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Diffusion MRI (dMRI) allows for non-invasive investigation of brain tissue microstructure. By fitting a model to the dMRI signal, various quantitative measures can be derived from the data, such as fractional anisotropy, neurite density and axonal radii maps. We investigate the Fisher Information Matrix (FIM) and uncertainty propagation as a generally applicable method for quantifying the parameter uncertainties in linear and non-linear diffusion MRI models. In direct comparison with Markov Chain Monte Carlo (MCMC) sampling, the FIM produces similar uncertainty estimates at much lower computational cost. Using acquired and simulated data, we then list several characteristics that influence the parameter variances, including data complexity and signal-to-noise ratio. For practical purposes we investigate a possible use of uncertainty estimates in decreasing intra-group variance in group statistics by uncertainty-weighted group estimates. This has potential use cases for detection and suppression of imaging artifacts.
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Imagem de Difusão por Ressonância Magnética , Neuritos , Humanos , Incerteza , Imagem de Difusão por Ressonância Magnética/métodos , Cadeias de Markov , AxôniosRESUMO
FIM-1 is an acquired metallo-ß-lactamase identified in a multidrug-resistant Pseudomonas aeruginosa (index strain FI-14/157) of clinical origin isolated in 2007 in Florence, Italy. Here we report on a second case of infection by FIM-1-positive P. aeruginosa (FI-17645), which occurred in 2020 in the same hospital. Both FIM-1-positive strains exhibited resistance to all anti-Pseudomonas antibiotics except colistin and cefiderocol. Comparative genomic characterization revealed that the two FIM-positive strains were closely related [core genome difference, 16 single nucleotide polymorphisms (SNPs)], suggesting a local circulation of similar strains. In the FI-14/157 index strain, the blaFIM-1 gene was associated with an ISCR19-like element that likely contributed to its capture downstream an integron platform inserted aboard a Tn21-like transposon, named Tn7703.1, which was associated with a large integrative and conjugative element (ICE) named ICE7705.1, integrated into an att site located within the 3'-end of tRNAGly CCC gene of the P. aeruginosa chromosome. In strain FI-17645, blaFIM-1 was associated with a closely related ICE, named ICE7705.2, integrated in the same chromosomal site. Similar ICE platforms, lacking the blaFIM-1-containing region, were detected in other ST235 P. aeruginosa strains from different geographic areas, suggesting a common ancestry and underscoring the role of these elements in the dissemination of resistance genes in P. aeruginosa. Sequence database mining revealed two draft P. aeruginosa genomes, one from Italy and one from the USA (both isolated in 2012), including a contig with blaFIM-1, suggesting that this resistance gene could have a broader distribution than originally anticipated.
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Infecções por Pseudomonas , Pseudomonas aeruginosa , beta-Lactamases , Humanos , Antibacterianos/farmacologia , beta-Lactamases/genética , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/isolamento & purificação , Infecções por Pseudomonas/microbiologiaRESUMO
AIMS: This research aims to construct and verify an accurate nomogram for forecasting the 3-, 5-, and 7-year outcomes in pediatric patients afflicted with spinal cord injury (SCI). METHODS: Pediatric patients with SCI from multiple hospitals in China, diagnosed between Jan 2005 and Jan 2020, were incorporated into this research. Half of these patients were arbitrarily chosen for training sets, and the other half were designated for external validation sets. The Cox hazard model was employed to pinpoint potential prognosis determinants related to the American Spinal Injury Association (ASIA) and Functional Independence Assessment (FIM) index. These determinants were then employed to formulate the prognostic nomogram. Subsequently, the bootstrap technique was applied to validate the derived model internally. RESULTS: In total, 224 children with SCI were considered for the final evaluation, having a median monitoring duration of 68.0 months. The predictive nomogram showcased superior differentiation capabilities, yielding a refined C-index of 0.924 (95% CI: 0.883-0.965) for the training cohort and a C-index of 0.863 (95% CI: 0.735-0.933) for the external verification group. Additionally, when applying the aforementioned model to prognostic predictions as classified by the FIM, it demonstrated a high predictive value with a C-index of 0.908 (95% CI: 0.863-0.953). Moreover, the calibration diagrams indicated a consistent match between the projected and genuine ASIA outcomes across both sets. CONCLUSION: The crafted and verified prognostic nomogram emerges as a dependable instrument to foresee the 3-, 5-, and 7-year ASIA and FIM outcomes for children suffering from SCI.
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Nomogramas , Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/diagnóstico , Criança , Feminino , Masculino , Prognóstico , Adolescente , Pré-Escolar , China/epidemiologiaRESUMO
PURPOSE: Sunken Skin Flap Syndrome (SSFS) is an uncommon, delayed complication after craniectomy characterized by a functional plateau or decline with variable neurologic symptoms, improving after cranioplasty. SSFS negatively impacts the rehabilitation course, with subjective reports of functional improvement after cranioplasty. However, no studies have assessed the impact of cranioplasty on functional recovery rate. This case series aims to analyze SSFS manifestations and management while awaiting cranioplasty. Also, to assess the role of cranioplasty on rehabilitation outcomes and recovery rate in SSFS patients. METHODS: Four patients were identified with SSFS in inpatient rehabilitation. Each patient had unique clinical manifestations, with multiple strategies used for symptomatic control. Patients spent an average of 23 days in rehabilitation with SSFS symptoms before cranioplasty. After cranioplasty, all patients had SSFS symptom resolution. Comparing change in functional independence measure (FIM) scores and FIM efficiency pre-and post-cranioplasty rehabilitation course, a mean improvement of 23 and 0.72 occurred after cranioplasty, respectively. CONCLUSION: A diagnosis of SSFS should be considered in craniectomy patients exhibiting functional decline or plateau with associated neurological symptoms. This study suggests that FIM and FIM efficiency increases in SSFS patients after cranioplasty, supporting prompt cranioplasty to improve functional outcomes and minimize rehabilitation delays.
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Craniectomia Descompressiva , Humanos , Craniectomia Descompressiva/efeitos adversos , Retalhos Cirúrgicos/efeitos adversos , Retalhos Cirúrgicos/cirurgia , Crânio/cirurgia , Resultado do Tratamento , Recuperação de Função Fisiológica , Complicações Pós-Operatórias/etiologiaRESUMO
As other European countries, France is experiencing a resurgence of pertussis in 2024. Between 1 January and 31 May 2024, 5,616 (24.9%) positive Bordetella pertussis qPCR tests were identified, following a 3-year period of almost null incidence. Of 67 cultured and whole genome sequenced B. pertussis isolates, 66 produced pertactin and 56 produced FIM2, in contrast to pre-COVID-19 years. One isolate of genotype Bp-AgST4 was resistant to macrolides. Pertussis resurgence may favour isolates that produce FIM2 and pertactin.
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Antibacterianos , Bordetella pertussis , Macrolídeos , Coqueluche , Bordetella pertussis/genética , Bordetella pertussis/isolamento & purificação , Bordetella pertussis/efeitos dos fármacos , Humanos , França/epidemiologia , Macrolídeos/farmacologia , Coqueluche/epidemiologia , Coqueluche/microbiologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Proteínas da Membrana Bacteriana Externa/genética , Sequenciamento Completo do Genoma , Fatores de Virulência de Bordetella/genética , Genótipo , Adulto , Criança , Incidência , Pré-EscolarRESUMO
BACKGROUND AND OBJECTIVES: It is well known that more than 40% of patients in the convalescent rehabilitation settings suffer from malnutrition, and that appropriate nutrition management can improve rehabilitation outcomes. METHODS AND STUDY DESIGN: In this study, we used a change in motor score of Functional Independent Measure (FIM-M) of convalescent rehabilitation to investigate whether daily energy intake could influence the rehabilitation outcomes. Of the 217 patients hospitalized in our convalescent rehabilitation ward (CRW) between September 2016 and February 2017, 162 met the eligibility criteria for this study. RESULTS: For a 25 kcal/ ideal body weight (IBW)/day cutoff point, 76 patients consumed more than 25 kcal/IBW/day of energy (H-E group), and 86 patients consumed up to 25 kcal/IBW/day of energy (L-E group). Patients in the L-E group had poorer nutritional status than those in the H-E group at CRW admission. Moreover, patients in the L-E group lost some body weight (BW) during hospitalization, whereas patients in the H-E group gained some BW. Furthermore, the FIM-M efficiency in the L-E group was significantly lower than that in the H-E group. CONCLUSIONS: We concluded that appropriate nutritional management given to rehabilitation patients for adequate energy intake to maintain or gain their BW could maximize the outcome of convalescent rehabilitation.
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Desnutrição , Estado Nutricional , Humanos , Recuperação de Função Fisiológica , Atividades Cotidianas , Ingestão de EnergiaRESUMO
Congenital anomalies of the kidney and urinary tract (CAKUT) constitute one of the most frequent birth defects and represent the most common cause of chronic kidney disease in the first three decades of life. Despite the discovery of dozens of monogenic causes of CAKUT, most pathogenic pathways remain elusive. We performed whole-exome sequencing (WES) in 551 individuals with CAKUT and identified a heterozygous de novo stop-gain variant in ZMYM2 in two different families with CAKUT. Through collaboration, we identified in total 14 different heterozygous loss-of-function mutations in ZMYM2 in 15 unrelated families. Most mutations occurred de novo, indicating possible interference with reproductive function. Human disease features are replicated in X. tropicalis larvae with morpholino knockdowns, in which expression of truncated ZMYM2 proteins, based on individual mutations, failed to rescue renal and craniofacial defects. Moreover, heterozygous Zmym2-deficient mice recapitulated features of CAKUT with high penetrance. The ZMYM2 protein is a component of a transcriptional corepressor complex recently linked to the silencing of developmentally regulated endogenous retrovirus elements. Using protein-protein interaction assays, we show that ZMYM2 interacts with additional epigenetic silencing complexes, as well as confirming that it binds to FOXP1, a transcription factor that has also been linked to CAKUT. In summary, our findings establish that loss-of-function mutations of ZMYM2, and potentially that of other proteins in its interactome, as causes of human CAKUT, offering new routes for studying the pathogenesis of the disorder.
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Proteínas de Ligação a DNA/genética , Epigênese Genética , Fatores de Transcrição Forkhead/genética , Mutação , Proteínas Repressoras/genética , Fatores de Transcrição/genética , Sistema Urinário/metabolismo , Anormalidades Urogenitais/genética , Proteínas de Anfíbios/antagonistas & inibidores , Proteínas de Anfíbios/genética , Proteínas de Anfíbios/metabolismo , Animais , Estudos de Casos e Controles , Criança , Pré-Escolar , Proteínas de Ligação a DNA/metabolismo , Família , Feminino , Fatores de Transcrição Forkhead/metabolismo , Heterozigoto , Humanos , Lactente , Larva/genética , Larva/crescimento & desenvolvimento , Larva/metabolismo , Masculino , Camundongos , Camundongos Knockout , Morfolinos/genética , Morfolinos/metabolismo , Linhagem , Ligação Proteica , Proteínas Repressoras/metabolismo , Fatores de Transcrição/metabolismo , Sistema Urinário/anormalidades , Anormalidades Urogenitais/metabolismo , Anormalidades Urogenitais/patologia , Sequenciamento do Exoma , XenopusRESUMO
PURPOSE: Despite the growing understanding of the carcinogenesis of pelvic high-grade serous carcinoma (HGSC) of the ovary and peritoneum and its precursor lesion serous tubal intraepithelial carcinoma (STIC), evidence-based proven recommendations on the clinical management of patients with STIC are lacking so far. METHODS: A questionnaire containing 21 questions was developed to explore the clinical experience with patients with the diagnosis of STICs and the diagnostic, surgical and histopathological approaches in Germany. Overall, 540 clinical heads of department in all German gynaecological centres were asked to participate. RESULTS: 131 questionnaires (response rate 24.3%) were included in this survey. 45.8% of the respondents had treated one to three STIC patients during their career. 75.6% of the respondents performed opportunistic bilateral salpingectomies during other gynaecological surgeries. Most of the participants (31.3%) started with the SEE-FIM (Sectioning and Extensively Examining the FIMbria) protocol in 2014. It was requested by 39.7% centres for prophylactic salpingectomies, by 13.7% for both prophylactic and opportunistic salpingectomies and by 22.1% for neither of both. 38.2%, 1.5% and 24.4% of the participants would use the laparoscopic, transverse and midline laparotomic approach for a surgical staging procedure, respectively. 25.6% (54.7%) of the respondents recommended a hysterectomy in premenopausal (versus postmenopausal) patients with a STIC, 24.4% (88.4%) a bilateral oophorectomy and 50.0% (4.7%) an affected side oophorectomy (all p values < 0.001). Omentectomy, pelvic and para-aortic lymphadenectomy would be performed by 60.5% (64.0%), 9.3% (11.6%) and 9.3% (11.6%) of respondents in premenopausal (versus postmenopausal) patients (all p values > 0.05). CONCLUSION: Our survey highlights significant inconsistency in the management of patients with STIC. Prospective data are urgently needed to elucidate the clinical impact of a STIC lesion and its clinical management.
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Carcinoma in Situ , Cistadenocarcinoma Seroso , Neoplasias das Tubas Uterinas , Neoplasias Ovarianas , Feminino , Humanos , Estudos Prospectivos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/patologia , Neoplasias das Tubas Uterinas/patologia , Cistadenocarcinoma Seroso/patologia , Inquéritos e Questionários , Carcinoma in Situ/patologiaRESUMO
PURPOSE: We investigated inpatient convalescent rehabilitation outcomes of Branch atheromatous disease (BAD). SUBJECTS AND METHODS: The subjects were 116 patients with lenticulostriate artery territory - BAD (LSA-BAD) and 29 with paramedian pontine artery territory - BAD (PPA-BAD). For all patients, the National Institutes of Health Stroke Scale (NIHSS), Functional Independence Measure (FIM) scores, and Brunnstrom recovery stages (BRS) of the upper limb, fingers, and lower limb were measured on admission and at discharge. RESULTS: There were no significant differences in clinical characteristics on admission between the LSA-BAD and PPA-BAD groups. The neurological severity of PPA-BAD, as measured by the NIHSS, was significantly milder compared with that of LSA-BAD upon admission (p = 0.015) and at discharge (p = 0.001). Patients with LSA-BAD had significantly less improvement in the BRS of the upper limb (p = 0.001), fingers (p < 0.001), and lower limb (p = 0.007) at discharge. Furthermore, they had significantly smaller changes in BRS between admission and discharge for the upper limb (p = 0.033) and fingers (p = 0.014) compared with patients with PPA-BAD. The improvement in BRS for patients with LSA-BAD tended to be limited to two stages; however, both patients with LSA-BAD and PPA-BAD saw sufficient gains in FIM at discharge. CONCLUSION: Rehabilitation outcomes following BAD in the convalescent period should be assessed in terms of improvements in pure-motor hemiparesis and activities of daily living. Furthermore, the disturbance patterns in the corticospinal tract by ischemic stroke lesions may be different between LSA-BAD and PPA-BAD.
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Placa Aterosclerótica , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Pacientes Internados , Atividades Cotidianas , Resultado do Tratamento , Artérias , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapiaRESUMO
OBJECTIVE: Digital microscopy is used to monitor particulates such as protein aggregates within biopharmaceutical products. The images that result encode a wealth of information that is underutilized in pharmaceutical process monitoring. For example, images of particles in protein drug products typically are analyzed only to obtain particle counts and size distributions, even though the images also reflect particle characteristics such as shape and refractive index. Multiple groups have demonstrated that convolutional neural networks (CNNs) can extract information from images of protein aggregates allowing assignment of the likely stress at the "root-cause" of aggregation. A practical limitation of previous CNN-based approaches is that the potential aggregation-inducing stresses must be known a priori, disallowing identification of particles produced by unknown stresses. METHODS: We demonstrate an expanded CNN analysis of flow imaging microscopy (FIM) images incorporating judiciously chosen particle standards within a recently proposed "fingerprinting algorithm" (Biotechnol. & Bioeng. (2020) 117:3322) that allows detection of particles formed by unknown root-causes. We focus on ethylene tetrafluoroethylene (ETFE) microparticles as standard surrogates for protein aggregates. We quantify the sensitivity of the new algorithm to experimental parameters such as microscope focus and solution refractive index changes, and explore how FIM sample noise affects statistical testing procedures. RESULTS & CONCLUSIONS: Applied to real-world microscopy images of protein aggregates, the algorithm reproducibly detects complex, distinguishing "textural features" of particles that are not easily described by standard morphological measurements. This offers promise for quality control applications and for detecting shifts in protein aggregate populations due to stresses resulting from unknown process upsets.
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Ensaios de Triagem em Larga Escala , Processamento de Imagem Assistida por Computador , Microscopia , Redes Neurais de Computação , Proteínas/análise , Composição de Medicamentos , Agregados Proteicos , Reprodutibilidade dos TestesRESUMO
Three-dimensional field ion microscopy is a powerful technique to analyze material at a truly atomic scale. Most previous studies have been made on pure, crystalline materials such as tungsten or iron. In this article, we study more complex materials, and we present the first images of an amorphous sample, showing the capability to visualize the compositional fluctuations compatible with theoretical medium order in a metallic glass (FeBSi), which is extremely challenging to observe directly using other microscopy techniques. The intensity of the spots of the atoms at the moment of field evaporation in a field ion micrograph can be used as a proxy for identifying the elemental identity of the imaged atoms. By exploiting the elemental identification and positioning information from field ion images, we show the capability of this technique to provide imaging of recrystallized phases in the annealed sample with a superior spatial resolution compared with atom probe tomography.
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BACKGROUND/OBJECTIVE: Previous research indicates a better improvement of functional independence measure (FIM) at discharge in acute-stroke patients who received physiatrist and registered therapist operating rehabilitation (PROr) within 24 hrs compared with those who received after 24 hrs was reported. The aim of this prospective cohort study was to determine whether PROr provided within 24 hrs for new-onset stroke patients affects home-discharge rate at 6 months later. METHODS: Acute new-onset stroke patients admitted to our hospital and received PROr (n = 227) and were conducted into 3 categories based on the time until starting PROr; within 24 hrs (very early mobilization; VEM; n = 47), 24-48 hrs (early mobilization; EM; n = 77) and >48 hrs (later mobilization; LM; n = 103). Home-discharge rates as well as changes in FIM, and rates of recurrence and mortality during the 6-month follow-up were assessed. RESULTS: A total of 139 patients [VEM (n = 32), EM (n = 43), LM (n = 64)] could be followed throughout the 6-month period. The home-discharge rate was â¼80% and significantly higher by â¼20% in VEM than EM. The gains in the motor subscale of FIM at 6 months were significantly higher in VEM than LM, while the mortality and recurrent rates were not significantly different among the categories. CONCLUSIONS: Starting PROr within 24 hrs of new-onset stroke may help to increase home-discharge rates at 6-month follow-up, simultaneously with a higher FIM. Very early mobilization in our hospital did not increase the risks of recurrence or death.
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Atividades Cotidianas , Avaliação de Resultados em Cuidados de Saúde , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral/terapia , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Fatores de TempoRESUMO
PURPOSE: The purpose of this retrospective cross-sectional case-control study was to evaluate an alternative imaging test for lateralization of the tibial tuberosity, unbiased towards knee rotation. METHODS: On axial CT images of 129 knees, classified as cases (two or more patellar luxations) and controls (no patellar luxations), two raters gauged the standard tibial tuberosity-trochlear groove (TT-TG) distance, tibial tuberosity-femoral intercondylar midpoint (TT-FIM) distance, and new tibial tuberosity-tibial intercondylar midpoint (TT-TIM) distance singly, and knee longitudinal rotation angles (LRAs), and the presence of femoral trochlear dysplasia (FTD) jointly. RESULTS: All imaging tests intercorrelated and discriminated between stability groups. TT-TIM had the lowest values with the highest precision. Though poorly, TT-TG and TT-FIM negatively correlated with age and LRAs regarding femur, but positively with presence of FTD, whereas TT-TIM was unbiased. The accuracy of TT-TG (> 20 mm), TT-FIM (> 20 mm), and TT-TIM (> 13 mm) was good with almost perfect reproducibility. Only TT-TIM was sex-biased (p = 0.009), with > 12 mm cut-off in females and (presumably) > 14 mm in males. CONCLUSION: TT-TIM is an alternative imaging test for lateralization of the tibial tuberosity, unbiased towards knee rotation.
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Instabilidade Articular , Articulação Patelofemoral , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Articulação do Joelho/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Articulação Patelofemoral/diagnóstico por imagem , Reprodutibilidade dos Testes , Estudos Retrospectivos , Rotação , Tíbia/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
At the end of 2019, the SARS-CoV-2 virus caused an outbreak of COVID-19 disease. The spread of this once-in-a-century pathogen increases demand for appropriate medical care, which strains the capacity and resources of hospitals in a critical way. Given the limited time available to prepare for the required demand, health care administrators fear they will not be ready to face patient's influx. To aid health managers with the Prioritization and Scheduling COVID-19 Patients problem, a tool based on Artificial Intelligence (AI) through the Artificial Neural Networks (ANN) method, and Operations Research (OR) through a Fuzzy Interval Mathematical model was developed. The results indicated that combining both models provides an effective assessment under scarce initial information to select a suitable list of patients for a set of hospitals. The proposed approach allows to achieve a key goal: minimizing death rates under each hospital constraints of available resources. Furthermore, there is a serious concern regarding the resurgence of the COVID-19 virus which could cause a more severe pandemic. Thus, the main outcome of this study is the application of the above-mentioned approaches, especially when combining them, as efficient tools serving health establishments to manage critical resources.
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Sensor placement is an important factor that may significantly affect the localization performance of a sensor network. This paper investigates the sensor placement optimization problem in three-dimensional (3D) space for angle of arrival (AOA) target localization with Gaussian priors. We first show that under the A-optimality criterion, the optimization problem can be transferred to be a diagonalizing process on the AOA-based Fisher information matrix (FIM). Secondly, we prove that the FIM follows the invariance property of the 3D rotation, and the Gaussian covariance matrix of the FIM can be diagonalized via 3D rotation. Based on this finding, an optimal sensor placement method using 3D rotation was created for when prior information exists as to the target location. Finally, several simulations were carried out to demonstrate the effectiveness of the proposed method. Compared with the existing methods, the mean squared error (MSE) of the maximum a posteriori (MAP) estimation using the proposed method is lower by at least 25% when the number of sensors is between 3 and 6, while the estimation bias remains very close to zero (smaller than 0.15 m).
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ABSTRACT Survival time in HIV/AIDS patients has increased as a result of improved treatments, but many acquire functional impairments that may necessitate multidisciplinary medical rehabilitation. In the United States, inpatient rehabilitation facilities (IRF) provide this care, but outcomes are not well described in this population. We used the Uniform Data System for Medical Rehabilitation (UDSMR) database to describe 11,051 HIV/AIDS IRF patients; HIV/AIDS patients were grouped according to the following admission criteria: (1) HIV/AIDS as primary reason for admission (n = 225); (2) HIV/AIDS symptomatic comorbidity (n = 6569); and (3) HIV/AIDS asymptomatic comorbidity (n = 4257). We used standard descriptive statistics to summarize demographic, medical, rehabilitation, and discharge setting characteristics by group. When compared to patients with HIV/AIDS as a comorbidity, primary HIV/AIDS patients had worse outcomes. They made less functional change (25.1 versus 29.8 and 28.9, p < .001), went home less (73.8% versus 74.5% and 77.8%, p < .001) and to an acute care hospital more frequently (18.2% versus 13.9% and 10.1%, p < .001). These findings help to characterize the HIV/AIDS patient population who receive inpatient medical rehabilitation, which helps inform clinical care, and highlight the positive impact IRF care can make to minimize functional disability among chronic HIV/AIDS patients and possibly decrease costs of home health care.
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Infecções por HIV , Pacientes Internados , Comorbidade , Infecções por HIV/reabilitação , Humanos , Tempo de Internação , Recuperação de Função Fisiológica , Centros de Reabilitação , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
The skin of the frog Xenopus laeevis is protected from microbial infections by a mucus barrier that contains frog integumentary mucins (FIM)-A.1, FIM-B.1, and FIM-C.1. These gel-forming mucins are synthesized in mucous glands consisting of ordinary mucous cells and one or more cone cells at the gland base. FIM-A.1 and FIM-C.1 are unique because their cysteine-rich domains belong to the trefoil factor family (TFF). Furthermore, FIM-A.1 is unusually short (about 400 amino acid residues). In contrast, FIM-B.1 contains cysteine-rich von Willebrand D (vWD) domains. Here, we separate skin extracts by the use of size exclusion chromatography and analyze the distribution of FIM-A.1 and FIM-C.1. Two mucin complexes were detected, i.e., a high-molecular-mass Complex I, which contains FIM-C.1 and little FIM-A.1, whereas Complex II is of lower molecular mass and contains the bulk of FIM-A.1. We purified FIM-A.1 by a combination of size-exclusion chromatography (SEC) and anion-exchange chromatography and performed first in vitro binding studies with radioactively labeled FIM-A.1. Binding of 125I-labeled FIM-A.1 to the high-molecular-mass Complex I was observed. We hypothesize that the presence of FIM-A.1 in Complex I is likely due to lectin interactions, e.g., with FIM-C.1, creating a complex mucus network.
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Tegumento Comum/fisiologia , Mucinas/metabolismo , Muco/metabolismo , Fatores Trefoil/metabolismo , Proteínas de Xenopus/metabolismo , Xenopus laevis/metabolismo , Animais , Glândulas Exócrinas , Mucinas/química , Pele/metabolismo , Proteínas de Xenopus/químicaRESUMO
About 23% of adnexal tumors are related to a hereditary syndrome, most often hereditary breast and ovarian cancer syndrome or Lynch syndrome, responsible of epithelial tumors. However, the pathologist should be aware of rare hereditary syndromes responsible of non-epithelial ovarian tumors. Ovarian tumors associated with germline mutation of BRCA genes are essentially high-grade serous carcinomas of tubal origin, while those seen in Lynch syndrome are most often endometrioid or clear cell carcinomas. Sex-cord tumors associated with a familial predisposition are Sertoli-Leydig cell tumors in DICER syndrome and sex-cord tumors with annular tubules in Peutz-Jeghers syndrome. Small cell carcinoma of hypercalcemic type may be associated with a rhabdoid tumor predisposition syndrome 2. Finally, rare germ cell tumors have been reported related to ataxia telangiectasia. The recognition of these entities by pathologists is crucial. Even though the morphologic features pointing toward an inherited mutation may vary depending on the syndrome, the diagnosis may contribute to refer the patient for genetic counselling, modifying the management and follow-up of the patient and her family.
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Neoplasias Ovarianas , Ataxia Telangiectasia/etiologia , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/patologia , RNA Helicases DEAD-box/genética , Diagnóstico Diferencial , Feminino , Genes BRCA1 , Genes BRCA2 , Aconselhamento Genético , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Neoplasias Embrionárias de Células Germinativas/complicações , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Ovário/patologia , Síndrome de Peutz-Jeghers/genética , Síndrome de Peutz-Jeghers/patologia , Ribonuclease III/genética , Tumores do Estroma Gonadal e dos Cordões Sexuais/genética , Tumores do Estroma Gonadal e dos Cordões Sexuais/patologiaRESUMO
During the 2008-2012 pertussis epidemic in Australia, pertactin (Prn)-negative Bordetella pertussis emerged. We analyzed 78 isolates from the 2013-2017 epidemic and documented continued expansion of Prn-negative ptxP3 B. pertussis strains. We also detected a filamentous hemagglutinin-negative and Prn-negative B. pertussis isolate.
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Adesinas Bacterianas/genética , Proteínas da Membrana Bacteriana Externa/genética , Bordetella pertussis/genética , Fatores de Virulência de Bordetella/genética , Coqueluche/epidemiologia , Coqueluche/microbiologia , Adesinas Bacterianas/imunologia , Alelos , Austrália/epidemiologia , Proteínas da Membrana Bacteriana Externa/imunologia , Bordetella pertussis/classificação , Bordetella pertussis/imunologia , História do Século XXI , Humanos , Vacina contra Coqueluche/administração & dosagem , Vacina contra Coqueluche/imunologia , Filogenia , Fatores de Virulência de Bordetella/imunologia , Coqueluche/história , Coqueluche/prevenção & controleRESUMO
BACKGROUND: In patients with moderate and severe paediatric traumatic brain injury (TBI), we investigated the presence and severity of white matter (WM) tract damage, cortical lobar and deep grey matter (GM) atrophies, their interplay and their correlation with outcome rating scales. METHODS: Diffusion tensor (DT) and 3D T1-weighted MRI scans were obtained from 22 TBI children (13 boys; mean age at insult = 11.6 years; 72.7% in chronic condition) and 31 age-matched healthy children. Patients were tested with outcome rating scales and the Wechsler Intelligence Scale for Children (WISC). DT MRI indices were obtained from several supra- and infra-tentorial WM tracts. Cortical lobar and deep GM volumes were derived. Comparisons between patients and controls, and between patients in acute (<6 months from the event) vs. chronic (≥6 months) condition were performed. RESULTS: Patients showed a widespread pattern of decreased WM FA and GM atrophy. Compared to acute, chronic patients showed severer atrophy in the right frontal lobe and reduced FA in the left inferior longitudinal fasciculus and corpus callosum (CC). Decreased axial diffusivity was observed in acute patients versus controls in the inferior fronto-occipital fasciculus and CC. Chronic patients showed increased axial diffusivity in the same structures. Uncinate fasciculus DT MRI abnormalities correlated with atrophy in the frontal and temporal lobes. Hippocampal atrophy correlated with reduced WISC scores, whereas putamen atrophy correlated with lower functional independence measure scores. CONCLUSIONS: The study isolated a distributed fronto-temporal network of structures particularly vulnerable to axonal damage and atrophy that may contribute to cognitive deficits following TBI.