Photopolymerizable platelet lysate hydrogels for customizable 3D cell culture platforms

3D cell culture platforms have emerged as a setting that resembles in vivo environments replacing the traditional 2D platforms. Over the recent years, an extensive effort has been made on the development of more physiologically relevant 3D cell culture platforms. Extracellular matrix-based materials have been reported as a bioactive and biocompatible support for cell culture. For example, human plasma derivatives have been extensively used in cell culture. Despite all the promising results, in most cases these types of materials have poor mechanical properties and poor stability in vitro. Here plasma-based hydrogels with increased stability are proposed. Platelet lysates are modified by addition of methacryloyl groups (PLMA) that polymerize in controlled geometries upon UV light exposure. The hydrogels could also generate porous scaffolds after lyophilization. The results show that PLMA materials have increased mechanical properties that can be easily adjusted by changing PLMA concentration or modification degree. Cells readily adhere, proliferate, and migrate, exhibiting high viability when encapsulated in PLMA hydrogels. The innovation potential of PLMA materials is based on the fact that it is a complete xeno-free solution for human cell culture, thus an effective alternative to the current gold standards for 3D cell culture based on animal products.publishe

Clinical decision support of therapeutic drug monitoring of phenytoin: measured versus adjusted phenytoin plasma concentrations

<p>Abstract</p> <p>Background</p> <p>Therapeutic drug monitoring of phenytoin by measurement of plasma concentrations is often employed to optimize clinical efficacy while avoiding adverse effects. This is most commonly accomplished by measurement of total phenytoin plasma concentrations. However, total phenytoin levels can be misleading in patients with factors such as low plasma albumin that alter the free (unbound) concentrations of phenytoin. Direct measurement of free phenytoin concentrations in plasma is more costly and time-consuming than determination of total phenytoin concentrations. An alternative to direct measurement of free phenytoin concentrations is use of the Sheiner-Tozer equation to calculate an adjusted phenytoin that corrects for the plasma albumin concentration. Innovative medical informatics tools to identify patients who would benefit from adjusted phenytoin calculations or from laboratory measurement of free phenytoin are needed to improve safety and efficacy of phenytoin pharmacotherapy. The electronic medical record for an academic medical center was searched for the time period from August 1, 1996 to November 30, 2010 for patients who had total phenytoin and free phenytoin determined on the same blood draw, and also a plasma albumin measurement within 7 days of the phenytoin measurements. The measured free phenytoin plasma concentration was used as the gold standard.</p> <p>Results</p> <p>In this study, the standard Sheiner-Tozer formula for calculating an estimated (adjusted) phenytoin level more frequently underestimates than overestimates the measured free phenytoin relative to the respective therapeutic ranges. Adjusted phenytoin concentrations provided superior classification of patients than total phenytoin measurements, particularly at low albumin concentrations. Albumin plasma concentrations up to 7 days prior to total phenytoin measurements can be used for adjusted phenytoin concentrations.</p> <p>Conclusions</p> <p>The results suggest that a measured free phenytoin should be obtained where possible to guide phenytoin dosing. If this is not feasible, then an adjusted phenytoin can supplement a total phenytoin concentration, particularly for patients with low plasma albumin.</p

Photodynamic therapy of early stage oral cavity and oropharynx neoplasms: an outcome analysis of 170 patients

The indications of photodynamic therapy (PDT) of oral cavity and oropharynx neoplasms are not well defined. The main reason is that the success rates are not well established. The current paper analyzes our institutional experience of early stage oral cavity and oropharynx neoplasms (Tis-T2) to identify the success rates for each subgroup according to T stage, primary or non-primary treatment and subsites. In total, 170 patients with 226 lesions are treated with PDT. From these lesions, 95 are primary neoplasms, 131 were non-primaries (recurrences and multiple primaries). The overall response rate is 90.7% with a complete response rate of 70.8%. Subgroup analysis identified oral tongue, floor of mouth sites with more favorable outcome. PDT has more favorable results with certain subsites and with previously untreated lesions. However, PDT can find its place for treating lesions in previously treated areas with acceptable results

Heat Generation During Ablation of Porcine Skin With Erbium:YAG Laser vs a Novel Picosecond Infrared Laser

Importance: Despite significant advances in surgery, most surgical tools remain basic. Lasers provide a means of precise surgical ablation, but their clinical use has remained limited because of undesired thermal, ionizing, or acoustic stress effects leading to tissue injury. A novel ultrafast, nonionizing, picosecond infrared laser (PIRL) system has recently been developed and is capable, in theory, of ablation with negligible thermal or acoustic stress effects. Objective: To measure and compare heat generation by means of thermography during ablation of ex vivo porcine skin by conventional microsecond-pulsed erbium:YAG (Er:YAG) laser and picosecond infrared laser (PIRL). Design and Setting: This study was conducted in an optics laboratory and used a pretest-posttest experimental design comparing 2 methods of laser ablation of tissue with each sample acting as its own control. Intervention: Ex vivo porcine skin was ablated in a 5-mm line pattern with both Er:YAG laser and PIRL at fluence levels marginally above ablation threshold (2 J/cm2 and 0.6 J/cm2, respectively). Main Outcomes and Measures: Peaks and maxima of skin temperature rises were determined using a thermography camera. Means of peak temperature rises were compared using the paired sample t test. Ablation craters were assessed by means of digital microscopy. Results: Mean peak rise in skin surface temperature for the Er:YAG laser and PIRL was 15.0°C and 1.68°C, respectively (P < .001). Maximum peak rise in skin surface temperature was 18.85°C for the Er:YAG laser and 2.05°C for the PIRL. Ablation craters were confirmed on digital microscopy. Conclusions and Relevance: Picosecond infrared laser ablation results in negligible heat generation, considerably less than Er:YAG laser ablation, which confirms the potential of this novel technology in minimizing undesirable thermal injury associated with lasers currently in clinical use

Bone Ablation without Thermal or Acoustic Mechanical Injury via a Novel Picosecond Infrared Laser (PIRL)

Background and Objective: A precise means to cut bone without significant thermal or mechanical injury has thus far remained elusive. A novel non-ionizing ultrafast pulsed picosecond infrared laser (PIRL) may provide the solution. Tissue ablation with the PIRL occurs via a photothermal process with thermal and stress confinement, resulting in efficient material ejection greatly enhanced through front surface spallation photomechanical effects. By comparison, the Er:YAG laser (EYL) ablates via photothermal and cavitation-induced photomechanical effects without thermal or acoustic confinement, leading to significant collateral tissue injury. This study compared PIRL and EYL bone ablation by infrared thermography (IRT), environmental scanning electron microscopy (ESEM), and histology. Study Design: Prospective, comparative, ex vivo animal model. Setting: Optics laboratory. Subjects and Methods: Ten circular area defects were ablated in ex vivo chicken humeral cortex using PIRL and EYL at similar average power (~70 mW) under IRT. Following fixation, ESEM and undecalcified light microscopy images were obtained and examined for signs of cellular injury. Results: Peak rise in surface temperature was negligible and lower for PIRL (1.56°C; 95% CI, 0.762-2.366) compared to EYL ablation (12.99°C; 95% CI, 12.189-13.792) (P < .001). ESEM and light microscopy demonstrated preserved cortical microstructure following PIRL ablation in contrast to diffuse thermal injury seen with EYL ablation. Microfractures were not observed. Conclusion: Ablation of cortical bone using the PIRL generates negligible and significantly less heat than EYL ablation while preserving cortical microstructure. This novel laser has great potential in advancing surgical techniques where precision osseous manipulation is required

Clinicopathological relevance of antithyroglobulin antibodies in low-risk papillary thyroid cancer

OBJECTIVE: The extent of initial surgical management in papillary thyroid cancer (PTC) is controversial. We examined whether the presence of perioperative antithyroglobulin antibodies (TGA) could predict long-term recurrence and occurrence of adverse features among a homogenous group of patients with PTC. METHODS: The clinical features of patients with PTC treated at a single institution (Jewish General Hospital, McGill University, Montreal, Canada) were obtained from the medical records, and all clinicopathologic information was reviewed. Only low-risk PTC without clinical evidence of nodal disease before surgery and treated with 30 mCi of radioactive iodine was included in the study. RESULTS: The chart review retrieved 361 patients with a median follow-up of 85.0 months (Q25-Q75 73-98). Forty-two (11.6%) patients had presence of perioperative TGA. Perioperative TGAs were associated with present extrathyroidal extension (P=.005), unsuspected nodal disease (P=.001) and autoimmune thyroiditis (P<.0001). Overall, 17 (4.7%) patients experienced locoregional recurrence. Perioperative TGAs were a significant predictor of recurrence in univariable (P=.021) but not in multivariable analysis (P=.13). CONCLUSION: Presence of perioperative TGAs is associated with aggressive histological features and the presence of thyroiditis. Detection of TGA perioperatively may encourage surgeons to consider more extensive initial surgery

Multi-dimensional analysis of oral cavity and oropharyngeal defects following cancer extirpation surgery, a cadaveric study

Abstract Background Defects following resection of tumors in the head and neck region are complex; more detailed and defect-specific reconstruction would likely result in better functional and cosmetic outcomes. The objectives of our study were: 1) to improve the understanding of the two- and three-dimensional nature of oral cavity and oropharyngeal defects following oncological resection and 2) to assess the geometric dimensions and the shapes of fasciocutaneous free flaps and locoregional tissue flaps required for reconstruction of these defects. Methods This study was an anatomic cadaveric study which involved creating defects in the oral cavity and oropharynx in two cadaveric specimens. Specifically, partial and total glossectomies, floor of mouth excisions, and base of tongue excisions were carried out. These subsites were subsequently geometrically analyzed and their volumes measured. The two-dimensional (2D) assessment of these three-dimensional (3D) structures included measures of surface area and assessment of tissue contours and shapes. Results The resected specimens all demonstrated unique dimensional geometry for the various anatomic sites. Using 2D analysis, hemiglossectomy defects revealed right triangle geometry, whereas total glossectomy geometry was a square. Finally, the base of tongue defects exhibited a trapezoid shape. Conclusions Customizing the geometry and dimensions of fasciocutaneous free flaps so that they are specific to the confronted head and neck defects will likely result in better functional and cosmetic outcomes

Metabarcoding prey DNA from fecal samples of adult dragonflies shows no predicted sex differences, and substantial inter-individual variation, in diets

Abstract Sexes often differ in foraging and diet, which is associated with sex differences in size, trophic morphology, use of habitats, and/or life history tactics. Herein, strikingly similar diets were found for adult sexes of a dragonfly (Leucorrhinia intacta), based on comparing 141 dietary taxa identified from the metabarcoding of mitochondrial DNA archived in feces. Arthropods in >5% of samples included five species of dipterans, two hemipterans, two spider species and one parasitic mite. The mite was not traditional prey as its presence was likely due to DNA contamination of samples arising through parasitism or possibly via accidental consumption during grooming, and therefore the mite was excluded from diet characterizations. Common prey species were found with statistically indistinguishable frequencies in male and female diets, with one exception of an aphid more often found in male diets, although this pattern was not robust to corrections for multiple statistical tests. While rare prey species were often found in diets of only one sex, instances of this were more frequent in the more oft-sampled females, suggesting sampling artefact. Sexes did not differ in the mean prey species richness in their diets. Overall, sexes showed statistically indistinguishable diets both on a prey species-by-species basis and in terms of multivariate characterizations of diet composition, derived from presence-absence data of prey species analyzed via PERMANOVA and accumulation curves. Males and females may have similar diets by being both opportunistic and generalist predators of arthropods, using the same foraging habitats and having similar sizes and flight agilities. Notably, similarities in diet between sexes occur alongside large interindividual differences in diet, within sexes. Researchers intending on explaining adaptive sex differences in diet should consider characteristics of species whose sexes show similar diets

Evaluating the impact of severe sepsis 3-hour bundle compliance on 28-day in-hospital mortality: A propensity adjusted, nested case-control study

OBJECTIVES: The Centers for Medicare and Medicaid Services Severe Sepsis and Septic Shock Management Bundle (SEP-1) assesses antibiotic administration, lactate measurement, and blood culture collection within 3 h of severe sepsis onset. The impact of the SEP-1 3-hour bundle among patients with severe sepsis is not extensively described. This investigation aimed to describe the impact of 3-hour bundle compliance on 28-day in-hospital mortality in patients with severe sepsis. STUDY DESIGN: This was a retrospective, propensity adjusted, nested case-control study assessing the impact of compliance with a 3-hour sepsis bundle among patients with severe sepsis. SETTING: This study was conducted at a large, academic, tertiary care medical center in Detroit, Michigan from July 1, 2017 to December 31, 2019. PATIENTS: Cases were defined as those suffering 28-day in-hospital mortality. Controls were defined as those surviving at or discharged by 28 days. Patients were separated based on 3-hour bundle compliance or noncompliance. Nested and overall cohorts were assessed. Severe sepsis time zero was manually validated. Patients with shock, requiring vasopressors within 8 h of time zero, or those not meeting SEP-1 inclusion criteria were excluded. INTERVENTION: The primary outcome was the propensity adjusted odds of 28-day in-hospital mortality among 3-hour bundle compliant versus noncompliant patients. Secondary outcomes included mortality for individual bundle element compliance, progression to septic shock, and predictors of mortality according to logistic regression. RESULTS: A total of 325 compliant and 325 noncompliant patients were included. The median Sequential Organ Failure Assessment (SOFA) score was three in each group. There was no difference in propensity adjusted odds of mortality among those compliant versus noncompliant with the 3-hour bundle (odds-ratio [OR] 1.039; 95% CI: 0.721-1.497; p = 0.838) or with individual bundle elements. SOFA score and female sex were predictors of mortality. CONCLUSIONS: Three-hour bundle compliance did not impact 28-day in-hospital mortality in patients with severe sepsis. Further research is needed to understand the impact of 3-hour bundle compliance on mortality in severe sepsis