RESUMO
Animals must integrate sensory cues with their current behavioral context to generate a suitable response. How this integration occurs is poorly understood. Previously, we developed high-throughput methods to probe neural activity in populations of Caenorhabditis elegans and discovered that the animal's mechanosensory processing is rapidly modulated by the animal's locomotion. Specifically, we found that when the worm turns it suppresses its mechanosensory-evoked reversal response. Here, we report that C. elegans use inhibitory feedback from turning-associated neurons to provide this rapid modulation of mechanosensory processing. By performing high-throughput optogenetic perturbations triggered on behavior, we show that turning-associated neurons SAA, RIV, and/or SMB suppress mechanosensory-evoked reversals during turns. We find that activation of the gentle-touch mechanosensory neurons or of any of the interneurons AIZ, RIM, AIB, and AVE during a turn is less likely to evoke a reversal than activation during forward movement. Inhibiting neurons SAA, RIV, and SMB during a turn restores the likelihood with which mechanosensory activation evokes reversals. Separately, activation of premotor interneuron AVA evokes reversals regardless of whether the animal is turning or moving forward. We therefore propose that inhibitory signals from SAA, RIV, and/or SMB gate mechanosensory signals upstream of neuron AVA. We conclude that C. elegans rely on inhibitory feedback from the motor circuit to modulate its response to sensory stimuli on fast timescales. This need for motor signals in sensory processing may explain the ubiquity in many organisms of motor-related neural activity patterns seen across the brain, including in sensory processing areas.
Assuntos
Caenorhabditis elegans , Neurônios , Animais , Caenorhabditis elegans/fisiologia , Retroalimentação , Neurônios/fisiologia , Interneurônios/fisiologia , Locomoção/fisiologiaRESUMO
MOTIVATION: The current paradigm of deep learning models for the joint representation of molecules and text primarily relies on 1D or 2D molecular formats, neglecting significant 3D structural information that offers valuable physical insight. This narrow focus inhibits the models' versatility and adaptability across a wide range of modalities. Conversely, the limited research focusing on explicit 3D representation tends to overlook textual data within the biomedical domain. RESULTS: We present a unified pre-trained language model, MolLM, that concurrently captures 2D and 3D molecular information alongside biomedical text. MolLM consists of a text Transformer encoder and a molecular Transformer encoder, designed to encode both 2D and 3D molecular structures. To support MolLM's self-supervised pre-training, we constructed 160K molecule-text pairings. Employing contrastive learning as a supervisory signal for learning, MolLM demonstrates robust molecular representation capabilities across four downstream tasks, including cross-modal molecule and text matching, property prediction, captioning, and text-prompted molecular editing. Through ablation, we demonstrate that the inclusion of explicit 3D representations improves performance in these downstream tasks. AVAILABILITY AND IMPLEMENTATION: Our code, data, pre-trained model weights, and examples of using our model are all available at https://github.com/gersteinlab/MolLM. In particular, we provide Jupyter Notebooks offering step-by-step guidance on how to use MolLM to extract embeddings for both molecules and text.
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Processamento de Linguagem Natural , Aprendizado Profundo , Biologia Computacional/métodosRESUMO
Here we report the design of a general, redox-switchable organophosphorus alkyl radical trap that enables the synthesis of a broad range of C(sp3)-P(V) modalities. This "plug-and-play" approach relies upon in situ activation of alcohols and OâP(R2)H motifs, two broadly available and inexpensive sources of molecular complexity. The mild, photocatalytic deoxygenative strategy described herein allows for the direct conversion of sugars, nucleosides, and complex pharmaceutical architectures to their organophosphorus analogs. This includes the facile incorporation of medicinally relevant phosphonate ester prodrugs.
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BACKGROUND AND AIMS: HCC risk in chronic hepatitis B (CHB) is higher in the indeterminate phase compared with the inactive phase. However, it is unclear if antiviral therapy reduces HCC risk in this population. We aimed to evaluate the association between antiviral therapy and HCC risk in the indeterminate phase. APPROACH AND RESULTS: We analyzed 855 adult (59% male), treatment-naïve patients with CHB infection without advanced fibrosis in the indeterminate phase at 14 centers (USA, Europe, and Asia). Inverse probability of treatment weighting (IPTW) was used to balance the treated (n = 405) and untreated (n = 450) groups. The primary outcome was HCC development. The mean age was 46±13 years, the median alanine transaminase was 38 (interquartile range, 24-52) U/L, the mean HBV DNA was 4.5±2.1 log 10 IU/mL, and 20% were HBeAg positive. The 2 groups were similar after IPTW. After IPTW (n = 819), the 5-, 10-, and 15-year cumulative HCC incidence was 3%, 4%, and 9% among treated patients (n = 394) versus 3%, 15%, and 19%, among untreated patients (n = 425), respectively ( p = 0.02), with consistent findings in subgroup analyses for age >35 years, males, HBeAg positive, HBV DNA>1000 IU/mL, and alanine transaminaseAssuntos
Carcinoma Hepatocelular
, Hepatite B Crônica
, Hepatite B
, Neoplasias Hepáticas
, Adulto
, Humanos
, Masculino
, Pessoa de Meia-Idade
, Feminino
, Carcinoma Hepatocelular/epidemiologia
, Carcinoma Hepatocelular/etiologia
, Carcinoma Hepatocelular/prevenção & controle
, Hepatite B Crônica/complicações
, Hepatite B Crônica/tratamento farmacológico
, Hepatite B Crônica/epidemiologia
, Neoplasias Hepáticas/epidemiologia
, Neoplasias Hepáticas/etiologia
, Neoplasias Hepáticas/prevenção & controle
, Alanina Transaminase
, DNA Viral
, Antígenos E da Hepatite B
, Antivirais/uso terapêutico
, Hepatite B/complicações
, Vírus da Hepatite B/genética
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PURPOSE: To report normative stiffness parameters obtained using shear wave elastography in dorsiflexion from the Achilles tendons in asymptomatic professional ballet dancers and compare them with college-level athletes. METHODS: An Institutional Review Board (IRB)-approved study consists of 28 professional ballet dancers and 64 asymptomatic collegiate athletes. The athletes were further subdivided into runner and non-runner disciplines. Shear wave elastography (SWE) measurements were made in maximum ankle dorsiflexion position. RESULTS AND DISCUSSION: Forty-eight (52%) males and 44 (48%) females were examined with an overall mean age of 22.2 (± 3.8 years). There were no significant SWE differences between dominant and non-dominant legs in both groups and comparing spin vs. non-spin leg of ballet dancers (p > 0.05). Ballet dancers had significantly higher short-axis velocity values than runners and non-runners (2.34 m/s increase and 2.79 m/s increase, respectively, p < 0.001). Long-axis velocity was significantly higher in ballet dancers compared to non-runners (by 0.80 m/s, p < 0.001), but was not different between ballet dancers and runners (p > 0.05). Short-axis modulus was significantly higher in dancers compared to runners and non-runners (by 135.2 kPa and 159.2 kPa, respectively, p < 0.001). Long-axis modulus (LAM) was not significantly different in ballet dancers when compared to runners. CONCLUSION: Asymptomatic professional ballet dancers exhibit greater short-axis tendon stiffness compared to athletes and greater long-axis tendon stiffness compared to non-runners but similar to runners. The functional benefit from elevated short-axis stiffness in dancers is not clear but may be related to greater axial loading and adaptations of the tendon matrix.
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Tendão do Calcâneo , Atletas , Dança , Técnicas de Imagem por Elasticidade , Humanos , Masculino , Feminino , Técnicas de Imagem por Elasticidade/métodos , Dança/fisiologia , Tendão do Calcâneo/diagnóstico por imagem , Tendão do Calcâneo/fisiologia , Adulto Jovem , AdultoRESUMO
BACKGROUND: Understanding the role of social determinants of health disparities (SDHDs) in surgical outcomes can better prepare providers to improve postoperative care. In this study, we use International Classification of Diseases (ICD) codes to identify SDHDs and investigate the risk of postoperative complication rates among patients undergoing total shoulder arthroplasty (TSA). METHODS: A retrospective cohort analysis was conducted using a national insurance claims database. Using ICD and Current Procedural Terminology (CPT) codes, patients who underwent primary TSA with at least 2 years of follow-up in the database were identified. Patients with a history of SDHDs were identified using appropriate ICD-9 and ICD-10 codes. Patients were grouped in one of 2 cohorts: (1) patients with no history of SDHDs (control) and (2) patients with a history of SDHDs (SDHD group) prior to TSA. The SDHD and control groups were matched 1:1 for comorbidities and demographics prior to conducting multivariable analysis for 90-day medical complications and 2-year surgical complications. RESULTS: After matching, there were 8023 patients in the SDHD group and 8023 patients in the control group. The SDHD group had significantly higher odds for 90-day medical complications including heart failure, cerebrovascular accident, renal failure, deep vein thrombosis, pneumonia, sepsis, and urinary tract infection. Additionally, the SDHD group had significantly higher odds for revision surgery within 2 years following TSA. Patients in the SDHD group also had a significantly longer length of hospital stay following TSA. DISCUSSION: This study highlights the association between SDHDs and postoperative complications following TSA. Quantifying the risk of complications and differences in length of stay for TSA patients with a history of SDHDs is important in determining value-based payment models and risk stratifying to optimize patient care.
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Artroplastia do Ombro , Humanos , Estudos Retrospectivos , Artroplastia do Ombro/efeitos adversos , Determinantes Sociais da Saúde , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , ComorbidadeRESUMO
PURPOSE OF REVIEW: Cardiovascular (CV) risk factors such as dyslipidemia, hypertension, diabetes, and obesity are associated with an increased risk for CV events in adults. Noninvasive measures of vascular health are associated with these CV events and can potentially help risk stratify children with CV risk factors. The purpose of this review is to summarize recent literature regarding vascular health in children with cardiovascular risk factors. RECENT FINDINGS: Adverse changes in pulse wave velocity, pulse wave analysis, arterial distensibility, and carotid intima-media thickness are seen in children with CV risk factors supporting potential utility in risk stratification. Assessing vascular health in children can be challenging due to growth-related changes in vasculature, multiple assessment modalities, and differences in normative data. Vascular health assessment in children with cardiovascular risk factors can be a valuable tool for risk stratification and help identify opportunities for early intervention. Future areas of research include increasing normative data, improving conversion of data between different modalities, and increasing longitudinal studies in children linking childhood risk factors to adult CV outcomes.
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Aterosclerose , Doenças Cardiovasculares , Rigidez Vascular , Adulto , Criança , Humanos , Adolescente , Espessura Intima-Media Carotídea , Análise de Onda de Pulso/métodos , Medição de Risco/métodos , Aterosclerose/diagnóstico por imagem , Fatores de Risco , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologiaRESUMO
BACKGROUND & AIMS: Due to ageing of the global population, hepatocellular carcinoma (HCC) is increasingly common among elderly patients, but outcomes after curative hepatic resection are unclear. Using a metanalytic approach, we aimed to estimate overall survival (OS), recurrence free survival (RFS) and complication rates in elderly HCC patients undergoing resection. METHODS: We searched PubMed, Embase, and Cochrane databases from inception to Nov 10, 2020 for studies reporting outcomes in elderly (age ≥ 65 years) patients with HCC undergoing curative surgical resection. Pooled estimates were generated using a random-effects model. RESULTS: We screened 8,598 articles and included 42 studies (7,778 elderly patients). The mean age was 74.45 years (95% CI 72.89-76.02), 75.54% were male (95% CI 72.53-78.32) and 66.73% had cirrhosis (95% CI 43.93-83.96). The mean tumor size was 5.50 cm (95% CI 4.71-6.29) and 16.01% had multiple tumors (95% CI 10.74-23.19). The 1-year (86.02% versus 86.66%, p=0.84) and 5-year OS (51.60% versus 53.78%) between non-elderly versus elderly patients were similar. Likewise, there were no differences in the 1-year (67.32% versus 73.26%, p=0.11) and 5-year RFS (31.57% versus 30.25%, p=0.67) in non-elderly versus elderly patients. There was a higher rate of minor complications (21.95% versus 13.71%, p=0.03) among elderly patients compared with non-elderly patients, but no difference in major complications (p=0.43) Conclusion: This data shows that overall survival, recurrence and major complications after liver resection for HCC are comparable between elderly and non-elderly patients, and may inform clinical management of HCC in this population.
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PURPOSE: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed among individuals <14 years of age. The disease and its treatments are associated with negative side effects, including pain, which is both prevalent and distressing. Little is known about pain experiences in this population, which has slowed efforts to identify strategies to mitigate and cope with this adverse effect. This study sought to explore youth's and their caregiver's experiences with, and perspectives of, pain in the context of pediatric cancer treatment. METHODS: Youth and one of their caregivers were recruited through (omitted for peer review). Following completion of a demographic survey, youth and one of their caregivers were interviewed separately using a semi-structured, one-on-one interview guide. Demographic information was analyzed with descriptive statistics, and interviews were transcribed verbatim and analyzed using reflexive thematic analysis. RESULTS: Youth (n = 19; Mage = 15.3 years) and caregiver (n = 19; Mage = 45.4 years) perspectives informed 4 themes: (1) my pain experience is nuanced, multidimensional, and is changing over time; (2) the cancer experience has changed the way I experience and respond to pain; (3) I used strategies to manage pain, and not all of them worked; and (4) my pain experience was influenced by people around me. CONCLUSIONS: Findings extend prior work, suggesting that pain is common, distressing, multidimensional, and influenced by social context. Results highlight the number of ways in which youth and their caregivers attempt to manage their pain and factors influencing pain experiences. Greater efforts are needed to address pain during cancer treatment and survivorship.
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Cuidadores , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Criança , Adolescente , Pessoa de Meia-Idade , Dor/etiologia , Meio Social , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Pesquisa QualitativaRESUMO
BACKGROUND: Incidence and treatment disparities for cutaneous melanomas have been documented among racial and sociodemographic minorities. However, the association between treatment types, race, and socioeconomic status remains unknown. OBJECTIVE: To characterize treatment differences for head and neck melanoma in situ (MIS) and lentigo maligna (LM) based on race and sociodemographic variables. MATERIALS AND METHODS: A population-based retrospective cohort study of the Surveillance Epidemiology and End Results database (1998-2016) was performed. Univariate and multivariate logistic regression modeling evaluated the association of race and US census-reported sociodemographic factors with Mohs micrographic surgery (MMS) utilization. RESULTS: A total of 76,328 adult patients with head and neck MIS/LM were included. MMS accounted for 11.8% of total cases, with increased utilization observed since 1998-2002. Compared with areas with greater percentages of individuals completing high school (first quartile), patients living in the second (Odds ratio [OR] 0.71; 95% confidence interval [CI] 0.64-0.80; p < .001), third (OR 0.74; 95% CI 0.63-0.86; p < .001), and fourth quartiles (OR 0.44; 95% CI 0.35-0.55; p < .001) were less likely to undergo MMS for their MIS/LM. CONCLUSION: Educational efforts and awareness can bridge the knowledge gaps of appropriate treatment in patients with head and neck MIS/LM.
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Sarda Melanótica de Hutchinson , Melanoma , Neoplasias Cutâneas , Adulto , Humanos , Estudos Retrospectivos , Melanoma/epidemiologia , Melanoma/cirurgia , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/cirurgia , Sarda Melanótica de Hutchinson/cirurgia , Escolaridade , Cirurgia de Mohs/métodos , Melanoma Maligno CutâneoRESUMO
Degenerative knee osteoarthritis is a progressive debilitating condition that affects millions of people worldwide. Most patients experience limited range of motion, inflammation, swelling, and pain. Management options can lead to short- and long-term pain relief. Short-term pain relief usually involves conservative medical treatments such as NSAIDs, weight loss, physical therapy, and corticosteroid injections. The ultimate long-term pain relief treatment method involves total knee arthroplasty. The treatment algorithm for knee OA also includes managing pain until a patient is eligible for arthroplasty. Furthermore, about 20% of patients experience chronic pain after TKA without complications such as hardware loosening and infection with limited treatment options. The pathophysiology of this is unknown. Cooled radiofrequency ablation has been demonstrated to be clinically effective by disrupting the integrity of deep sensory nerves and hence interfering with transmission of pain signal. The analgesic effect after c-RFA has been reported up to 24 months. Here, we present an overview of the clinical application of cooled radiofrequency ablation and a summary of its effectiveness in the treatment of pain in the setting of advanced OA and symptomatic TKA.
Assuntos
Artroplastia do Joelho , Dor Crônica , Osteoartrite do Joelho , Ablação por Radiofrequência , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Ablação por Radiofrequência/efeitos adversos , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/cirurgia , Dor Crônica/etiologia , Resultado do TratamentoRESUMO
BACKGROUND: The acromion morphology in a shoulder with posterior instability differs from that of a shoulder without glenohumeral instability. Specifically, the acromion with a flatter sagittal tilt, greater posterior acromial height, and less posterior coverage is associated with posterior instability. However, the association between acromion morphology and glenoid bone loss (GBL) in the setting of posterior glenohumeral instability has not previously been investigated. The purpose of this study was to determine whether acromial morphology influences the extent or pattern of posterior GBL in a cohort of patients with posterior glenohumeral instability. METHODS: This multicenter retrospective study identified 89 shoulders with unidirectional posterior glenohumeral instability. Total area GBL was measured using the best-fit circle method on magnetic resonance imaging (MRI). Shoulders were divided into 3 groups: (1) no GBL (n = 30), (2) GBL 0%-13.5% (n = 45), or (3) GBL ≥13.5% (n = 14). Acromion measurements were performed on MRI and included acromial tilt, posterior acromial height, anterior acromial coverage, and posterior acromial coverage. RESULTS: Patients without GBL had a steeper acromial tilt (58.5° ± 1.4°) compared with those with 0%-13.5% GBL (64.3° ± 1.5°) or GBL ≥13.5% (67.7° ± 1.8°) (P = .004). Patients without GBL also had greater posterior coverage (65.4° ± 1.7°) compared with those with GBL (60.3° ± 1.4°) (P = .015). Posterior acromion height was not significantly different among groups. CONCLUSION: The results demonstrate that an acromion with a flatter sagittal tilt and less posterior coverage is associated with GBL in the setting of posterior glenohumeral instability. This is important to consider as posterior GBL has been identified as a risk factor for failure of posterior soft tissue-stabilizing procedures.
Assuntos
Doenças Ósseas Metabólicas , Instabilidade Articular , Articulação do Ombro , Humanos , Acrômio/diagnóstico por imagem , Acrômio/patologia , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/patologia , Estudos Retrospectivos , Instabilidade Articular/diagnóstico por imagem , Instabilidade Articular/patologia , Tomografia Computadorizada por Raios XRESUMO
Vismodegib is used in patients suffering from advanced basal cell carcinoma (BCC), but 100% of the patients taking it report dysgeusia and 50% discontinue the treatment. Treatment with neurotrophic factors can stimulate neuronal survival and functional improvement in injured organs. Here, we analysed novel transgenic mouse lines in which brain-derived neurotrophic factor (BDNF) is overexpressed in taste buds, to examine whether higher levels of BDNF would reduce or prevent negative side effects of vismodegib in the taste system. BDNF plays crucial roles for development, target innervation, and survival of gustatory neurons and taste buds. The behavioural test in this study showed that vehicle-treated wild-type mice prefered 10 mM sucrose over water, whereas vismodegib treatment in wild-type mice caused total taste loss. Gustducin-BDNF mice had a significantly increased preference for low concentration of sucrose solution over water compared to wild-type mice, and most importantly the transgenic mice were able to detect low concentrations of sucrose following vismodegib treatment. We evaluated taste cell morphology, identity, innervation and proliferation using immunohistochemistry. All drug-treated mice exhibited deficits, but because of a possible functional upcycled priming of the peripheral gustatory system, GB mice demonstrated better morphological preservation of the peripheral gustatory system. Our study indicates that overexpression of BDNF in taste buds plays a role in preventing degeneration of taste buds. Counteracting the negative side effects of vismodegib treatment might improve compliance and achieve better outcome in patients suffering from advanced BCC.
Assuntos
Ageusia , Antineoplásicos , Fator Neurotrófico Derivado do Encéfalo , Papilas Gustativas , Ageusia/induzido quimicamente , Ageusia/metabolismo , Anilidas , Animais , Antineoplásicos/efeitos adversos , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Camundongos , Camundongos Transgênicos , Piridinas , Sacarose , Paladar/fisiologia , Papilas Gustativas/fisiopatologia , Língua/inervação , Língua/fisiopatologiaRESUMO
OBJECTIVE: Pulse wave analysis estimates arterial wave reflections relating to left ventricular dysfunction and cardiovascular event risk in adults. Forward and backward waves (Pf and Pb) may improve risk stratification for cardiovascular events. Data in youth are lacking. We hypothesized that a significant difference in wave reflections would be identified in young subjects with adverse cardiovascular risk factors. Approach and Results: Vital signs and labs were obtained in 551 patients aged 10 to 24 years who were lean (L=199), obese (O=173), or had type 2 diabetes (T=179). Wave separation was performed. Differences in cardiovascular risk factors and wave reflections were assessed using ANOVA. General linear models were constructed to elucidate independent predictors of wave reflections. O and T subjects had an adverse cardiovascular risk profile versus L. O and T subjects had higher Pf and Pb versus L (P≤0.05). When adjusted for adiposity and other cardiovascular risk factors, reflection magnitude increased from L to O to T with higher T versus L values (P≤0.05) and near-significant O versus L values (P=0.06). Adiposity and blood pressure were major determinants of wave reflections. Pb influenced log left ventricular mass index, log E/e', and log composite carotid intima-media thickness. CONCLUSIONS: Adolescents and young adults with obesity and type 2 diabetes have altered forward and backward wave reflections versus lean controls related to adiposity, BP, and insulin levels. These parameters may help risk stratify patients with adverse cardiovascular risk factors.
Assuntos
Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/complicações , Obesidade Infantil/complicações , Análise de Onda de Pulso , Rigidez Vascular , Adiposidade , Adolescente , Fatores Etários , Pressão Sanguínea , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/fisiopatologia , Criança , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Hipoglicemiantes/sangue , Hipoglicemiantes/uso terapêutico , Insulina/sangue , Insulina/uso terapêutico , Masculino , Obesidade Infantil/diagnóstico , Obesidade Infantil/fisiopatologia , Valor Preditivo dos Testes , Medição de Risco , Adulto JovemRESUMO
BACKGROUND: The interplay of host, agent, and environment implicated in traumatic brain injury (TBI) events is difficult to account for in hypothesis-driven research. Data-driven analysis of injury data can enable insight into injury events in novel ways. This research dissected complex and multidimensional data at the time of the TBI event by exploiting data mining and information visualization methods. METHODS: We drew upon population-based decade-long health administrative data collected through the routine operation of the publicly funded health system in Ontario, Canada. We applied a computational approach to categorize health records of 235,003 patients with TBI versus the same number of reference patients without TBI, individually matched based on sex, age, place of residence, and neighbourhood income quantile. We adopted the basic concepts of the Haddon Matrix (host, agent, environment) to organize emerging factors significantly related to TBI versus non-TBI events. To explore sex differences, the data of male and female patients with TBI were plotted on heatmaps and clustered using hierarchical clustering algorithms. RESULTS: Based on detected similarities, the computational technique yielded 34 factors on which individual TBI-event codes were loaded, allowing observation of a set of definable patterns within the host, the agent, and the environment. Differences in the patterns of host, agent and environment were found between male and female patients with TBI, which are currently not identified based on data from injury surveillance databases. The results were internally validated. CONCLUSIONS: The study outlines novel areas for research relevant to TBI and offers insight into how computational and visual techniques can be applied to advance the understanding of TBI event. Results highlight unique aspects of sex differences of the host and agent at the injury event, as well as differences in exposure to adverse social and environmental circumstances, which can be a function of gender, aiding in future studies of injury prevention and gender-transformative care.
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Lesões Encefálicas Traumáticas , Visualização de Dados , Lesões Encefálicas Traumáticas/terapia , Mineração de Dados , Feminino , Humanos , Masculino , Ontário/epidemiologiaRESUMO
OBJECTIVE: To evaluate group differences in social adjustment in survivors of pediatric acute lymphoblastic leukemia (ALL) compared to survivor siblings and controls; identify disease-related predictors of social adjustment in survivors; and explore whether executive functioning explained differences in social adjustment across groups and between disease-related predictors. METHODS: Survivors of pediatric ALL (n = 38, average age at diagnosis = 4.27 years [SD = 1.97]; average time off treatment = 4.83 years [SD = 1.52]), one sibling (if available, n = 20), and one parent from each family were recruited from a long-term survivor clinic. Healthy age- and sex-matched controls (n = 38) and one parent from each family were recruited from the community. Parents completed the Behavioral Assessment System for Children, Parent Rating Scale (BASC-3) Social Withdrawal subscale as a measure of social adjustment, and the Behavior Rating Inventory of Executive Functions (BRIEF-2) as a measure of executive function for each of their children. Multilevel modeling and mediation analysis were used to achieve the study aims. RESULTS: Parents reported that survivors had significantly worse social adjustment compared to controls (b = 6.34, p = .004), but not survivor siblings. Among survivors, greater time off treatment (b = 2.06, p = .058) and poorer executive functioning (b = 0.42, p = .006) were associated with worse social adjustment. Executive function did not mediate differences in social withdrawal between survivors and controls or the relationship between time off treatment and social withdrawal among survivors. CONCLUSIONS: Survivors of pediatric ALL presenting to follow-up programs should be screened for difficulties with social adjustment. Future research should examine treatment- and nontreatment-related factors contributing to poorer social outcomes.
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Irradiação Craniana , Leucemia-Linfoma Linfoblástico de Células Precursoras , Ajustamento Social , Criança , Humanos , Pais , SobreviventesRESUMO
INTRODUCTION: Chronic hepatitis B (CHB) patients with metabolic syndrome (MetS) may present increased risk of liver-related outcomes (LROs), but prior studies were limited by small sample size and/or conflicting results. Using a systematic review and meta-analytic approach, we aimed to determine the association between MetS and LROs in CHB. METHODS: Two researchers independently screened studies from the PubMed, Embase, Web of Science, and Cochrane Library databases from inception to January 21, 2020, and extracted the data. Estimates were pooled using a random-effects model. RESULTS: We screened 2,228 articles and included 10 eligible studies (18,360 CHB patients, 2,557 with MetS). MetS was significantly associated with LROs overall (odds ratio = 2.45, 95% confidence interval = 1.39-4.32) but not the individual LRO components but subgroup analyses were limited by small study numbers. DISCUSSION/CONCLUSION: MetS is associated with almost 3-folds higher risk of LROs in CHB and should be considered in management decisions. However, additional studies are needed.
Assuntos
Hepatite B Crônica , Síndrome Metabólica , Humanos , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Hepatite B Crônica/complicações , Razão de ChancesRESUMO
Osteoarthritis (OA) of the shoulder and hip is a leading cause of physical disability and mental distress. Traditional nonsurgical management alone is often unable to completely address the associated chronic joint pain. Moreover, a large number of patients are not eligible for joint replacement surgery owing to comorbidities or cost. Radiofrequency ablation (RFA) of articular sensory nerve fibers can disrupt the transmission of nociceptive signals by neurolysis, thereby providing long-term pain relief. A subtype of RFA, cooled RFA (CRFA), utilizes internally cooled electrodes to generate larger ablative zones compared with standard RFA techniques. Given the complex variable innervation of large joints such as the glenohumeral and hip joints, a larger ablative treatment zone, such as that provided by CRFA, is desired to capture a greater number of afferent nociceptive fibers. The suprascapular, axillary, and lateral pectoral nerve articular sensory branches are targeted during CRFA of the glenohumeral joint. The obturator and femoral nerve articular sensory branches are targeted during CRFA of the hip. CRFA is a promising tool in the interventionalist's arsenal for management of OA-related pain and symptoms, particularly in patients who cannot undergo, have long wait times until, or have persistent pain following joint replacement surgery. An invited commentary by Tomasian is available online. ©RSNA, 2022.
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Dor Crônica , Osteoartrite , Ablação por Radiofrequência , Artralgia , Dor Crônica/etiologia , Dor Crônica/cirurgia , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/cirurgia , Humanos , Ablação por Radiofrequência/métodos , Ombro , Resultado do TratamentoRESUMO
OBJECTIVE: To introduce cooled radiofrequency nerve ablation (C-RFA) as an alternative to managing symptomatically moderate to severe glenohumeral osteoarthritis (OA) in patients who have failed other conservative treatments and who are not surgical candidates or refuse surgery. MATERIAL AND METHODS: This prospective pilot study includes a total of 12 patients experiencing chronic shoulder pain from moderate to severe glenohumeral OA. Patients underwent anesthetic blocks of the axillary, lateral pectoral, and suprascapular nerves to determine candidacy for C-RFA treatment. Adequate response after anesthetic block was over 50% immediate pain relief. Once patients were deemed candidates, they underwent C-RFA of the three nerves 2-3 weeks later. Treatment response was evaluated using the clinically validated American Shoulder and Elbow Surgeons (ASES) score and visual analog scale (VAS) to assess pain, stiffness, and functional activities of daily living. Follow-up outcome scores were collected up to 6 months after C-RFA procedure. RESULTS: Twelve patients underwent C-RFA procedure for shoulder OA. VAS scores significantly improved from 8.8 ± 0.6 to 2.2 ± 0.4 6 months after the C-RFA treatment (p < 0.001). Patient's ASES score results significantly improved in total ASES from 17.2 ± 6.6 to 65.7 ± 5.9 (p < 0.0005). No major complications arose. No patients received re-treatment or underwent shoulder arthroplasty. CONCLUSION: Image-guided axillary, lateral pectoral, and suprascapular nerve C-RFA has minimal complications and is a promising alternative to treat chronic shoulder pain and stiffness from glenohumeral arthritis.
Assuntos
Ablação por Cateter , Osteoartrite , Articulação do Ombro , Atividades Cotidianas , Humanos , Osteoartrite/diagnóstico por imagem , Osteoartrite/cirurgia , Projetos Piloto , Estudos Prospectivos , Ombro/cirurgia , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/cirurgia , Dor de Ombro/diagnóstico por imagem , Dor de Ombro/cirurgia , Resultado do TratamentoRESUMO
OBJECTIVE: To establish the effectiveness of cooled radiofrequency ablation in managing hip pain from osteoarthritis at 6 months after receiving treatment in patients who failed conservative treatments and are not surgical candidates due to comorbidities or unwillingness to undergo arthroplasty surgery by targeting the femoral and obturator branches and assessing the degree of hip pain relief and change of function. MATERIALS AND METHODS: This prospective pilot study includes a total of 11 consecutive patients experiencing persistent chronic hip pain in the setting of advanced osteoarthritis. Patients initially underwent anesthetic blocks of the obturator and femoral nerve branches to determine cooled radiofrequency ablation candidacy. After adequate response to the anesthetic blocks (> 50% immediate pain relief), patients were subjected to the procedures 2-3 weeks later. Treatment response was evaluated utilizing clinically validated questionnaires and visual analog score in order to assess impact on pain severity, stiffness, and functional activities of daily living. Follow-up outcome scores were collected up to 6 months after cooled radiofrequency ablation procedure. RESULTS: A total of 11 hips were treated consecutively between August 2019 and March 2020 (mean patient age 61.4 years; 8 M:3F). The mean total HOOS score improved significantly from baseline at 17.0 ± 6.0 to 52.9 ± 5.4 at a mean of 6.2 months after treatment (p < 0.0001), with significant improvement in mean pain score from 16.1 ± 6.6 to 53.4 ± 7.4 (p < 0.0001) and mean stiffness score from 15.0 ± 8.1 to 53.6 ± 11.0 (p < 0.0001). No major complications were encountered. No patients went on to re-treatment, surgery, or other intervention. CONCLUSION: Image-guided obturator and femoral nerve cooled radiofrequency ablation is effective and safe in treating chronic hip pain/stiffness in the setting of advanced osteoarthritis.