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(1) Background: Preclinical and clinical data about a novel radiofrequency ablation (RFA) system (STARmed Co, Ltd.; Koyang, Korea) designed to be used under endoscopic ultrasound (EUS) control for pancreatic lesion ablation, are limited, obtained with non-standardized procedures and heterogeneous results. The aim of this study is to standardize the RFA procedure of this system in order to define the optimal ablation power and time. (2) Methods: RFA was performed on an ex-vivo porcine liver at different powers (40, 30, 20, 10 Watts (W)) and times (1, 3, 5, 7, 15 min) with a 1-centimeter monopolar electrode (perfused by chilled solution) positioned on the distal tip of a 19-Gauge needle. A blinded expert pathologist histologically analyzed each ablation area. (3) Results: The size of the total macroscopic ablated area was negatively correlated with ablation power (R −0.74): the largest was obtained at 10 W (p = 4.7 × 10−4) for longer times (R 0.92; p = 8.9 × 10−8). Central histologic coagulative necrosis did not differ among ablation settings (mean size 3.25 mm). External “parenchymal hypochromia” or “diaphanization” resulted the widest at 10 W, for longer times (R 0.8, p = 3.6 × 10−4). (4) Conclusions: The RFA system can produce small sizes of coagulative necrosis, regardless of the setting. Larger areas of diaphanization surrounding the necrosis can be produced at lower powers for longer times.

Autologous cranioplasty is an increasingly common procedure performed in neurosurgical centers following a decompressive craniectomy. Available evidence on the safety of autologous bone flap preservation and cranioplasty is limited due to a large diversity in study conducted, nature of pathology and reported outcomes. In this Institutional Review Board-approved retrospective observational study, patients who underwent neurosurgical intervention as“craniectomy followed by cranioplasty” at the Department of Neurological Surgery, Kathmandu Medical College Teaching Hospital were enrolled retrospectively from 1st May 2012 to 30th April2019. The craniectomy bone flap was preserved exvivo, dipped in spirit solution in deep freeze, then autoclaved prior to cranioplasty. Data were collected from the hospital’s electronic database. Information analyzed included patient age, sex, indication forcraniectomy, interval between craniectomy and cranioplasty, length of hospital stay, peri-operativecomplications and mean time of follow-up. Patients who underwent a cranioplasty following removal of an infected bone flap after a craniotomy were excluded from the study. Associated complications were assessed and statistical analysis was performed using a Fisher’s exact test. There were a total of 210 patients with 92vascular, 58 post traumatic. With all these surgeries undergone we had 9% complication rate, all of whom underwent cranioplasty later than four weeks of primary surgery (p =

In 2021, as the situation due to COVID-19 pandemic was still uncertain, the 18 th annual meeting of the Interuniversity Institute of Myology (IIM), took place on a virtual platform, following the same organization already tested for the previous edition. Participants from Italy, European countries, Canada and USA included clinicians, scientists, pharmaceutical companies and representatives of patient organizations. Four keynote speakers presented new insights into the modulation of muscle stem cell self-renewal in the treatment of neuromuscular disease, the role of nuclear positioning in muscle function, regeneration and tumorigenesis in the heart and advances on therapies of muscular dystrophies. Young PhD students and trainees presented oral communications distributed in five scientific sessions and posters in two poster sessions. On October 21, 2021, selected young scientists participated in the “High Training Course on Advanced Myology”, organized with the University of Perugia, Italy. This course consisted of lectures on muscle regeneration and therapeutic perspectives by internationally recognized speakers, followed by roundtable discussions on “Omics technologies in myology” and “New therapeutic approaches”, plus the meeting itself. Young trainees, winners of past IIM conferences, forming the Young IIM Committee, selected one of Keynote speakers and were involved in the organization of scientific sessions and roundtable discussions. The friendly welcoming of the meeting, which has strongly characterized this event and is of great help in facilitating scientific exchanges and stimulating novel collaborations, was the hallmark of the conference this year again, even on virtual platform. Breakthrough studies showing interdisciplinary works are fostering new avenues in the field of myology. This year again, scientists and students attended the meeting at the huger number, challenging the difficulties due to the COVID-19 pandemic. All participants shared the wish to continue and implement IIM meeting with new insights on muscle biology, perspectives in the understanding of the muscle-related diseases and in novel therapeutic approaches. We report here abstracts of the meeting describing basic, translational, and clinical research contributing to the large field of myology.

Background: Given the current organ shortage crisis, split liver transplantation (SLT) has emerged as a promising alternative for select end-stage liver disease patients., Aim: To introduce an ex-vivo liver graft splitting approach and evaluate its safety and feasibility in SLT., Methods: A retrospective analysis was conducted on the liver transplantation data from cases performed at our center between April 1, 2022, and May 31, 2023. The study included 25 SLT cases and 81 whole liver transplantation (WLT) cases. Total ex-vivo liver splitting was employed for SLT graft procurement in three steps. Patient outcomes were determined, including liver function parameters, postoperative complications, and perioperative mortality. Group comparisons for categorical variables were performed using the χ² -test., Results: In the study, postoperative complications in the 25 SLT cases included hepatic artery thrombosis ( n = 1) and pulmonary infections ( n = 3), with no perioperative mortality. In contrast, among the 81 patients who underwent WLT, complications included perioperative mortality ( n = 1), postoperative pulmonary infections ( n = 8), abdominal infection ( n = 1), hepatic artery thromboses ( n = 3), portal vein thrombosis ( n = 1), and intra-abdominal bleeding ( n = 5). Comparative analysis demonstrated significant differences in alanine aminotransferase (176.0 vs 73.5, P = 0.000) and aspartate aminotransferase (AST) (42.0 vs 29.0, P = 0.004) at 1 wk postoperatively, and in total bilirubin (11.8 vs 20.8, P = 0.003) and AST (41.5 vs 26.0, P = 0.014) at 2 wk postoperatively. However, the overall incidence of complications was comparable between the two groups ( P > 0.05)., Conclusion: Our findings suggest that the total ex-vivo liver graft splitting technique is a safe and feasible approach, especially under the expertise of an experienced transplant center. The approach developed by our center can serve as a valuable reference for other transplantation centers., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interests or disclosures to report., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Four-dimensional flow magnetic resonance imaging (4D flow MRI) can accurately visualize and quantify flow and provide hemodynamic information such as wall shear stress (WSS). This imaging technique can be used to obtain more insight in the hemodynamic changes during cardiac cycle in the true and false lumen of uncomplicated acute Type B Aortic Dissection (TBAD). Gaining more insight of these forces in the false lumen in uncomplicated TBAD during optimal medical treatment, might result in prediction of adverse outcomes. Methods: A porcine aorta dissection model with an artificial dissection was positioned in a validated ex-vivo circulatory system with physiological pulsatile flow. 4D flow MR images with 3 set heartrates (HR; 60 bpm, 80 bpm and 100 bpm) were acquired. False lumen volume per cycle (FLV), mean and peak systolic WSS were determined from 4D flow MRI data. For validation, the experiment was repeated with a second porcine aorta dissection model. Results: During both experiments an increase in FLV (initial experiment: ΔFLV = 2.05 ml, p < 0.001, repeated experiment: ΔFLV = 1.08 ml, p = 0.005) and peak WSS (initial experiment: ΔWSS = 1.2 Pa, p = 0.004, repeated experiment: ΔWSS = 1.79 Pa, p = 0.016) was observed when HR increased from 60 to 80 bpm. Raising the HR from 80 to 100 bpm, no significant increase in FLV (p = 0.073, p = 0.139) was seen during both experiments. The false lumen mean WSS increased significant during initial (2.71 to 3.85 Pa; p = 0.013) and non-significant during repeated experiment (3.22 to 4.00 Pa; p = 0.320). Conclusion: 4D flow MRI provides insight into hemodynamic dimensions including WSS. Our ex-vivo experiments showed that an increase in HR from 60 to 80 bpm resulted in a significant increase of FLV and WSS of the false lumen. We suggest that strict heart rate control is of major importance to reduce the mean and peak WSS in uncomplicated acute TBAD. Because of the limitations of an ex-vivo study, 4D flow MRI will have to be performed in clinical setting to determine whether this imaging model would be of value to predict the course of uncomplicated TBAD. [ABSTRACT FROM AUTHOR]

The evaluation of the corneal biomechanical behaviour has important clinical applications. To name a few, the accuracy of the intraocular pressure measurement, the study of corneal ectatic diseases and the assessment and optimisation of corneal surgical procedures are all highly influenced by corneal biomechanics. Over the last 45 years different ex-vivo methods were developed to study corneal biomechanical behaviour. Different tissue maintenance, support, loading systems, as well as different monitoring strategies of corneal deformations were employed. In this review, the most important and commonly used methods are outlined, including strip extensiometry, inflation, compression, indentation and tissue separation testing. Their particularities, applications, pros and cons and main applications are discussed.

The aim of this document is to present an overview of gene electrotransfer in ophthalmological disorders. In order to ensure an adequate variety of the assessed studies, several electronic databases were considered and studies published between January 1998 and December 2021 were analysed. Three investigators carried out data extraction and analysis, focusing on both technical (i.e., electrical protocol, type of electrode, plasmid) and medical (i.e., type of study, threated disease) aspects and highlighting the main differences in terms of results obtained. Moreover, the IGEA experience in the project “Transposon-based, targeted ex vivo gene therapy to treat age-related macular degeneration” (TargetAMD) was reported in the results section. No clinical trial was found on international literature and on ClinicalTrials.gov. Twelve preclinical studies were found including in vivo and ex-vivo applications. The studied showed that electrotransfer could be very efficient for plasmid DNA transfection. Many attempts such as modification of the electric field, buffers and electrodes have been made and the optimization of electric field setting seems to be very important. Using this technique, gene replacement can be designed in cases of retinal inheritance or corneal disease and a wide range of human eye diseases could, in the future, benefitfrom these gene therapy technologies.

Several different bioreactors have been developed to study bone biology. Keeping a bone viable for long-term studies is still a challenge. We have developed an ex-vivo bone bioreactor that can keep the ex-vivo live bone viable for more than 4 weeks. Keeping a bone viable for over a month can be used as an alternative model for in-vivo experiments in animals. We hypothesize that the perfusion flow and mechanical load on the bone provide a real-time environment for the bone to survive. Cancellous bones were harvested from the bovine metatarsals and were placed in the dynamic culture with cyclic loading at regular intervals. After a period of week 4, the bone cores were retrieved from the bioreactor and tested for viability using calcein-AM and ethidium homodimer −1 fluorescent dyes and were compared with the cores that were placed in static culture with and without any loads on them and Day 0 bone core that acted as a positive control. The bone blocks were then fixed in 10% formalin, and bone mineral density was evaluated using a DXA scanner before staining them for H&E to study the morphological changes. Results revealed that the bone cultured in the bioreactor was viable as compared to the one in the static culture with and without constant load. Bone cores cultured in our ex-vivo bioreactor system also maintained their morphology and no statistical difference was found in the bone mineral density compared to positive controls and the statistical difference was found when compared with the cores cultured in static culture. This tool can be used to study bone biology for various applications such as bone ingrowth studies, to study the effect of drugs, hormones, or any growth factors, and much more.

Background: Spontaneous hyperinflation is reported to the Food and Drug Administration as a complication of intragastric balloons. It is postulated that orogastric contamination of the intragastric balloon may cause this phenomenon. We sought to investigate the effects of intentional balloon contamination with gastric contents on intragastric balloon perimeter and contents, whether methylene blue plays a role in preventing spontaneous hyperinflation, and review the available literature on spontaneous hyperinflation.Methods: Four pairs of balloons with different combinations of sterile saline, orogastric contaminants, and methylene blue were incubated in a 37 °C water bath for six months to simulate physiological conditions with serial measurements of balloon perimeter. Our findings were compared against a systematic review across multiple databases to summarize the available literature.Results: Balloon mean perimeter decreased from 33.5 cm ± 0.53 cm to 28.5 cm ± 0.46 cm (p < 0.0001). No significant differences were seen with the methylene blue group. Only 11 cases were found reported in the literature.Conclusions: Despite contaminating intragastric balloons with gastric aspirates, hyperinflation did not occur, and other factors may be in play to account for this phenomenon, when observed. Rates of hyperinflation remain under-reported in the literature. Further controlled experiments are needed. [ABSTRACT FROM AUTHOR]

Wound is an injury of living tissue or break in the epithelial integrity of the upper layer of skin. This may lead to disturbance of skin anatomical structure and their function. The normal wounds start to heal immediately after an injury. Normal healing process involved: inflammatory phase, proliferation phase and maturation phase. Now a day wound healing is a challenging clinical problem. So, necessity of effective wound management is required. The various screening models play important role to understand the basic process of tissue repair and treatment of wounds. Wide varieties of in-vitro, ex-vivo and in-vivo models have been developed for evaluation of wound healing activity. The in-vitro models includes Chick chorioallantoic membrane assay, Fibroblast assay, Collagen assay, Scratch assay, Endothelial cell in vitro tube formation assay, Keratinocytes assay. Ex-vivo models includes organotypic culture, human ex vivo skin culture, porcine model, Human organotypic skin explanted culture and the in-vivo models includes Excision wound model, Incision wound Model, Burn wound model, Dead space wound model.The aim of this review article is detailed study of different types of in-vitro, ex-vivo and in-vivo models for evaluation of wound healing activity.

To evaluate the strengthening effect of five different fibers with different placement designs in root canal treated and intracoronally bleached premolars. Seventy extracted single-rooted premolars were distributed into 7 groups (G1-G7). Group 1 (G1) included the intact (I) teeth as the negative control. Group 2 (G2) included root canal treated, intra-coronally bleached and composite (C) restored teeth as the positive control. In the other five test groups after root canal treatment the teeth were intra-coronally bleached and fiber materials were placed into standard MOD cavities in the following different designs: an intracanal rigid fiber/Reforpost (G3,RF), an intracanal flexible fiber/ Everstick (G4, FF), four intracanal flexible pin fibers/Dentapreg Pin (G5,PF), an intercuspal flexible fiber /Dentapreg SFU (G6, IF) or an intra-coronal horseshoe-shaped/ Dentapreg SFU (G7,CF). All cavities were filled with a microfilled resin composite. Fracture resistance was tested using a universal testing machine under a crosshead speed of 1 mm/minute. One-way ANOVA and Duncan's Multiple Range tests were used for statistical analysis. Fracture types were recorded. The fracture resistance values in descending order were G1(I): 1190.97 N > G6 (IF): 1138.78 N > G5 (PF): 942.45 N > G3 (RF): 737.40 N > G4 (FF):694.29 N > G2 (C): 611.83 N > G7 (CF): 542.78 N. There were statistically significant differences among the groups (p ≤ 0.05). In all groups, repairable coronal oblique fractures were mostly observed. Flexible fibers placed intercuspally exhibited a significantly better strengthening effect than those of the intracanal flexible and rigid fibers (p < 0.05). [ABSTRACT FROM AUTHOR]

In this study, a deep burn wound model was established using a 3D human skin equivalent (HSE) model and this was compared to native skin. HSEs were constructed from dermis derived from abdominoplasty/breast surgery and this dermal template was seeded with primary keratinocytes and fibroblasts. The HSE model was structurally similar to native skin with a stratified and differentiated epidermis. A contact burn (60 °C, 80 °C, 90 °C) was applied with a modified soldering iron and wounds were observed at day 1 and 7 after burn. The HSEs demonstrated re-growth with keratinocyte proliferation and formation of a neo-epidermis after burn injury, whereas the ex vivo native skin did not. To assess the suitability of the 3D HSE model for penetration and toxicity studies, a nanocrystalline silver dressing was applied to the model for 7 days, with and without burn injury. The effect of silver on skin re-growth and its penetration and subcellular localization was assessed in HSEs histologically and with laser ablation-inductively coupled plasma mass spectrometry (LA-ICPMS). The silver treatment delayed or reduced skin re-growth, and silver particles were detected on the top of the epidermis, and within the papillary dermis. This novel in vitro 3D multicellular deep burn wound model is effective for studying the pathology and treatment of burn wound injury and is suitable for penetration and toxicity studies of wound healing treatments. [ABSTRACT FROM AUTHOR]

Myocardial infarction is one of the major causes of death and disability. Various diagnostic modalities used to investigate cardiac ischaemia. Advances in Magnetic Resonance Imaging technology has opened up new horizons for investigating the cardiac function and quantifying any pathology that may be present. The present study was designed to quantify the cardiac area at risk and infarction reperfusion areas using the mismatch of iron oxide contrast and gadolinium (Gd) contrast imaging (MRIs) and to test if a combination of T1, T2, and iron oxide T2* contrasts will distinguish the infarction and AAR zones. A well-established mouse model was used to induced cardiac ischaemia and reperfusion. Six mice models' hearts were harvested and processed according to various protocols. MI was induced through ligation technique for five mice, and one was kept as normal control. MR imaging and Reperfusion were performed using a Three-dimensional gradient-echo fast low angle shot (3DFLASH) and three-dimensional multi-slice multi-echo sequence (3DMSME). Generation of T1 and T2 maps, image post-processing including segmentation and mismatch measurement and drawing of the area of interest. The edematous myocardium had significant high signal intensity in 3DMSME with variable echo time (14, 28, 42 ms). The combination of 3DFLASH and 3DMSME at an echo time of 42 ms was statistically significant, detecting the AAR more accurately. Both T1 and T2 sequences had the potential to determine the AAR zone. The infarct area has significantly high signal intensity compared to normal areas (p = 0.04 for the T1 map and p = 0.01 for the T2 map). The study demonstrated that Cardiac MRI was a valuable technology to investigate infarct areas and zones that are at risk. [ABSTRACT FROM AUTHOR]

An optical approach for pigmented lesions detection in human skin is presented. As differences between normal skin tissue and pigmentation tissue (and even a change in pigmentation development) can be detected by their optical properties, this paper presents a new, potentially noninvasive approach for skin cancer detection. Since each wavelength has different penetration depth into the tissue and different absorption, the goal was to check whether a combination of information obtained from five different wavelengths, can increase the detection probability and reduce the false positive probability, compared to using only one wavelength. Temporal tracking of back-reflected secondary speckle patterns generated while illuminating the tested area with several lasers and applying periodic vibrations to the surface via a controlled vibration source at several stimulation frequencies. As a sequel to the previous work conducted in our laboratory which investigated pigmented lesions interaction with one light source, this work deals with increasing the number of parameters that are being looked at and considered at the same time. Using five wavelengths, 9 vibration frequencies and 19 signal analysis parameters, ex-vivo experiments were performed on porcine skin tissues and were analyzed using artificial intelligence tools which could detect the strong features for each wavelength individually. Combining the wavelengths produced impressive results compared to the results by each wavelength separately: both types of errors, false positive and false negative, decreased to less than 2%. Such a significant change in its impact on patients shows the value of this method. This paper shows the possibility of optically separating normal skin from pigmentation tissue, by using the advantages of multi-spectral optimization. This is a necessary proof of concept as a preliminary step toward our future experiments, which may differentiate between different types of pigmentation, and even malignancy and benign tissues. [ABSTRACT FROM AUTHOR]

In 2020, due to the COVID-19 pandemic, the annual meeting of the Interuniversity Institute of Myology (IIM), took place on a virtual platform. Attendees were scientists and clinicians, as well as pharmaceutical companies and patient organization representatives from Italy, several European countries, Canada and USA. Four internationally renowned Keynote speakers presented recent advances on muscle stem cells regulation, skeletal muscle regeneration, quantitative biology approaches, and metabolic regulation of muscle homeostasis. Novel, unpublished data by young trainees were presented as oral communications or posters, in five scientific sessions and two poster sessions. On October 15, 2020, selected young trainees participated to the High Training Course on “Advanced Myology”, organized together with the University of Perugia, Italy. The course, on a virtual platform, showcased lectures on muscle development and regulation of muscle gene expression by international speakers, and roundtables discussions on “Single cell analysis of skeletal muscle” and “Skeletal muscle stem cell in healthy muscle and disease”. The Young IIM Committee, composed by young trainee winners of awards in the past IIM Meeting editions, was directly involved in the selection of keynote speakers, the organization of scientific sessions and roundtables discussions tailored to the interests of their peers. A broad audience of Italian, European and North American participants contributed to the different initiatives. The meeting was characterized by a friendly and inclusive atmosphere, facilitating lively and stimulating discussions on emerging areas of muscle research. The meeting stimulated scientific cross-fertilization fostering novel ideas and scientific collaborations aimed at better understanding muscle normal physiology and the mechanisms underlaying muscle diseases, with the ultimate goal of developing better therapeutic strategies. The meeting was a success, and the number of meeting attendees was the highest of all IIM Meeting editions. Despite the current difficulties imposed by the COVID-19 pandemic, we are confident that the IIM community will continue to grow and deliver significant contributions to the understanding of muscle development and function, the pathogenesis of muscular diseases and the development of novel therapeutic approaches. Here, abstracts of the meeting illustrate the new results on basic, translational, and clinical research, confirming that our field is strong and healthy.

Diffusion-weighted magnetic resonance imaging (DW-MRI) tractography is a non-invasive tool to probe neural connections and the structure of the white matter. It has been applied successfully in studies of neurological disorders and normal connectivity. Recent work has revealed that tractography produces a high incidence of false-positive connections, often from “bottleneck” white matter configurations. The rich literature in histological connectivity analysis studies in the macaque monkey enables quantitative evaluation of the performance of tractography algorithms. In this study, we use the intricate connections of frontal, cingulate, and parietal areas, well established by the anatomical literature, to derive a symmetrical histological connectivity matrix composed of 59 cortical areas. We evaluate the performance of fifteen diffusion tractography algorithms, including global, deterministic, and probabilistic state-of-the-art methods for the connectivity predictions of 1711 distinct pairs of areas, among which 680 are reported connected by the literature. The diffusion connectivity analysis was performed on a different ex-vivo macaque brain, acquired using multi-shell DW-MRI protocol, at high spatial and angular resolutions. Across all tested algorithms, the true-positive and true-negative connections were dominant over false-positive and false-negative connections, respectively. Moreover, three-quarters of streamlines had endpoints location in agreement with histological data, on average. Furthermore, probabilistic streamline tractography algorithms show the best performances in predicting which areas are connected. Altogether, we propose a method for quantitative evaluation of tractography algorithms, which aims at improving the sensitivity and the specificity of diffusion-based connectivity analysis. Overall, those results confirm the usefulness of tractography in predicting connectivity, although errors are produced. Many of the errors result from bottleneck white matter configurations near the cortical grey matter and should be the target of future implementation of methods.

Total extract of Tephrosia purpurea ( T. purpurea ) expressed potent ex-vivo bronchodilator effect in isolated Guinea pigs' tracheal muscles. Fractionation of T. purpurea total extract ( TPTE) using liquid-liquid technique followed by ex-vivo bronchodilator testing indicated that the activity was trapped to the chloroform (CHCl 3 ) soluble fraction. Phytochemical study of the CHCl 3 fraction guided by ex-vivo bronchodilator activity led to the isolation of 7 active flavones of which compounds 1 ( epi- Tephroapollin G), 3 (Acetyltephroapollin C), 4 (4''-Dehydroxytephroapollin E), and 5 ( epi- Tephroapollin F) were new. Structures were identified using relevant spectroscopic tools including optical rotations and CD data. Compounds 1 , 3 , 4 and lanceolatin A ( 6 ) behaved like papaverine by inhibiting carbachol (CCh) as well as high potassium (K + )-mediated contractions at equivalent concentrations with varied potencies whereas (-)-Tephroapollin G ( 2 ) selectively inhibited CCh-mediated contractions but was not found active against high K + . epi -Tephroapollin F ( 5 ) and (-)-Pseudosemiglabrin ( 7 ) in contrast were significantly more potent to abolish CCh induced contraction when compared with high K + similar to dicyclomine. Papaverine like dual phosphodiesterase enzyme Ca ++ ion inhibitory activities of 1, 3, 4 and 6 were confirmed indirectly by the bolster of the isoprenaline curves against CCh to the left whereas Ca ++ inhibitory effect of 1 and 3 - 7 was confirmed by the rightward deflection of Ca ++ concentration-response curves (CRCs) towards right with quashing of the maximum response in same fashion like verapamil. Moreover, compounds 2, 5 and 7 at lower concentrations showed selective blockade of muscarinic receptor similar to atropine. Oral administration of the TPTE , CHCl 3 and 7 to guinea pigs significantly protected against bronchospasm induced by 0.2 % histamine aerosol in vivo ., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V. on behalf of King Saud University.)

It is widely recognized that extracellular vesicles subserve non-classical signal transmission in the central nervous system. Here we assess if the astrocyte processes, that are recognized to play crucial roles in intercellular communication at the synapses and in neuron-astrocyte networks, could convey messages through extracellular vesicles. Our findings indicate, for the first time that freshly isolated astrocyte processes prepared from adult rat cerebral cortex, can indeed participate to signal transmission in central nervous system by releasing exosomes that by volume transmission might target near or long-distance sites. It is noteworthy that the exosomes released from the astrocyte processes proved ability to selectively target neurons. The astrocyte-derived exosomes were proven positive for neuroglobin, a protein functioning as neuroprotectant against cell insult; the possibility that exosomes might transfer neuroglobin to neurons would add a mechanism to the potential astrocytic neuroprotectant activity. Notably, the exosomes released from the processes of astrocytes maintained markers, which prove their parental astrocytic origin. This potentially allows the assessment of the cellular origin of exosomes that might be recovered from body fluids.

Objective(s): Human superoxide dismutase 1 (SOD1) is the cytosolic form of this enzyme it detoxifies superoxide anions and attenuates their toxicities and concomitant detrimental effects on the cells. It is believed that the amount of these enzymes present in the oxidative stress-induced diseases is crucial for preventing disease progression. Transfection of rat bone marrow stromal cells (BMSCs) by a constructed vector carrying the human wild-type SOD1 gene, a non-viral gene transfer method, was the main aim of this study. Materials and Methods: For this purpose, the rat BMSCs were transfected with the vector using Turbofect reagent and then stabilized. Western-blot and real-time PCR were also used for evaluation of SOD1 expression. Results: Data analysis from RT-PCR and Western-blot techniques revealed that the stable transfected cells could secrete human wild-type SOD1 in the supernatant. Also, the total activity of SOD1 was about 0.5±0.09 U/ml and 0.005±0.002 U/ml in the supernatants of the transfected and not-transfected of rat BMSCs, respectively. Conclusion: This study showed that expansion of the stable transfected rat BMSCs by a constructed vector carrying the human wild-type SOD1 gene is capable of secreting the active SOD1 enzyme under ex-vivo conditions. The recommendation of this study is that the same experiment would be applicable for expression of the other form of this enzyme, SOD3, as well. More valuable information could probably be provided about the variety of the diseases caused by superoxide anions toxicities by intervention and application of the non-viral method for expressions of SOD1 and SOD3 enzymes.

A well-designed drug delivery platform improves the pharmacological properties of therapeutics. Here, we report a biodegradable interpenetrating polymer network (IPN) microbeads delivery technology developed by crosslinking a polymer blend of poly(vinyl alcohol), xanthan gum, and sodium alginate to enhance the solubility of poorly soluble drugs. The microbeads effectively improve the solubility of a model BCS Class IV drug, norfloxacin, known for its low solubility and low permeability. Differential scanning calorimetry, powdered X-ray diffractometry, and FT-IR data showed that the IPN microbeads solubilised and encapsulated the drug within the network. We found over 83% encapsulation efficiency for norfloxacin and this efficiency increases with the concentration of polymer. Ex vivo experiments using caprine intestine revealed that the IPN microbeads adhered to the intestinal epithelium, a mucoadhesive behaviour that could be beneficial to the drug pharmacokinetics while in vitro experiments in phosphate buffer show that the IPN enables significant drug release. We believe that these IPN microbeadsare an excellent drug delivery system to solubilise norfloxacin, ensure adhesion to the intestinal wall, thereby localising the drug release to enhance bioavailability of poorly soluble drugs. [ABSTRACT FROM AUTHOR]

Background: Our research team obtained a human heart with the right lung attached from a recent transplantation patient via a research collaboration with LifeSource, a local organ procurement organization. The heart and lungs were not viable for transplant given the patient's medical history and were subsequently offered to the University of Minnesota for research purposes.Methods: Using Visible Heart® methodologies, we reanimated the specimen en bloc and collected multimodal direct visualization from inside the cardiac chambers and great vessels of the functioning heart.Results: Video footage, using videoscopic and fluoroscopic imaging, was captured and is presented in this report as supporting material. Multiple still images highlight the surgical suture sites of the transplantation procedures.Conclusions: This multimodal imaging offers unique educational value for medical students, clinicians, and medical device designers for improving transplantation techniques and patient outcomes. [ABSTRACT FROM AUTHOR]

Introduction: The "Barbed Snore Surgery" is one of the last technical innovations in palatal surgery for Obstructive Sleep Apnea. The availability of a low-cost surgical model able to replicate tissue consistency and main anatomical structures could be fundamental for the spreading of this surgery. The aim of this study was to assess the feasibility of an ex-vivo ovine model in the surgical training of BSS. Methods: After adequate preparation of adult lamb heads, a post-graduate student with no surgical expertise was guided by a skilled surgeon in the execution of two BSS procedures: "Barbed Roman Blinds Technique" and "Barbed Anterior Pharyngoplasty". Anatomical limitations and similarity with the human tissue were assessed and recorded during the simulation. Results: All the procedures were successfully completed. Despite proportional differences, the palatal tissue was assessed as similar in consistency and thickness to the human tissue. The simulation was considered satisfactory and suitable for surgical training. Conclusion: This ex-vivo ovine surgical model could represent the right tool for BSS training thanks to readily available and inexpensive specimens. Moreover, it appears to present the realistic anatomy and tissue consistence essential for an adequate surgical simulation. [ABSTRACT FROM AUTHOR]

With the advancements of high throughput computational screening procedures, drug repurposing became the privileged framework for drug discovery. The structure-based drug discovery is the widely used method of drug repurposing, consisting of computational screening of compounds and testing them in-vitro. This current method of repurposing leaves room for mechanistic insights into how these screened hits interact with and influence their targets. We addressed this gap in the current study by integrating highly sensitive biophysical methods into existing computational repurposing methods. We also corroborated our computational and biophysical findings on H37Rv for the anti-mycobacterial action of selected drugs in-vitro and ex-vivo conditions. Atosiban and Rutin were screened as highly interacting hits against HemD through multi-stage docking and were cross-validated in biophysical studies. The affinity of these drugs (K ~ 106 M−1) was quantified using fluorescence quenching studies. Differential Scanning Fluorimetry (DSF) and urea-based chemical denaturation studies revealed a destabilizing effect of these drugs on target which was further validated using MD simulations. Conformational rearrangements of secondary structures were established using CD spectra and intrinsic fluorescence. Furthermore, Atosiban and Rutin inhibited M.tb growth in-vitro and ex-vivo while remaining non-toxic to mice peritoneal macrophages. [ABSTRACT FROM AUTHOR]

In 2021, as the situation due to COVID-19 pandemic was still uncertain, the 18 th annual meeting of the Interuniversity Institute of Myology (IIM), took place on a virtual platform, following the same organization already tested for the previous edition. Participants from Italy, European countries, Canada and USA included clinicians, scientists, pharmaceutical companies and representatives of patient organizations. Four keynote speakers presented new insights into the modulation of muscle stem cell self-renewal in the treatment of neuromuscular disease, the role of nuclear positioning in muscle function, regeneration and tumorigenesis in the heart and advances on therapies of muscular dystrophies. Young PhD students and trainees presented oral communications distributed in five scientific sessions and posters in two poster sessions. On October 21, 2021, selected young scientists participated in the "High Training Course on Advanced Myology", organized with the University of Perugia, Italy. This course consisted of lectures on muscle regeneration and therapeutic perspectives by internationally recognized speakers, followed by roundtable discussions on "Omics technologies in myology" and "New therapeutic approaches", plus the meeting itself. Young trainees, winners of past IIM conferences, forming the Young IIM Committee, selected one of Keynote speakers and were involved in the organization of scientific sessions and roundtable discussions. The friendly welcoming of the meeting, which has strongly characterized this event and is of great help in facilitating scientific exchanges and stimulating novel collaborations, was the hallmark of the conference this year again, even on virtual platform. Breakthrough studies showing interdisciplinary works are fostering new avenues in the field of myology. This year again, scientists and students attended the meeting at the huger number, challenging the difficulties due to the COVID-19 pandemic. All participants shared the wish to continue and implement IIM meeting with new insights on muscle biology, perspectives in the understanding of the musclerelated diseases and in novel therapeutic approaches. We report here abstracts of the meeting describing basic, translational, and clinical research contributing to the large field of myology. [ABSTRACT FROM AUTHOR]

Abstract Background Hydrolyzed diets are used in companion animals for the diagnosis and treatment of adverse food reaction. Similarly, hydrolyzed formulas are used in human infants with severe inflammatory bowel disease or milk allergy, and these must meet the standard of hypoallergenicity through rigorous testing. Unfortunately, no standards are currently applied to hydrolyzed veterinary therapeutic diets, and data for the immunogenicity of feline diets is also not available. Therefore, the main aim of this pilot study was to determine if ex-vivo whole blood stimulation assays could be used to characterize the cytokine response to hydrolyzed commercial diets in a small number of individual healthy immunotolerant cats. This approach has also been used to investigate cytokine production in response to cow milk protein in humans and currently similar studies do not exist in companion animals. Nine healthy cats previously eating the same basal diet were divided into groups and fed one of three hydrolyzed diets exclusively for 6 weeks. Heparinized whole blood was collected from each cat before and after the feeding trial. Ex-vivo whole blood stimulation assays were performed using crude extracts of the basal diet as a positive control, as this diet contained the same proteins present in the hydrolyzed diet but were intact, saline as a negative control, and each cat’s respective hydrolyzed diet. Supernatants were collected and analyzed for tumor necrosis factor-alpha, interleukin-10 (IL-10), and interleukin-4 using enzyme-linked immunosorbant assay. Results Seven cats produced detectable amounts of the anti-inflammatory cytokine IL-10 upon stimulation with the basal diet. Two cats produced detectable amounts of IL-10 upon stimulation with a hydrolyzed soy-based diet and one cat produced a detectable amount of IL-10 upon stimulation with a hydrolyzed chicken-based diet (>125 pg/mL). Conclusions Results from this pilot study suggest that in some healthy immunotolerant cats, some hydrolyzed diets may elicit a similar cytokine response compared to their basal diet, which contained the same proteins intact. Therefore, animals may be able to recognize and react to some hydrolyzed forms of tolerated proteins, and may also suggest IL-10 as a target for investigation as a potential marker for dietary tolerance in cats, however further studies would be necessary to corroborate this. Further studies are also needed to determine if this would also be the same in immunologically naïve, sensitized and clinically hypersensitized cats.

This study reports on the development of an original, ex-vivo wounded skin culture protocol using autologous Platelet Rich Plasma (PRP) and enriched Dulbecco's Modified Eagle's Medium (DMEM). Human skin samples obtained from specimens harvested during reduction mammoplasty procedures, were injured in their central portion—to create a standard wound—and cultured under three different conditions:– enriched DMEM with saline solution in the central wound (control)– enriched DMEM with the same medium in the central wound– enriched DMEM plus 2.5% autologous PRP, with the same PRP added medium in the central wound.Morphological analysis was carried out at 0 h (T0) and on days 1, 3, 5 and 10 (T1-T3-T5-T10) using Hematoxylin and Eosin; Masson's trichrome staining; Weigert staining and Ki-67 staining to identify the skin histological features in the different experimental conditions. The combination of DMEM and PRP allowed a favorable modulation of the epithelial cells and fibroblasts proliferation, and a relevant anti-inflammatory action. PRP also demonstrated an inhibitory effect on both the collagen and elastic fibers' de-structuration and a favorable modulation of the re-organization of these fibers. The step by step histological and immune-histo-chemical regenerative effects of PRP on human skin wound repair and regeneration process was observed over a period of 10 days.

Mozhgan Rezaei Kanavi,1 Somayeh Asadi,1,2 Hamid Ahmadieh2 1Ocular Tissue Engineering Research Center, 2Ophthalmic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IranStudies on combined radiotherapy and nanoparticles (NPs) have shown that a greater therapeutic ratio can be achieved using gold nanoparticles (GNPs) as radiosensitizing agents within the tumor.1 Recent Monte Carlo studies demonstrated that GNPs enhance the absorbed dose by choroidal melanoma during brachytherapy with sources such as 103Pd and 125I.2 Given that the energy range of these sources is low, NPs with high atomic number can be suitable to yield a higher absorbed dose when used alongside the mentioned sources.3 Although it has been a long time since the merit and priority of using NPs in treating cancer by low-energy sources has been studied, regarding eye cancers a major concern has been the way these NPs would be spread in the ocular tissues. A principal question is the form and method by which the NPs disperse within the intraocular tumor after intralesional injection. Will the NPs be also absorbed by the nearby healthy tissues?

Autologous cranioplasty is an increasingly common procedure performed in neurosurgical centers following a decompressive craniectomy. Available evidence on the safety of autologous bone fl ap preservation and cranioplasty is limited due to a large diversity in study conducted, nature of pathology and reported outcomes. In this Institutional Review Board-approved retrospective observational study, patients who underwent neurosurgical intervention as "craniectomy followed by cranioplasty" at the Department of Neurological Surgery, Kathmandu Medical College Teaching Hospital were enrolled retrospectively from 1st May 2012 to 30th April 2019. The craniectomy bone fl ap was preserved exvivo, dipped in spirit solution in deep freeze, then autoclaved prior to cranioplasty. Data were collected from the hospital's electronic database. Information analyzed included patient age, sex, indication for craniectomy, interval between craniectomy and cranioplasty, length of hospital stay, peri-operative complications and mean time of follow-up. Patients who underwent a cranioplasty following removal of an infected bone flap after a craniotomy were excluded from the study. Associated complications were assessed and statistical analysis was performed using a Fisher's exact test. There were a total of 210 patients with 92 vascular, 58 post traumatic. With all these surgeries undergone we had 9% complication rate, all of whom underwent cranioplasty later than four weeks of primary surgery (p = <0.0001). Ex-vivo preservation and autoclaving of bone flap is a simple technique with significant benefits in our hospital and national scenario with significantly less financial burden to patients. [ABSTRACT FROM AUTHOR]

Summary: Background: Electrical stimulation therapy (EST) and transcutaneous electrical neuromuscular stimulation (TENS), a modality of EST, have become widely applied, accepted and effective methods for the treatment of musculoskeletal and other pain conditions. According to the rising number of permanent pacemaker (PM) wearers the number of potential candidates for EST with concomitant device implantation is growing. Contradictory recommendations exist regarding the application of EST or TENS on PM wearers. Aim: The study was carried out to evaluate the impact of EST on PM function. Methods: A full size model mimicking the electrical characteristics of the human body was used to evaluate the application of EST on permanent PM devices. Various configurations with respect to energy modality, position of the stimulation electrodes and PM device models were evaluated. Intracardiac PM electrogram tracings (iEGM) were analyzed for the interference of EST with PM function. Results: Unilateral EST application did not cause interference with PM function in any of the configurations (0%; n = 700). On the contrary, bilateral stimulation (350 configurations in total) caused either ventricular inhibition or switch to V00 back-up pacing due to electrical interference in 165 cases (47.1%) depending on the applied stimulation parameters. Conclusion: The use of EST potentially interferes with PM therapy, especially if the electrodes are positioned bilaterally; however, unilateral EST application appeared to be safe in all tested configurations. [ABSTRACT FROM AUTHOR]

Pressurized intra-peritoneal aerosol chemotherapy (PIPAC) has been introduced to the clinical setting as a novel approach for the treatment of peritoneal metastasis. The local interaction of chemoaerosol droplets with the peritoneal surface as well as their distribution pattern is considered the main advantage over conventional liquid intraperitoneal chemotherapy. The aim of the present study was to investigate the behavior of these aerosol particles during PIPAC application via electron microscopy. Solutions of doxycycline, liposomal doxorubicin and macrophage cells were aerosolized using an established ex-vivo model. PIPAC was performed on peritoneum samples via microcatheter (MC) at a pressure of 12 mmHg C02 at 27°C. Following PIPAC the surface structure of applied particles was measured via electron microscopy. The aerosol particle contact of doxycyclin created a nanofilm of ~200 nm height on the peritoneal surface, and this height was revealed to be independent of the size of the initial particle hitting. These nanofilm blocks of 'cylinders' are of different diameters depending on the initial aerosol particle hitting that spot. Diameters of these 'cylinders' are far wider than the original diameter of the initial aerosol particle. However, coated particles such as liposomal doxorubicin and macrophages remained intact following contact with the peritoneal surface. Based on this and other data, the concept that aerosol particles exhibit a gas-like behavior in the abdomen creating a therapeutic capnoperitoneum should be revised. Fluid aerosol particles collide with the peritoneum creating a nanofilm. The interaction of pressurized intraperitoneal aerosol on the peritoneum is therefore closer to the distribution of a liquid film than to that of a gas. Further studies are required to further analyze the interaction of this nanofilm on the peritoneum. [ABSTRACT FROM AUTHOR]

Surgical staplers represent one of the important instruments in modern surgery. Laparoscopic Roux-en-Y gastric bypass is one of the most commonly performed bariatric procedures. Various techniques have been described for performing gastrojejunal (GJ) anastomosis, including linear stapled anastomosis (LSA), circular stapled anastomosis (CSA) and hand-sewn anastomosis (HSA). An ex-vivo porcine-based experiment was designed to compare the mechanical integrity of the GJ anastomosis among the 3 different techniques by measuring burst pressure (BP). Laboratory-based study conducted at the clinical skills laboratory at Birmingham Heartlands Hospitals, Birmingham, United Kingdom. Porcine stomachs and small bowels were used to create a GJ model. Four GJ anastomosis models each were created using circular stapler (CSA group) and hand-sewn techniques (HSA group). Stomach and small bowel thickness were recorded. BP was measured by sequential injections of methylene-blue diluted saline until a leak was detected. Total volume until leak is recorded. Compliance (C) was calculated using the formula C = ΔP/ΔV. Results from our previous experiment for the LSA group are included. One model was excluded from the CSA and the HSA groups due to technical errors. Results were presented as mean ± standard deviation. Total volume in LSA, CSA, and HSA groups was 60 ± 4.08 mL, 73.67 ± 3.22 mL, and 51.67 ± 20.21 mL, respectively. BP in LSA, CSA, and HSA groups was 18 ± 4.69 mm Hg, 20.33 ± 5.77 mm Hg, and 9.67 ± 3.79 mm Hg, respectively. There was a statistically significant difference in BP among the 3 groups (P =.033; Kruskal-Wallis test). C in LSA, CSA, and HSA were 3.50 ±.88 mm Hg/mL, 3.78 ±.85 mm Hg/mL, and 5.39 ± 1.34 mm Hg/mL, respectively (P =.064). BP was higher in CSA and LSA groups compared with the HSA group, suggesting a mechanically stronger anastomosis. Despite the lack of statistical significance, higher BP recorded in the CSA group than in the LSA group suggests better anastomotic integrity. • Gastro-jejunal anastomosis remains to be one of the most debatable steps in RYGB. • Mechanical anastomosis, linear or circular stapled, showed higher burst pressure in our simulated gastro-jejunal models when compared to hand-sewn anastomosis, suggesting a better anastomotic mechanical integrity. • Tissue compliance needs to be further investigated in order to evaluate its effect on anastomotic integrity and stapler function. [ABSTRACT FROM AUTHOR]

ObjectiveTo investigate the influence of plate and screw hole position on the stability of simulated radial fractures stabilized with a 1.5 mm condylar locking compression plate (LCP).Study DesignIn vitro mechanical testing of paired cadaveric limbs.Sample PopulationPaired radii (n = 7) stabilized with a 1.5 mm condylar LCP with an open screw hole positioned either proximal to (PG), or over (OG), a simulated small fracture gap.MethodsConstructs were cycled in axial compression at a simulated trot load until failure or a maximum of 200,000 cycles. Specimens that sustained 200,000 cycles without failure were then loaded in axial compression in a single cycle to failure. Construct cyclic axial stiffness and gap strain, fatigue life, and residual strength were evaluated and compared between constructs using analysis of variance.ResultsOf pairs that had a failure during cyclic loading, OG constructs survived fewer cycles (54,700 ± 60,600) than PG (116,800 ± 49,300). OG constructs had significantly lower initial stiffness throughout cyclic loading and higher gap strain range within the first 1,000 cycles than PG constructs. Residual strength variables were not significantly different between constructs, however yield loads occurred at loads only marginally higher than approximated trot loads. Fatigue life decreased with increasing body weight.ConclusionFracture fixation stability is compromised by an open screw hole directly over a fracture gap compared to the open screw hole being buttressed by bone in the model studied. The 1.5 mm condylar LCP may be insufficient stabilization in dogs with appropriate radial geometry but high body weights.

In 2020, due to the COVID-19 pandemic, the annual meeting of the Interuniversity Institute of Myology (IIM), took place on a virtual platform. Attendees were scientists and clinicians, as well as pharmaceutical companies and patient organization representatives from Italy, several European countries, Canada and USA. Four internationally renowned Keynote speakers presented recent advances on muscle stem cells regulation, skeletal muscle regeneration, quantitative biology approaches, and metabolic regulation of muscle homeostasis. Novel, unpublished data by young trainees were presented as oral communications or posters, in five scientific sessions and two poster sessions. On October 15, 2020, selected young trainees participated to the High Training Course on "Advanced Myology", organized together with the University of Perugia, Italy. The course, on a virtual platform, showcased lectures on muscle development and regulation of muscle gene expression by international speakers, and roundtables discussions on "Single cell analysis of skeletal muscle" and "Skeletal muscle stem cell in healthy muscle and disease". The Young IIM Committee, composed by young trainee winners of awards in the past IIM Meeting editions, was directly involved in the selection of keynote speakers, the organization of scientific sessions and roundtables discussions tailored to the interests of their peers. A broad audience of Italian, European and North American participants contributed to the different initiatives. The meeting was characterized by a friendly and inclusive atmosphere, facilitating lively and stimulating discussions on emerging areas of muscle research. The meeting stimulated scientific cross-fertilization fostering novel ideas and scientific collaborations aimed at better understanding muscle normal physiology and the mechanisms underlaying muscle diseases, with the ultimate goal of developing better therapeutic strategies. The meeting was a success, and the number of meeting attendees was the highest of all IIM Meeting editions. Despite the current difficulties imposed by the COVID-19 pandemic, we are confident that the IIM community will continue to grow and deliver significant contributions to the understanding of muscle development and function, the pathogenesis of muscular diseases and the development of novel therapeutic approaches. Here, abstracts of the meeting illustrate the new results on basic, translational, and clinical research, confirming that our field is strong and healthy. [ABSTRACT FROM AUTHOR]

The 16th Meeting of the Interuniversity Institute of Myology (IIM), October 17-20, 2019, Assisi, Italy brought together scientists, pharma and patient organization representatives discussing new results on muscle research. Internationally renowned Keynote speakers presented advances on muscle development, homeostasis, metabolism, and disease. Speakers selected among submitted abstracts presented their new, unpublished data in seven scientific sessions. The remaining abstracts were showcased in two poster sessions. Young trainees where directly involved in the selection of keynote speakers, the organizing scientific sessions and roundtables discussions tailored to the interests of their peers. A broad Italian, European and North-American audience participated to the different initiatives. The meeting allowed muscle biology researchers to discuss ideas and scientific collaborations aimed at better understanding the mechanisms underlying muscle diseases in order to develop better therapeutic strategies. The active participation of young trainees was facilitated by the friendly and inclusive atmosphere, which fostered lively discussions identifying emerging areas of myology research and stimulated scientific cross-fertilization. The meeting was a success and the IIM community will continue to bring forward significant contributions to the understanding of muscle development and function, the pathogenesis of muscular diseases and the development of novel therapeutic approaches. Here, we report abstracts of the meeting illustrating novel results of basic, translational, and clinical research, which confirms that the Myology field is strong and healthy. [ABSTRACT FROM AUTHOR]

Introduction: The application of extracorporeal circulation (ECC) systems is known to be associated with several implications regarding hemolysis, inflammation, and coagulation. In the last years, systems with pulsatile blood flow are increasingly used with the intention to improve hemodynamics in reperfusion. However, their implications on the aforementioned aspects remain largely unknown. To investigate the effects of pulsatility, this ex-vivo study was initiated., Methods: Test circuits (primed with human whole blood) were set up in accordance with the recommendations of international standards for in-vitro evaluation of new components and systems of ECC. Diagonal pumps were either set up with non-pulsatile (n = 5, NPG) or pulsatile (n = 5, PG) pump settings and evaluated for 6 h. All analyses were conducted with human whole blood. Blood samples were repeatedly drawn from the test circuits and analyzed regarding free hemoglobin, interleukin 8 (IL-8), platelet aggregation and acquired von Willebrand syndrome (AVWS)., Results: After 1 h of circulation, a significant coagulation impairment (impaired platelet function and AVWS) was observed in both groups. After 6 h of circulation, increased IL-8 concentrations were measured in both groups (NPG: 0.05 ± 0.03 pg./mL, PG: 0.03 ± 0.01 pg./mL, p  = 0.48). Pulsatile pump flow resulted in significantly increased hemolysis after 6 h of circulation (NPG: 37.3 ± 12.4 mg/100 L; PG: 59.6 ± 14.5 mg/100 L; p  < 0.05)., Conclusion: Our results indicate that the coagulative impairment takes place in the early phase of ECC. Pulsatility did not affect the occurrence of AVWS ex-vivo . Prolonged durations of pulsatile pump flow led to increased hemolysis and therefore, its prolonged use should be employed cautiously in clinical practice with appropriate monitoring., Competing Interests: FB is founder and shareholder and CB, and GT are shareholders of Resuscitec GmbH, Freiburg, Germany, which is a start-up company from the University Medical Centre Freiburg. CB, J-SP, SB and CS are part-time employees of Resuscitec GmbH, Freiburg, Germany. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zieger, Schneider, Brixius, Scherer, Buchwald, Trummer, Czerny, Beyersdorf, Busch, Benk and Pooth.)

Background: Airway inflammation is a feature of many respiratory diseases and there is a need for newer, more effective anti-inflammatory compounds. The aim of this study was to develop an ex vivo human lung explant model which can be used to help study the mechanisms underlying inflammatory responses and which can provide a tool to aid drug discovery for inflammatory respiratory diseases such as asthma and COPD. Method: Parenchymal lung tissue from 6 individual donors was dissected and cultured with two pro-inflammatory stimuli, lipopolysaccharide (LPS) (1 µg/ml) and interleukin-1 beta (IL-1β) (10 ng/ml) in the presence or absence of dexamethasone (1 µM). Inflammatory responses were assessed using Luminex analysis of tissue culture supernatants to measure levels of 21 chemokines, growth factors and cytokines. Results: A robust and reproducible inflammatory signal was detected across all donors for 12 of the analytes measured following LPS stimulation with a modest fold increase (4-fold in CCL3, CCL4, GM-CSF, IL-10, TNF-α and IL-1β. The inflammatory signal induced by IL-1β stimulation was less than that observed with LPS but resulted in elevated levels of 7 analytes (CXCL8, CCL3, CCL4, GM-CSF, IL-6, IL-10 and TNF-α). The inflammatory responses induced by both stimulations was supressed by dexamethasone for the majority of analytes. Conclusions: These data provide proof of concept that this ex vivo human lung explant model is responsive to inflammatory signals and could be used to investigate the anti-inflammatory effects of existing and novel compounds. In addition this model could be used to help define the mechanisms and pathways involved in development of inflammatory airway disease. Abbreviations: COPD: Chronic Obstructive Pulmonary Disease; ICS: inhaled corticosteroids; LPS: lipopolysaccharide; IL-1β: interleukin-1 beta; PSF: penicillin, streptomycin and fungizone

In this paper, we investigate the use of fat tissue as a communication channel between in-body, implanted devices at R-band frequencies (1.7-2.6 GHz). The proposed fat channel is based on an anatomical model of the human body. We propose a novel probe that is optimized to efficiently radiate the R-band frequencies into the fat tissue. We use our probe to evaluate the path loss of the fat channel by studying the channel transmission coefficient over the R-band frequencies. We conduct extensive simulation studies and validate our results by experimentation on phantom and ex-vivo porcine tissue, with good agreement between simulations and experiments. We demonstrate a performance comparison between the fat channel and similar waveguide structures. Our characterization of the fat channel reveals propagation path loss of ~0.7 dB and ~1.9 dB per cm for phantom and ex-vivo porcine tissue, respectively. These results demonstrate that fat tissue can be used as a communication channel for high data rate intra-body networks. [ABSTRACT FROM AUTHOR]

Abstract: Background: Descemet’s membrane endothelial keratoplasty (DMEK) might be a promising technique for future xeno‐corneal transplantation due to its ultrathin graft, extremely low rejection occurrence, suture‐free graft fixation, and minimal immunosuppressive regime usage. The aim of this study is to explore the feasibility and efficacy of preparing porcine DMEK grafts by 2 techniques and investigate the graft ultrastructure. Methods: Two mainstream techniques, mechanical stripping technique and liquid bubble technique, were modified to prepare the porcine DMEK grafts. In all, 40 corneas harvested from WZS‐pigs (aged 10‐12 months) were subjected to the techniques (20 corneas for each technique). The success rate, time consumption, and endothelial cell density (ECD) before and after preparation were recorded and compared between the 2 techniques. And the ultrastructure of the porcine DEMK graft was investigated by transmission electron microscope. In addition, 9 WZS‐pigs with different ages were sacrificed to explore the correlation between the thickness of Descemet’s membrane and porcine age. Results: After modifying several technical details, the porcine DMEK grafts were successfully prepared by either mechanical stripping technique or liquid bubble technique, and the mark technique to distinguish the 2 sides of the graft was also explored. In all, 13 DMEK grafts (65%) were prepared successfully by the mechanical stripping technique, whereas 14 successful cases (70%) were prepared by the liquid bubble technique. The success rates between the 2 techniques showed no significant difference (P = .847). However, the mechanical stripping technique was significantly time‐consuming when compared with the liquid bubble technique (P < .0001). The ECDs reduced significantly after preparation no matter what techniques were used (P < .0001), but the ECD after the liquid bubble preparation was significantly higher than the ECD after mechanical stripping (P = .032). The ECD reduction positively correlated to the time consumption for both mechanical stripping technique (P = .0014, R2 = 0.621) and liquid bubble technique (P = .013, R2 = 0.412). The ultrastructure showed the graft was comprised of stromal residuals, non‐banded layer, and endothelial layer. Unlike human Descemet’s membrane (DM), anterior banded layer was not observed. The thickness of porcine DM increased with the age, and a significant positive correlation between them was found (P < .0001, R2 = 0.949), and the predict equation was Y = 0.3764*X + 7.378 (Y indicates the thickness, whereas X indicates the age). Conclusions: Porcine DMEK grafts could be prepared either by mechanical stripping technique or liquid bubble technique, and the liquid bubble technique seems superior over the mechanical stripping technique regarding time consumption and ECD preservation. Although there are several technical barriers to overcome, xeno‐DMEK might be a promising direction for future xeno‐corneal transplantation. [ABSTRACT FROM AUTHOR]

The growing use of genomic testing presents new treatment options but also new dilemmas. We describe here a heavily-pretreated metastatic triple negative breast cancer patient who failed to respond to conventional treatment. Genomic analyses were performed that discovered several targetable alterations (e.g. FGFR1, CDK6, INSR) and created a clinical challenge - which target to target first? Our solution to this relatively common scenario was using ex-vivo organ culture (EVOC) system to prioritize treatment directed toward the best molecular target. EVOC enabled the trial of several potent targeted agents (Everolimus, Linsitinib, Palbociclib, AZD4547) and allowed semi-quantitative measurement of tumor response. The best response was to FGFR inhibitor, AZD4547. Consequently, the most accessible FGFR inhibiting agents (Pazopanib, then Nintedanib) were administered and some response was achieved. This report provides a potential rationale for utilizing EVOC system to predict tumor response to targeted therapy when multiple targets are proposed. [ABSTRACT FROM AUTHOR]