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The pathogenic expansion of the intronic GGGGCC hexanucleotide located in the non-coding region of the C9orf72 gene represents the most frequent genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). This mutation leads to the accumulation of toxic RNA foci and dipeptide repeats (DPRs), as well as reduced levels of the C9orf72 protein. Thus, both gain and loss of function are coexisting pathogenic aspects linked to C9orf72-ALS/FTD. Synaptic alterations have been largely described in C9orf72 models, but it is still not clear which aspect of the pathology mostly contributes to these impairments. To address this question, we investigated the dynamic changes occurring over time at the synapse upon accumulation of poly(GA), the most abundant DPR. Overexpression of this toxic form induced a drastic loss of synaptic proteins in primary neuron cultures, anticipating autophagic defects. Surprisingly, the dramatic impairment characterizing the synaptic proteome was not fully matched by changes in network properties. In fact, high-density multi-electrode array analysis highlighted only minor reductions in the spike number and firing rate of poly(GA) neurons. Our data show that the toxic gain of function linked to C9orf72 affects the synaptic proteome but exerts only minor effects on the network activity.
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Autofagia , Proteína C9orf72 , Neurônios , Sinapses , Neurônios/metabolismo , Animais , Sinapses/metabolismo , Proteína C9orf72/genética , Proteína C9orf72/metabolismo , Células Cultivadas , Peptídeos/metabolismo , Humanos , Agregados ProteicosRESUMO
Division plane positioning is crucial for proper growth and development in many organisms. In plants, the division plane is established before mitosis, by accumulation of a cytoskeletal structure called the preprophase band (PPB). The PPB is thought to be essential for recruitment of division site-localized proteins, which remain at the division site after the PPB disassembles. Here, we show that the division site-localized protein TANGLED1 (TAN1) is recruited independently of the PPB to the cell cortex by the plant cytokinetic machinery, the phragmoplast, from experiments using both the PPB-defective mutant discordia1 (dcd1) and chemical treatments that disrupt the phragmoplast in maize. TAN1 recruitment to de novo sites on the cortex is partially dependent on intact actin filaments and the myosin XI motor protein OPAQUE1 (O1). These data imply a yet unknown role for TAN1 and possibly other division site-localized proteins during the last stages of cell division when the phragmoplast touches the cell cortex to complete cytokinesis.
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Citocinese , Proteínas de Plantas , Zea mays , Zea mays/metabolismo , Zea mays/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Citoesqueleto de Actina/metabolismoRESUMO
INTRODUCTION: Silver amalgam, glass ionomer, resin-modified glass ionomer, compomers, light polymerized hybrid composite resin, and hybrid glass ionomer are among the most frequent restorative materials used as cavity-based or post-endodontics. Thus, to meet the needs of both patients and dentists, Cention N reimagines the traditional filling by integrating bulk placement, ion release, and durability into a dual-curing, aesthetically pleasing solution. Hoewver, we do not have enough information from studies comparing this hybrid restorative material's shear bond strengths to dentin to draw any firm conclusions. Cention N, zirconomer, and Vitremer are three hybrid tooth-colored restorative materials that were evaluated for their shear bond strength to dentin. This research aimed to compare and evaluate these materials. METHODOLOGY: The purpose of this research was to use a universal Instron machine to measure the shear bond stress of three distinct hybrid tooth-colored restorative materials in relation to dentin. The research samples consisted of 45 extracted lower first premolars from humans. The teeth were then assigned into three groups of 15 samples each according to different color acrylic resin blocks, namely, group A (pink acrylic blocks), which had Cention in cement; group B (white acrylic blocks), which has zirconomer cement; and group C (violet acrylic blocks), which had Vitremer cement. RESULTS: There was no statistically significant difference between the three groups and the normal distribution, as shown by the negligible values in the tests involving the three groups. Put simply, each of the three categories exhibits data that follows a normal distribution. This allows for further data analysis to be conducted using the parametric test of significance. CONCLUSION: The shear bond strength of hybrid glass ionomer restorative materials has to be further investigated in both laboratory and living organism settings.
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Sickle cell disease (SCD) is well recognized as a hypercoagulablestate, however, it remains unclear whether a subgroup of children with SCD at higher risk of venous thromboembolic event (VTE) during hospitalization may benefit from thromboprophylaxis. Our objectives were to describe the clinical characteristics, outcomes and recurrence of hospital acquired VTE in patients with SCD younger than 21 years. This was a single center retrospective study. Data regarding demographics, reason for admission, location of VTE, risk factors like central venous catheter (CVC), intensive care unit (ICU) admission among others were extracted from electronic medical records over a 10-year study period (2011-2021). Recurrence of VTE at 1 and 5 years was assessed. Descriptive statistics were used as indicated. We identified a total of 20 VTE events over the 10-year study period. Six of these events occurred in those younger than 12 years of age. Fourteen (70%) VTE events occurred in the HbSS or HbSßThal0 genotypes compared to 6 (30%) in HbSC. Most common VTE was isolated pulmonary embolism (PE) (n = 10, 50%). VTE were most often associated with acute chest syndrome (ACS) (n = 14, 70%), ICU admissions (n = 10, 50%) and CVC (n = 5/9, 55%). One patient died from the VTE event. One patient with additional underlying risk factors had a recurrent VTE at 13 months. Our study suggests that ICU admission, ACS and presence of CVC increases the risk of VTE in children and young adults with SCD, but larger studies are indicated to validate our findings.
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Division plane positioning is critical for proper growth and development in many organisms. In plants, the division plane is established before mitosis, by accumulation of a cytoskeletal structure called the preprophase band (PPB). The PPB is thought to be essential for recruitment of division site localized proteins, which remain at the division site after the PPB disassembles. Here, we show that a division site localized protein, TANGLED1 (TAN1), is recruited independently of the PPB to the cell cortex at sites, by the plant cytokinetic machinery, the phragmoplast. TAN1 recruitment to de novo sites on the cortex is partially dependent on intact actin filaments and the myosin XI motor protein OPAQUE1 (O1). These data imply a yet unknown role for TAN1 and possibly other division site localized proteins during the last stages of cell division when the phragmoplast touches the cell cortex to complete cytokinesis.
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PURPOSE: Time to antibiotic administration (TTA) in <60 minutes for children with neutropenic fever presenting to an emergency room is associated with reduced incidence of sepsis and intensive care admission. As such, TTA is used as a national quality metric for pediatric oncology patients. At our center, in 2020, 19% of the hospitalized patients with a new fever encounter were receiving antibiotics in <60 minutes, prompting a multidisciplinary approach to reach a goal of >90% in all pediatric patients with cancer with a new fever. METHODS: A multidisciplinary team completed four Plan-Do-Study-Act cycles between March 2021 and September 2023. We implemented education initiatives, an updated handoff smartphrase guiding the on-call team, an antibiotic champion (AC) nursing role, a revised fever plan for handoff, a rapid-response team to address new fevers, and an algorithm for blood culture collection. Data were collected, analyzed, and reported biweekly with feedback sought for delays in TTA. RESULTS: There was a total of 639 new fevers in 329 unique oncology patients. As of September 4, 2023, average TTA decreased from 89 minutes at baseline to 46.4 minutes for more than 12 months. The percentage of patients receiving first dose of antibiotic in <60 minutes also increased from 19% to 93.7%, which was sustained as well. The most effective interventions were creation of the AC role and streamlining the blood culture collection process. CONCLUSION: This project demonstrates the importance of multidisciplinary involvement for providing optimal care. Specific implementation of targeted education, an AC role, and development of an algorithm streamlining the processes led to meaningful targeted improvements. Further analyses will explore the impact of these interventions on patient outcomes.
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Antibacterianos , Febre , Neoplasias , Humanos , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Criança , Febre/tratamento farmacológico , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Feminino , Masculino , Pré-Escolar , Adolescente , Tempo para o TratamentoRESUMO
BACKGROUND: A posterior tooth's occlusal surfaces and the proximal surface can be restored by using an inlay, which is an intra-crown cast reconstruction without affecting the cusps of the tooth. When an inlay is prepared using an indirect approach, issues with traditional filling approaches, including poor morphology of the occlusal aspect or proximal aspect, inadequate resistance to wear, or subpar mechanical qualities of the directly inserted filler substance, are overcome. AIM: The current study was conducted in order to compare and assess the resistance to fracture of dental materials used in the preparation of inlay restorations indirectly, like composite restorations prepared by laboratories indirectly, inlays formed indirectly of monolithic translucent ceramic derived from zirconia, and inlays formed indirectly of traditional monolithic ceramic derived from zirconia. METHODS AND MATERIALS: For the investigation, 100 human premolars of the maxilla that were extracted recently were chosen. A self-polymerizing acrylic resin was used to incorporate the tooth roots in a band made up of polyvinyl chloride up to 2 mm below the cement-enamel junction. The dimension of the band was 1.3 cm by 1.9 cm. Five categories of 20 specimens of such teeth were formed. Category one, featuring teeth in good condition, acted as the positive control category. The remaining four categories of teeth received inlay tooth preparation. The research samples underwent thermocycling after having been preserved for a full week following the cementation of inlay replacements. Then, in a universal testing apparatus, every sample endured axial compressive force with a metal globe delivered vertically at a crosshead rate of 1 mm/minute. The amount of force necessary to cause a fracture was measured in Newtons (N). RESULTS: The mean values of resistance against fracture in specimens in categories 1-5 were 1208.87 N, 614.89 N, 733.05 N, 1179.14 N, and 1148.49 N, respectively. The values of fracture resistance in specimens where an inlay cavity preparation was done but not filled were lower than those in traditional monolithic ceramic derived from zirconia and tooth specimens with inlays formed of monolithic translucent ceramic derived from zirconia, and the difference was significant statistically (p=0.001). The values of fracture resistance in composite inlay restorations prepared by laboratories were indirectly lower than those of monolithic ceramic derived from zirconia and tooth specimens with inlays formed of monolithic translucent ceramic derived from zirconia, and the difference was significant statistically (p=0.004). CONCLUSION: Within the constraints of the current investigation, we can state that indirect zirconia-based ceramic products offer adequate fracture resistance, but additional research is needed to determine how well these materials hold up under different types of pressures before employing them in clinical tooth restoration.
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Pregnancy and sickle cell disease (SCD) both individually carry a risk of thromboembolism (TE). Pregnancy in people with SCD may further enhance the prothrombotic effect of the underlying disease. The objectives of this study were to determine the rate and risk factors for arterial and venous thrombosis in pregnant people with SCD. Administrative claims data from the United States Centers for Medicare and Medicaid Service Analytic eXtract from 2006 to 2018 were used. The study population included people with SCD from the start of their first identified pregnancy until 1 year postpartum and a control cohort of pregnant people without SCD of similar age and race. Outcomes of interest were identified with ICD-9 or 10 codes. Logistic regression analyses were used to analyze risk factors. We identified infant deliveries in 6388 unique people with SCD and 17 110 controls. A total of 720 venous thromboembolism (11.3%) and 335 arterial TE (5.2%) were observed in people with SCD compared to 202 (1.2%) and 95 (0.6%) in controls. People with SCD had an 8-11 times higher odds of TE compared to controls (p < .001). Within the SCD cohort, age, hemoglobin SS (HbSS) genotype, hypertension, and history of thrombosis were identified as independent risk factors for pregnancy-related TE. Pregnancy-specific factors (pre-eclampsia, eclampsia, multigestational pregnancy) were not associated with TE. In conclusion, the risk of pregnancy-related TE is considerably higher in people with SCD compared with controls without SCD. Hence, people with SCD, particularly those with multiple risk factors may be candidates for thromboprophylaxis during pregnancy and the postpartum period.
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Anemia Falciforme , Tromboembolia Venosa , Idoso , Gravidez , Humanos , Feminino , Estados Unidos/epidemiologia , Medicaid , Anticoagulantes , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Medicare , Anemia Falciforme/complicações , Anemia Falciforme/epidemiologiaRESUMO
Mutations in the C9orf72 gene are the most common cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The pathogenetic mechanisms linked to this gene are a direct consequence of an aberrant intronic expansion of a GGGGCC hexanucleotide located between the 1a and 1b non-coding exons, which can be transcribed to form cytotoxic RNA foci or even translated into aggregation-prone dipeptide repeat proteins. Importantly, the abnormal length of these repeats affects also the expression levels of C9orf72 itself, which suggests haploinsufficiency as additional pathomechanism. Thus, it appears that both toxic gain of function and loss of function are distinct but still coexistent features contributing to the insurgence of the disease in case of C9orf72 mutations. In this study, we aimed at identifying a strategy to address both aspects of the C9orf72-related pathobiochemistry and provide proof-of-principle information for a better understanding of the mechanisms leading to neuronal loss. By using primary neurons overexpressing toxic poly(GA), the most abundant protein product of the GGGGCC repeats, we found that the antiarrhythmic drug propranolol could efficiently reduce the accumulation of aberrant aggregates and increase the survival of C9orf72-related cultures. Interestingly, the improved catabolism appeared to not depend on major degradative pathways such as autophagy and the proteasome. By analyzing the proteome of poly(GA)-expressing neurons after exposure to propranolol, we found that the drug increased lysosomal degradation through a mechanism directly involving C9orf72 protein, whose levels were increased after treatment. Further confirmation of the beneficial effect of the beta blocker on aggregates' accumulation and survival of hiPSC-derived C9orf72-mutant motoneurons strengthened the finding that addressing both facets of C9orf72 pathology might represent a valid strategy for the treatment of these ALS/FTD cases.
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Vascular anomalies are rare disorders that encompass a group of lesions characterized by abnormal development of the lymphovascular system. Majority of these anomalies are present at birth and could potentially be detected during the prenatal period on imaging. This allows for early intervention and prompt management to improve outcomes. However, they can be difficult to diagnose, given the rarity and overlapping findings. In this review article, we provide a comprehensive overview of congenital vascular anomalies with a liberal use of images of recent cases at our center emphasizing prenatal imaging findings and the natural history of these conditions.
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Anormalidades Cardiovasculares , Malformações Vasculares , Recém-Nascido , Feminino , Gravidez , Humanos , Ultrassonografia Pré-Natal/métodos , Diagnóstico Pré-Natal/métodos , Malformações Vasculares/diagnóstico por imagemRESUMO
Background: Intracardiac thrombi (ICT) are associated with significant morbidity and mortality. Anticoagulation is the first line of treatment and may be complemented by thrombectomy or thrombolysis. However, optimal anticoagulant duration remains ill-defined. High-risk features of ICT that may warrant long-term anticoagulation therapy have not been established. Objectives: To describe anticoagulation duration and patterns of ICT resolution. To identify potential risk factors for persistent ICT despite anticoagulation. Methods: A single-institution retrospective chart review identified patients diagnosed with ICT by echocardiogram between January 2014 and March 2022. Descriptive statistics and logistic regression were used. Results: Fifty-one patients with ICT were identified. Median age at diagnosis was 9.2 years (IQR, 0.4-15.2). The most common underlying diagnoses were congenital heart disease (41%), infection (25%), and malignancy (24%). The majority of ICT were in the right atrium (n = 30). The median longest ICT dimension was 1.5 cm (range, 0.4-4.0). The median duration of anticoagulation was 4.3 months (IQR, 2.2-9.1). Among 48 patients who received anticoagulation as first-line treatment, 32 had partial or complete response with 3 to 6 months of anticoagulation, while remaining 16 patients had no response to anticoagulation. Patients with a central venous line had a delayed resolution of ICT [hazards ratio = 0.45 (95% CI, 0.22-0.93)]. Conclusion: Our study demonstrates the wide variability in duration of anticoagulation for children with ICT. Majority of the individuals benefit from 3-to-6 month treatment; however, individuals with a central venous line may benefit from a longer course of anticoagulation. Further large-scale studies are recommended to validate our findings.
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Context: The novel coronavirus disease 2019 (COVID-19) that has emerged as a pandemic now has put health care workers (HCWs) at great risk as they are the warriors in frontlines screening and treating the infected patients. When a COVID-19-positive HCW is identified, its contacts need to be traced to check the spread of the infection among patients and other HCWs. Aims: This study was aimed to study epidemiology and risk factors associated with severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection among HCWs and to quantify the risk of infection among HCWs in a tertiary level health care setting. Settings and Design: This cross-sectional study enrolled all the HCWs who were exposed to a patient with COVID-19 in a tertiary level health care center, Rishikesh, Uttarakhand from 1st May to 30th July, 2020. Methods and Material: All the exposed HCWs were followed up for 14 days after the last exposure to a patient with confirmed COVID-19 infection. Epidemiological data were obtained using structured interviews. Statistical Analysis Used: The data were analyzed using SPSS 23.0. Frequencies and proportions were calculated for descriptive variables, and risk ratios were calculated for risk factors affecting the transmission of disease. Results: We observed that 1,141 HCWs of the tertiary level health care hospital were exposed to COVID-19 patients during the study period. A total of 22 HCWs were tested COVID-19 positive among these exposed HCWs. Univariate analysis revealed a high risk of exposure to be significantly associated with a higher secondary attack rate of SARS CoV-2. Conclusions: The study demonstrates the risk of COVID-19 transmission through asymptomatic carriers. Therefore, periodic testing of all health care workers is necessary to ensure early mitigation of the shortage of health care providers.
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Introduction: Healthcare providers are vulnerable to occupational health hazards. However, they do not appropriately apprehend the serious health consequences of occupational exposures. This study was conducted to assess the effectiveness of "Occupational health hazards and vaccination" workshop organized periodically in institute. Material and Methods: We validated the questionnaire prior to assess the effectiveness of workshop. Expert performed "key check" of questionnaire. Item analysis of one best item questions was performed using difficulty index (p value), discrimination indices (DI), distractor efficiency (DE), and reliability using Kuder-Richardson 20 coefficients (KR20). Pre-test and post-test scores of study participants were compared. Effectiveness of workshop was determined using class average normalized gain. Result: The 14 item one-best questions had acceptable difficulty level (60.35 ± 9.46%) and ideal discriminating power (0.75 ± 0.17) with mean DE 73.81 ± 22.46%. The test was found highly reliable with KR20 as 0.90. Mean score in pre-test and post-test were 6.47 ± 3.38 and 13.69 ± 1.51, respectively, and significant improvement in post-test score was found compared to pre-test score. Class average normalized gain was 0.84. Conclusion: The Occupational health hazards and vaccination workshop effectively improved healthcare providers' knowledge regarding workplace safety protocols. Questionnaire was found to be valid and reliable. Low baseline knowledge highlights the fact that implementation of such training on regular basis is the need of hour.
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Oral or mouth cancer is the 16th most common form of cancer among the world's topmost malignancies. Healthy lifestyle and control of known risk factors can reduce its incidences further. Patients succumb to oral cancer when diagnosed late and lack timely access to tertiary care. Molecular biomarkers might help in early detection of oral cancer. Recently, researchers have identified numerous microRNAs which play a crucial role in promoting and suppressing oral cancers. miRNAs are short non-coding RNA molecules (18-22 nucleotides) that play a pivotal role in regulating gene expression. Understanding the miRNA interplays in oral cancers could augment the development of potential diagnostic, prognostic, and therapeutic tools. Liquid biopsy- a non-invasive approach that has been used lately, allows the determination of miRNAs in biological fluids that play essential roles in tumor suppression and cancer promotion. Herein, we summarize an update on the role of miRNAs in the diagnosis and treatment of oral cancer.
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MicroRNAs , Neoplasias Bucais , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Detecção Precoce de Câncer , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/genética , Neoplasias Bucais/terapia , Prognóstico , Regulação Neoplásica da Expressão GênicaRESUMO
Unique molecular vulnerabilities have been identified in the aggressive MCD/C5 genetic subclass of diffuse large B-cell lymphoma (DLBCL). However, the premalignant cell-of-origin exhibiting MCD-like dependencies remains elusive. In this study, we examined animals carrying up to 4 hallmark genetic lesions found in MCD consisting of gain-of-function mutations in Myd88 and Cd79b, loss of Prdm1, and overexpression of BCL2. We discovered that expression of combinations of these alleles in vivo promoted a cell-intrinsic accumulation of B cells in spontaneous splenic germinal centers (GCs). As with MCD, these premalignant B cells were enriched for B-cell receptors (BCRs) with evidence of self-reactivity, displayed a de novo dependence on Tlr9, and were more sensitive to inhibition of Bruton's tyrosine kinase. Mutant spontaneous splenic GC B cells (GCB) showed increased proliferation and IRF4 expression. Mice carrying all 4 genetic lesions showed a >50-fold expansion of spontaneous splenic GCs exhibiting aberrant histologic features with a dark zone immunophenotype and went on to develop DLBCL in the spleen with age. Thus, by combining multiple hallmark genetic alterations associated with MCD, our study identifies aberrant spontaneous splenic GCBs as a likely cell-of-origin for this aggressive genetic subtype of lymphoma.
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Linfoma Difuso de Grandes Células B , Baço , Animais , Linfócitos B/patologia , Centro Germinativo/patologia , Linfoma Difuso de Grandes Células B/patologia , Camundongos , Mutação , Baço/patologiaRESUMO
BACKGROUND: Chylothorax can be a presenting symptom of complex lymphatic anomaly in children and is associated with significant respiratory morbidity. Historically, the traditional pharmacological treatment has been octreotide. There are several treatments that have been utilized in the past few years including sirolimus; however, data regarding their efficacy and outcomes is limited. Furthermore, sirolimus has proven efficacy in complex vascular malformations, and hence, its utility/efficacy in infantile primary chylous effusions warrants further investigation. METHODS: In this retrospective study at Texas Children's Hospital, data were extracted for all infants with chylothorax who were treated with sirolimus between 2009 and 2020. Details regarding underlying diagnosis, comorbidities, and number of days from sirolimus initiation to resolution of effusion were collected. RESULTS: Initially a total of 12 infants were identified. Among them, seven patients had complete data and were included in the study. Reasons for chylous effusions include presumed complex lymphatic anomaly, generalized lymphatic anomaly, and complex congenital lymphatic anomaly. The mean duration of sirolimus treatment needed for chest tube removal was 16 days, with a median of 19 days and range of 7-22 days. No patients had progression of effusions while on sirolimus. CONCLUSION: With close monitoring, sirolimus appears to be an effective therapy for pediatric lymphatic effusions even in critically ill infants. The study also demonstrates shorter duration of chest tube requirement after initiation of sirolimus compared to previous studies. Larger multi-institutional studies are needed to further support our findings.
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Quilotórax , Anormalidades Linfáticas , Derrame Pleural , Criança , Quilotórax/tratamento farmacológico , Estado Terminal , Humanos , Lactente , Anormalidades Linfáticas/complicações , Anormalidades Linfáticas/tratamento farmacológico , Octreotida/uso terapêutico , Derrame Pleural/tratamento farmacológico , Estudos Retrospectivos , Sirolimo/uso terapêuticoRESUMO
BACKGROUND: Whether arthroscopic or open surgical management for diffuse-type tenosynovial giant cell tumor (D-TGCT) of the knee is associated with a lower rate of recurrence is unknown. METHODS: PubMed, Scopus, Web of Science, Cochrane, and EMBASE were searched on December 3, 2020. Retrospective studies that reported on recurrence rates for arthroscopic versus open management of D-TGCT were included. A total of 16 studies evaluating 1143 patients with D-TGCT of the knee were included (nopen = 551, narthroscopic = 350 patients, and narthroscopic/open = 23 patients). Random-effects meta-analyses were used to summarize and compare the reported recurrence rates, stratified by approach and overall recurrence. The meta-analysis was registered with PROSPERO. RESULTS: The recurrence rate per year (incidence) for arthroscopic procedures was 0.11 (95% CI 0.08 to 0.16, P < 0.0001) and for open procedures was 0.07 (95% CI 0.04 to 0.13, P < 0.0001). There was a 1.56 times (95% CI 1.04 to 2.34, P = 0.0332) increased risk of recurrence when treating D-TGCT of the knee with an arthroscopic approach. When evaluating only the subset of studies that had data for both arthroscopic and open approaches, the incidence rate per year for arthroscopic procedures was 0.17 (95% CI 0.11 to 0.27, P < 0.0001) and for open procedures was 0.11 (95% CI 0.06 to 0.19, P < 0.0001). The rate of overall complications was 0.04 (95% CI 0.01 to 0.08, P < 0.0001). CONCLUSION: Arthroscopic surgical management of D-TGCT of the knee in our study resulted in a 1.56 times risk of recurrence as compared with the open approach. The percent of overall complications was minimal.
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Tumor de Células Gigantes de Bainha Tendinosa , Sinovite Pigmentada Vilonodular , Artroscopia , Tumor de Células Gigantes de Bainha Tendinosa/epidemiologia , Tumor de Células Gigantes de Bainha Tendinosa/cirurgia , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Estudos RetrospectivosRESUMO
Antimicrobial resistance (AMR) mediated by ß-lactamases is the major and leading cause of resistance to penicillins and cephalosporins among Gram-negative bacteria. ß-Lactamases, periplasmic enzymes that are widely distributed in the bacterial world, protect penicillin-binding proteins (PBPs), the major cell wall synthesizing enzymes, from inactivation by ß-lactam antibiotics. Developing novel PBP inhibitors with a non-ß-lactam scaffold could potentially evade this resistance mechanism. Based on the structural similarities between the evolutionary related serine ß-lactamases and PBPs, we investigated whether the potent ß-lactamase inhibitor, vaborbactam, could also form an acyl-enzyme complex with Pseudomonas aeruginosa PBP3. We found that this cyclic boronate, vaborbactam, inhibited PBP3 (IC50 of 262 µM), and its binding to PBP3 increased the protein thermal stability by about 2°C. Crystallographic analysis of the PBP3:vaborbactam complex reveals that vaborbactam forms a covalent bond with the catalytic S294. The amide moiety of vaborbactam hydrogen bonds with N351 and the backbone oxygen of T487. The carboxyl group of vaborbactam hydrogen bonds with T487, S485, and S349. The thiophene ring and cyclic boronate ring of vaborbactam form hydrophobic interactions, including with V333 and Y503. The active site of the vaborbactam-bound PBP3 harbors the often observed ligand-induced formation of the aromatic wall and hydrophobic bridge, yet the residues involved in this wall and bridge display much higher temperature factors compared to PBP3 structures bound to high-affinity ß-lactams. These insights could form the basis for developing more potent novel cyclic boronate-based PBP inhibitors to inhibit these targets and overcome ß-lactamases-mediated resistance mechanisms.
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Ácidos Borônicos/química , Proteínas de Ligação às Penicilinas/metabolismo , Pseudomonas aeruginosa/metabolismo , Inibidores de beta-Lactamases/química , Domínio Catalítico , Simulação de Dinâmica Molecular , Proteínas de Ligação às Penicilinas/química , Ligação Proteica , Homologia Estrutural de Proteína , Temperatura , Difração de Raios X , beta-Lactamases/química , beta-Lactamases/metabolismo , beta-Lactamas/químicaRESUMO
BACKGROUND: Children with cancer diagnosis are overall at a higher risk of thrombosis. For a newly diagnosed blood clot, patients are commonly started on anticoagulants to prevent further extension and embolization of the clot. In the rare instance that a pediatric patient has a tumor thrombus, role of anticoagulation is less clear. PROCEDURE/METHODS: Patients under 21 years of age with a finding of tumor thrombus on imaging from 2010 to 2020 at Texas Children's Hospital were identified and their medical records were reviewed. RESULTS: A total of 50 patients were identified. Most thrombi were incidental findings at diagnosis; however, two patients presented with pulmonary embolism (PE). Inferior vena cava extension was noted in 36% of the patients, and 24% patients had an intracardiac tumor thrombus. Anticoagulation was initiated in 10 patients (20%). There was no difference in the rate of bland thrombus formation and/or embolization in patients who did or did not receive anticoagulation. However, three of the six patients with asymptomatic tumor thrombus who were started on anticoagulation had bleeding complications compared to only two patients in the no anticoagulation cohort (p < .05). CONCLUSION: Children with intravascular extension of solid tumors were not commonly started on anticoagulation at the time of diagnosis, irrespective of the extent of tumor thrombus. Furthermore, we observed a significant trend toward higher incidence of bleeding complications after initiation of anticoagulation for asymptomatic tumor thrombus. There is inadequate evidence at this time to support routine initiation of anticoagulation in pediatric patients with intravascular extension of solid tumors.
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Anticoagulantes , Embolia Pulmonar , Trombose , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Criança , Humanos , Embolia Pulmonar/tratamento farmacológico , Estudos Retrospectivos , Trombose/tratamento farmacológico , Veia Cava InferiorRESUMO
Spontaneous expectoration of the tissue fragments in primary lung carcinoma is an extremely unusual event. Expectoration of tumor fragments is a significant event that should not be ignored as it serves itself as a noninvasive tool to diagnose underlying malignancy if such samples are immediately preserved and subjected to histopathological examination. More so, expectoration of a large-sized fragment may provide substantial relief from the breathlessness. Reported here is the case of a middle-aged male patient with adenocarcinoma in the right lung, and mass extended up to trachea, who spontaneously coughed out pieces of tumor tissue.