RESUMEN
Protein adsorption on solid surfaces is a process relevant to biological, medical, industrial, and environmental applications. Despite this wide interest and advancement in measurement techniques, the complexity of protein adsorption has frustrated its accurate prediction. To address this challenge, here, data regarding protein adsorption reported in the last four decades was collected, checked for completeness and correctness, organized, and archived in an upgraded, freely accessible Biomolecular Adsorption Database, which is equivalent to a large-scale, ad hoc, crowd-sourced multifactorial experiment. The shape and physicochemical properties of the proteins present in the database were quantified on their molecular surfaces using an in-house program (ProMS) operating as an add-on to the PyMol software. Machine learning-based analysis indicated that protein adsorption on hydrophobic and hydrophilic surfaces is modulated by different sets of operational, structural, and molecular surface-based physicochemical parameters. Separately, the adsorption data regarding four "benchmark" proteins, i.e., lysozyme, albumin, IgG, and fibrinogen, was processed by piecewise linear regression with the protein monolayer acting as breakpoint, using the linearization of the Langmuir isotherm formalism, resulting in semiempirical relationships predicting protein adsorption. These relationships, derived separately for hydrophilic and hydrophobic surfaces, described well the protein concentration on the surface as a function of the protein concentration in solution, adsorbing surface contact angle, ionic strength, pH, and temperature of the carrying fluid, and the difference between pH and the isoelectric point of the protein. When applying the semiempirical relationships derived for benchmark proteins to two other "test" proteins with known PDB structure, i.e., ß-lactoglobulin and α-lactalbumin, the errors of this extrapolation were found to be in a linear relationship with the dissimilarity between the benchmark and the test proteins. The work presented here can be used for the estimation of operational parameters modulating protein adsorption for various applications such as diagnostic devices, pharmaceuticals, biomaterials, or the food industry.
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Minería de Datos , Interacciones Hidrofóbicas e Hidrofílicas , Propiedades de Superficie , Adsorción , Proteínas/química , Muramidasa/química , Muramidasa/metabolismo , Bases de Datos de Proteínas , Aprendizaje AutomáticoAsunto(s)
Personas con Discapacidad , Suicidio Asistido , Humanos , Principios Morales , Pacientes , Consentimiento InformadoRESUMEN
In many jurisdictions, legal frameworks afford patients the opportunity to make prospective medical decisions or to create directives that contain a special provision forfeiting their own ability to object to those decisions at a future time point, should they lose decision-making capacity. These agreements have been described with widely varying nomenclatures, including Ulysses Contracts, Odysseus Transfers, Psychiatric Advance Directives with Ulysses Clauses, and Powers of Attorney with Special Provisions. As a consequence of this terminological heterogeneity, it is challenging for healthcare providers to understand the terms and uses of these agreements and for ethicists to engage with the nuances of clinical decision-making with such unique provisions surrounding patient autonomy. In theory, prospective self-binding agreements may safeguard patient's "authentic" wishes from future "inauthentic" changes of mind. In practice, it is unclear what may be comprised within these agreements or how-and to what effect-they are used. The primary focus of this integrative review is to curate the existing literature describing Ulysses Contracts (and analogous decisions) used in the clinical arena, in order to empirically synthesize their shared essence and provide insights into the traditional components of these agreements when used in practice, the requirements of their consent processes, and the outcomes of their utilization.
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Trastornos Mentales , Humanos , Trastornos Mentales/psicología , Autonomía Personal , Competencia Mental , Estudios Prospectivos , Directivas Anticipadas , ContratosRESUMEN
Intracranial metastatic disease (IMD) complicates the course of nearly 2-4% of patients with systemic cancer. The prevalence of IMD has been increasing over the past few decades. Historically, definitive treatment for brain metastases (BM) has been limited to radiation therapy or surgical resection. Chemotherapies have not typically proven valuable in the treatment of IMD, with the exception of highly chemotherapy-sensitive lesions. Recent data have supported a role for systemic targeted therapies and immune checkpoint inhibitors (ICIs) in the treatment of select patients with IMD. There remains, however, a clear clinical need for further investigation to delineate the role of ICIs in patients with BM. In this review, we outline and describe recent and current efforts to identify the efficacy of ICI therapy in patients with IMD.
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Neoplasias Encefálicas , Inhibidores de Puntos de Control Inmunológico , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Encefálicas/terapia , InmunoterapiaRESUMEN
Intraoperative hemodynamics can affect postoperative kidney function. We aimed to investigate the effect of intraoperative mean arterial pressure (MAP) as well as other risk factors on the occurrence of acute kidney injury (AKI) after robot-assisted laparoscopic prostatectomy (RALP). We retrospectively evaluated the medical records of 750 patients who underwent RALP. The average real variability (ARV)-MAP, standard deviation (SD)-MAP, time-weighted average (TWA)-MAP, area under threshold (AUT)-65 mmHg, and area above threshold (AAT)-120 mmHg were calculated using MAPs collected within a 10-s interval. Eighteen (2.4%) patients developed postoperative AKI. There were some univariable associations between TWA-MAP, AUT-65 mmHg, and AKI occurrence; however, multivariable analysis found no association. Alternatively, American Society of Anesthesiologists physical status ≥ III and the low intraoperative urine output were independently associated with AKI occurrence. Moreover, none of the five MAP parameters could predict postoperative AKI, with the area under the receiver operating characteristic curve values for ARV-MAP, SD-MAP, TWA-MAP, AUT-65 mmHg, and AAT-120 mmHg being 0.561 (95% confidence interval [CI], 0.424-0.697), 0.561 (95% CI, 0.417-0.704), 0.584 (95% CI, 0.458-0.709), 0.590 (95% CI, 0.462-0.718), and 0.626 (95% CI, 0.499-0.753), respectively. Therefore, intraoperative MAP changes may not be a determining factor for AKI after RALP.
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Lesión Renal Aguda , Laparoscopía , Robótica , Masculino , Humanos , Estudios Retrospectivos , Presión Arterial , Lesión Renal Aguda/etiología , Laparoscopía/efectos adversos , Prostatectomía/efectos adversosRESUMEN
BACKGROUND: In adults, the use of lower oxygen concentration during induction is associated with less atelectasis formation without an increase in incidence of hypoxia. However, it is unknown whether this remains true in the pediatric patients. METHODS: Fifty-four pediatric patients who were scheduled to undergo elective lower abdominal surgery were randomized to one of three oxygenation groups: 100%, 80%, or 60% oxygen (in air). During anesthesia induction, patients were ventilated with sevoflurane in 100%, 80%, or 60% oxygen. Endotracheal intubation and mechanical ventilation were performed. Atelectasis was diagnosed using LUS, which was performed after anesthetic induction and at the end of surgery. RESULTS: We assessed atelectasis after anesthetic induction and at the end of surgery. After anesthetic induction, the number of atelectatic lung regions was significantly different among the three groups (median [IQR], 2.0 [1.0-2.5], 2.0 [1.0-2.8], and 3.0 [2.0-3.0] in the 60%, 80%, and 100% oxygen groups, p = .033) and between the 60% and 100% groups (p = .015), but not between 80% and 100% groups (p = .074). However, no differences in the number of atelectatic lung regions were found among the three groups at the end of surgery (2.0 [1.3-3.8], 3.0 [1.8-3.0], and 4.0 [2.0-4.0] in the 60%, 80%, and 100% oxygen groups; p = .169). CONCLUSION: Lower oxygen concentration during anesthetic induction is associated with less atelectasis formation immediately after anesthetic induction in children. In addition, applying 80% oxygen instead of 100% oxygen is not enough to prevent atelectasis formation, and 60% oxygen should be applied to prevent atelectasis. However, this effect does not last until the end of surgery.
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Respiración con Presión Positiva , Atelectasia Pulmonar , Adulto , Anestesia General/efectos adversos , Niño , Humanos , Pulmón , Oxígeno , Estudios Prospectivos , Atelectasia Pulmonar/prevención & controlRESUMEN
When determining human microbiota composition, shotgun sequencing is a powerful tool that can generate high-resolution taxonomic and functional information at once. However, the technique is limited by missing information about host-to-microbe ratios observed in different body compartments. This limitation makes it difficult to plan shotgun sequencing assays, especially in the context of high sample multiplexing and limited sequencing output and is of particular importance for studies employing the recently described shallow shotgun sequencing technique. In this study, we evaluated the use of a quantitative PCR (qPCR)-based assay to predict host-to-microbe ratio prior to sequencing. Combining a two-target assay involving the bacterial 16S rRNA gene and the human beta-actin gene, we derived a model to predict human-to-microbe ratios from two sample types, including stool samples and oropharyngeal swabs. We then validated it on two independently collected sample types, including rectal swabs and vaginal secretion samples. This assay enabled accurate prediction in the validation set in a range of sample compositions between 4% and 98% nonhuman reads and observed proportions varied between -18.8% and +19.2% from the expected values. We hope that this easy-to-use assay will help researchers to plan their shotgun sequencing experiments in a more efficient way. IMPORTANCE When determining human microbiota composition, shotgun sequencing is a powerful tool that can generate large amounts of data. However, in sample compositions with low or variable microbial density, shallowing sequencing can negatively affect microbial community metrics. Here, we show that variable sequencing depth decreases measured alpha diversity at differing rates based on community composition. We then derived a model that can determine sample composition prior to sequencing using quantitative PCR (qPCR) data and validated the model using a separate sample set. We have included a tool that uses this model to be available for researchers to use when gauging shallow sequencing viability of samples.
RESUMEN
BACKGROUND: Oral and gut microbiomes have emerged as potential biomarkers in cancer. We characterised the oral and gut microbiomes in a prospective observational cohort of HPV+ oropharyngeal squamous cell carcinoma (OPSCC) patients and evaluated the impact of chemoradiotherapy (CRT). METHODS: Saliva, oropharyngeal swabs over the tumour site and stool were collected at baseline and post-CRT. 16S RNA and shotgun metagenomic sequencing were used to generate taxonomic profiles, including relative abundance (RA), bacterial density, α-diversity and ß-diversity. RESULTS: A total of 132 samples from 22 patients were analysed. Baseline saliva and swabs had similar taxonomic composition (R2 = 0.006; p = 0.827). Oropharyngeal swabs and stool taxonomic composition varied significantly by stage, with increased oral RA of Fusobacterium nucleatum observed in stage III disease (p < 0.05). CRT significantly reduced the species richness and increased the RA of gut-associated taxa in oropharyngeal swabs (p < 0.05), while it had no effect in stool samples. These findings remained significant when adjusted by stage, smoking status and antibiotic use. CONCLUSIONS: Baseline oral and gut microbiomes differ by stage in this HPV+ cohort. CRT caused a shift towards a gut-like microbiome composition in oropharyngeal swabs. Stage-specific features and the transitions in oral microbiome might have prognostic and therapeutic implications.
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Quimioradioterapia/efectos adversos , Microbioma Gastrointestinal , Mucosa Bucal/microbiología , Neoplasias Orofaríngeas/terapia , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/complicaciones , Saliva/microbiología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/virología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Mucosa Bucal/efectos de los fármacos , Mucosa Bucal/efectos de la radiación , Neoplasias Orofaríngeas/patología , Neoplasias Orofaríngeas/virología , Infecciones por Papillomavirus/virología , Pronóstico , Estudios Prospectivos , Saliva/efectos de los fármacos , Saliva/efectos de la radiaciónRESUMEN
BACKGROUND: Ongoing controversy exists on postoperative weightbearing status after open reduction and internal fixation of an ankle fracture. This prospective randomized controlled trial aimed to compare patient-based and physician-based outcomes after early weightbearing at 2 vs 6 weeks postoperatively. METHODS: Fifty patients with unstable rotational-type ankle fractures were treated operatively with subsequent immobilization in a below-the-knee cast for 2 weeks and were then randomly allocated to 2 groups. The first group had early weightbearing at 2 weeks postoperation and the second group at 6 weeks postoperation. Follow-up included subjective and objective evaluations performed at 2, 6, 12, and 26 weeks postoperatively. The primary outcome was the patient-based general health status as measured with the EuroQol-5D (EQ-5D) scoring system. Secondary outcome was the Olerud and Molander ankle score. Power analysis revealed a study group of 50 patients was needed to show a clinically relevant effect size of 10 points in both EQ-5D visual analog scale (VAS) score and Olerud and Molander score. RESULTS: Patients in the early weightbearing group had higher mean EQ-5D VAS scores at a 6-week follow-up (P = .014) of 77 ± 14 compared to 66 ± 15 for late mobilization. No difference was found at other follow-up points or between groups for physician-based outcome measures. At 26 weeks postoperatively, mean Olerud and Molander ankle scores were similar at 84 ± 16 and 81 ± 17 for mobilization at 2 and 6 weeks postoperation, respectively. CONCLUSION: Early weightbearing after operative fixation of rotational-type ankle fractures had a clinically relevant and statistically significant benefit in patient-based general health status, as quantified with EQ-5D VAS scores, at 6 weeks postoperation. These results contribute to our understanding of early weightbearing and may encourage consideration of weightbearing at 2 weeks postoperatively in standard protocols. LEVEL OF EVIDENCE: Therapeutic Level I, prospective randomized controlled trial.
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Fracturas de Tobillo/rehabilitación , Fracturas de Tobillo/cirugía , Fijación Interna de Fracturas/métodos , Soporte de Peso , Adulto , Moldes Quirúrgicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Recuperación de la Función , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
BACKGROUND: Increases in the incidence of basal cell carcinoma (BCC) in women, younger age groups and in aggressive scalp subtypes in younger women have been reported. OBJECTIVE: To describe lesion and patient characteristics in scalp BCC. MATERIALS AND METHODS: Retrospective audit of scalp BCCs from 3 pathology laboratories in Adelaide, South Australia, January 2009-December 2013. RESULTS: Scalp BCC was 2.6% of all BCC. Of 2,202 patients with scalp BCC, 62% were male and 78% were >60 years. Histologic subtypes included nodular (55%), mixed (30%), and superficial (8%). The concordance between biopsy and excision was 83% for division into nonaggressive and aggressive subtypes. The incomplete excision rate was 16%. Aggressive subtypes were larger and had perineural invasion (PNI) in 8.5% and incomplete excision in 26%. CONCLUSION: Basal cell carcinoma on the scalp was less common. Men and the elderly had the majority of cases, with no predilection for women, including aggressive histologic subtypes in younger women. Aggressive subtypes were associated with increased size, incomplete excision, and PNI. A preliminary biopsy assisted division into aggressive and nonaggressive histologic subtypes. Incomplete excision rates were higher and increased in aggressive histologic subtypes and PNI. Mohs surgery or wider margins are suggested in these cases.