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The multi-subunit bacterial RNA polymerase (RNAP) and its associated regulators carry out transcription and integrate myriad regulatory signals. Numerous studies have interrogated RNAP mechanism, and RNAP mutations drive Escherichia coli adaptation to many health- and industry-relevant environments, yet a paucity of systematic analyses hampers our understanding of the fitness trade-offs from altering RNAP function. Here, we conduct a chemical-genetic analysis of a library of RNAP mutants. We discover phenotypes for non-essential insertions, show that clustering mutant phenotypes increases their predictive power for drawing functional inferences, and demonstrate that some RNA polymerase mutants both decrease average cell length and prevent killing by cell-wall targeting antibiotics. Our findings demonstrate that RNAP chemical-genetic interactions provide a general platform for interrogating structure-function relationships in vivo and for identifying physiological trade-offs of mutations, including those relevant for disease and biotechnology. This strategy should have broad utility for illuminating the role of other important protein complexes.
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ARN Polimerasas Dirigidas por ADN/química , ARN Polimerasas Dirigidas por ADN/genética , Mutación/genética , Amdinocilina/farmacología , Proteínas Bacterianas/metabolismo , Muerte Celular/efectos de los fármacos , Cromosomas Bacterianos/genética , Citoprotección/efectos de los fármacos , Proteínas del Citoesqueleto/metabolismo , Escherichia coli/genética , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Mutagénesis Insercional/genética , Péptidos/metabolismo , Fenotipo , Relación Estructura-Actividad , Transcripción Genética , Uridina Difosfato Glucosa/metabolismoRESUMEN
PURPOSE: This study explores the biomechanics underlying the sit-to-stand (STS) functional maneuver in chronic LBP patients to understand how different spinal disorders and levels of pain severity relate to unique compensatory biomechanical behaviors. This work stands to further our understanding of the relationship between spinal loading and symptoms in LBP patients. METHODS: We collected in-clinic motion data from 44 non-specific LBP (NS-LBP) and 42 spinal deformity LBP (SD-LBP) patients during routine clinical visits. An RGB-depth camera tracked 3D joint positions from the frontal view during unassisted, repeated STS maneuvers. Patient-reported outcomes (PROs) for back pain (VAS) and low back disability (ODI) were collected during the same clinical visit. RESULTS: Between patient groups, SD-LBP patients had 14.3% greater dynamic sagittal vertical alignment (dSVA) and 10.1% greater peak spine torque compared to NS-LBP patients (p < 0.001). SD-LBP patients also had 11.8% greater hip torque (p < 0.001) and 86.7% greater knee torque (p = 0.04) compared to NS-LBP patients. There were no significant differences between patient groups in regard to anterior or vertical torso velocities, but anterior and vertical torso velocities correlated with both VAS (r = - 0.38, p < 0.001) and ODI (r = - 0.29, p = 0.01). PROs did not correlate with other variables. CONCLUSION: Patients with LBP differ in movement biomechanics during an STS transfer as severity of symptoms may relate to different compensatory strategies that affect spinal loading. Further research aims to establish relationships between movement and PROs and to inform targeted rehabilitation approaches.
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Dolor de la Región Lumbar , Fenómenos Biomecánicos , Humanos , Movimiento , Dimensión del Dolor , Columna VertebralRESUMEN
BACKGROUND: The fecal immunochemical test (FIT) is a cost-effective colorectal cancer (CRC) screening tool. However, longitudinal adherence, a factor that is critical to the success to any FIT-based screening program, often is poor. The authors hypothesized that reminders sent via mobile messengers, such as WhatsApp, improve such adherence. METHODS: In the current single-blind, randomized study, subjects from an opportunistic FIT screening program who had a negative FIT result the year prior were randomly allocated (1:1) to receive either a 1-off reminder via the WhatsApp messenger (WR) 1 month prior to the due appointments or no reminder (NR). All subjects were blinded to study participation and group allocation. At 24 months after randomization, a crossover of intervention was performed among those individuals who remained in the FIT program. The primary outcome was FIT adherence, defined as the pick-up and on-time return of the FIT. The secondary outcome was FIT adherence after the crossover. RESULTS: A total of 500 subjects were randomized to receive WR (250 subjects) or NR (250 subjects). Three individuals were excluded from analysis (1 died and 2 underwent colonoscopy). Both the FIT pick-up rate (80.3% vs 59.3%; P < .001) and return rate (79.9% vs 57.3%; P < .001) were significantly higher in the WR group compared with the NR group. After crossover of intervention (452 subjects), the WR group again was found to have a higher FIT pick-up rate (79.1% vs 52.9%; P < .001) and return rate (78.2% vs 52.4%; P < .001). CONCLUSIONS: Text reminders sent via mobile messenger appear to improve the longitudinal adherence to FIT-based opportunistic CRC screening programs. The routine use of this technology in CRC screening should be considered.
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Neoplasias Colorrectales/diagnóstico , Detección Precoz del Cáncer/métodos , Sangre Oculta , Envío de Mensajes de Texto , Anciano , Estudios Cruzados , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cooperación del Paciente , Método Simple CiegoRESUMEN
BACKGROUND AND AIM: Nonattendance of outpatient colonoscopy leads to inefficient use of health-care resources. We aimed to study the effectiveness of using Short Message Service (SMS) reminder prior in patients scheduled for outpatient colonoscopy on their nonattendance rate. METHODS: Patients who scheduled for an outpatient colonoscopy and had access of SMS were recruited from three clinics in Hong Kong. Patients were randomized to SMS group and standard care (SC) group. All patients were given a written appointment slip on the booking date. In addition, patients in the SMS group received an SMS reminder 7-10 days before their colonoscopy appointment. Patients' demographics, attendance, colonoscopy completion, and bowel preparation quality were recorded. Logistic regression was performed to identify predictors of nonattendance. RESULTS: From November 2013 to October 2019, a total of 2225 eligible patients were recruited. A total of 1079 patients were allocated to the SMS group and 1146 to the SC group. The nonattendance rate of patients in the SMS group was significantly lower than that in the SC group (8.9% vs 11.9%, P = 0.022). There were no significant differences in their baseline characteristics and colonoscopy completion rate and bowel preparation quality. A trend towards a higher rate of adequate bowel preparation was observed in the SMS group when compared with the SC group (69.9% vs 65.8%, P = 0.053). Independent predictors for nonattendance included younger age, underprivilege, and existing diabetes. CONCLUSIONS: An SMS reminder for outpatient colonoscopy is effective in reducing the nonattendance rate and may potentially improve the bowel preparation quality.
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Citas y Horarios , Colonoscopía/estadística & datos numéricos , Pacientes no Presentados/estadística & datos numéricos , Pacientes Ambulatorios/estadística & datos numéricos , Cooperación del Paciente/estadística & datos numéricos , Sistemas Recordatorios/estadística & datos numéricos , Envío de Mensajes de Texto , Factores de Edad , Femenino , Disparidades en Atención de Salud , Hong Kong/epidemiología , Humanos , Modelos Logísticos , MasculinoRESUMEN
Background and aims Chemoradiotherapy for head and neck cancer (HNC) with/without laryngectomy commonly causes dysphagia. Pharyngoesophageal junction (PEJ) stricturing is an important contributor. We aimed to validate a functional lumen imaging probe (the EndoFLIP system) as a tool for quantitating pretreatment PEJ distensibility and treatment-related changes in HNC survivors with dysphagia and to evaluate the diagnostic accuracy of EndoFLIP-derived distensibility in detecting PEJ strictures. Methods We studied 34 consecutive HNC survivors with long-term (>â12 months) dysphagia who underwent endoscopic dilation for suspected strictures. Twenty non-dysphagic patients undergoing routine endoscopy served as controls. PEJ distensibility was measured at endoscopy with the EndoFLIP system pre- and post-dilation. PEJ stricture was defined as the presence of a mucosal tear post-dilation. Results PEJ stricture was confirmed in 22/34 HNC patients (65â%). During distension up to 60âmmHg, the mean EndoFLIP-derived narrowest cross-sectional area (nCSA) in HNC patients with strictures, without strictures, and in controls were 58âmm2 (95â% confidence interval [CI] 22 to 118), 195âmm2 (95â%CI 129 to 334), and 227âmm2 (95â%CI 168 to 316), respectively. A cutoff of 114âmm2 for the nCSA at the PEJ had perfect diagnostic accuracy in detecting strictures (area under the receiver operating characteristic curveâ=â1). In patients with strictures, a single session of dilation increased the nCSA by 29âmm2 (95â%CI 20 to 37; Pâ<â0.001). In patients with no strictures, dilation caused no change in the nCSA (mean difference 13âmm2 [95â%CI -4 to 30]; Pâ=â0.13). Conclusions EndoFLIP is a highly accurate technique for the detection of PEJ strictures. EndoFLIP may complement conventional diagnostic tools in the detection of pharyngeal outflow obstruction.
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Trastornos de Deglución/etiología , Estenosis Esofágica/diagnóstico , Neoplasias de Cabeza y Cuello/terapia , Faringe/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Quimioradioterapia/efectos adversos , Constricción Patológica/diagnóstico , Constricción Patológica/etiología , Constricción Patológica/terapia , Trastornos de Deglución/terapia , Dilatación , Estenosis Esofágica/etiología , Estenosis Esofágica/terapia , Femenino , Humanos , Laringectomía/efectos adversos , Masculino , Persona de Mediana Edad , Pletismografía de Impedancia , Curva ROC , Radioterapia Adyuvante/efectos adversos , Adulto JovenRESUMEN
BACKGROUND AND AIMS: Accurate assessment of patient-reported oropharyngeal dysphagia (OPD) is essential to guide appropriate management and evaluate response. The Sydney Swallow Questionnaire (SSQ) is a paper-based 17-item inventory developed and validated to objectively detect risk of OPD. An easy-to-use electronic version with digital output has significant potential in streamlining patient assessment. This study aims to develop and validate an electronic version of the SSQ (eSSQ) against the original paper version. METHOD: The English-based paper SSQ was adapted on the online REDcap (Research Electronic Data Capture) platform to be accessible on computer and mobile devices. Patients with OPD and asymptomatic controls completed both electronic and paper versions in randomized order. Patients with stable symptoms then repeated the eSSQ after ≥14 days for test-retest reliability. Paper-based and eSSQs were also collected from an independent cohort for external validation. Agreement of total scores between both versions and eSSQ test-retest reliability were calculated using two-way mixed-effects intra-class correlation coefficient (ICC). RESULTS: 47 dysphagic patients, 32 controls, and 31 patients from an external validation cohort were recruited. The most common underlying etiology was head and neck cancer. Mean eSSQ total score was 789 in dysphagic patients, and 68 in controls. eSSQ had excellent agreement with paper SSQ in total scores among all participants, with ICC 0.97 (95% CI [0.93, 0.98]) in controls, 0.97 (95% CI [0.94, 0.98]) in dysphagic patients and 0.96 (95% CI [0.92, 0.98]) in validation cohort. Test-retest reliability was also excellent (ICC 0.96, 95% CI [0.90, 0.98]). CONCLUSION: The newly developed eSSQ shows excellent agreement with the paper version and test-retest reliability. Future applications of its use may allow for more efficient and accessible patient assessment.
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Trastornos de Deglución , Humanos , Trastornos de Deglución/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios/normas , Anciano , Reproducibilidad de los Resultados , Adulto , Deglución/fisiologíaRESUMEN
Poor nutrient transport through the cartilage endplate (CEP) is a key factor in the etiology of intervertebral disc degeneration and may hinder the efficacy of biologic strategies for disc regeneration. Yet, there are currently no treatments for improving nutrient transport through the CEP. In this study we tested whether intradiscal delivery of a matrix-modifying enzyme to the CEP improves solute transport into whole human and bovine discs. Ten human lumbar motion segments harvested from five fresh cadaveric spines (38-66 years old) and nine bovine coccygeal motion segments harvested from three adult steers were treated intradiscally either with collagenase enzyme or control buffer that was loaded in alginate carrier. Motion segments were then incubated for 18 h at 37 °C, the bony endplates removed, and the isolated discs were compressed under static (0.2 MPa) and cyclic (0.4-0.8 MPa, 0.2 Hz) loads while submerged in fluorescein tracer solution (376 Da; 0.1 mg/ml). Fluorescein concentrations from site-matched nucleus pulposus (NP) samples were compared between discs. CEP samples from each disc were digested and assayed for sulfated glycosaminoglycan (sGAG) and collagen contents. Results showed that enzymatic treatment of the CEP dramatically enhanced small solute transport into the disc. Discs with enzyme-treated CEPs had up to 10.8-fold (human) and 14.0-fold (bovine) higher fluorescein concentration in the NP compared to site-matched locations in discs with buffer-treated CEPs (p < 0.0001). Increases in solute transport were consistent with the effects of enzymatic treatment on CEP composition, which included reductions in sGAG content of 33.5% (human) and 40% (bovine). Whole disc biomechanical behavior-namely, creep strain and disc modulus-was similar between discs with enzyme- and buffer-treated CEPs. Taken together, these findings demonstrate the potential for matrix modification of the CEP to improve the transport of small solutes into whole intact discs.
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Pulmonary aspiration continues to be a major cause of anesthesia-related mortality. Anesthesiologists are encouraged to perform bronchoscopy to manage aspiration of particulate matter; however, they have limited training and experience in clearing luminal obstructions endoscopically. In our report, an adult with achalasia aspirated during induction for a per-oral endoscopic myotomy (POEM), resulting in desaturation and high airway pressures. Bronchoscopy by the anesthesiologist was ineffective. However, bronchoscopy by the gastroenterologist using a pediatric gastroscope cleared the bronchi of debris and led to immediate clinical improvement. Anesthesiologists, faced with particulate matter aspiration, could consider assistance from a gastrointestinal endoscopist.
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BACKGROUND: Adequate bowel preparation is an important colonoscopy quality indicator. Reinforced education is effective in improving bowel preparation quality of colonoscopy with mixed indications. However, it remains unclear whether such improvement can be consistently observed in pre- and post-irrigation during colonoscopy in screening population. OBJECTIVE: We aimed to study the effectiveness of nurse-led reinforced education delivered via mobile messenger (WhatsApp Messenger) on pre- and post-irrigation bowel preparation adequacy in colonoscopies for positive fecal immunochemical test in a population-based colorectal cancer screening program. DESIGN: Randomized controlled trial. SETTING: A hospital-based endoscopy centre in Hong Kong, China. PARTICIPANTS: Patients undergoing colonoscopy for positive fecal immunochemical test in a population-based colorectal cancer screening program. METHODS: The recruited patients were randomized to receive either WhatsApp Reinforced Education (WRE) or No Reinforced Education (NRE) (1:1). Patients in WRE group received one-off reinforced education of bowel preparation in text and video formats via WhatsApp Messenger four days prior to colonoscopy sent by investigator while NRE group received standard-of-care only. Primary outcome was the bowel preparation adequacy rate as evaluated by Aronchick Scale. Secondary outcomes included bowel preparation adequacy rate as evaluated by Boston Bowel Preparation Scale, adenoma detection rate and risk factors of bowel preparation inadequacy. Continuous variables were described as means with standard deviation (SD) and analyzed with Student's t-test. The Pearson Chi Square Test or Fisher Exact Test was used to assess categorical variables when appropriate. Risk factors were determined by logistic regression. RESULTS: From July 2017 to April 2019, 685 eligible patients were randomized to WRE (nâ¯=â¯343) and NRE (nâ¯=â¯342) groups. Patients in WRE group had higher bowel preparation adequacy rate as evaluated by Aronchik Scale (83.4% vs 75.4%, pâ¯=â¯0.010) and Boston Bowel Preparation Scale (94.2% vs 88.9%, pâ¯=â¯0.013). Adenoma detection rate was higher in WRE group but without statistical significance (71.4% vs 67.5%, pâ¯=â¯0.27). In logistic regression, WhatsApp Reinforced Education reduced the inadequate bowel preparation risk (Adjusted odds ratio: 0.564; 95% confidence interval: 0.371-0.856, pâ¯=â¯0.007). Male gender (Adjusted odds ratio [AOR]: 1.638; 95% confidence interval [CI]: 1.054-2.546, pâ¯=â¯0.028) and diabetes (AOR: 2.062; 95% CI: 1.215-3.497, pâ¯=â¯0.007) were risk factors of bowel preparation inadequacy. CONCLUSIONS: Nurse-led mobile messenger-initiated reinforced education improves both pre- and post-irrigation bowel preparation quality of screening colonoscopy following positive fecal immunochemical test. It is readily incorporable in clinical practice because of its low setup cost. REGISTRATION NUMBER: Registered on 4 July 2017 on https://clinicaltrials.gov/ (NCT03209739).
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Adenoma , Neoplasias Colorrectales , Adenoma/inducido químicamente , Adenoma/diagnóstico , Adenoma/tratamiento farmacológico , Catárticos/efectos adversos , Colonoscopía , Neoplasias Colorrectales/diagnóstico , Detección Precoz del Cáncer , Humanos , Masculino , Rol de la EnfermeraRESUMEN
Despite the demonstrated success of genome-wide genetic screens and chemical genomics studies at predicting functions for genes of unknown function or predicting new functions for well-characterized genes, their potential to provide insights into gene function has not been fully explored. We systematically reanalyzed a published high-throughput phenotypic dataset for the model Gram-negative bacterium Escherichia coli K-12. The availability of high-quality annotation sets allowed us to compare the power of different metrics for measuring phenotypic profile similarity to correctly infer gene function. We conclude that there is no single best method; the three metrics tested gave comparable results for most gene pairs. We also assessed how converting quantitative phenotypes to discrete, qualitative phenotypes affected the association between phenotype and function. Our results indicate that this approach may allow phenotypic data from different studies to be combined to produce a larger dataset that may reveal functional connections between genes not detected in individual studies.
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Escherichia coli K12 , Escherichia coli , Genómica , FenotipoRESUMEN
Background and study aims Oropharyngeal dysphagia (OPD) is prevalent in patients with Parkinson's disease (PD). Upper esophageal sphincter (UES) dysfunction is an important pathophysiological factor for OPD in PD. The cricopharyngeus (CP) is the main component of UES.âWe assessed the preliminary efficacy of cricopharyngeal peroral endoscopic myotomy (C-POEM) as a treatment for dysphagia due to UES dysfunction in PD. Patients and methods Consecutive dysphagic PD patients with UES dysfunction underwent C-POEM. Swallow metrics derived using high-resolution pharyngeal impedance manometry (HRPIM) including raised UES integrated relaxation pressure (IRP), raised hypopharyngeal intrabolus pressure (IBP), reduced UES opening caliber and relaxation time defined UES dysfunction. Sydney Swallow Questionnaire (SSQ) and Swallowing Quality of Life Questionnaire (SWAL-QOL) at before and 1 month after C-POEM measured symptomatic improvement in swallow function. HRPIM was repeated at 1-month follow-up. Results C-POEM was performed without complications in all (nâ=â8) patients. At 1 month, there was an improvement in both the mean SSQ (from 621.5 to 341.8, mean difference -277.3, 95â%CI [-497.8, -56.7], P â=â0.02) and SWAL-QOL (from 54.9 to 68.3, mean difference 9.1, 95â%CI [0.7, 17.5], P â=â0.037) scores. Repeat HRPIM confirmed a decrease in both the mean UES IRP (13.7âmm Hg to 3.6âmm Hg, mean difference -10.1âmm Hg, 95â%CI [-16.3, -3.9], P â=â0.007) and the mean hypopharyngeal IBP (23.5âmm Hg to 10.4âmm Hg, mean difference -11.3âmm Hg, 95â%CI [-17.2, -5.4], P â=â0.003). Conclusions In dysphagic PD patients with UES dysfunction, C-POEM is feasible and enhances UES relaxation and reduces sphincteric resistance to flow during the swallow, thereby improving dysphagia symptoms.
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The aim of this paper is to review esophageal electrical impedance technologies and to discuss the use of these technologies for physiological measurements, diagnostics, and therapy of esophageal disease. In order to develop a better understanding of the pathophysiology of and improve the diagnosis of esophageal disorders, such as gastroesophageal reflux disease (GERD) and achalasia, several new diagnostic tests, including intraluminal impedance, esophageal mucosal impedance, and the functional luminal imaging probe, have been developed. These technologies have proven valuable for assessment of the esophagus in recent years. They provide information on esophageal flow properties, mucosal integrity, lumen shape, and distensibility in esophageal disorders, in particular for GERD and achalasia. Despite their promise and novel clinical studies, the potential of these technologies has been far from realized. New multidisciplinary approaches will contribute to our understanding and interpretation of esophageal impedance data and disease mechanisms.
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Impedancia Eléctrica , Acalasia del Esófago , Mucosa Esofágica/fisiopatología , Reflujo Gastroesofágico , Acalasia del Esófago/diagnóstico , Acalasia del Esófago/fisiopatología , Monitorización del pH Esofágico , Esofagoscopía , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/fisiopatología , Humanos , ManometríaRESUMEN
A long-standing effort in biology is to precisely define and group phenotypes that characterize a biological process, and the genes that underpin them. In Saccharomyces cerevisiae and other organisms, functional screens have generated rich lists of phenotypes associated with individual genes. However, it is often challenging to identify sets of phenotypes and genes that are most closely associated with a given biological process. Here, we focused on the 166 phenotypes arising from loss-of-function and the 86 phenotypes from gain-of-function mutations in 571 genes currently assigned to cell cycle-related ontologies in S. cerevisiae To reduce this complexity, we applied unbiased, computational approaches of correspondence analysis to identify a minimum set of phenotypic variables that accounts for as much of the variability in the data as possible. Loss-of-function phenotypes can be reduced to 20 dimensions, while gain-of-function ones to 14 dimensions. We also pinpoint the contributions of phenotypes and genes in each set. The approach we describe not only simplifies the categorization of phenotypes associated with cell cycle progression but might also potentially serve as a discovery tool for gene function.
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Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Ciclo Celular/genética , Biología Computacional , Genes cdc , Fenotipo , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genéticaRESUMEN
Esophageal squamous cell carcinoma (ESCC) is a deadly disease, partly because it is often diagnosed late in disease stage. An accurate early diagnosis by endoscopy could detect advanced carcinoma as well as curable dysplasia and early ESCC. This could save patients from incurable advanced malignancy. Important progress has been made in high-quality endoscopic diagnosis, including magnifying endoscopy, narrowband imaging, and other image enhancement, as well as in techniques in endoscopic resection. These emerging techniques will aid the early diagnosis of ESCC that lead to higher chance of curing the cancer.
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Carcinoma de Células Escamosas de Esófago/diagnóstico , Esofagectomía/métodos , Esofagoscopía/métodos , Carcinoma de Células Escamosas/patología , Endoscopía/métodos , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/cirugía , Esófago/patología , Femenino , Humanos , Aumento de la Imagen , Masculino , Neoplasias de la Boca/patología , Imagen de Banda EstrechaRESUMEN
Current therapeutic strategies for pharyngoesophageal stricture, while effective in the short term, are protracted and costly in the longer term. Conceptually, if a stricture can be dilated with minimal tissue injuries, the rate of fibrosis and the resultant stricture recurrence could be reduced. We evaluated a prototype computer-controlled syringe pump device programmed to distend a commercially available balloon dilator at variable rate, asserting incremental lumen distension pressures tailored to the resistive force encountered within the stricture. We completed 17 graded dilatation procedures among 4 total laryngectomy patients. All patients had a short-term response (1 month), with a mean decrement (improvement) in Sydney Swallow Questionnaire score of 448 (total score range, 0-1700; normal <234). The overall procedural tolerability and safety were encouraging; the only complication was the displacement of the voice prosthesis during 1 dilatation. From a technical viewpoint, the main challenge was to maintain the balloon in position during dilatation.
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Trastornos de Deglución/terapia , Dilatación/instrumentación , Estenosis Esofágica/terapia , Laringectomía/efectos adversos , Faringe/patología , Complicaciones Posoperatorias/terapia , Constricción Patológica , Trastornos de Deglución/etiología , Dilatación/métodos , Estenosis Esofágica/etiología , Estudios de Factibilidad , Humanos , Complicaciones Posoperatorias/etiología , Resultado del TratamientoRESUMEN
BACKGROUND: Microbial genetics has formed a foundation for understanding many aspects of biology. Systematic annotation that supports computational data mining should reveal further insights for microbes, microbiomes, and conserved functions beyond microbes. The Ontology of Microbial Phenotypes (OMP) was created to support such annotation. RESULTS: We define standards for an OMP-based annotation framework that supports the capture of a variety of phenotypes and provides flexibility for different levels of detail based on a combination of pre- and post-composition using OMP and other Open Biomedical Ontology (OBO) projects. A system for entering and viewing OMP annotations has been added to our online, public, web-based data portal. CONCLUSIONS: The annotation framework described here is ready to support projects to capture phenotypes from the experimental literature for a variety of microbes. Defining the OMP annotation standard should support the development of new software tools for data mining and analysis in comparative phenomics.
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Ontologías Biológicas , Curaduría de Datos/métodos , Microbiología , Fenotipo , MetadatosRESUMEN
As local drug delivery continues to emerge as a clinical force, so does understanding of its potentially narrow therapeutic window. Classic molecular transport studies are of value but do not typically account for the local nature of drug transport or the effects of regional dynamic function in target tissues like muscle that may undergo cyclical and variable mechanical motion and loading. We examined the impact of dynamic architecture on intramuscular drug distribution. We designed a tissue mounting technique and mechanical loading system that uniquely enables pharmacokinetics investigations in association with control of muscle biomechanics while preserving physiologic tissue architecture. The system was validated and used to elucidate the influence of architecture and controlled cyclic strain on intramuscular drug distribution. Rat soleus muscles underwent controlled deformations within a drug delivery chamber that preserved in vivo physiology. Penetration of 1mM 20 kDa FITC-dextran at planar surfaces of the soleus axial cross-section increased significantly from 0.52+/-0.09 mm under 80 min of static (0%) strain to 0.81+/-0.09 mm under cyclic (3 Hz, 0-20% peak-to-peak) strain, demonstrating the driving effect of cyclic loading on transport. Penetration at curved margins was 1.57- and 2.53-fold greater than at planar surfaces under static and cyclic strain, respectively, and was enhanced 1.6-fold more by cyclic strain, revealing architecturally dictated spatial heterogeneity in transport and modulation of motion dynamics. Architectural geometry and dynamics modulate the impact of mechanical loading on local drug penetration and intramuscular distribution. Future work will use the biomechanical test system to investigate mechanisms underlying transport effects of specific loading regimens. It is hoped that this work will initiate a broader understanding of intramuscular pharmacokinetics and guide local drug delivery strategies.
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Fenómenos Biomecánicos/fisiología , Heparina/farmacología , Músculo Esquelético/fisiología , Animales , Fenómenos Biomecánicos/efectos de los fármacos , Heparina/administración & dosificación , Heparina/farmacocinética , Masculino , Músculo Esquelético/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Estrés Mecánico , Distribución Tisular , Soporte de Peso/fisiologíaRESUMEN
Objectives Dysphagia is common in total laryngectomees, with some symptoms suggesting esophageal dysmotility. Tracheoesophageal (TE) phonation requires effective esophagopharyngeal air passage. Hence, esophageal dysmotility may affect deglutition or TE phonation. This study aimed to determine (1) the characteristics of esophageal dysmotility in laryngectomees, (2) whether clinical history is sensitive in detecting esophageal dysmotility, and (3) the relationship between esophageal dysmotility and TE prosthesis dysfunction. Study Design Multidisciplinary cross-sectional study. Setting Tertiary academic hospital. Subjects and Methods For 31 participants undergone total laryngectomy 1 to 12 years prior, clinical histories were taken by a gastroenterologist and a speech pathologist experienced in managing dysphagia. Esophageal high-resolution manometry was performed and analyzed using Chicago Classification v3.0. Results Interpretable manometric studies were obtained in 23 (1 normal manometry). Esophageal dysmotility patterns included achalasia, esophagogastric junction outflow obstruction, diffuse esophageal spasm, and other major (30%) and minor (50%) peristaltic disorders. The sensitivity of predicting any esophageal dysmotility was 28%, but it is noteworthy that patients with achalasia and diffuse esophageal spasm (DES) were predicted. Two of 4 participants with TE puncture leakage had poor esophageal clearance. Of 20 TE speakers, 12 had voice problems, no correlation between poor voice, and any dysmotility pattern. Conclusions Peristaltic and lower esophageal sphincter dysfunction are common in laryngectomees. Clinical history, while not predictive of minor motor abnormalities, predicted correctly cases with treatable spastic motor disorders. Dysmotility was not associated with poor phonation, although TE puncture leakage might be linked to poor esophageal clearance. Esophageal dysmotility should be considered in the laryngectomees with persisting dysphagia or leaking TE puncture.
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Trastornos de la Motilidad Esofágica/epidemiología , Trastornos de la Motilidad Esofágica/fisiopatología , Laringectomía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/fisiopatología , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Fluoroscopía , Humanos , Masculino , Manometría/métodos , Persona de Mediana Edad , Estudios Prospectivos , Prótesis e ImplantesRESUMEN
Platelet-rich plasma (PRP) is a growing and robust therapeutic option in musculoskeletal medicine. PRP is a preparation of autologous plasma enriched with a platelet concentration above that normally contained in whole blood. The rationale for use and therapeutic potential of a high concentration of platelets is based on their capacity to supply supraphysiologic amounts of essential growth factors to provide a regenerative stimulus that promotes repair in tissues with low healing potential. This article reviews the latest basic science on PRP, clinical evidence for its use in musculoskeletal medicine, limitations in current knowledge, and critical areas for future research.
Asunto(s)
Péptidos y Proteínas de Señalización Intercelular/fisiología , Enfermedades Musculoesqueléticas/terapia , Plasma Rico en Plaquetas , HumanosRESUMEN
OBJECTIVE: Postlaryngectomy, pharyngeal weakness, and pharyngoesophageal junction (PEJ) restriction are the candidate mechanisms of dysphagia. The aims were, in laryngectomees, whether (1) hypopharyngeal propulsion is reduced and/or PEJ resistance is increased, (2) dilatation improves dysphagia, and (3) whether symptomatic improvement correlates with reduced PEJ resistance. DESIGN: Multidisciplinary cross-sectional study. SETTING: Tertiary academic hospital. SUBJECTS AND METHODS: Swallow biomechanics were assessed in 30 laryngectomees. Patients were stratified into severe dysphagia (Sydney Swallow Questionnaire >500) and mild/nil dysphagia (Sydney Swallow Questionnaire ≤500). Average hypopharyngeal peak (contractile) pressure (hPP) and hypopharyngeal intrabolus pressure (hIBP) were measured from high-resolution manometry with concurrent videofluoroscopy based on barium swallows (2.5 and 10 mL). In consecutive 5 patients, measurements were repeated after dilatation. RESULTS: Dysphagia was reported by 87%, and 57% had severe and 43% had mild/nil dysphagia. hIBP increased with larger bolus volumes (P < .0001), while hPP stayed stable and PEJ diameter plateaued at 9 mm. Laryngectomees had lower hPP (110 ± 14 vs 170 ± 15 mm Hg; P = .0162) and higher hIBP (29 ± 5 vs 6 ± 5 mm Hg; P = .156) than controls. There were no differences in hPP between patient groups. However, hIBP was higher in severe than in mild/nil dysphagia (41 ± 10 vs 13 ± 3 mm Hg; P = .02). Predilation hIBP (R(2) = 0.97) and its decrement postdilatation (R(2) = 0.98) well predicted symptomatic improvement. CONCLUSIONS: PEJ resistance correlates better with dysphagia severity than peak pharyngeal pressure and is more sensitive to bolus sizes than PEJ diameter. Both baseline PEJ resistance and its decrement following dilatation are strong predictors of treatment outcome. PEJ resistance is vital to detect, as it is reversible and can predict the response to dilatation regimens.