Workshop on the characterization of fiber-based scaffolds: Challenges, progress, and future directions.

A critical component of many tissue-engineered medical products (TEMPs) is the scaffold or biomaterial. The industry's understanding of scaffold properties and their influence on cell behavior has advanced, but our technical capability to reliably characterize scaffolds requires improvement, especially to enable large-scale manufacturing. In response to the key findings from the 2013 ASTM International Workshop of Standards and Measurements for Tissue Engineering Scaffolds, the National Institute of Standards and Technology (NIST), ASTM International, BiofabUSA, and the Standards Coordinating Body (SCB) organized a workshop in 2018 titled, "Characterization of Fiber-Based Scaffolds". The goal was to convene a group of 40 key industry stakeholders to identify major roadblocks in measurements of fiber-based scaffold properties. This report provides an overview of the findings from this collaborative workshop. The four major consensus findings were that (a) there is need for a documentary standard guide that would aid developers in the selection of test methods for characterizing fiber-based scaffolds; (b) there is a need for a strategy to assess the quality of porosity and pore size measurements, which could potentially be ameliorated by the development of a reference material; (b) there are challenges with the lexicon used to describe and assess scaffolds; and (d) the vast array of product applications makes it challenging to identify consensus test methods. As a result of these findings, a working group was formed to develop an ASTM Standard Guide for Characterizing Fiber-Based Constructs that will provide developers guidance on selecting measurements for characterizing fiber-based scaffolds.

On-Channel Integrated Optofluidic Pressure Sensor with Optically Boosted Sensitivity.

A novel optofluidic sensor that measures the local pressure of the fluid inside a microfluidic channel is presented. It can be integrated directly on-channel and requires no additional layers in fabrication. The detection can be accomplished at a single wavelength; and thereby, only a single laser diode and a single photodetector are required. This renders the sensor to be compact, cheap and easy to fabricate. Basically, the sensor consisted of a Fabry⁻Pérot microresonator enclosing the fluidic channel. A novel structure of the Fabry⁻Pérot was employed to achieve high-quality factor, that was essential to facilitate the single wavelength detection. The enhanced performance was attributed to the curved mirrors and cylindrical lenses used to avoid light diffraction loss. The presented sensor was fabricated and tested with deionized water liquid and shown to exhibit a sensitivity up to 12.46 dBm/bar, and a detection limit of 8.2 mbar. Numerical simulations are also presented to evaluate the mechanical⁻fluidic performance of the device.

A multilayer scaffold design with spatial arrangement of cells to modulate esophageal tissue growth.

Esophageal diseases may require resectioning of the damaged portion. The current standard of care requires the replacement of the esophagus with the stomach or the intestine. Such procedures have high rates of mortality and morbidity; therefore, the use of alternative conduits is needed. A tissue engineering approach that allows for the regeneration of esophageal tissues would have significant clinical application. A cell-seeded synthetic scaffold could replace the resected part of the esophagus and elicit tissue regrowth. In order to ideally recreate a functioning esophagus, its two crucial tissue layers should be induced: an epithelium on the luminal surface and a muscle layer on the exterior surface. To create a bioengineered esophagus with both tissue layers, a multilayer (ML) tubular scaffold design was considered. Luminal and exterior layers were electrospun with broad pore size to promote penetration and proliferation of mesenchymal stem cells on the lumen and smooth muscle cells on the external. These two layers would be separated by a thin layer with substantially narrower pore size intended to act as a barrier for the two cell types. This ML scaffold design was achieved via electrospinning by tuning the solution and the process parameters. Analysis of the scaffold demonstrated that this tuning enabled the production of three integrated layers with distinguishable microstructures and good mechanical integrity. In vitro validation was conducted on the separated unilayer components of the ML scaffold. The resultant proof-of-concept ML scaffold design could possibly support the spatial arrangement of cells needed to promote esophageal tissue regeneration. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 107B: 324-331, 2019.

The Shanfield anastomosis revisited: Its applications and early outcome.

BACKGROUND: Shanfield first described a simple ureteric implantation technique involving a U-stitch anchoring the spatulated end of the transplant ureter to the interior of the intact bladder through a small stab wound. We present an extrapolation of this principle to Mitrofanoff channels and native ureteric reimplantations and further extend it to a laparoscopic approach in some. METHODS: A retrospective case-note reviewing the Shanfield ureteric reimplantation in fifteen children between October 2014 and May 2017 was performed. RESULTS: Fifteen children (females n = 9), median age 6 years (range 8 months-15 years), underwent a Shanfield anastomosis for ureteric (n = 3) or Mitrofanoff (n = 12) implantation into the bladder. Their diagnoses were: vesicoureteric reflux (n = 2), vesicoureteric obstruction (n = 1), neuropathic bladder (n = 4), exstrophy (n = 2, bladder and cloacal), nonneuropathic bladder (n = 3), cloaca (n = 2), and one with failed urethral reconstruction of a Y-duplication. Two ureteric reimplantations and one appendix-Mitrofanoff were undertaken entirely laparoscopically. The bladder was not opened in 9/15, with the remaining six in an ileocystoplasty and one complex cloaca. Fourteen patients were available for follow-up at a median 18.2 (5.8-43.3) months. There was no anastomotic leakage in any, and one stenosis was successfully managed with simple dilatation. One complex patient required a new Mitrofanoff channel. CONCLUSION: Our preliminary data suggest that the Shanfield anastomosis offers a safe, robust, and simple antireflux implantation technique without the need to formally open the bladder. The technique offers several advantages as it allows overcoming the problem of inadequate tunnelling when the bladder template is deficient. Meanwhile, its simplicity permits it to be faithfully reproduced with laparoscopy in select patients. TYPE OF STUDY: Treatment study. LEVEL OF EVIDENCE: IV.

Fabrication and In Vitro Characterization of a Tissue Engineered PCL-PLLA Heart Valve.

Heart valve diseases are among the leading causes of cardiac failure around the globe. Nearly 90,000 heart valve replacements occur in the USA annually. Currently, available options for heart valve replacement include bioprosthetic and mechanical valves, both of which have severe limitations. Bioprosthetic valves can last for only 10-20 years while patients with mechanical valves always require blood-thinning medications throughout the remainder of the patient's life. Tissue engineering has emerged as a promising solution for the development of a viable, biocompatible and durable heart valve; however, a human implantable tissue engineered heart valve is yet to be achieved. In this study, a tri-leaflet heart valve structure is developed using electrospun polycaprolactone (PCL) and poly L-lactic acid (PLLA) scaffolds, and a set of in vitro testing protocol has been developed for routine manufacturing of tissue engineered heart valves. Stress-strain curves were obtained for mechanical characterization of different valves. The performances of the developed valves were hemodynamically tested using a pulse duplicator, and an echocardiography machine. Results confirmed the superiority of the PCL-PLLA heart valve compared to pure PCL or pure PLLA. The developed in vitro test protocol involving pulse duplicator and echocardiography tests have enormous potential for routine application in tissue engineering of heart valves.

Long-term regeneration and remodeling of the pig esophagus after circumferential resection using a retrievable synthetic scaffold carrying autologous cells.

Treatment of esophageal disease can necessitate resection and reconstruction of the esophagus. Current reconstruction approaches are limited to utilization of an autologous conduit such as stomach, small bowel, or colon. A tissue engineered construct providing an alternative for esophageal replacement in circumferential, full thickness resection would have significant clinical applications. In the current study, we demonstrate that regeneration of esophageal tissue is feasible and reproducible in a large animal model using synthetic polyurethane electro-spun grafts seeded with autologous adipose-derived mesenchymal stem cells (aMSCs) and a disposable bioreactor. The scaffolds were not incorporated into the regrown esophageal tissue and were retrieved endoscopically. Animals underwent adipose tissue biopsy to harvest and expand autologous aMSCs for seeding on electro-spun polyurethane conduits in a bioreactor. Anesthetized pigs underwent full thickness circumferential resection of the mid-lower thoracic esophagus followed by implantation of the cell seeded scaffold. Results from these animals showed gradual structural regrowth of endogenous esophageal tissue, including squamous esophageal mucosa, submucosa, and smooth muscle layers with blood vessel formation. Scaffolds carrying autologous adipose-derived mesenchymal stem cells may provide an alternative to the use of a gastro-intestinal conduit for some patients following resection of the esophagus.

Isolating automatic photism generation from strategic photism use in grapheme-colour synaesthesia.

Grapheme-colour synaesthesia is a phenomenon in which ordinary black numbers and letters (graphemes) trigger the experience of highly specific colours (photisms). The Synaesthetic Stroop task has been used to demonstrate that graphemes trigger photisms automatically. In the standard Stroop task, congruent trial probability (CTP) has been manipulated to isolate effects of automaticity from higher-order strategic effects, with larger Stroop effects at high CTP attributed to participants strategically attending to the stimulus word to facilitate responding, and smaller Stroop effects at low CTP reflecting automatic word processing. Here we apply this logic for the first time to the Synaesthetic Stroop task. At high CTP we showed larger Stroop effects due to synaesthetes using their synaesthetic colours strategically. At low CTP Stroop effects were reduced but were still significant. We directly isolate automatic processing of graphemes from strategic effects and conclusively show that, in synaesthesia, viewing black graphemes automatically triggers colour experiences.

Psychometric evaluation of the Work Readiness Questionnaire in schizophrenia.

OBJECTIVE/INTRODUCTION: Unemployment can negatively impact quality of life among patients with schizophrenia. Employment status depends on ability, opportunity, education, and cultural influences. A clinician-rated scale of work readiness, independent of current work status, can be a valuable assessment tool. A series of studies were conducted to create and validate a Work Readiness Questionnaire (WoRQ) for clinicians to assess patient ability to engage in socially useful activity, independent of work availability. METHODS: Content validity, test-retest and inter-rater reliability, and construct validity were evaluated in three separate studies. RESULTS: Content validity was supported. Cronbach's α was 0.91, in the excellent range. Clinicians endorsed WoRQ concepts, including treatment adherence, physical appearance, social competence, and symptom control. The final readiness decision showed good test-retest reliability and moderate inter-rater reliability. Work readiness was associated with higher function and lower levels of negative symptoms. Low positive and high negative predictive values confirmed the concept validity. DISCUSSION: The WoRQ has suitable psychometric properties for use in a clinical trial for patients with a broad range of symptom severity. The scale may be applicable to assess therapeutic interventions. It is not intended to assess eligibility for supported work interventions. CONCLUSIONS: The WoRQ is suitable for use in schizophrenia clinical trials to assess patient work functional potential.

Forensic issues in medical evaluation: competency and end-of-life issues.

Decision-making capacity is a common reason for psychiatric consultation that is likely to become more common as the population ages. Capacity assessments are frequently compromised by misconceptions, such as the belief that incapacity is permanent or that patients with dementia categorically lack capacity. This chapter will review the conceptual framework of decision-making capacity and discuss its application to medical decision-making. We will review selected developments in capacity assessment and recommend an approach to assessing decision-making capacity. We will discuss the unique challenges posed by end-of-life care, including determining capacity, identifying surrogate decision-makers, and working with surrogate decision-makers. We will discuss clinical and legal approaches to incapacity, including advance directives, surrogate decision-makers, and guardians. We will discuss the legal standards based on which surrogates make medical decisions and outline options for resolving disagreements between clinical staff and surrogate decision-makers. We will offer recommendations for approaching decision-making capacity assessments.

Control over the strength of connections between modules: a double dissociation between stimulus format and task revealed by Granger causality mapping in fMRI.

Drawing on theoretical and computational work with the localist dual route reading model and results from behavioral studies, Besner et al. (2011) proposed that the ability to perform tasks that require overriding stimulus-specific defaults (e.g., semantics when naming Arabic numerals, and phonology when evaluating the parity of number words) necessitate the ability to modulate the strength of connections between cognitive modules for lexical representation, semantics, and phonology on a task- and stimulus-specific basis. We used functional magnetic resonance imaging to evaluate this account by assessing changes in functional connectivity while participants performed tasks that did and did not require such stimulus-task default overrides. The occipital region showing the greatest modulation of BOLD signal strength for the two stimulus types was used as the seed region for Granger causality mapping (GCM). Our GCM analysis revealed a region of rostromedial frontal cortex with a crossover interaction. When participants performed tasks that required overriding stimulus type defaults (i.e., parity judgments of number words and naming Arabic numerals) functional connectivity between the occipital region and rostromedial frontal cortex was present. Statistically significant functional connectivity was absent when the tasks were the default for the stimulus type (i.e., parity judgments of Arabic numerals and reading number words). This frontal region (BA 10) has previously been shown to be involved in goal-directed behavior and maintenance of a specific task set. We conclude that overriding stimulus-task defaults requires a modulation of connection strengths between cognitive modules and that the override mechanism predicted from cognitive theory is instantiated by frontal modulation of neural activity of brain regions specialized for sensory processing.

Planning, writing, and editing forensic psychiatric reports.

Forensic psychiatric reports are often the final product of a psychiatrist's work in a particular case because most cases do not go to trial but instead are settled through negotiation or plea bargaining. This article addresses the planning, writing, and editing of forensic reports. Planning a report requires thorough data gathering, and thoughtful organization of the report into specific subheadings. Throughout the report there should be a clear separation of factual data from professional opinions. Ten pitfalls of report writing are identified. The most important part of the forensic report is the opinion section. The evidence for the opinion should begin with the strongest points and the reasons supporting the opinion should be completely explained. Finally, ethical issues are addressed.

Reel forensic experts: Forensic psychiatrists as portrayed on screen.

The lay public is much more likely to have encountered a forensic psychiatrist on television or in the movies than to have encountered a real one. Thus, by way of popular culture, the jury's perceptions and expectations of forensic expert witnesses may have been formed long before they take the stand. We describe a typology of five categories of forensic experts portrayed in fiction: Dr. Evil, The Professor, The Hired Gun, The Activist, and the Jack of All Trades. As art imitates life, these categories (aside from Dr. Evil) mirror real-life criticisms that have been made about forensic experts.

Controlling the porosity of fibrous scaffolds by modulating the fiber diameter and packing density.

Porosity has been shown to be a key determinant of the success of tissue engineered scaffolds. A high degree of porosity and an appropriate pore size are necessary to provide adequate space for cell spreading and migration as well as to allow for proper exchange of nutrients and waste between the scaffold and the surrounding environment. Electrospun scaffolds offer an attractive approach for mimicking the natural extracellular matrix (ECM) for tissue engineering applications. The efficacy of electrospinning is likely to depend on the interaction between cells and the geometric features and physicochemical composition of the scaffold. A major problem in electrospinning is the tendency of fibers to accumulate densely, resulting in poor porosity and small pore size. The porosity and pore sizes in the electrospun scaffolds are mainly dependent on the fiber diameter and their packing density. Here we report a method of modulating porosity in three dimensional (3D) scaffolds by simultaneously tuning the fiber diameter and the fiber packing density. Nonwoven poly(ε-caprolactone) mats were formed by electrospinning under various conditions to generate sparse or highly dense micro- and nanofibrous scaffolds and characterized for their physicochemical and biological properties. We found that microfibers with low packing density resulted in improved cell viability, proliferation and infiltration compared to tightly packed scaffolds.

Retinoid treatment of Emphysema in Patients on the Alpha-1 International Registry. The REPAIR study: study design, methodology and quality control of study assessments.

Emphysema is characterized by the destruction of alveolar wall and enlargement of alveolar airspaces, resulting in a reduction of the total lung gas exchange area, loss of lung elastic recoil and hyperinflation. The REPAIR study (Retinoid treatment of Emphysema in Patients on the Alpha-1 International Registry) is the first proof-of-concept study of a new potential disease-modifying drug, Palovarotene©, an orally active, gamma selective retinoid agonist in patients with emphysema secondary to alpha-1-antitrypsin deficiency (AATD) as a model population for the general smoke-induced emphysema population. This article describes the study design as well as the effectiveness of the quality control that was implemented on the key efficacy endpoints, based on data derived from the placebo-treated subjects. In this multicentre, multinational study the implementation of standardized procedures included: careful site selection, use of trained staff, regular monitoring and machine calibration, use of biological controls and regular feedback to sites by an independent quality control centre. All of these procedures resulted in high-quality measurements of lung density, spirometry, static lung volumes and gas transfer. It was also confirmed that CT lung density was the most sensitive endpoint followed by TLco, FEV(1) and RV measured by body box.

Feigning in adjudicative competence evaluations.

Competence to stand trial (adjudicative competence) is the most requested forensic psychiatric evaluation, with an estimated 60,000 referrals annually. The challenge of detecting feigned incompetence has not been systematically studied until the past decade. Estimates of feigned adjudicative incompetence vary from 8 to 21%. This article reviews techniques for detecting malingered psychosis and malingered cognitive impairment during competence evaluations. Specific techniques for assessing feigned adjudicative incompetence and estimating the malingerer's genuine abilities are discussed. A stepwise approach to suspected feigned adjudicative incompetence is proffered.

Multiscale three-dimensional scaffolds for soft tissue engineering via multimodal electrospinning.

A novel (scalable) electrospinning process was developed to fabricate bio-inspired multiscale three-dimensional scaffolds endowed with a controlled multimodal distribution of fiber diameters and geared towards soft tissue engineering. The resulting materials finely mingle nano- and microscale fibers together, rather than simply juxtaposing them, as is commonly found in the literature. A detailed proof of concept study was conducted on a simpler bimodal poly(epsilon-caprolactone) (PCL) scaffold with modes of fiber distribution at 600 nm and 3.3 microm. Three conventional unimodal scaffolds with mean diameters of 300 nm and 2.6 and 5.2 microm, respectively, were used as controls to evaluate the new materials. Characterization of the microstructure (i.e. porosity, fiber distribution and pore structure) and mechanical properties (i.e. stiffness, strength and failure mode) indicated that the multimodal scaffold had superior mechanical properties (Young's modulus approximately 40MPa and strength approximately 1MPa) in comparison with the controls, despite the large porosity ( approximately 90% on average). A biological assessment was conducted with bone marrow stromal cell type (mesenchymal stem cells, mTERT-MSCs). While the new material compared favorably with the controls with respect to cell viability (on the outer surface), it outperformed them in terms of cell colonization within the scaffold. The latter result, which could neither be practically achieved in the controls nor expected based on current models of pore size distribution, demonstrated the greater openness of the pore structure of the bimodal material, which remarkably did not come at the expense of its mechanical properties. Furthermore, nanofibers were seen to form a nanoweb bridging across neighboring microfibers, which boosted cell motility and survival. Lastly, standard adipogenic and osteogenic differentiation tests served to demonstrate that the new scaffold did not hinder the multilineage potential of stem cells.

Primary ablation of posterior urethral valves in low birth weight neonates by a visually guided fogarty embolectomy catheter.

PURPOSE: In low birth weight neonates primary ablation of posterior urethral valves represents a particular difficulty. The tiny caliber of the urethra presents a challenge for even the smallest commercially available pediatric resectoscope. Transurethral ablation by wired electrodes is difficult due to the narrow field of neonatal scopes with slow irrigation and restricted maneuverability. A Fogarty embolectomy catheter under fluoroscopic control does not allow direct visual assessment, and can be a lengthy procedure with numerous manipulations at the radiology suite. We describe a hybrid technique for primary valve ablation in neonates using a Fogarty catheter working retrograde under direct visual guidance of a neonatal cystoscope. MATERIALS AND METHODS: A total of 17 low birth weight newborns (median 2,100 gm, range 1,760 to 2,690) underwent primary valve ablation using a 2Fr Fogarty catheter working through a 7.5Fr neonatal cystoscope with an offset lens. Both components were withdrawn as a single unit to avulse the valve leaflets under vision. Vesicoureteral reflux was present in 13 patients (76%) involving 24 renal units. A voiding cystourethrogram was performed 8 to 10 weeks postoperatively to delineate adequate decompression of the posterior urethra and mark the end point of the study in evaluating the efficiency of the technique. RESULTS: There were no immediate perioperative complications. Three patients died of causes unrelated to the procedure, leaving 14 boys (21 refluxing units) for evaluation. Voiding cystourethrogram revealed effective decompression of the posterior urethra with adequate drainage in all but 1 remaining patient (93%) due to a persistent left leaflet. Of 21 refluxing units reflux resolved in 6 (29%), was downgraded in 10 (48%) and remained unchanged in 5 (24%). CONCLUSIONS: In low birth weight neonates primary valve ablation by a visually guided Fogarty catheter ensures effective disruption of the valvular obstructive mechanism. The technique maintains the transurethral visual standard and avoids the difficult manipulation of wired electrodes in a restricted field. It is devoid of radiation exposure and its simplicity enables safe performance at the neonatal intensive care unit, where the support needs of this fragile subset of patients are optimally provided for.

Hypoplastic gonadal vessels exiting the deep ring during laparoscopy for impalpable testes: when is inguinal exploration necessary?

BACKGROUND/PURPOSE: During laparoscopy for impalpable testes (IT), if the vas and vessels are found exiting the deep ring, many surgeons proceed to inguinal exploration as a routine, regardless of the adequacy of the vessels or the presence or absence of the processus vaginalis (PV). We tried to find out whether this was necessary in cases with hypoplastic vessels. PATIENTS AND METHODS: This was a retrospective study of cases of IT where during laparoscopy, the vas deferens and the gonadal vessels were seen passing through the deep inguinal ring. Cases were divided into four groups, according to the condition of the PV: present (whether patent or closed) or absent and the adequacy of the vessels. Findings at inguinal exploration and histopathologic examination were compared. RESULTS: Over a period of 4 years, 27 children had laparoscopy for 36 IT. Twenty-three cases (64%) had the vas and vessels passing through the deep ring. Eleven cases (48%) had hypoplastic vessels: 5 (22%) with PV, and on inguinal exploration, 3 (60%) had atrophic testes, and 2 small "nubbins," and 6 (26%) with no PV; 3 with blind ended vas and vessels and 3 with small "nubbins." No case in the last group showed testicular tissue on histopathology. CONCLUSIONS: In cases with hypoplastic vessels exiting the deep inguinal ring, it is the presence or absence of PV that should determine the next step. If it is present, inguinal exploration should follow. If it is absent, exploration is unnecessary.