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Deficiency in mevalonate kinase (MVK) causes systemic inflammation. However, the molecular mechanisms linking the mevalonate pathway to inflammation remain obscure. Geranylgeranyl pyrophosphate, a non-sterol intermediate of the mevalonate pathway, is the substrate for protein geranylgeranylation, a protein post-translational modification that is catalyzed by protein geranylgeranyl transferase I (GGTase I). Pyrin is an innate immune sensor that forms an active inflammasome in response to bacterial toxins. Mutations in MEFV (encoding human PYRIN) result in autoinflammatory familial Mediterranean fever syndrome. We found that protein geranylgeranylation enabled Toll-like receptor (TLR)-induced activation of phosphatidylinositol-3-OH kinase (PI(3)K) by promoting the interaction between the small GTPase Kras and the PI(3)K catalytic subunit p110δ. Macrophages that were deficient in GGTase I or p110δ exhibited constitutive release of interleukin 1ß that was dependent on MEFV but independent of the NLRP3, AIM2 and NLRC4 inflammasomes. In the absence of protein geranylgeranylation, compromised PI(3)K activity allows an unchecked TLR-induced inflammatory responses and constitutive activation of the Pyrin inflammasome.
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Alquil e Aril Transferases/metabolismo , Febre Familiar do Mediterrâneo/metabolismo , Inflamassomos/metabolismo , Macrófagos/fisiologia , Mutação/genética , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Pirina/genética , Alquil e Aril Transferases/genética , Animais , Células Cultivadas , Febre Familiar do Mediterrâneo/genética , Humanos , Imunidade Inata , Interleucina-1beta/metabolismo , Camundongos Endogâmicos C57BL , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Fosfatos de Poli-Isoprenil/metabolismo , Processamento de Proteína Pós-Traducional , Transdução de Sinais , Receptores Toll-Like/metabolismoRESUMO
The growth of therapeutic monoclonal antibodies (mAbs) continues to accelerate due to their success as treatments for many diseases. As new therapeutics are developed, it is increasingly important to have robust bioanalytical methods to measure the pharmacokinetics (PK) of circulating therapeutic mAbs in serum. Ligand-binding assays such as enzyme-linked immunosorbent assays (ELISAs) with anti-idiotypic antibodies (anti-IDs) targeting the variable regions of the therapeutic antibody are sensitive and specific bioanalytical methods to measure levels of therapeutic antibodies in a biological matrix. However, soluble circulating drug mAb targets can interfere with the anti-IDs binding to the therapeutic mAb, thereby resulting in an underestimation of total drug concentration. Therefore, in addition to a high binding affinity for the mAb, the selection of anti-IDs and the assay format that are not impacted by soluble antigens and have low matrix interference is essential for developing a robust PK assay. Standardized automated approaches to screen and select optimal reagents and assay formats are critical to increase efficiency, quality, and PK assay robustness. However, there does not exist an integrated screening and analysis platform to develop robust PK assays across multiple formats. We have developed an automated workflow and scoring platform with multiple bioanalytical assay parameters that allow for ranking of candidate anti-IDs. A primary automated indirect electrochemiluminescence (ECL) was utilized to shortlist the anti-IDs that were selected for labeling and screening in pairs. A secondary screen using an ECL sandwich assay with labeled-anti-ID pairings was used to test multiple PK assay formats to identify the best anti-ID pairing/PK assay format. We developed an automated assay using fixed plate maps combined with a human-guided graphical user interface-based scoring system and compared it to a data-dependent scoring system using Gaussian mixture models for automated scoring and selection. Our approach allowed for screening of anti-IDs and identification of the most robust PK assay format with significantly reduced time and resources compared with traditional approaches. We believe that such standardized, automated, and integrated platforms that accelerate the development of PK assays will become increasingly important for supporting future human clinical trials.
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Anticorpos Monoclonais , Antígenos , Humanos , Fluxo de Trabalho , Ligantes , Anticorpos Monoclonais/análise , Ensaio de Imunoadsorção Enzimática/métodosRESUMO
PURPOSE: Core body temperature has been extensively investigated as a thereuptic target in care after cardiac arrest. Nevertheless, the integrity of thermoregulation in patients after cardiac arrest has not been well studied. We sought to evaluate whether low spontaneous body temperature after cardiac arrest is associated with increased death and a worse neurologic outcome, and whether patients with low spontaneous body temperature exhibit features suggestive of impaired thermoregulation. METHODS: We conducted a single-centre retrospective cohort study. We included all adult patients who underwent temperature control with hypothermia after cardiac arrest between 1 January 2014 and 30 June 2020. The primary exposure was low spontaneous core body temperature (< 35 °C) at initiation of hypothermia therapy. The primary outcome was in-hospital death and the secondary outcome was poor neurologic outcomes at discharge. RESULTS: Five hundred and ninety-seven adult patients, comprising both in- and out-of-hospital cardiac arrests, were included. Patients with low spontaneous body temperature also had slightly lower average temperature, and more frequent transient but controlled breakthrough fever episodes in the first 24 hr. In the multivariable logistic regression analysis, low spontaneous body temperature was associated with higher odds of in-hospital death (odds ratio, 2.9; 95% confidence interval, 1.9 to 4.2; P < 0.001). CONCLUSION: In this single-centre retrospective cohort study, low spontaneous core body temperature was associated with poor outcomes in patients after cardiac arrest. Patients with low spontaneous body temperature also exhibited features suggestive of impaired thermoregulation. Further research is needed to determine whether body temperature upon presentation reflects the robustness of the patient's underlying physiology and severity of brain insult after a cardiac arrest.
RéSUMé: OBJECTIF: La température corporelle centrale a fait l'objet d'études approfondies en tant que cible thérapeutique dans les soins après un arrêt cardiaque. Néanmoins, l'intégrité de la thermorégulation après un arrêt cardiaque n'a pas été bien étudiée. Nous avons cherché à évaluer si une température corporelle spontanément basse après un arrêt cardiaque était associée à une augmentation de la mortalité et à une issue neurologique plus grave, et si les individus ayant une température corporelle spontanément basse présentaient des caractéristiques suggérant une altération de la thermorégulation. MéTHODE: Nous avons mené une étude de cohorte rétrospective monocentrique. Nous avons inclus tou·tes les patient·es adultes ayant bénéficié d'un contrôle de température lors d'une hypothermie après un arrêt cardiaque entre le 1er janvier 2014 et le 30 juin 2020. L'exposition principale était une température corporelle centrale spontanément basse (< 35 °C) au début du traitement de l'hypothermie. Le critère d'évaluation principal était le décès à l'hôpital, et le critère d'évaluation secondaire était de mauvaises issues neurologiques à la sortie de l'hôpital. RéSULTATS: Cinq cent quatre-vingt-dix-sept patient·es adultes, ayant subi des arrêts cardiaques à l'hôpital ou hors de l'hôpital, ont été inclus·es. Les patient·es ayant une température corporelle spontanément basse avaient également une température moyenne légèrement plus basse et des épisodes de fièvre paroxystique transitoires mais contrôlés plus fréquents au cours des premières 24 heures. Dans l'analyse de régression logistique multivariée, une température corporelle spontanément basse était associée à une probabilité plus élevée de décès à l'hôpital (rapport de cotes, 2,9; intervalle de confiance à 95 %, 1,9 à 4,2; P < 0,001). CONCLUSION: Dans cette étude de cohorte rétrospective monocentrique, une température corporelle centrale spontanément basse a été associée à de mauvais devenirs après un arrêt cardiaque. Les patient·es présentant une température corporelle spontanément basse présentaient également des caractéristiques suggérant une altération de la thermorégulation. D'autres recherches sont nécessaires pour déterminer si la température corporelle lors de la présentation reflète la robustesse de la physiologie sous-jacente des patient·es et la gravité de la lésion cérébrale après un arrêt cardiaque.
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Reanimação Cardiopulmonar , Parada Cardíaca , Hipotermia Induzida , Hipotermia , Adulto , Humanos , Estudos Retrospectivos , Mortalidade Hospitalar , Hipotermia Induzida/efeitos adversos , Parada Cardíaca/terapia , Regulação da Temperatura CorporalRESUMO
BACKGROUND: Albuterol is the drug most widely used as asthma treatment among African Americans despite having a lower bronchodilator drug response (BDR) than other populations. Although BDR is affected by gene and environmental factors, the influence of DNA methylation is unknown. OBJECTIVE: This study aimed to identify epigenetic markers in whole blood associated with BDR, study their functional consequences by multi-omic integration, and assess their clinical applicability in admixed populations with a high asthma burden. METHODS: We studied 414 children and young adults (8-21 years old) with asthma in a discovery and replication design. We performed an epigenome-wide association study on 221 African Americans and replicated the results on 193 Latinos. Functional consequences were assessed by integrating epigenomics with genomics, transcriptomics, and environmental exposure data. Machine learning was used to develop a panel of epigenetic markers to classify treatment response. RESULTS: We identified 5 differentially methylated regions and 2 CpGs genome-wide significantly associated with BDR in African Americans located in FGL2 (cg08241295, P = 6.8 × 10-9) and DNASE2 (cg15341340, P = 7.8 × 10-8), which were regulated by genetic variation and/or associated with gene expression of nearby genes (false discovery rate < 0.05). The CpG cg15341340 was replicated in Latinos (P = 3.5 × 10-3). Moreover, a panel of 70 CpGs showed good classification for those with response and nonresponse to albuterol therapy in African American and Latino children (area under the receiver operating characteristic curve for training, 0.99; for validation, 0.70-0.71). The DNA methylation model showed similar discrimination as clinical predictors (P > .05). CONCLUSIONS: We report novel associations of epigenetic markers with BDR in pediatric asthma and demonstrate for the first time the applicability of pharmacoepigenetics in precision medicine of respiratory diseases.
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Asma , Broncodilatadores , Criança , Adulto Jovem , Humanos , Adolescente , Adulto , Broncodilatadores/uso terapêutico , Epigenoma , Multiômica , Asma/tratamento farmacológico , Asma/genética , Asma/metabolismo , Albuterol/uso terapêutico , Metilação de DNA , Estudo de Associação Genômica Ampla , Fibrinogênio/metabolismoRESUMO
Most Pseudomonas aeruginosa strains produce bacteriocins derived from contractile or noncontractile phage tails known as R- and F-type pyocins, respectively. These bacteriocins possess strain-specific bactericidal activity against P. aeruginosa and likely increase evolutionary fitness through intraspecies competition. R-type pyocins have been studied extensively and show promise as alternatives to antibiotics. Although they have similar therapeutic potential, experimental studies on F-type pyocins are limited. Here, we provide a bioinformatic and experimental investigation of F-type pyocins. We introduce a systematic naming scheme for genes found in R- and F-type pyocin operons and identify 15 genes invariably found in strains producing F-type pyocins. Five proteins encoded at the 3' end of the F-type pyocin cluster are divergent in sequence and likely determine bactericidal specificity. We use sequence similarities among these proteins to define eleven distinct F-type pyocin groups, five of which had not been previously described. The five genes encoding the variable proteins associate in two modules that have clearly reassorted independently during the evolution of these operons. These proteins are considerably more diverse than the specificity-determining tail fibers of R-type pyocins, suggesting that F-type pyocins may have emerged earlier. Experimental studies on six F-type pyocin groups show that each displays a distinct spectrum of bactericidal activity. This activity is strongly influenced by the lipopolysaccharide O-antigen type, but other factors also play a role. F-type pyocins appear to kill as efficiently as R-type pyocins. These studies set the stage for the development of F-type pyocins as antibacterial therapeutics. IMPORTANCE Pseudomonas aeruginosa is an opportunistic pathogen that causes antibiotic-resistant infections with high mortality rates, particularly in immunocompromised individuals and cystic fibrosis patients. Due to the increasing frequency of multidrug-resistant P. aeruginosa infections, there is great need for the development of alternative therapeutics. In this study, we investigate one such potential therapeutic: F-type pyocins, which are bacteriocins naturally produced by P. aeruginosa that resemble noncontractile phage tails. We show that they are potent killers of P. aeruginosa and identify their probable bactericidal specificity determinants, which opens up the possibility of engineering them to precisely target strains of pathogenic bacteria. The resemblance of F-type pyocins to well-characterized phage tails will greatly facilitate their development into effective antibacterials.
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Bacteriocinas , Bacteriófagos , Humanos , Piocinas/farmacologia , Pseudomonas aeruginosa/metabolismo , Bacteriocinas/genética , Bacteriocinas/farmacologia , Bacteriocinas/metabolismo , Antibacterianos/farmacologia , Antibacterianos/metabolismo , Bacteriófagos/metabolismoRESUMO
Neurodegenerative diseases, including Alzheimer's disease (AD), are challenging to diagnose. Currently the field must rely on imperfect diagnostic modalities. A recent study identified differences in several key bio-mechano-physiological parameters of the skin between AD patients and healthy controls. Here, we visually align these differences with the relevant histological, aging, and embryological paradigms to raise awareness for these potential biomarkers. In a study conducted by Wu et al., a series of n = 41 patients (n = 29 with AD and n = 12 healthy controls) were evaluated, demonstrating that AD patients exhibit a less acidic skin pH, increased skin hydration, and reduced skin elasticity compared to healthy controls. We constructed a visual overview and explored the relevant paradigms. We present a visual comparison of these factors, highlighting four paradigms: (1) the findings emphasize a shared ectodermal origin of the brain and the skin; (2) functional systems such as micro-vascularization, innervation, eccrine excretory functions, and the extracellular matrix undergo distinct changes in patients with AD; (3) the human skin mirrors the alterations in brain stiffness observed in aging studies; (4) assessment of physiological features of the skin is cost-effective, accessible, and easily amenable for monitoring and integration with cognitive assessment studies. Understanding the relationship between aging skin and aging brain is an exciting frontier, holding great promise for improved diagnostics. Further prospective and larger-scale investigations are needed to solidify the brain-skin link and determine the extent to which this relationship can be leveraged for diagnostic applications.
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Doença de Alzheimer , Humanos , Doença de Alzheimer/diagnóstico , Gerociência , Encéfalo , Pele , BiomarcadoresRESUMO
BACKGROUND: The risk of pancreatic ductal adenocarcinoma (PDAC) is increased in patients with diabetes mellitus (DM), particularly in those with new-onset DM. However, the impact of DM on outcomes following pancreatic surgery is not fully understood. We sought to explore the effects of DM on post-resection outcomes in patients undergoing either upfront resection or following neoadjuvant treatment (NAT). METHODS: Resections for PDAC between 2007 and 2016 were identified from a prospectively-maintained database. Data on demographics, pathology, and perioperative outcomes were compared between patients with or without DM. Survival analysis was performed using Kaplan-Meier curves and adjusted for confounders by a Cox-proportional hazards model. RESULTS: 662 patients were identified, of whom 277 (41.8%) had DM. Diabetics were more likely to be male, had higher BMI, and higher ASA-scores. At pathology, DM was associated with larger tumors (30 vs. 26â¯mm; pâ¯=â¯0.041), higher rates of lymph-node involvement (69% vs. 59%; pâ¯=â¯0.031) and perineural invasion (88% vs. 82%; pâ¯=â¯0.026). Despite having similar rates of complications, diabetics experienced higher 30-day mortality (3.2% vs. 0.8%; pâ¯=â¯0.019). Median overall survival was worse in diabetic patients (18 vs. 34 months; pâ¯<â¯0.001); this effect was more pronounced in patients with NAT (18 vs. 54 months; pâ¯<â¯0.001). At multivariate analysis, DM was confirmed as an independent predictor of post-resection survival. CONCLUSION: DM is a common comorbidity in PDAC and is associated with unfavorable pathology, as well as worse postoperative and oncologic outcomes. The blunted effect on survival is more pronounced in patients who undergo resection following NAT.
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Diabetes Mellitus , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidadeRESUMO
BACKGROUND AND OBJECTIVE: C-reactive protein (CRP) is a widely used cardiovascular risk marker, but questions remain about its role in the disability process in old age. This study examines the associations between CRP levels and physical performance in old age in different societies. METHODS: data were collected during the baseline survey of IMIAS in 2012 in Kingston (Canada), Saint-Hyacinthe (Canada), Manizales (Colombia) and Natal (Brazil). Approximately 200 men and 200 women aged 65-74 were recruited at each site. CRP was assessed using a high sensitivity assay and categorised as low (<1 mg/l), moderate (1-3 mg/l), high (3-10 mg/l) and very high (≥10 mg/l). Participants were interviewed at home; blood pressure, weight and height were measured. Physical function was assessed with the Short Physical Performance Battery (SPPB) and hand grip strength. Data were analysed using descriptive statistics, bivariate analysis (χ²) and linear or logistic regression. RESULTS: CRP was significantly associated with low hand grip strength and poor physical performance in bivariate analyses. Hand grip strength association with CRP disappeared after adjustment by socioeconomic factors and health behaviours. The odds of poor physical function was OR = 2.67 [95% CI 1.43-4.99] comparing the highest and lowest CRP categories after adjustment by relevant covariates. The three SPPB components were assessed separately. Graded associations between low CRP and faster gait speed and shorter time to rise from a chair were observed in adjusted models. Association between impaired balance and CRP was attenuated after adjustment by relevant covariates, OR = 1.15 [0.65-2.04]. CONCLUSIONS: CRP could be a possible pathway from inflammation to physical decline in older populations.
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Envelhecimento/sangue , Proteína C-Reativa/análise , Nível de Saúde , Mediadores da Inflamação/sangue , Aptidão Física , Fatores Etários , Idoso , Biomarcadores/sangue , Brasil , Canadá , Distribuição de Qui-Quadrado , Colômbia , Estudos Transversais , Avaliação da Deficiência , Feminino , Avaliação Geriátrica , Força da Mão , Inquéritos Epidemiológicos , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Análise Multivariada , Razão de Chances , Fatores de RiscoRESUMO
BACKGROUND: Recent studies suggest potential associations between childhood adversity and chronic inflammation at older ages. Our aim is to compare associations between childhood health, social and economic adversity and high sensitivity C-reactive protein (hsCRP) in populations of older adults living in different countries. METHODS: We used the 2012 baseline data (n = 1340) from the International Mobility in Aging Study (IMIAS) of community-dwelling people aged 65-74 years in Natal (Brazil), Manizales (Colombia) and Canada (Kingston, Ontario; Saint-Hyacinthe, Quebec). Multiple linear and Poisson regressions with robust covariance were fitted to examine the associations between early life health, social, and economic adversity and hsCRP, controlling for age, sex, financial strain, marital status, physical activity, smoking and chronic conditions both in the Canadian and in the Latin American samples. RESULTS: Participants from Canadian cities have less adverse childhood conditions and better childhood self-reported health. Inflammation was lower in the Canadian cities than in Manizales and Natal. Significant associations were found between hsCRP and childhood social adversity in the Canadian but not in the Latin American samples. Among Canadian older adults, the fully-adjusted mean hsCRP was 2.2 (95% CI 1.7; 2.8) among those with none or one childhood social adversity compared with 2.8 (95% CI 2.1; 3.8) for those with two or more childhood social adversities (p = 0.053). Similarly, the prevalence of hsCRP > 3 mg/dL was 40% higher among those with higher childhood social adversity but after adjustment by health behaviors and chronic conditions the association was attenuated. No associations were observed between hsCRP and childhood poor health or childhood economic adversity. CONCLUSIONS: Inflammation was higher in older participants living in the Latin American cities compared with their Canadian counterparts. Childhood social adversity, not childhood economic adversity or poor health during childhood, was an independent predictor of chronic inflammation in old age in the Canadian sample. Selective survival could possibly explain the lack of association between social adversity and hsCRP in the Latin American samples.
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Envelhecimento/fisiologia , Saúde da Criança/estatística & dados numéricos , Inflamação , Idoso , Brasil/epidemiologia , Proteína C-Reativa/análise , Canadá/epidemiologia , Causalidade , Criança , Doença Crônica , Efeito de Coortes , Colômbia/epidemiologia , Estudos Transversais , Feminino , Humanos , Inflamação/sangue , Inflamação/etnologia , Inflamação/fisiopatologia , Masculino , Prevalência , Fatores SocioeconômicosRESUMO
BACKGROUND: Companion diagnostics are an essential component of oncology. Timing, cost, and adaptability to new drug/biomarker approvals represent challenges in assuring value-based care. Overcoming these challenges requires strategies for equitable access and efficient integration. METHODS: Based on prior laboratory improvements and payor policy implementations, we define equitable access in laboratory testing and conceptualized a framework for initiatives that optimize diagnostic performance. RESULTS: We define equitable access as an imperative goal seeking to remove disparities that may arise due to financial hardships, geographical isolation, cultural differences, or other social determinants of health. We distinguish (a) utilization, as the practice pattern of ordered tests, (b) utilization management, as the evidence-based guidance of the utilization decisions, and (c) utilization management strategies, defined as the tools and techniques used to influence decision-making. These 3 dimensions establish a standardized vocabulary to clarify equitable alignment of strategies in specific care pathways. Alignment of logistic, administrative, and financial incentive structures is paramount when creating sustainable personalized care pathway programs. CONCLUSIONS: Strategies to accomplish equitable and meaningful use of diagnostic tests can help enhance access to timely and accurate diagnoses, ultimately leading to improved patient outcomes.
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Testes Diagnósticos de Rotina , Equidade em Saúde , Acessibilidade aos Serviços de Saúde , HumanosRESUMO
The sternum, or "breastbone," is a principal bony component of the anterior thoracic wall and comprises the manubrium of the sternum, the body of the sternum, and the xiphoid process. The xiphoid process is the most inferior of these elements and commonly presents as a small, solid bone shaped like an inverted triangle. However, clinical literature has reported numerous variations in its size, shape, and presentation, likely the result of its lengthy embryological development from cartilage into fully ossified bone. In this case report, a rare, anteriorly deviated, partially ossified xiphoid process with a large, teardrop-shaped foramen is presented that was discovered during a routine cadaveric dissection of a 75-year-old male within an undergraduate anatomy course. Although anatomical variations in the xiphoid process are often asymptomatic and often only found incidentally through CT or X-ray scans, healthcare professionals should be aware of such variations to avoid both misdiagnoses as well as iatrogenic complications.
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This case report explores the physical characteristics and clinical significance of the sternalis muscle, an uncommon anatomical variation of the anterior thoracic wall. If present, the sternalis muscle may distort diagnostic images and can be associated with incorrect interpretation of such medical images, misdiagnoses, and even surgical complications. As such, enhancing clinicians' knowledge of this muscle and improving its recognition is of the utmost importance. In this case report, a rare bilateral sternalis muscle that was discovered during an educational human cadaveric dissection of a 73-year-old Black male is described. The right sternalis muscle fibres extended from the mid-sternal level to the right sternocostal arch, measuring 11.5 cm in length and 3.4 cm at its largest width. In contrast, the smaller left sternalis muscle fibres measured only 5.6 cm in length and 1.2 cm at its greatest width. This rare bilateral presentation of the sternalis muscle is documented in approximately one-third of all reported sternalis cases with an associated estimated prevalence as low as 1.7% among the general population. Serving as a reminder of the intricate anatomical complexities that continue to challenge and intrigue medical professionals, this report advocates for continued education of anatomical variations to enhance patient care and medical practices.
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INTRODUCTION: We examined data from a large, high acuity, pediatric psychiatric emergency department (ED) to assess both the immediate and longer-term impact of the pandemic on ED visits for suicidal thoughts and behaviors (STBs) among youth. METHODS: Youth ages 5-17 years presenting at a pediatric psychiatric ED in New York, NY from March 2019-November 2021 were included in this study. Visits were categorized as pre-pandemic, pandemic year 1, or pandemic year 2. We examined changes in demographic and clinical characteristics among patients presenting across the three time periods, as well as multivariable associations between these characteristics and STBs. RESULTS: Over 32 months, 2728 patients presented at 4161 visits. The prevalence of a discharge diagnosis of STBs increased from 21.2% pre-pandemic to 26.3% (p < 0.001) during pandemic year 1, and further increased to 30.1% (p = 0.049) during pandemic year 2. Youth were 21% more likely to receive a discharge diagnosis of STBs in pandemic year 1 (RR 1.21, 95% CI 1.07, 1.36) and 35% more likely in pandemic year 2 (RR 1.35, 95% CI 1.19, 1.52) compared to pre-pandemic baseline. CONCLUSIONS: In a large, high-acuity ED, STBs continued to increase 20 months after the initial COVID-19 lockdown. These findings highlight the persistent detrimental impact of the pandemic on youth mental health.
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Benzofuranos , COVID-19 , Diterpenos do Tipo Caurano , Compostos de Espiro , Criança , Adolescente , Humanos , COVID-19/epidemiologia , Ideação Suicida , Controle de Doenças Transmissíveis , Visitas ao Pronto Socorro , Pandemias , Serviço Hospitalar de EmergênciaRESUMO
BACKGROUND: An alveolar ridge preservation (ARP) procedure is commonly performed to preserve ridge width and height for optimal dental implant placement. Mixing different sources of bone grafts may help maximize their properties to obtain predictable ARP results. OBJECTIVE: The aim of this case series is to highlight the clinical and radiographic outcomes of a combined allograft and xenograft approach for a predictable ARP procedure. MATERIALS AND METHODS: Eleven clinical cases that required tooth extraction and future implant placement were selected for this case series. All surgeries were performed by a single clinician in a private practice setting. All cases underwent an ARP procedure, which included atraumatic extraction, degranulation, assessment of the socket, and the use of a combination of allograft and xenograft fibers/granules in a 1:1 mixing approach. Based on the socket defect, either a type I or type III collagen membrane was used during the procedure. In all cases CBCT imaging was done prior to surgical implant placement, and digital implant planning was performed integrating interdisciplinary best practices. Implant placement was carried out using manufacturer's recommendations. RESULTS: Five male and five female patients were included in the study, with one of the male patients having two teeth extracted for a total of 11 cases. The reasons for teeth extraction included fracture, endodontic failure, periodontal infection, and subgingival decay. Healing was uneventful after the ARP procedure for all patients. A minimum of 120 days elapsed between ARP and the surgical implant procedure. Complete radiographic bone fill was observed in the CBCT image for all extraction sites, and no additional bone augmentation was needed at the time of implant placement. CONCLUSION: This case series demonstrates that based on clinical and radiographic outcomes, a combination of allogenic and xenogenic bone substitute can be utilized to obtain predictable results following ARP. Future randomized controlled trials that can compare different ratios between the two biomaterials are indicated to guide clinicians in the mixing protocols and their outcomes.
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Perda do Osso Alveolar , Aumento do Rebordo Alveolar , Humanos , Feminino , Masculino , Processo Alveolar/cirurgia , Alvéolo Dental/diagnóstico por imagem , Alvéolo Dental/cirurgia , Xenoenxertos , Materiais Biocompatíveis , Extração Dentária , Aumento do Rebordo Alveolar/métodos , Aloenxertos/cirurgia , Perda do Osso Alveolar/cirurgiaRESUMO
The splenic artery is the largest branch of the celiac trunk and frequently presents with anatomical variability. These variations relate to its origin, trajectory, location relative to the pancreas, terminal branching pattern, and the potential presence of polar arteries. Knowledge of the splenic artery's variability may inform gastrointestinal surgeons as they plan and execute surgical interventions, resulting in improved success rates while minimizing both operative complications and procedural time. The case presentation of a splenic artery dissected from an elderly male cadaver initially demonstrated normal anatomical arrangement. The artery branched off the celiac trunk of the abdominal aorta and followed a tortuous suprapancreatic route to split into two lobar arteries terminating in the spleen. However, upon closer inspection, a superior polar splenic artery was uncovered with two unique characteristics. Firstly, the presented polar artery lacked branching gastric arteries, a rare variation with a prevalence of only 3.27%. Secondly, the distance between the origin of the superior polar splenic artery and the splenic hilum was greater than what is often reported in clinical literature. While similar previous case reports have observed arterial origins of greater distance, these have often been accompanied by a compensatory arterial length. Interestingly, the case presented in this report contained a superior polar splenic artery with an arterial length shorter than its distance to the splenic hilum, resulting in an atypically taut vessel. This bears clinical importance, as this arterial presentation may be susceptible to a surgical rupture if neglected. By including this anatomical variation in the expanding library of splenic artery variations, surgeons and their collaborative healthcare teams may broaden their understanding of splenic artery anatomy as they conceptualize new techniques for pancreatomy and splenectomy procedures that consider arterial variations while minimizing surgical complications, operative time, and patient blood loss.
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BACKGROUND: The prevalence of neonatal abstinence syndrome is increasing, but the number and quality of clinical practice guidelines available are unknown. This systematic review aimed to identify, appraise and evaluate clinical practice guidelines for neonatal abstinence syndrome. METHODS: A systematic search of databases and the grey literature was conducted between 1 June and 1 July 2022. Full-text guidelines published by national or state-wide institutions were included. The recommendations from each guideline were extracted. The AGREE-II instrument was used to assess guideline quality. Sufficient-quality scores were defined as >60 and good-quality scores were >80 for each domain of AGREE-II. RESULTS: A total of 1703 records were identified, and 22 guidelines from the United States, Australia, Canada and the United Kingdom, published between 2012 to 2021, were included. The quality scores were low, with median scores of 37/100 for stakeholder involvement, 33/100 for methodology, 34/100 for applicability and 0 for editorial independence. Scope and purpose scored 72/100, and presentation scored 85/100. Sixteen (73%) guidelines did not meet the cut-offs for clinical use. CONCLUSION: Many guidelines were of insufficient quality to guide clinical practice for neonatal abstinence syndrome. This emphasises the need for high-quality studies to inform clinical practice guidelines, improve care and reduce the risk of poor outcomes in these high-risk infants.
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Suicidal thoughts and behaviors (STB) and emergency department (ED) utilization are prevalent in autistic youth. The current study surveyed clinicians in a pediatric psychiatric ED to examine differences in attitudes on suicide-related care for autistic and non-autistic patient populations. While clinicians rated addressing STB in ASD as important and adaptations to care as necessary, less than half identified ASD as a suicide risk factor and confidence ratings were significantly lower for autistic patients. Previous ASD training predicted confidence and accounted for approximately 25% of the variance in confidence scores. Findings highlight the urgency to develop and disseminate ED clinician training, and address the lack of validated assessment tools, adapted suicide prevention practices, and evidence-based treatments for STB in autistic youth.
Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Suicídio , Criança , Humanos , Adolescente , Transtorno do Espectro Autista/psicologia , Ideação Suicida , Prevenção do Suicídio , Transtorno Autístico/diagnóstico , Transtorno Autístico/terapia , Transtorno Autístico/psicologia , Serviço Hospitalar de EmergênciaRESUMO
LAY ABSTRACT: Autistic children and adolescents experience high rates of co-occurring mental health conditions, including depression and suicidality, which are frequently identified by stakeholders as treatment priorities. Unfortunately, accessing community-based mental health care is often difficult for autistic youth and their families. The first obstacle families confront is finding a provider that offers mental health treatment to autistic youth within the many service systems involved in supporting the autism community. The mental health and developmental disability systems are two of the most commonly accessed, and previous work has shown there is often confusion over which of these systems is responsible for providing mental health care to autistic individuals. In this study, we conducted a telephone survey to determine the availability of outpatient mental health services for autistic youth with depressive symptoms or suicidal thoughts or behaviors in New York City across the state's mental health and developmental disability systems. Results showed that while a greater percentage of clinics in the mental health system compared with in the developmental disability system offered outpatient mental health services to autistic youth (47.1% vs 25.0%), many more did not offer care to autistic youth and there were very few options overall. Therefore, it is important that changes to policy are made to increase the availability of services and that mental health care providers' knowledge and confidence in working with autistic youth are improved.
Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Serviços de Saúde Mental , Criança , Humanos , Adolescente , Transtorno Autístico/terapia , Transtorno Autístico/psicologia , Cidade de Nova Iorque , Deficiências do Desenvolvimento , Transtorno do Espectro Autista/terapiaRESUMO
This article explores the ways East Asian American (EAA) children and adolescents have experienced disparities in the United States throughout the COVID-19 pandemic. The history of racism toward Asian American and Pacific Islanders (AAPI) and the complexities of acculturation are reflected through this contemporary lens. Traditional East Asian (EA) values were disrupted during this period. Implications for children and families are discussed. Persistent underlying xenophobia and racism, such as the model minority myth or perpetual foreigner stereotype, rose to new prominence, furthering emotional distress in EA and EAA youths beyond those already experienced universally by AAPI families during the pandemic.
Assuntos
COVID-19 , Pandemias , Aculturação , Adolescente , Asiático/psicologia , Criança , Humanos , Havaiano Nativo ou Outro Ilhéu do Pacífico , Estados UnidosRESUMO
Heat generation during the Kirschner wire (K-wire) insertion process, under either unidirectional or oscillatory drilling mode, places bone at risk of thermal osteonecrosis which can lead to infection. There is a lack of quantitative understanding of the heat generation difference between the two drilling modes and knowledge of optimal thrust force level under each mode is missing. The goal of this study is to investigate the effects of drilling modes and thrust force levels on the bone drilling outcomes. Controlled machine-based constant thrust force K-wire insertion experiments were conducted with key process parameters monitored and compared quantitatively. Statistical analysis showed that the oscillatory mode consumed 2.6 times more electricity than the unidirectional mode but generated 53% less thermal energy and 23% lower peak temperature. However, the oscillation also led to 18% higher peak torque in the transient drilling stage and 23% shallower drilling depth. The optimal choice of the drilling mode depends on specific surgical needs to minimize bone damage (control of peak temperature vs. exposure time and torque control). Heat generation was dominated by the torque and corresponding rotational power under both modes. To minimize the bone temperature while keeping high drilling speed efficiency, a moderate thrust force is preferred under the unidirectional mode to balance between feed force and compressed debris resistance. For oscillatory mode, a small thrust force to keep the K-wire engaged with the bone is optimal.