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Background: Normothermic machine perfusion (NMP) allows for the assessment and resuscitation of ex‐vivo human livers prior to transplantation. Commercially available NMP systems are closed circuits that accumulate metabolic waste and cytokines over time, potentially limiting organ preservation times. Dialysis has been proposed as a method to remove waste and excess fluid from such systems. This study aimed to demonstrate the utility of integrating dialysis into a commercially available system by quantifying solute removal. Methods: A dialysis filter was attached in parallel to a commercially available liver perfusion system. Three livers declined for transplantation were split before undergoing long‐term NMP with blood using the modified system. During perfusion, dialysate flow rates were set in the range of 100–600 mL/h for short periods of time. At each flow rate, perfusate and spent dialysate samples were collected and analyzed for solute clearance. Results: The addition of dialysis to a commercial NMP system removed water‐soluble waste and helped regulate electrolyte concentrations. Interleukin‐6 was successfully removed from the perfusate. Solute clearance was proportional to dialysate flow rate. A guide for our perfusion setup was created for the appropriate selection of dialysis flow rates and duration based on real‐time perfusate composition. Conclusions: Dialysis circuits can efficiently remove waste and regulate perfusate composition, and can be easily incorporated to improve the performance of commercially available systems. Quantification of the effect of dialysis on perfusate composition enables refined dialysis control to optimize electrolyte profiles and avoid the over‐ or under‐correction of key solutes. [ABSTRACT FROM AUTHOR]

Abstract With cancer immunotherapy and precision medicine dynamically evolving, there is greater need for pre-clinical models that can better replicate the intact tumor and its complex tumor microenvironment (TME). Precision-cut tumor slices (PCTS) have recently emerged as an ex vivo human tumor model, offering the opportunity to study individual patient responses to targeted therapies, including immunotherapies. However, little is known about the physiologic status of PCTS and how culture conditions alter gene expression. In this study, we generated PCTS from head and neck cancers (HNC) and mesothelioma tumors (Meso) and undertook transcriptomic analyses to understand the changes that occur in the timeframe between PCTS generation and up to 72 h (hrs) in culture. Our findings showed major changes occurring during the first 24 h culture period of PCTS, involving genes related to wound healing, extracellular matrix, hypoxia, and IFNγ-dependent pathways in both tumor types, as well as tumor-specific changes. Collectively, our data provides an insight into PCTS physiology, which should be taken into consideration when designing PCTS studies, especially in the context of immunology and immunotherapy.

Artemisia monosperma is a plant with many traditional uses including some affecting smooth muscles. The A. momosperma essential oil (AMEO) prepared by hydrodistillation from fresh and dry aerial parts was compared qualitatively and quantitatively using GC/MS. The drying process affected the yield and composition of AMEO. The bronchodilator potential was explored using isolated guinea-pig trachea in ex-vivo organ bath setup. In the tracheal contractions induced by different spasmogens, AMEO was able to completely relax contractions induced by carbachol (CCh; 1 μM) and high K+ (80 mM) at closely related doses (p > 0.05) indicating a dual inhibition of phosphodiesterase enzyme (PDE) and voltage-mediated L-type Ca++ channels blocker (CCB) as papaverine. The current study provides scientific support to the medicinal use A. monosperma in respiratory disorders. [ABSTRACT FROM AUTHOR]

Many investigators are looking into the possibility of using platelet-rich. hemoderivatives as a source of the protein structures and cytokines necessary for. periodontal healing of wounds. The objective of the study was to evaluate and. compare the structural, mechanical, and histochemical characteristics of L-PRF and TPRF. membranes prepared by using three different centrifugation protocols. Thirty participants around the ages of 20 and 35 who were in good overall. health had their antecubital veins pricked for ten milliliters of the blood. Venous blood. was centrifuged immediately after collection in silica-coated glass tubes and titaniumcoated. tubes utilizing the APRF machine. The mechanical properties of PRF. membranes (n = 30) for L-PRF and T-PRF each protocol) were assessed using a. desktop universal testing machine. The forces around 700 g (3200 rpm, 15 min) yielded a PRF membrane with. desirable mechano-degradation characteristics for its clinical application. Histochemical examination revealed mixed inflammatory infiltrate with predominantly. platelets followed by lymphocytes, neutrophils& monocytes in T-PRF. Whereas, in. LPRF thin strands of mixed inflammatory infiltrate predominantly neutrophils &. monocytes are seen in the connective tissue stroma. This study demonstrated that centrifugation speed, force, and time. influenced the structural, and mechanical properties of PRF membranes prepared with. various protocols. This is the first study to reveal the marked impact of glass and. titanium-reinforced centrifugation tubes on the final production of PRF. It was further. found that a significant difference was observed between L-PRF and T-PRF at. 3200 rpm and 2700 rpm protocols. [ABSTRACT FROM AUTHOR]

With cancer immunotherapy and precision medicine dynamically evolving, there is greater need for pre-clinical models that can better replicate the intact tumor and its complex tumor microenvironment (TME). Precision-cut tumor slices (PCTS) have recently emerged as an ex vivo human tumor model, offering the opportunity to study individual patient responses to targeted therapies, including immunotherapies. However, little is known about the physiologic status of PCTS and how culture conditions alter gene expression. In this study, we generated PCTS from head and neck cancers (HNC) and mesothelioma tumors (Meso) and undertook transcriptomic analyses to understand the changes that occur in the timeframe between PCTS generation and up to 72 h (hrs) in culture. Our findings showed major changes occurring during the first 24 h culture period of PCTS, involving genes related to wound healing, extracellular matrix, hypoxia, and IFNγ-dependent pathways in both tumor types, as well as tumor-specific changes. Collectively, our data provides an insight into PCTS physiology, which should be taken into consideration when designing PCTS studies, especially in the context of immunology and immunotherapy. [ABSTRACT FROM AUTHOR]

Invasive neuronal tract-tracing is not permitted in very large or endangered animals. This is especially the case in marine mammals like dolphins. Diffusion-weighted imaging of fiber tracts could be an alternative if feasible even in brains that have been fixed in formalin for a long time. This currently is a problem, especially for detecting crossing fibers. We applied a state-of-the-art algorithm of Diffusion-weighted imaging called Constrained Spherical Deconvolution on diffusion data of three fixed brains of bottlenose dolphins using clinical human MRI parameters and were able to identify complex fiber patterns within a voxel. Our findings indicate that in order to maintain the structural integrity of the tissue, short-term post-mortem fixation is necessary. Furthermore, pre-processing steps are essential to remove the classical Diffusion-weighted imaging artifacts from images: however, the algorithm is still able to resolve fiber tracking in regions with various signal intensities. The described imaging technique reveals complex fiber patterns in cetacean brains that have been preserved in formalin for extended periods of time and thus opens a new window into our understanding of cetacean neuroanatomy. • Importance of non-invasive study of large brains • DWI data analysis using the CSD technique to get crossing fibers through the dolphin brain • Data preprocessing steps overcome the tissue abnormality of the postmortem brain. [ABSTRACT FROM AUTHOR]

Background: This study was to develop loratadine (LTD) emulgels to treat localized skin allergy. Method: Initially oil-in-water emulsion was prepared by 3 different types of surfactants & finally gelling agent carbopol 940 was incorporated into emulsion to produce emulgel (i.e., standard conventional method). Results: The developed formulations were characterized using various parameters including particle size (PS), zeta potential (ZP), polydispersity index (PDI), entrapment efficacy (EE), pH, extrusion efficacy, physical stability, in-vitro drug release studies, and scanning electron microscopy (SEM). PS, EE, PDI, ZP and In-vitro studies ranges between 186.25 ± 6.42 mm (LE-F4) to 395.24 ± 8.64 mm (LE-F1), 62.38 ± 0.36 % (LE-F2) to 76.48 ± 0.69 % (LE-F4), 0.276 ± 0.02 (LE-F4) to 0.652 ± 0.02 (LE-F1), 16.45 ± 2.13 mV (LE-F1) to 29.46 ± 2.78 mV (LE-F3) and 21.90 ± 0.3 % (LE-F1) to 68.30±0.9 % (LE-F4) respectively. Conclusion: Based on all physicochemical properties, LE-F4 formulation was considered to be optimized with minimum PS (186.25±6.42 nm), PDI (0.276±0.02), satisfactory positive surface charge (23.15 ± 1.89 mV) and maximum EE (76.48±0.69 %). FTIR studies were confirmed that there is no physical interaction between drug and excipients and SEM studies revealed that vesicle size was spherical with smooth texture. A significantly greater rate of drug release (i.e., 68.30 ± 0.90%) was seen in the LTD emulgels that were made with cationic surfactant (i.e., LE-F4) and found to be good spreadability and extrudability.

This article offers a comprehensive perspective on the transformative role of organoid technology on mammary gland biology research across a diverse array of mammalian species. The mammary gland's unique development and regenerative capabilities render this organ an ideal model for studying developmental evolution, stem cell behavior, and regenerative processes. The discussion extends to the use of cross-species mammary organoids to address key biological inquiries in evolution, tissue regeneration, cancer research, and lactation, highlighting the limitations of traditional mouse models and the benefits of incorporating a more diverse range of animal models. Advances in organoid biology have been critical in overcoming ethical and practical constraints of in-vivo studies, especially in human research. The generation of human and mouse mammary organoids that faithfully recapitulate in-vivo tissues marks a significant stride in this field. Parallel capabilities are now emerging for other mammals, as well. Utilizing mammary organoids from various species has the potential to make invaluable contributions to our understanding of mammary gland biology, with implications for regenerative medicine, cancer research, and lactation studies, thereby contributing to advancements in human health, agriculture, and nutrition science. [ABSTRACT FROM AUTHOR]

Abstract Introduction Vitamin D performs various functions as a hormone by promoting calcium absorption but plays a major role in innate immunity,cell differentiation, cell maturation through its genomic effects via vitamin D receptor. The immune response also plays a major role in tooth surface and supporting structure destruction and playing a major factor in high caries formation. The inflammatory cytokines are released has proinflammatory cytokines and stimulate cells in disease process. Therefore, in the present study we have evaluated the association of salivary vitamin D, LL-37, interleukins 6 and 17A in various levels of severity of dental caries. Method Ethical approval was obtained (NU/CEC/2020/0339), 377 individuals reporting to department of conservative dentistry and endodontics, AB Shetty memorial institute of dental sciences were included based on inclusion criteria. The individuals were further divided into caries free(N = 105) and caries active(N = 272) based on their caries prevalence. The salivary were collected and evaluated for vitamin D, LL-37,IL-17A and IL-6.Results were statistically analysed with SPSS vs 22 (IBM Corp, USA). Normally distributed data were expressed as mean ± SD. Skewed data were expressed as median and interquartile range. To compare (mean) outcome measures between the two groups unpaired independent t-test was applied and for values in median IQR, Mann Whitney U test was used. All statistical analysis for P value were two-sided and significance was set to P ≤ 0.05. Results The study showed that, the salivary vitamin D statistically decreased with increasing severity of caries which showed that vitamin D plays an important role in prevention of caries. Antimicrobial peptide LL-37 was higher in caries free group but was not statistically significant, salivary IL-6 level was higher in caries active group but intergroup comparison did not show significant difference. Salivary IL-17A did not show statistically significant between caries active and caries free group. Conclusion The salivary levels of vitamin D may play a vital role in prevalence of dental caries and its severity which can be a underlying cause in presence of other etiological factors.

Background/Aim: A native non-pathogenic bacterial microflora was identified in Comano (TN, Italy) spring water. The aim of this study was to investigate the regenerative effects of some of the bacterial lysates extracted from this water in a human ex-vivo skin experimental wound model. Materials and Methods: Bacterial lysates were extracted from four new isolates: lysate 1 (L1) - closest relative Rudaea cellulosilytica, phylum Proteobacteria; lysate 2 (L2) - closest relative Mesorhizobium erdmanii, phylum Proteobacteria; lysate 3 (L3) - closest relative Herbiconiux ginseng, phylum Actinobacteria; lysate 4 (L4) - closest relative Fictibacillus phosphorivorans, phylum Firmicutes. Their regenerative effects were investigated in a human ex-vivo skin experimental wound healing model at 3 (T1), 5 (T2), and 10 days (T3). Results: The samples cultured with the L2 lysate displayed both an earlier and complete restoration of all the skin layers and their features were the closest to the normal skin. The regenerated epidermis demonstrated a complete maturation as the normal epidermis. The papillary dermis appeared mature, and the reticular dermis displayed both collagen and elastic fibres regularly parallel to the skin surface. An anti-inflammatory effect was displayed by the L1 lysate, but this action did not constitute a regenerative effect, suggesting that pathways for inflammation and regeneration might be different. Conclusion: The therapeutic power of spring waters is not exclusively related to their mineral composition, but it may also be attributable to their native non-pathogenic bacterial microflora. [ABSTRACT FROM AUTHOR]

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 (CHCl3) soluble fraction. Phytochemical study of the CHCl3 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, CHCl3 and 7 to guinea pigs significantly protected against bronchospasm induced by 0.2 % histamine aerosol in vivo.

Background: Rupture of the common calcaneal tendon is the second most frequent tendon rupture in dogs and may lead to severe lameness and pain. Surgical repair consists of re-apposition of the damaged tendon ends using sutures, but this type of repair is not always possible especially if the tendon has retracted. Tendon augmentation with an ultra-high molecular weight polyethylene (UHMWPE) implant is a recent solution to support the sutures and allow the repair of the canine calcaneal tendon. However, its biomechanical fixation strength remains untested for this pathology. Aim: To evaluate the biomechanical fixation strength of an UHMWPE implant for the repair of the canine calcaneal tendon. Methods: Ex-vivo biomechanical study was carried out on eight cadaveric hindlimbs from four adult dogs. Hindlimbs were tested under two independent modalities: proximal tendinous fixation (PTF) and distal calcaneus fixation (DCF), using a testing machine. PTF was achieved by eight simple interrupted polypropylene sutures performed through the UHMWPE implant. The latter was sandwiched inside the gastrocnemius tendon, which had previously been incised over about 5 cm longitudinally, and through the tendon of the superficial digital flexor. DCF was performed using an interference screw, which locked the UHMWPE implant into a calcaneus tunnel drilled perpendicularly. Results: Yield, failure load and linear stiffness (mean ± SD) for the DCF modality were 920 ± 139 N, 1007 ± 146 N and 92 ± 15.21, respectively, which were greater than for the PTF modality (663 ± 92 N, 685 ± 84 N and 25.71 ± 5.74, respectively, P [Open Vet J 2023; 13(5.000): 645-653]

Background: Rupture of the common calcaneal tendon is the second most frequent tendon rupture in dogs and may lead to severe lameness and pain. Surgical repair consists of re-apposition of the damaged tendon ends using sutures, but this type of repair is not always possible especially if the tendon has retracted. Tendon augmentation with an ultrahigh molecular weight polyethylene (UHMWPE) implant is a recent solution to support the sutures and allow the repair of the canine calcaneal tendon. However, its biomechanical fixation strength remains untested for this pathology. Aim: To evaluate the biomechanical fixation strength of a UHMWPE implant for the repair of the canine calcaneal tendon. Methods: Ex-vivo biomechanical study was carried out on eight cadaveric hindlimbs from four adult dogs. Hindlimbs were tested under two independent modalities: proximal tendinous fixation (PTF) and distal calcaneus fixation (DCF), using a testing machine. PTF was achieved by eight simple interrupted polypropylene sutures performed through the UHMWPE implant. The latter was sandwiched inside the gastrocnemius tendon, which had previously been incised over about 5 cm longitudinally, and through the tendon of the superficial digital flexor. DCF was performed using an interference screw, which locked the UHMWPE implant into a calcaneus tunnel drilled perpendicularly. Results: Yield, failure load, and linear stiffness (mean ± SD) for the DCF modality were 920 ± 139 N, 1,007 ± 146 N, and 92 ± 15.21, respectively, which were greater than for the PTF modality (663 ± 92 N, 685 ± 84 N and 25.71 ± 5.74, respectively, p < 0.05). Failure modes were different between fixation modalities: for PTF it was suture breakage (n = 7/8), while for DCF it was implant damage and slippage (n = 8/8). Conclusion: The biomechanical fixation strength of the UHMWPE implant was greater for DCF than that of PTF, and should be suitable for calcaneal tendon repair in dogs. The clinical prediction of rupture of this calcaneal tendon repair will occur at the level of the PTF. [ABSTRACT FROM AUTHOR]

IntroductionThe 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.MethodsTest 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).ResultsAfter 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

Haemonchus contortus is the most prevalent and pathogenic gastrointestinal nematodes (GINs) in ruminants causing extensive economic losses. It is essential to estimate the efficacy of common commercially available anthelmintics against Haemonchus contortus parasite. Here, we standardized an ex-vivo culture platform for H. contortus and evaluated the efficacy of commonly used anthelmintics namely, albendazole (ABZ), levamisole (LVM), ivermectin (IVM), closantel (CLS) and rafoxanide (RFX). Adult worms were collected from abomasa of slaughtered animals, cultured in MEM, DMEM, M199 or RPMI with or without 20% FBS for up to 72 h. Cultured worms were incubated with ABZ, LVM, IVM, RFX or CLS in DMEM supplemented with 20% FBS at different concentrations (0.5–50 µg/ml) in triplicates and examined at 0, 3, 6, 12, 24, 36 and 48 h post treatment. Of the culture conditions, DMEM supplemented with 20% FBS supported the survival of H. contortus for (P < 0.001) longer period of time which was used in the evaluation of anthelmintics. The efficacy of CLS and RFX were significantly (P < 0.001) higher than other drugs and 100% mortality was observed at 2 µg/ml of CLS and RFX within 12 h post treatment. However, ABZ, LVM, and IVM showed significant effect at the concentration of 50 µg/ml with 48, 36, and 24 h, respectively. Morphological changes included severe cuticle disruption around the buccal cavity, posterior region and vulva as well as loss of cuticle structure integrity coupled with expulsion and fragmentation of digestive components of parasites when treated with 50 µg/ml of ABZ, LVM, and IVM and 2 µg/ml of RFX and CLS. Collectively, DMEM supplemented with 20% FBS can be used as ex-vivo culture platform for maintenance of H. contortus, and RFX and CLS can be used as the promising drugs for the prevention, control and treatment of H. contortus infections. [ABSTRACT FROM AUTHOR]

Aims : This study was designed to provide both ex-vivo and in-vivo methods for the extraction and expansion of spermatogonial stem cells (SSCs). Methods: For in-vivo experiments, azoospermic mouse model was performed with Busulfan. Isolation, culture, and characterization of neonate mouse SSC were also achieved. We performed an in-vivo injection of labeled SSCs to the testes with azoospermia. In ex-vivo experiments, extracted SSCs were seeded on the fabricated scaffold consisting of hyaluronic acid (HA) and decellularized testis tissues (DTT). Immunofluorescence staining with PLZF, TP1, and Tekt 1 was performed for SSCs differentiation and proliferation. Results: Several studies demonstrated efficient spermatogenic arrest in seminiferous tubules and proved the absence of spermatogenesis. Transplanted SSCs moved and settled in the basement covering the seminiferous tubules. Most of the cells were positive for Dil, after 4 weeks. An epithelium containing spermatogonia-like cells with Sertoli-like, and Leydig cells were evident in the seminiferous tubules of biopsies, and the IHC staining was significantly positive, 4 weeks after injection of SSCs. The results of the ex-vivo experiments showed positive staining for all markers, which was significantly enhanced in scaffolds of ex-vivo experiments compared with in-vitro seeded scaffolds. Conclusion: Ex-vivo SSC differentiation and proliferation using cell-seeded microfluidic testis scaffolds maybe effective for treatment of the azoospermia. [ABSTRACT FROM AUTHOR]

Abstract Methotrexate on its oral and intravenous administration results in unwanted adverse effects. This drawback can be overcome by transdermal delivery because of its painless objective for systemic drug administration. Transfersomes are ultra-deformable vesicles with the flexibility to reach deeper tissues of the skin. The objective of this research work was to develop methotrexate transfersomal gel by thin film hydration technique, evaluated for entrapment efficiency, deformability, mean vesicle size, and stability, and incorporated into carbopol gel for ease of handling and skin applicability for a longer period of retention on skin. MTX-TFS gel & conventional gel were characterized for consistency, transparency, viscosity, and pH. Ex-vivo skin permeation studies were performed using abdominal goat skin and drug release kinetic parameters and transdermal flux were calculated using mathematical models. The results indicate that MTX was successfully entrapped (84.77 ± 2.35 %w/w) in transfersomes having 240±1.6 nm vesicle sizes and 27.13±0.7 deformability index. The gel was permeated through the skin at a rate of 28.12±2.58 µg/cm2/hr as compared to the conventional gel (10.35±2.14 µg/cm2/ hr). From the study, it was concluded that the MTX-TFS gel can be used as a possible substitute for the conventional formulation for transdermal drug delivery due to 3 times improvement in transdermal flux.

Abstract Objective Endoscopic ultrasound (US)‐guided radiofrequency ablation (RFA) has been investigated for pancreatic ductal adenocarcinoma (PDAC) but studies are limited and heterogeneous. Computed tomography (CT) scan features may predict RFA response after chemotherapy but their role is unexplored. The primary aim was to investigate the efficacy of ex‐vivo application of a dedicated RFA system at three power on surgically resected PDAC in patients who underwent neoadjuvant chemotherapy. The secondary aim was to explore the association between pre‐treatment CT‐based quantitative features and RFA response. Methods Fifteen ex‐vivo PDAC samples were treated by RFA under US control at three power groups (10, 30, and 50 W). Short axis necrosis diameter was measured by two expert blinded pathologists as the primary outcome. Two radiologists independently reviewed preoperative CT images. Results Eighty percent of specimens showed coagulative necrosis consisting of few millimeters: 5.7 ± 3.9 mm at 10 W, 3.7 ± 2.2 mm at 30 W, and 3.5 ± 2.4 mm at 50 W (p = 0.3), without a significant correlation between power setting and mean necrosis short axis (rho = –0.28; p = 0.30). Good agreement was seen between pathologists (k = 0.76; 95% confidence interval 0.55–0.98). Logistic regression analysis did not show associations between CT features and RFA response. Conclusions RFA causes histologically evident damage with coagulative necrosis of a few millimeters in 80% of ex‐vivo PDAC samples after chemotherapy and no clinical or pre‐operative CT features can predict efficacy. Power settings do not correlate with the histological ablation area. These results are of relevance when employing RFA in vivo and planning clinical trials on its role in PDAC patients.

The American Transplant Congress 2022, which took place between June 4th and June 8th of 2022, was a hybrid meeting with in‐person attendance in Boston‐MA and a real‐time virtual experience via an online platform. First, we identified abstracts discussing machine perfusion preservation for all organs, a hot topic and approach that may develop into the new gold standard of organ preservation in the near future. A total of 39 abstracts on organ machine preservation were presented at the meeting. Next, we selected abstracts which focus on advances including new approaches to organ preservation, promising biomarkers, ex‐situ treatment including cellular therapies, and novel research areas. Here, we summarized the latest developments on machine perfusion preservation in both experimental and clinical studies. [ABSTRACT FROM AUTHOR]

To counteract early morning pathology like hypertension a time-dependent release of the drug is required. This study is focused to formulate a pulsatile and mucoadhesive drug delivery system of an ACE inhibitor Perindopril Erbumine. Two matrix tablets were punched with Eudragit RSPO, Eudragit RLPO, and HPMC K15M using a 3-3-3 Box-Behnken Design of Response Surface Methodology. Based on the design-optimized formulation P1T3 and P2T8 were coated for a lag time with compression coating of HPMC K4M and a blend of 1:1 ratio of ethylcellulose and carbopol polymer and further encapsulated in a Eudracap™ capsule to provide gastric resistance. The in-vitro release data confirmed an initial pause phase of 4.5 h then release of the drug for 5.2 ± 0.3 h to cope with the early morning rush in blood pressure. After that, a gap of 6 h and then sustained release of the drug for 10.5 ± 0.5 h. From the ex-vivo study, mucoadhesive strength was obtained as 55.13 ± 0.03 gm and 56.39 ± 0.02 gm for P1T3 and P2T8 respectively. The lag time for coated tablet P1T3 came to 2.15 ± 0.15 h and for P2T8 11.9 ± 0.10 h proving the coating efficiency of polymers. The current study strongly suggests that perindopril Erbumine in association with Eudragit and Hypromellose polymer can open a path for the time-regulated release of the drug for hypertension chronotherapy with less risk of dose dumping. [ABSTRACT FROM AUTHOR]

The inclusion complex of α, β-arteether with β-cyclodextrin was prepared. The ratio was selected by implementing the QbD approach to get the best host-guest complex ratio. Further, the formation of the best complex was compared with stability analysis. Also, the enhancement in dissolution profile, as well as solubility, was compared with the pure α, β-arteether. The cyclodextrin derivative with maximum enhanced solubility and best dissolution profile was further used for PKPD modeling, permeability studies, and in-vivo and ex-vivo studies. By QbD approach as well as phase solubility studies it was confirmed that 1:1 fits best for the ART-CD inclusion complex formation. This was substantiated by a saturation solubility investigation, which found that in the presence of PVPK30, the solubility of α, β-arteether was enhanced by 77.05 times. The crystalline nature of the drug was lost or diminished greatly in the inclusion complex, showing the drug was present in a solubilized form in the formulation, according to scanning electron microscopy, X-ray diffraction, and differential scanning calorimetry. Further, the complex powder was converted into spheroids by the spheronization technique and filled in empty enteric-coated shells. In vitro release studies for spheroids-filled enteric capsules were carried out for 6 h by progressive dissolution technique. The pharmacokinetic model using Ecosim Pro 6.2.0 software confirms the enhancement of the bioavailability of the arteether. Further, the in vivo studies also confirm the enhancement in absolute bioavailability by 48.29% when compared with i.v. data of pure drugs. The complex shows an 11% maximum enhancement in antimalarial activity when compared with pure drugs. From the research, it was concluded that inclusion complexation is a suitable approach to improvise the solubility as well as bioavailability of hydrophobic drugs like α, β-arteether. [ABSTRACT FROM AUTHOR]

In this paper, we report on the delivery efficiency of needle-free jet injections using injectors with typical jet speed v j ≈ 140 m/s , orifice diameter d o = 157 μ m , and volume V = 0. 1 mL. The target substrates were either hydrogel tissue phantoms or porcine tissues combined with excised human skin. The novelty of this study is two-fold: First, we investigate the influence of injection angle relative to the skin surface, and second, we also study the influence of the jet path relative to the orientation of muscle fibers. While most commercial jet injectors employ a fitting that would render the device normal to the skin surface, recent studies have proposed oblique injections, which may be beneficial for intradermal or subcutaneous tissue injection. Furthermore, for deeper intramuscular injections, we propose that an angled jet path taking the muscle fiber orientation into account may result in a bolus or dispersion zone that is conducive to increased cellular uptake of the drug. [Display omitted] [ABSTRACT FROM AUTHOR]

Trazodone is a triazolpyridine derivative approved for the treatment of depression, and currently marketed as oral formulations. The transdermal administration of this drug could reduce side effects, related to peak plasma concentration, and improve patient adherence due to a reduced administration frequency. The aims of this work were: (a) the evaluation of the effect of pH vehicle and permeation enhancers on trazodone permeability across porcine skin ex-vivo ; (b) the development and optimization of a transdermal drug delivery system containing trazodone hydrochloride. From the results obtained, it was found that the effect of pH of the vehicle on the permeation of trazodone across the skin is quite complex, because it influences both solubility and partitioning and that the presence of fatty acids in the vehicle has a notable effect on permeation (the enhancement factor obtained was approx. 100). For both the fatty acid selected (oleic and lauric) a parabolic relationship between the transdermal flux and the concentration was found, with an optimum activity in the range 2-3 %. In the second part of the work, different patches were prepared and tested ex-vivo. Overall, the results obtained seem to highlight that drug loading, rather than the components of the adhesive matrix, plays the most relevant role for the permeation of trazodone. The addition of lauric acid, which produced a considerable enhancement in solution, was not effective when included in the patch. The obtained data are promising although probably not clinically relevant for the treatment of depression, but might be interesting for the treatment of insomnia and anxiety disorder, which require much lower doses. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • There is paucity of available preclinical psoriasis models that exactly mimic the state of human psoriasis. • The imiquimod-induced psoriasis is a widely used and acceptable animal model for psoriasis. • The newer and more trustworthy techniques such as 3D skin models, and zebrafish models for future purposes have also been discussed in this article. Psoriasis is a chronic, inflammatory, papulosquamous, noncontagious disease characterized by scaly, demarcated erythematous plaque, affecting skin, nails, and scalp. The IL-23/Th17 axis is the main operator in the development of psoriasis. Psoriasis is affecting worldwide, and new treatment options are urgently needed. Various local and systemic treatments are available for psoriasis but they only provide symptomatic relief because of numerous unknown mechanisms. Clinical trials demand overwhelming resources; therefore, drug development predominantly depends on the in-vivo , in-vitro, and ex-vivo techniques. Immediate attention is required to develop experimental techniques that completely imitate human psoriasis to assist drug development. This review portrays the various in-vivo, in-vitro, and ex-vivo techniques used in psoriasis research. It describes these techniques' characteristics, pathological presentations, and mechanisms. The experimental techniques of psoriasis provide significant information on disease progression mechanisms and possible therapeutic targets. However, until now, it has been challenging to invent a timely, affordable model that precisely imitates a human disease. Only the xenotransplantation model is reckoned as the closer, that mimics the complete genetic, and immunopathogenic event. Imiquimod-induced psoriasis and HaCat cell lines are popular among researchers because of their convenience, ease of use, and cost-effectiveness. There need to further improve the experimental techniques to best serve the disease imitation and meet the research goal. [ABSTRACT FROM AUTHOR]

Objective:To 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 Design:In vitro mechanical testing of paired cadaveric limbs. Sample Population:Paired 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. Methods:Constructs 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. Results:Of 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. Conclusion:Fracture 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.

Limbic predominant age-related transactive response DNA binding protein 43 (TDP-43) encephalopathy neuropathological change (LATE-NC) is common in persons older than 80 years of age and is associated with cognitive decline and increased likelihood of dementia. The MRI signature of LATE-NC has not been fully determined. In this study, the association of LATE-NC with the transverse relaxation rate, R 2 , was investigated in a large number of community-based older adults. Cerebral hemispheres from 738 participants of the Rush Memory and Aging Project, Religious Orders Study, and Minority Aging Research Study, were imaged ex-vivo with multi-echo spin-echo MRI and underwent detailed neuropathologic examination. Voxel-wise analysis revealed a novel spatial pattern of lower R 2 for higher LATE-NC stage, controlling for other neuropathologies and demographics. This pattern was consistent with the distribution of LATE-NC in gray matter, and also involved white matter providing temporo-temporal, fronto-temporal, and temporo-basal ganglia connectivity. Furthermore, analysis at different LATE-NC stages showed that R 2 imaging may capture the general progression of LATE-NC, but only when TDP-43 inclusions extend beyond the amygdala. [ABSTRACT FROM AUTHOR]

[Display omitted] Polymer-based formulations present an attractive strategy in intraarticular drug-delivery to refrain biologicals from early leakage from the joint. In this study, co-formulations of hyaluronic acid and polyvinylpyrrolidone were investigated for their potential as viscosupplements and their influence on the transsynovial loss of adalimumab. For this purpose, polymer mixtures were evaluated for their viscosity and elasticity behavior while their influence on the permeation of adalimumab across a porcine ex-vivo synovial membrane was determined. Hyaluronic acid showed strong shear thinning behavior and exhibited high viscosity and elasticity at low motions, while combinations with polyvinylpyrrolidone provided absorption and stiffness at high mechanical stress, so that they can potentially restore the rheological properties of the synovial fluid over the range of joint motion. In addition, the formulations showed significant influence on transsynovial permeation kinetics of adalimumab and hyaluronic acid, which could be decelerated up to 5- and 3-fold, respectively. Besides viscosity effects, adalimumab was retained primarily by an electrostatic interaction with hyaluronic acid, as detected by isothermal calibration calorimetry. Furthermore, polymer-mediated stabilization of the antibody activity was detected. In summary, hyaluronic acid - polyvinylpyrrolidone combinations can be efficiently used to prolong the residence of adalimumab in the joint cavity while simultaneously supplying viscosupplementation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Cardiac arrhythmia, is a medical condition that reduces the heart's efficiency in pumping blood, and can be fatal, requires long-term management with conventional drugs, despite their limited efficacy. Diltiazem hydrochloride, chosen as a model drug, has a short biological half-life and extensive metabolism. Administering drug through skin is challenging, particularly due to the penetration via stratum corneum. However, solid lipid nanoparticles as a particulate carrier system can enhance its permeation and bioavailability., Objective: The study aimed to develop a matrix type transdermal patch with diltiazem hydrochloride encapsulated in solid lipid nanoparticles Methods: The study used the solvent diffusion technique to prepare SLNs by mixing the drug and solid lipid in an organic phase at 80°C, then slowly adding it to an aqueous phase with continuous stirring for 45 minutes. The resulting nanodispersion was freeze-dried and analyzed for morphological studies, encapsulation efficiency & drug content. A patch was formulated using solvent evaporation technique, incorporating HPMC E50 (2% w/v), propylene glycol, and ethanolic oleic acid (1.5% v/v). SLNs loaded with diltiazem hydrochloride taken equivalent to diltiazem hydrochloride dose in the transdermal patch. The patch was then evaluated for In vitro and skin permeation studies., Results: The result showed a positive correlation between lipid concentration and particle size. Probe sonication and homogenization increased particle size, while stirring speed reduced it. SEM and TEM images confirmed spherical particles with a size of 488.1±4.01nm and an entrapment efficiency of 55.03±1.99%. Drug release studies demonstrated 70.7% drug release from lipid matrix over 24 hrs. The formulated patch with uniform SLN distribution, had a drug content 89.37 ± 0.04% with a surface pH of 6.1 ± 0.53, close to skin pH. The uniformity of content in 3x3 patch estimated to be 14.587 ± 1.404 mg, close to the theoretical content 16.318 ± 1.08 mg, confirmed homogenous distribution of diltiazem hydrochloride SLNs throughout the patch diameter. Cumulative amount released from patch formulation at pH 5.6 and pH 7.4 was 518.1414μg/cm2 and 404.4466 μg/cm2. Synergistic flux enhancement was observed with oleic acid propylene glycol blend. Ex vivo study of the patch showed steady-state flux of 6.9 μg/cm2/hr, permeability coefficient 0.00362 cm/hr, diffusion coefficient 0.000103 cm/hr, cumulative drug permeation (Dmax) 814.885 μg after 24 hrs, and followed a Higuchi-matrix release model., Conclusion: The developed patch possessed improved bioavailability with reduced dosing and enhanced patient compliance., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This paper describes high-frequency nerve block experiments carried out on rat sciatic nerves to measure the speed of recovery of A fibres from block carryover. Block carryover is the process by which nerve excitability remains suppressed temporarily after High Frequency Alternative (HFAC) block is turned off following its application. In this series of experiments 5 rat sciatic nerves were extracted and prepared for ex-vivo stimulation and recording in a specially designed perfusion chamber. For each nerve repeated HFAC block and concurrent stimulation trials were carried out to observe block carryover after signal shutoff. The nerve was allowed to recover fully between each trial. Time to recovery from block was measured by monitoring for when relative nerve activity returned to within 90% of baseline levels measured at the start of each trial. HFAC block carryover duration was found to be dependent on accumulated dose by statistical test for two different HFAC durations. The carryover property of HFAC block on A fibres could enable selective stimulation of autonomic nerve fibres such as C fibres for the duration of carryover. Block carryover is particularly relevant to potential chronic clinical applications of block as it reduces power requirements for stimulation to provide the blocking effect. This work characterizes this process toward the creation of a model describing its behavior. [ABSTRACT FROM AUTHOR]

Abstract 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

BackgroundHydrolyzed 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.ResultsSeven 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).ConclusionsResults 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 paper describes high-frequency nerve block experiments carried out on rat sciatic nerves to measure the speed of recovery of A fibres from block carryover. Block carryover is the process by which nerve excitability remains suppressed temporarily after High Frequency Alternative (HFAC) block is turned off following its application. In this series of experiments 5 rat sciatic nerves were extracted and prepared for ex-vivo stimulation and recording in a specially designed perfusion chamber. For each nerve repeated HFAC block and concurrent stimulation trials were carried out to observe block carryover after signal shutoff. The nerve was allowed to recover fully between each trial. Time to recovery from block was measured by monitoring for when relative nerve activity returned to within 90% of baseline levels measured at the start of each trial. HFAC block carryover duration was found to be dependent on accumulated dose by statistical test for two different HFAC durations. The carryover property of HFAC block on A fibres could enable selective stimulation of autonomic nerve fibres such as C fibres for the duration of carryover. Block carryover is particularly relevant to potential chronic clinical applications of block as it reduces power requirements for stimulation to provide the blocking effect. This work characterizes this process toward the creation of a model describing its behavior.

Little research exists on extending ex-vivo systems to large animal nerves, and to the best of our knowledge, there has yet to be a study comparing these against in-vivo data. This paper details the first ex-vivo system for large animal peripheral nerves to be compared with in-vivo results. Detailed ex-vivo and in-vivo closed-loop neuromodulation experiments were conducted on pig ulnar nerves. Temperatures from 20 °C to 37 °C were evaluated for the ex-vivo system. The data were analysed in the time and velocity domains, and a regression analysis established how evoked compound action potential amplitude and modal conduction velocity (CV) varied with temperature and time after explantation. Pig ulnar nerves were sustained ex-vivo up to 5 h post-explantation. CV distributions of ex-vivo and in-vivo data were compared, showing closer correspondence at 37 °C. Regression analysis results also demonstrated that modal CV and time since explantation were negatively correlated, whereas modal CV and temperature were positively correlated. Previous ex-vivo systems were primarily aimed at small animal nerves, and we are not aware of an ex-vivo system to be directly compared with in-vivo data. This new approach provides a route to understand how ex-vivo systems for large animal nerves can be developed and compared with in-vivo data. The proposed ex-vivo system results were compared with those seen in-vivo, providing new insights into large animal nerve activity post-explantation. Such a system is crucial for complementing in-vivo experiments, maximising collected experimental data, and accelerating neural interface development. • We present the first large animal nerve ex-vivo system compared to in-vivo data. • The ex-vivo system successfully sustained pig ulnar nerves for up to five hours. • Nerve activity ex-vivo at 37 °C showed improved correspondence with in-vivo results. • The modal nerve conduction velocity increased with temperature. • The modal nerve conduction velocity decreased with time since explanting the nerve. [ABSTRACT FROM AUTHOR]

Purpose: The pre-clinical testing of cardiovascular implants gains increasing attention due to the complexity of novel implants and new medical device regulations. It often relies on large animal experiments that are afflicted with ethical and methodical challenges. Thus, a method for simulating physiological heart motions is desired but lacking so far. Methods: We developed a robotic platform that allows simulating the trajectory of any point of the heart (one at a time) in six degrees of freedom. It uses heart motion trajectories acquired from cardiac magnetic resonance imaging or accelero-meter data. The rotations of the six motors are calculated based on the input trajectory. A closed-loop controller drives the platform and a graphical user interface monitors the functioning and accuracy of the robot using encoder data. Results: The robotic platform can mimic physiological heart motions from large animals and humans. It offers a spherical work envelope with a radius of 29 mm, maximum acceleration of 20 m/s2 and maximum deflection of ±19° along all axes. The absolute mean positioning error in x-, y- and z-direction is 0.21 ±0.06, 0.31 ±0.11 and 0.17 ±0.12 mm, respectively. The absolute mean orientation error around x-, y- and z-axis (roll, pitch and yaw) is 0.24 ±0.18°, 0.23 ±0.13° and 0.18 ±0.18°, respectively. Conclusion: The novel robotic approach allows reproducing heart motions with high accuracy and repeatability. This may benefit the device development process and allows re-using previously acquired heart motion data repeatedly, thus avoiding animal trials. [ABSTRACT FROM AUTHOR]

Nano Structured Lipid Carriers (NLCs) are potential alternative of the tradition colloidal drug carrier. The main benefit is related to the well-known concept that lipids used in nanoparticle formulation promote drug oral absorption because they go through the same physiological mechanism as food lipid digestion. The objective of the present work is to use potential carrier NLCs for the oral delivery of poorly soluble drug Febuxostat (FEB). FEB-NLCs were formulated by High Speed Homogenization with Ultra sonication method using Capmul GMS 50 K as solid lipid and Transcutol HP as a liquid lipid. The 32 full factorial design utilized to study the effect of influence of solid lipid to liquid lipid ratio and concentration of surfactant, on the particle size and entrapment efficiency. Mean particle size and entrapment efficiency were found for all prepared formulation in the range of 196.66±2.08 nm to 368.33±2.51 nm and 74.80±0.52 % to 86.47±0.749 % respectively. Zeta potential was -15.2mv which is negative enough to give good stability. TEM study shows good spherical morphology of particle with diameter less than 200nm. In-vitro and Ex-Vivo study revel that NLCs gives biphasic release of the drug; first initial burst release and then sustained release up to 24 hour. The formulated NLCs dispersion was successfully converted in to the free flowing powder using trehalose as a cryoprotectant. In conclusion, FEB-NLCs potential carrier for the oral delivery and controlled release of drug which may reduce dosing frequency and improve patient compliance. [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.

This paper presents numerical modeling and experimental validation of the signal path loss at the 5.8 GHz Industrial, Scientific, and Medical (ISM) band, performed in the context of fat-intrabody communication (fat-IBC), a novel intrabody communication platform using the body-omnipresent fat tissue as the key wave-guiding medium. Such work extends our previous works at 2.0 and 2.4 GHz in the characterization of its performance in other useful frequency range. In addition, this paper also includes studies of both static and dynamic human body movements. In order to provide with a more comprehensive characterization of the communication performance at this frequency, this work focuses on investigating the path loss at different configurations of fat tissue thickness, antenna polarizations, and locations in the fat channel. We bring more realism to the experimental validation by using excised tissues from porcine cadaver as both their fat and muscle tissues have electromagnetic characteristics similar to those of human with respect to current state-of-art artificial phantom models. Moreover, for favorable signal excitation and reception in the fat-IBC model, we used topology optimized waveguide probes. These probes provide an almost flat response in the frequency range from 3.2 to 7.1 GHz which is higher than previous probes and improve the evaluation of the performance of the fat-IBC model. We also discuss various aspects of real-world scenarios by examining different models, particularly homogeneous multilayered skin, fat, and muscle tissue. To study the effect of dynamic body movements, we examine the impact of misalignment, both in space and in wave polarization, between implanted nodes. We show in particular that the use of fat-IBC techniques can be extended up in frequency to a broadband channel at 5.8 GHz.

Abstract Hydralazine hydrochloride is an anti-hypertensive drug. The drug has poor oral bioavailability (BA) of about 30- 50% due to extensive first-pass metabolism. Hence, the buccal delivery was used to enhance the BA of hydralazine hydrochloride. Buccal muco-adhesive tablets were prepared by direct compression technique, using carbopol 934P, HPMC K4M, sodium alginate and sodium carboxy methyl cellulose (NaCMC) as muco-adhesive polymers. Prepared formulations were evaluated for physico-chemical characterization, ex-vivo residence time and in-vitro release studies. The some of the parameters viz hardness, thickness, weight variation are showing the values within the pharmacopeial limits. However, the swelling and bio-adhesive strength were increased with increasing polymer concentrations. From the in-vitro release studies, F9 buccal tablets prepared with NaCMC exhibited better release (96.56%, 6 h) profile than all other formulations and considerd as optimized. The release mechanism from kinetic methods suggests that, the drug release follows zero-order kinetics with diffusion mechanism. Thus, the buccal tablets of hydralazine hydrochloride showed enhanced BA and were further confirmed by in-vivo studies.

Background and aimsRecent development of high resolution MRI techniques have enabled imaging of intracranial atherosclerotic plaque in vivo. However, identifying plaque composition remains challenging given the small size and the lack of histological validation. This study aims to quantify the relaxation times of intracranial plaque components ex vivo at 3 T and to determine whether multi-contrast MRI could classify intracranial plaque according to the American Heart Association classification with histological validation.MethodsA total of 53 intracranial arteries with atherosclerotic plaques from 20 cadavers (11 male, age 73.8 ± 10.9) were excised. Quantitative T1/T2/T2* mapping sequences and multi-contrast fast-spin echo sequences (T1, T2, proton-density weighted and short time inversion recovery) were acquired. Plaque components including: fibrous cap, lipid core, fibrous tissue, calcification, and healthy wall were segmented on histology, and their relaxation times were derived from quantitative images. Two radiologists independently classified plaque type blinded to the histology results.ResultsRelaxation times of plaque components are distinct and different. T2 and T2* values of lipid core are lower than fibrous cap (p = 0.026 & p

Background: A surgical margin is the apparently healthy tissue around a tumor which has been removed. In oral cavity carcinoma, a negative margin is considered ≥ 5 mm, a close margin between 1 and 5 mm, and a positive margin ≤ 1 mm. Currently, the intraoperative surgical margin status is based on the visual inspection and tissue palpation by the surgeon and intraoperative histopathological assessment of the resection margins by frozen section analysis (FSA). FSA technique is limited and susceptible to sampling errors. Definitive information on the deep resection margins requires postoperative histopathological analysis. Methods: We described a novel approach for the assessment of intraoperative surgical margins by examining a surgical specimen oriented through a 3D-printed specific patient tongue with real-time Magnetic Resonance Imaging (MRI). We reported the preliminary results of a case series of 10 patients, prospectively enrolled, with oral tongue carcinoma who underwent surgery between February 2020 and April 2021. Two radiologists with 5 and 10 years of experience, respectively, in Head and Neck radiology in consensus evaluated specimen MRI and measured the distance between the tumor and the specimen surface. We performed intraoperative bedside FSA. To compare the performance of bedside FSA and MRI in predicting definitive margin status we computed the weighted sensitivity (SE), specificity (SP), accuracy (ACC), area under the ROC curve (AUC), F1-score, Positive Predictive Value (PPV), and Negative Predictive Value (NPV). To express the concordance between FSA and ex-vivo MRI we reported the jaccard index. Results: Intraoperative bedside FSA showed SE of 90%, SP of 100%, F1 of 95%, ACC of 0.9%, PPV of 100%, NPV (not a number), and jaccard of 90%, and ex-vivo MRI showed SE of 100%, SP of 100%, F1 of 100%, ACC of 100%, PPV of 100%, NPV of 100%, and jaccard of 100%. These results needed to be validated in a larger sample size of 21- 44 patients. Conclusion: The presented method allows a more accurate evaluation of surgical margin status, and the first clinical experiences underline the high potential of integrating FSA with ex-vivo MRI of the fresh surgical specimen. [ABSTRACT FROM AUTHOR]

The aim of this work was the development of an isolated heart setup to delineate the interactions between intraventricular flow features, hemodynamic parameters and mechano-energetics after certain mitral valve therapies. Five porcine hearts were explanted and prepared for (i) edge-to-edge mitral valve repair, (ii) implantation of a rotatable biscupid mechanical valve prosthesis. Flow structures were visualized using echocardiography while hemodynamics was recorded in terms of pressures, flow rates and ventricular volume. Hemodynamic and cardiac mechano-energetics implied a marginal effect (