6 million children between the ages of 6 and 17 participated in baseball in 2021. National Electronic Injury Surveillance System reported 861,456 injuries resulting from baseball and 511,117 injuries resulting from softball in 2021, with ~500,000 of those injuries being to the face/head/neck. While participation in baseball and other youth sports has tremendous physical and mental health benefits, facial and other athletic injuries are concerning beyond the pain and disability caused by the incident itself. Severe injury can result in lost time from school as well as other social activities. Players and their families often experience financial strain as a result of physical trauma as well. The use of protective equipment has decreased the incidence of emergency department visits due to baseball-related trauma, especially mouthguards. However, adherence to using mouthguards is relatively low in baseball, with over 80% of players reporting not being told by a coach to wear mouthpieces. Youth from low-income areas often lack financial means to provide protective equipment and health insurance in the case of injury. The authors, along with the University of Miami Miller School of Medicine Division of Plastic and Reconstructive Surgery and Miami Marlins RBI Program, created an outreach program by which over 400 mouthguards were given to players and caretakers at inner-city baseball and softball programs. Two community outreach events took place in South Florida. One event was held at a University of Miami Men's Baseball Game, and another was held on the opening day of the Miami Marlins RBI Program youth baseball league. In addition to handing out protective equipment and informational pamphlets, a question and answers session was held to discuss injury prevention. In conclusion, our community safety initiative created an interactive dialogue and message to hundreds of youth baseball players about the importance of protective gear to prevent injuries.