Embedded Printing of Hydrogels and Watery Suspensions of Cells in Patterned Granular Baths.

Bioprinting within support media has emerged as the superior alternative to conventional extrusion printing. Not only because it allows for more freedom over the shapes that can be printed but also because it allows for the printing of inks that would not retain shape fidelity in freeform deposition such as watery liquids. Apart from functioning as mechanical support during embedded printing, hydrogel microparticle support media can provide the unique advantage of offering distinct chemotactic cues to cells printed in the baths by varying the composition of the hydrogel microparticles. There is great potential in compartmentalized granular baths consisting of different hydrogel particle materials in the field of tissue engineering, as these allow for the local inclusion of properties or cues to guide tissue development. In this work, we present a method to create compartmentalized embedding baths by printing multiple granular hydrogel materials that are widely used in tissue engineering. After adapting the volume fraction (φp) of the particles in the bath, we print within them using both inks composed of hydrogel or of cells and other particles suspended in watery liquid. Our process consists of the following three steps: First, the hydrogel microparticles are packed at a φp that allows them to be extruded while being reversibly jammed, facilitating the localized deposition of the granular media to form a compartmentalized bath. Second, each granular media is deposited in succession to create a packed suspension compartment, and by adding liquid post deposition, φp is reduced to allow for embedded printing. Finally, we demonstrate the printing of multiple inks within the compartmentalized embedding bath and highlight the distinct differences between using inks composed of hydrogels or inks composed of particles suspended in watery liquid. This approach combines the advantages of embedded printing through the use of granular media with the added ability to pattern multiple bioactive granular materials to locally affect the behavior of cells printed within the bath. We expect that this workflow will allow researchers to create spatially compartmentalized, customized bioactive embedding baths that allow for the embedded printing of inks composed of hydrogels, cells, and other particles adapted to their need.

Transcatheter closure of patent foramen ovale using the Cocoon occluder: A multicenter retrospective study.

BACKGROUND: The Cocoon patent foramen ovale (PFO) occluder is a new device especially designed for transcatheter closure of PFO. This occluder has some distinctive structural modifications aimed at reducing the risk of major complications of transcatheter PFO closure. In this report we present our initial experience to evaluate the efficacy and safety of the Cocoon PFO occluder in 253 patients who underwent transcatheter PFO closure. METHODS: The study cohort included 253 patients (median age 45 years) with embolic stroke of undetermined source who underwent attempted transcatheter closure of PFO for secondary prevention of paradoxical embolism. Patients were enrolled retrospectively from five sites in Greece and one in Romania between December 2016 and January 2021, and the median follow-up period was 28 months (range 12-48 months). Clinical and laboratory data from each participating center were sent to an electronic registry for evaluation and statistical analysis. RESULTS: The Cocoon PFO occluder was permanently implanted in all patients. At 6 months, complete occlusion of PFO was observed in 251/253 (99.2%) patients. Three (1.2%) patients had a trivial residual shunt. Thrombus formation on the device, which was successfully treated with recombinant tissue plasminogen activator infusion, was observed in one (0.4%) patient. No other complications occurred. During a median follow-up period of 28 months, 3 (1.2%) patients, aged 64-67 years, developed new onset paroxysmal atrial fibrillation. No neurologic events, cardiac erosions, allergic reactions to nickel, or thrombus formation occurred. CONCLUSION: The Cocoon PFO occluder is an effective and safe device that adds to our armamentarium for transcatheter closure of PFO.

Embedded 3D printing of dilute particle suspensions into dense complex tissue fibers using shear thinning xanthan baths.

In order to fabricate functional organoids and microtissues, a high cell density is generally required. As such, the placement of cell suspensions in molds or microwells to allow for cell concentration by sedimentation is the current standard for the production of organoids and microtissues. Even though molds offer some level of control over the shape of the resulting microtissue, this control is limited as microtissues tend to compact towards a sphere after sedimentation of the cells. 3D bioprinting on the other hand offers complete control over the shape of the resulting structure. Even though the printing of dense cell suspensions in the ink has been reported, extruding dense cellular suspensions is challenging and generally results in high shear stresses on the cells and a poor shape fidelity of the print. As such, additional materials such as hydrogels are added in the bioink to limit shear stresses, and to improve shape fidelity and resolution. The maximum cell concentration that can be incorporated in a hydrogel-based ink before the ink's rheological properties are compromised, is significantly lower than the concentration in a tissue equivalent. Additionally, the hydrogel components often interfere with cellular self-assembly processes. To circumvent these limitations, we report a simple and inexpensive xanthan bath based embedded printing method to 3D print dense functional linear tissues using dilute particle suspensions consisting of cells, spheroids, hydrogel beads, or combinations thereof. Using this method, we demonstrated the self-organization of functional cardiac tissue fibers with a layer of epicardial cells surrounding a body of cardiomyocytes.

Unilateral aural atresia: a case report.

Congenital aural atresia refers to abnormal embryological development of the external auditory canal. The treatment of this anatomical malformation is only surgical repair. This article reports a case of unilateral congenital aural atresia, the surgical procedure performed and the post-operative findings.

Assessment of flow within developing chicken vasculature and biofabricated vascularized tissues using multimodal imaging techniques.

Fluid flow shear stresses are strong regulators for directing the organization of vascular networks. Knowledge of structural and flow dynamics information within complex vasculature is essential for tuning the vascular organization within engineered tissues, by manipulating flows. However, reported investigations of vascular organization and their associated flow dynamics within complex vasculature over time are limited, due to limitations in the available physiological pre-clinical models, and the optical inaccessibility and aseptic nature of these models. Here, we developed laser speckle contrast imaging (LSCI) and side-stream dark field microscopy (SDF) systems to map the vascular organization, spatio-temporal blood flow fluctuations as well as erythrocytes movements within individual blood vessels of developing chick embryo, cultured within an artificial eggshell system. By combining imaging data and computational simulations, we estimated fluid flow shear stresses within multiscale vasculature of varying complexity. Furthermore, we demonstrated the LSCI compatibility with bioengineered perfusable muscle tissue constructs, fabricated via molding techniques. The presented application of LSCI and SDF on perfusable tissues enables us to study the flow perfusion effects in a non-invasive fashion. The gained knowledge can help to use fluid perfusion in order to tune and control multiscale vascular organization within engineered tissues.

Central Retinal Artery Occlusion Secondary to Patent Foramen Ovale: The Unexpected Journey of a Paradoxical Embolus.

Central retinal artery occlusion (CRAO) represents one of the most devastating ophthalmic emergencies, since the inner two-thirds of the retina lose their blood supply. The acute obstruction of the central retinal artery is characterized by severe, sudden and unilateral painless visual loss and usually occurs secondary to an embolus of cardiovascular origin. A paradoxical thromboembolic event of the central retinal artery through patent foramen ovale is an exceptionally unusual clinical entity as well as a great diagnostic challenge since the source of initial thrombus formation requires extensive investigation. Herein, we aim to describe a patient with no significant comorbidities who experienced a paradoxical thromboembolic episode of central retinal artery associated with patent foramen ovale.

Assessment of Cone-beam Computed Tomographic Referral Reasons and the Impact of Cone-beam Computed Tomographic Evaluation on Decision Treatment Planning Procedure in Endodontics.

INTRODUCTION: The aim of the present study was to assess the number of cone-beam computed tomographic (CBCT) referral cases from a private endodontic practice during a 1-year observation period and to investigate if preoperative use of CBCT imaging has an impact on the final diagnosis and decision treatment planning. METHODS: The data of the patients who attended a private endodontic office in Athens, Greece, seeking endodontic treatment from January 2018 to December 2018 were scanned to retrieve all the cases that were further referred for CBCT evaluation. Two qualified (University of Athens) and experienced (more than 10 years of daily practicing) endodontists referred the cases for CBCT imaging. All CBCT cases were evaluated to collect information about the number of cases, the reason for referral, the diagnosis before and after CBCT interpretation, and the treatment planning decision and management of each case. Descriptive statistics were used to describe the clinical characteristics of the study sample. Logistic regression was used to estimate the odds ratios and their 95% confidence intervals. RESULTS: Of a total of 1029 patients (1269 teeth) referred for endodontic treatment, 86 patients were further referred for CBCT imaging (8.35% of the patients). A total of 104 teeth (8.2% of the teeth) were scanned. The most frequent reason for CBCT referral was surgical treatment planning. In 18 of 104 (17.3%) cases, there has been a change of the initial diagnosis after CBCT interpretation. Posterior and endodontically treated teeth without lesions presented 4.35 and 6.6 times times higher odds, respectively, of having a change in the initial diagnosis after CBCT evaluation. CONCLUSIONS: A small percentage of patients referred for endodontic treatment or retreatment are further referred by specialists for CBCT imaging. CBCT scanning was considered necessary both for all surgical treatment planning cases and the evaluation of inflammatory resorptive defects.

Magnetic skyrmions in FePt nanoparticles having Reuleaux 3D geometry: a micromagnetic simulation study.

The magnetization reversal in magnetic FePt nanoelements having Reuleaux 3D geometry is studied using micromagnetic simulations employing Finite Element discretizations. Magnetic skyrmions are revealed in different systems generated by the variation of the magnitude of the magnetocrystalline anisotropy which was kept normal to the nanoelement's base and parallel to the applied external field. The topological quantity of skyrmion number is computed in order to characterize micromagnetic configurations exhibiting skyrmionic formations. Micromagnetic configurations with a wide range of skyrmion numbers between -3 and 3 are indicative for the existence of one or multiple skyrmions that have been detected and stabilized in a range of external fields. Internal magnetic structures are shown consisting of Bloch type skyrmionic entities in the bulk altered to Néel skyrmions on the nanoelement's bottom and top base surfaces. The actual sizes of the formed skyrmions and the internal magnetization structures were computed. In particular, the sizes of the generated and persistent skyrmions were calculated as functions of the magnetocrystalline anisotropy value and of the applied external magnetic field. It is shown that the size of skyrmions is linearly dependent on the external field value. The slope of the linear curve can be controlled by the magnetocrystalline anisotropy value. The magnetic skyrmions can be created for FePt magnetic systems lacking of chiral interactions by designing the geometry-shape of the nanoparticle and by controlling the value of magnetocrystalline anisotropy.

A novel deep learning architecture outperforming 'off­the­shelf' transfer learning and feature­based methods in the automated assessment of mammographic breast density.

Potentially suspicious breast neoplasms could be masked by high tissue density, thus increasing the probability of a false­negative diagnosis. Furthermore, differentiating breast tissue type enables patient pre­screening stratification and risk assessment. In this study, we propose and evaluate advanced machine learning methodologies aiming at an objective and reliable method for breast density scoring from routine mammographic images. The proposed image analysis pipeline incorporates texture [Gabor filters and local binary pattern (LBP)] and gradient­based features [histogram of oriented gradients (HOG) as well as speeded­up robust features (SURF)]. Additionally, transfer learning approaches with ImageNet trained weights were also used for comparison, as well as a convolutional neural network (CNN). The proposed CNN model was fully trained on two open mammography datasets and was found to be the optimal performing methodology (AUC up to 87.3%). Thus, the findings of this study indicate that automated density scoring in mammograms can aid clinical diagnosis by introducing artificial intelligence­powered decision­support systems and contribute to the 'democratization' of healthcare by overcoming limitations, such as the geographic location of patients or the lack of expert radiologists.

Use of a temporary shunt to preserve the patency of a hemodialysis graft while performing ipsilateral axillo-femoral bypass.

Increased blood flow in the subclavian artery feeding a vascular access for hemodialysis can rarely induce steal phenomena in the vertebral and internal mammary artery leading to potentially life-threatening conditions. On the contrary, transient interruption of blood flow in the subclavian artery feeding a dialysis arteriovenous fistula can theoretically induce access thrombosis. Here, we describe a technical maneuver preserving continuous ipsilateral upper arm access flow when constructing a unilateral axillo-femoral polytetrafluoroethylene bypass operation for critical limb ischemia in a hemodialysis patient.

Ultrahigh-Throughput Production of Monodisperse and Multifunctional Janus Microparticles Using in-Air Microfluidics.

Compartmentalized Janus microparticles advance many applications ranging from chemical synthesis to consumer electronics. Although these particles can be accurately manufactured using microfluidic droplet generators, the per-nozzle throughputs are relatively low (∼µL/min). Here, we use "in-air microfluidics" to combine liquid microjets in midair, thereby enabling orders of magnitude faster production of Janus microparticles (∼mL/min) as compared to chip-based microfluidics. Monodisperse Janus microparticles with diameters between 50 and 500 µm, tunable compartment sizes, and functional cargo are controllably produced. Furthermore, these microparticles are designed as magnetically steerable microreactors, which represents a novel tool to perform enzymatic cascade reactions within continuous fluid flows.

Headache Linked to Intracranial Hypertension and Hypertrophic Pachymeningitis as the Initial and Dominant Presentation of Granulomatosis With Polyangiitis. Case Report and Review of the Recent Literature.

OBJECTIVE: The objective of this article is to report a rare case of headache as the initial symptom of granulomatosis with polyangiitis (GPA) and to review the recent literature. BACKGROUND: Granulomatosis with polyangiitis is a rare, systemic, autoimmune disease of unknown etiology. GPA has a wide spectrum of clinical symptomatology, including involvement of the nervous system, even as the initial manifestation. Symptoms of the peripheral nervous system used to dominate the clinical symptomatology. However, recent reports are focusing increasingly in granulomatous lesions of the central nervous system, and especially on the increased frequency of patients with hypertrophic pachymeningitis (HP). We report the case of a patient with headache linked to intracranial hypertension and hypertrophic pachymeningitis as the initial and dominant presentation of GPA and we review the recent literature. METHODS: A 54-year-old male, without any related medical history developed a severe headache. In the following 2 months, he gradually developed hoarseness and diplopia at the left and lower fields of vision. A brain MRI revealed wide-spread fattening and meningeal enhancement over the left hemisphere and the left cerebellar hemisphere. An endoscopy of the pharynx revealed the presence of a tumor-like mass in the left half of the nasopharynx. A biopsy showed inflammation with presence of polykaryocyte Langhans giant cells. The laboratory testing revealed important albuminuria and microhematuria, positive c-ANCA and negative p-ANCA. A diagnosis of GPA was established. RESULTS: A steroid treatment was administered initially, which improved the headache drastically, followed by the administration of a combination of cyclophosphamide and corticosteroid, which led to a gradual resolve of the remaining symptomatology. A follow-up brain MRI showed a decrease in meningeal enhancement, whereas a second one, 2 years later, was completely normal. CONCLUSIONS: HP was considered an extremely rare manifestation of GPA. However, recent studies are reporting an increased frequency of HP and are distinguishing a granulomatous and a vasculitic phenotype, with different localization and relapse rates, that may eventually constitute a different clinical spectrum of GPA.

Great trochanter bursitis vs sciatica, a diagnostic-anatomic trap: differential diagnosis and brief review of the literature.

PURPOSE: The purpose of this study is to point out the difficulty of differentiating great trochanter bursitis (GTB) from sciatica and estimating the prevalence of GTΒ, in patients poorly diagnosed with sciatica in their first visit to the general practitioner and referred to a spine infirmary. METHODS: The diagnosis of GTΒ was made based on history and physical examination, and was confirmed by ultrasonography and/or response to an anesthetic plus corticosteroid injection to the trochanteric bursa. Demographic and clinical characteristics of the study group were evaluated. The statistical analysis was held with the SPSS pc package (version 24.0). RESULTS: In a total of 657 referrals for sciatica, 72 patients (10.95%) were incorrectly diagnosed as suffering from sciatica, whereas, in fact, they were suffering from GTΒ. In addition, 18 patients (2.74%) were diagnosed as suffering from persistent sciatica with coexisting GTΒ. More women than men had GTΒ (79-11). Mean age for patients with sciatica diagnosis but suffering from GTΒ was 60 years. Mean age for patients with both sciatica and GTΒ was 61 years. CONCLUSIONS: The GTB is a common clinical entity in middle-aged women, which can escape from the physician in cases of incomplete medical history and clinical examination, leading to unnecessary imaging tests and treatment approaches, burdening both the patient and the health system. Early diagnosis of GTB may dramatically reduce cost, prevent unwanted and inappropriate imaging exams and treatment, and make the patient free of symptoms immediately. These slides can be retrieved under Electronic Supplementary Material.

A Bayesian Model for the Prediction and Early Diagnosis of Alzheimer's Disease.

Alzheimer's disease treatment is still an open problem. The diversity of symptoms, the alterations in common pathophysiology, the existence of asymptomatic cases, the different types of sporadic and familial Alzheimer's and their relevance with other types of dementia and comorbidities, have already created a myth-fear against the leading disease of the twenty first century. Many failed latest clinical trials and novel medications have revealed the early diagnosis as the most critical treatment solution, even though scientists tested the amyloid hypothesis and few related drugs. Unfortunately, latest studies have indicated that the disease begins at the very young ages thus making it difficult to determine the right time of proper treatment. By taking into consideration all these multivariate aspects and unreliable factors against an appropriate treatment, we focused our research on a non-classic statistical evaluation of the most known and accepted Alzheimer's biomarkers. Therefore, in this paper, the code and few experimental results of a computational Bayesian tool have being reported, dedicated to the correlation and assessment of several Alzheimer's biomarkers to export a probabilistic medical prognostic process. This new statistical software is executable in the Bayesian software Winbugs, based on the latest Alzheimer's classification and the formulation of the known relative probabilities of the various biomarkers, correlated with Alzheimer's progression, through a set of discrete distributions. A user-friendly web page has been implemented for the supporting of medical doctors and researchers, to upload Alzheimer's tests and receive statistics on the occurrence of Alzheimer's disease development or presence, due to abnormal testing in one or more biomarkers.

Optimal primary management of bulky stage IIIC ovarian, fallopian tube and peritoneal carcinoma: Are the only options complete gross resection at primary debulking surgery or neoadjuvant chemotherapy?

OBJECTIVE: To explore the impact of primary debulking surgery (PDS) to minimal but gross residual disease (RD) in women with bulky stage IIIC ovarian, fallopian tube, or primary peritoneal cancer. METHODS: We retrospectively reviewed all patients with the aforementioned diagnosis who underwent PDS at our institution from 01/2001-12/2010. Those with disease of non-epithelial histology or borderline tumors were excluded. Clinicopathologic data were abstracted, and appropriate statistical tests were used. RESULTS: We identified 496 eligible patients. Median age was 62years; 91% had disease of serous histology. Patients were grouped by RD status: no gross RD, 184 (37%); RD of 1-5mm, 127 (26%); RD of 6-10mm, 54 (11%); and RD >10mm, 131 (26%). With a median follow-up of 53months, the median progression-free survivals (PFS) were: 26.7, 20.7, 16.2, and 13.6months, respectively (p<0.001). The median overall survivals (OS) were 83.4, 54.5, 43.8, and 38.9months, respectively (p<0.001). Among patients with RD following PDS, those with RD of 1-10mm had improved PFS (p<0.001) and OS (p=0.001) compared with those with RD >10mm. Patients with RD 1-10mm who received intravenous/intraperitoneal (IV/IP) chemotherapy were younger and had prolonged OS compared with those solely exposed to IV chemotherapy (p<0.001 and p=0.002, respectively). CONCLUSIONS: PDS to no gross RD was associated with the longest PFS and OS. However, cytoreduction to 1-10mm of RD was also associated with better survival outcomes compared with cytoreduction to >10mm of RD. We conclude that PDS remains an appropriate option for patients with a high likelihood of achieving RD 1-10mm, especially for younger patients who can receive IV/IP chemotherapy after PDS.

Multicompartment Artificial Organelles Conducting Enzymatic Cascade Reactions inside Cells.

Cell organelles are subcellular structures entrapping a set of enzymes to achieve a specific functionality. The incorporation of artificial organelles into cells is a novel medical paradigm which might contribute to the treatment of various cell disorders by replacing malfunctioning organelles. In particular, artificial organelles are expected to be a powerful solution in the context of enzyme replacement therapy since enzymatic malfunction is the primary cause of organelle dysfunction. Although several attempts have been made to encapsulate enzymes within a carrier vehicle, only few intracellularly active artificial organelles have been reported to date and they all consist of single-compartment carriers. However, it is noted that biological organelles consist of multicompartment architectures where enzymatic reactions are executed within distinct subcompartments. Compartmentalization allows for multiple processes to take place in close vicinity and in a parallel manner without the risk of interference or degradation. Here, we report on a subcompartmentalized and intracellularly active carrier, a crucial step for advancing artificial organelles. In particular, we develop and characterize a novel capsosome system, which consists of multiple liposomes and fluorescent gold nanoclusters embedded within a polymer carrier capsule. We subsequently demonstrate that encapsulated enzymes preserve their activity intracellularly, allowing for controlled enzymatic cascade reaction within a host cell.

Robotically Assisted Laparoscopic Ovarian Transposition in Women with Lower Gastrointestinal Cancer Undergoing Pelvic Radiotherapy.

BACKGROUND: Pelvic radiotherapy (RT) is a standard component of the management for patients with locally advanced rectal cancer or squamous cell carcinoma of the anus. Pelvic RT leads to permanent and irreversible ovarian failure in young women. This study aimed to determine the effectiveness of robotically assisted laparoscopic ovarian transposition (OT) before RT in women with rectal or anal cancer who wanted to preserve normal ovarian function. METHODS: The study reviewed the medical records of all patients treated at our institution from August 2009 to October 2014 who received robotically assisted laparoscopic OT for rectal or anal cancer before RT. Clinical and hormonal data were abstracted to determine ovarian function. RESULTS: The study identified 22 women with rectal (n = 20) or anal (n = 2) cancer. The median age of the women was 39 years (range 26-45 years). For one patient, OT was technically not feasible. The postoperative course was uneventful in all but one case. Follow-up data on ovarian function were unavailable for 3 patients. The median times from RT initiation to the last gynecologic or hormonal evaluation were 9 months (range 5-47 months) and 10.5 months (range 5-47 months), respectively. At the last gynecologic or hormonal follow-up visit, ovarian function was preserved in 12 (67%) of 18 evaluable patients, including 9 (90%) of 10 patients 40 years of age or younger and 3 (38%) of 8 patients older than 40 years (P = 0.07). CONCLUSIONS: Robotically assisted laparoscopic bilateral OT is safe and can lead to preservation of ovarian function in two-thirds of patients with low gastrointestinal cancer undergoing pelvic RT. It should be considered in this setting, especially for women age 40 years or younger, to avoid premature menopause and its associated sequelae.

Fenestrated and Branched Stent Grafting in Complex Aneurysmatic Aortic Disease: A Single-Center Early Experience.

BACKGROUND: The aim of this study is to present our early experience and highlight the technical difficulties associated with the use of fenestrated and branched stent grafts to treat patients with juxtarenal abdominal aortic aneurysm (AAA), pararenal AAA, and thoracoabdominal aortic aneurysms (TAAAs). METHODS: A prospectively held database maintained at our department was queried for patients who have undergone branched and fenestrated stent grafting for AAA or TAAA treatment. Indication for repair, comorbidity precluding open repair, technical challenges associated with the repair, as well as operative mortality, morbidity, and reintervention rate were evaluated. RESULTS: A total of 8 patients underwent repair with a fenestrated or branched stent graft. All patients had aneurysmal degeneration of the juxtarenal aorta, pararenal aorta, and thoracoabdominal aorta not suitable to standard endovascular techniques. Two patients had a prior aortic repair, a failed migrated stent graft, and an old surgical tube graft after an open repair. One patient had a type III TAAA and 1 patient had a postdissection TAAA type I. For all patients, target vessel success rate was 96.4% (27/28) and mean hospital stay was 6.0 days (range 3-21). Thirty-day and 1-year mortality were 0%. Mean follow-up was 23 months (range 7-45). Two endoleaks occurred, 1 type III and 1 type II, which were treated endovascularly. No death or major complication occurred during follow-up. CONCLUSIONS: Fenestrated and branched endovascular stent grafts can be used to repair juxtarenal AAA, pararenal AAA, and TAAA in patients with significant comorbidities. However, several technical challenges have to be overcome due to the unique complex aortic pathology of each patient.

Endovascular Treatment of Type Ib Endoleak after Evar Using the IBD Device: A Case Report.

In the modern endovascular era, abdominal aortic aneurysm repair is still not free of complications with re-interventions following endovascular aneurysm repair (EVAR) being more common than with open surgical repair. A variety of endovascular, open surgical and combined techniques were described according to the anatomical considerations and general health of the patient to achieve the best possible result after these complications. In cases of type Ib endoleak following aorto-uni-lateral EVAR for an abdominal aortic aneurysm, the use of the internal branched device (IBD) constitutes a safe and effective technique.