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Objectives: Our study aimed to evaluate the effect of superior hypogastric nerve plexus (SHNP) block in postoperative pain management in the first 24 h after minimally invasive gynecological (MIG) surgeries., Methods: We conducted a double-blinded, randomized controlled trial in the Department of Obstetrics and Gynecology at a tertiary care centre from May 1, 2023 to September 30, 2023 in women undergoing major MIG surgeries. At the completion of the surgery, women were randomized to the intervention group who received SHNP block with ropivacaine 10 mL (0.75%) before port removal, whereas no intervention was taken in the control group. The extubation time was noted, and the pain score was assessed after 1, 2, 6, 12, and 24 h of extubation in the postoperative period using the visual analog scale (VAS). Statistical analysis was done, with a significance level of 0.05, to test the differences between the two groups., Results: A total of 64 patients were randomly allocated to intervention and control groups. The median pain score was lower at 1 and 2 h post-extubation and comparable between the two groups at 6, 12, and 24 h. The surrogate markers that is need for additional analgesia and duration of stay did not differ significantly in the two groups, with P-values of 0.08 and 0.943, respectively., Conclusion: Although the SHNP group experienced considerably lower immediate postoperative pain levels in the initial hours following extubation, the impact of this benefit remains uncertain in the longer postoperative period. The effectiveness of this modality for pain control needs further study, particularly at later postoperative hours., (© 2024 International Federation of Gynecology and Obstetrics.)

Purpose: To evaluate the influence of a previous caesarean section on adverse composite maternal and perinatal outcome in women who attempted a trial of labor., Methods: This historical cohort study analyzed maternal and perinatal outcome in women with otherwise low risk pregnancies at term who underwent a trial of labor after a caesarean section (TOLAC). The primary outcome measure was the adverse composite outcome. Secondary outcome measures were amongst others the caesarean section rate and the mode of vaginal delivery., Results: The adverse composite outcome was more frequently in the previous caesarean section group compared to women with no previous caesarean Sect. (22.3% vs. 15.6%, p < 0.0001). The percentage of caesarean Sect. (15.4% vs. 8.2%, p < 0,0001), uterine rupture (1.0% vs. 0.02%, p < 0.0001), placental abruption (1.1% vs. 0.3%, p = 0.0014), vaginal operative delivery (16.0% vs. 8.6%, p < 0.0001), pH < 7.10 (3.7% vs. 2.5%, p = 0.0151), base excess < -12 (3.2% vs. 2.2%, p = 0.0297), abnormal cardiotocography (22.5% vs. 13.9%, p < 0,0001) and fetal blood analysis (6.2% vs. 2.6%, p < 0.0001) was significantly higher in women with a previous caesarean section. Taking the parity into account, these differences could only been seen in women without a previous vaginal delivery. In parous women with a previous vaginal delivery and a caesarean section in history, the adverse composite did not differ between the groups. Only the rate of pH < 7.1 was higher in women after a caesarean Sect. (4.5% vs. 1.8%, p = 0.0436)., Conclusion: Trial of labor after caesarean in otherwise low risk pregnancies is associated with a higher rate of complications especially if there is no history of vaginal delivery., (© 2024. The Author(s).)

Objective: To accumulate the currently available literature on the safety and efficacy of the use of knotless barbed sutures for the reconstruction of the uterine wall during laparoscopic myomectomy based on comparison with traditional suture studies., Data Sources: We searched PubMed/Medline, Scopus, ClinicalTrials.gov, and Google Scholar up to February 29, 2024., Methods of Study Selection: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines and PICO criteria, we included all English-language, full-text articles that evaluated the perioperative outcomes of patients who had laparoscopic myomectomy and repair of the uterine wall defect with either barbed or traditional (extracorporeal or intracorporeal sutures)., Tabulation, Integration, and Results: The application of barbed sutures resulted in significantly reduced operative time (2,111 patients, mean difference -12.04 minutes, 95% CI, -16.94 to -7.14, P<.001). This was also reflected when suturing time was separately analyzed (437 patients, mean difference -6.04 minutes, 95% CI, -7.43 to -4.65, P<.001) The mean difference in hemoglobin levels before and after surgery was significantly lower in the barbed suture group (1,277 patients, mean difference -0.40 g/dL, 95% CI, -0.72 to -0.09, P<.01) This was also observed in case of estimated blood loss, which was found to be lower in the barbed suture group (1,823 patients, mean difference -47.22 mL, 95% CI, -78.54 to -15.90, P=.003). Finally, the barbed suture group presented lower transfusion rates (1,217 patients, odds ratio 0.43, 95% CI, 0.19-1.00, P=.05). Concerning visual analog scale (VAS) score as evaluated by the surgeons for surgical difficulty, the control group proved to be more technically challenging compared with the barbed sutures group (184 patients, mean difference -1.66 95% CI, -2.37 to -0.94, P<.001). The VAS score for pain at 24 hours postoperatively, postoperative complication rates, and length of hospital stay were similar for both groups. Regarding reproductive outcomes, there was no difference in pregnancy, live birth, and birth complication rates., Conclusion: The use of barbed sutures during laparoscopic myomectomy presents many clinical benefits for the patient and the surgeon in terms of shorter operative and suturing time, less estimated blood loss, and ease of use. This pioneer technology may contribute to the expansion of laparoscopy on more complex myomectomies., Systematic Review Registration: PROSPERO, CRD42023477304., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Cattle have a significant impact on human societies in terms of both economics and health. Viral infections pose a relevant problem as they directly or indirectly disrupt the balance within cattle populations. This has negative consequences at the economic level for producers and territories, and also jeopardizes human health through the transmission of zoonotic diseases that can escalate into outbreaks or pandemics. To establish prevention strategies and control measures at various levels (animal, farm, region, or global), it is crucial to identify the viral agents present in animals. Various techniques, including virus isolation, serological tests, and molecular techniques like PCR, are typically employed for this purpose. However, these techniques have two major drawbacks: they are ineffective for non-culturable viruses, and they only detect a small fraction of the viruses present. In contrast, metagenomics offers a promising approach by providing a comprehensive and unbiased analysis for detecting all viruses in a given sample. It has the potential to identify rare or novel infectious agents promptly and establish a baseline of healthy animals. Nevertheless, the routine application of viral metagenomics for epidemiological surveillance and diagnostics faces challenges related to socioeconomic variables, such as resource availability and space dedicated to metagenomics, as well as the lack of standardized protocols and resulting heterogeneity in presenting results. This review aims to provide an overview of the current knowledge and prospects for using viral metagenomics to detect and identify viruses in cattle raised for livestock, while discussing the epidemiological and clinical implications., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: This study investigated the influence of cleanroom conditions on the discard rates of donor corneas in a German university eye bank., Methods: Discard rates were analysed from 2017 to 2020 at the LIONS Cornea Bank at Saarland University Medical Center. 1941 corneas from 971 donors were included. 1262 corneas (65.1%) were stored in a class D cleanroom from 2017 to 2019 and processed in a cleanroom class A sterile bank (group 1). 679 corneas (34.9%) were continuously stored in a class B cleanroom and processed in a class A cleanroom safety cabinet in the same room from 2019 to 2020 (group 2). The target parameter of this work was the number of contamination-related discards. Although they cannot be influenced by the spatial conditions, the discards due to insufficient endothelial quality, serology, contraindications, scars and technical causes were also recorded. Statistical analysis was performed using SPSS and various testing procedures., Results: In group 1, significantly more corneas were discarded due to positive serology (6.9%|3.8%, p = 0.020). There was no significant change between both groups for either contamination or the other reasons for discard., Conclusion: Optimization of hygiene standards from cleanroom class D to B did not reduce contamination. Serology, endothelial quality, medical contraindications and the presence of scars cannot be influenced by cleanroom conditions., (© 2023 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Congenital and chronic liver diseases have a substantial health burden worldwide. The most effective treatment available for these patients is whole organ transplantation; however, due to the severely limited supply of donor livers and the side effects associated with the immunosuppressive regimen required to accept allograft, the mortality rate in patients with end-stage liver disease is annually rising. Stem cell-based therapy aims to provide alternative treatments by either cell transplantation or bioengineered construct transplantation. Human amnion epithelial cells (AEC) are a widely available, ethically neutral source of cells with the plasticity and potential of multipotent stem cells and immunomodulatory properties of perinatal cells. AEC have been proven to be able to achieve functional improvement towards hepatocyte-like cells, capable of rescuing animals with metabolic disorders; however, they showed limited metabolic activities in vitro. Decellularised extracellular matrix (ECM) scaffolds have gained recognition as adjunct biological support. Decellularised scaffolds maintain native ECM components and the 3D architecture instrumental of the organ, necessary to support cells' maturation and function. We combined ECM-scaffold technology with primary human AEC, which we demonstrated being equipped with essential ECM-adhesion proteins, and evaluated the effects on AEC differentiation into functional hepatocyte-like cells (HLC). This novel approach included the use of a custom 4D bioreactor to provide constant oxygenation and media perfusion to cells in 3D cultures over time. We successfully generated HLC positive for hepatic markers such as ALB, CYP3A4 and CK18. AEC-derived HLC displayed early signs of hepatocyte phenotype, secreted albumin and urea, and expressed Phase-1 and -2 enzymes. The combination of liver-specific ECM and bioreactor provides a system able to aid differentiation into HLC, indicating that the innovative perfusion ECM-scaffold technology may support the functional improvement of multipotent and pluripotent stem cells, with important repercussions in the bioengineering of constructs for transplantation. [ABSTRACT FROM AUTHOR]

Human cerebral organoids are readily generated from human embryonic stem cells and human induced pluripotent stem cells and are useful in studying human neurodevelopment. Recent work with human cerebral organoids have explored the creation of different brain regions and the impacts of soluble and mechanical cues. Matrigel is a gelatinous, heterogenous mixture of extracellular matrix proteins, morphogens, and growth factors secreted by Engelbreth-Holm-Swarm mouse sarcoma cells. It is a core component of almost all cerebral organoid protocols, generally supporting neuroepithelial budding and tissue polarization; yet, its roles and effects beyond its general requirement in organoid protocols are not well understood, and its mode of delivery is variable, including the embedding of organoids within it or its delivery in soluble form. Given its widespread usage, we asked how H9 stem cell-derived hCO development and composition are affected by Matrigel dosage and delivery method. We found Matrigel exposure influences organoid size, morphology, and cell type composition. We also showed that greater amounts of Matrigel promote an increase in the number of choroid plexus (ChP) cells, and this increase is regulated by the BMP4 pathway. These results illuminate the effects of Matrigel on human cerebral organoid development and the importance of delivery mode and amount on organoid phenotype and composition. [ABSTRACT FROM AUTHOR]

Pharmaceutical application of therapeutic proteins has been continuously expanded for the treatment of various diseases. Efficient and reliable bioanalytical methods are essential to expedite the identification and successful clinical development of therapeutic proteins. In particular, selective quantitative assays in a high-throughput format are critical for the pharmacokinetic and pharmacodynamic evaluation of protein drugs and to meet the regulatory requirements for new drug approval. However, the inherent complexity of proteins and many interfering substances presented in biological matrices have a great impact on the specificity, sensitivity, accuracy, and robustness of analytical assays, thereby hindering the quantification of proteins. To overcome these issues, various protein assays and sample preparation methods are currently available in a medium- or high-throughput format. While there is no standard or universal approach suitable for all circumstances, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay often becomes a method of choice for the identification and quantitative analysis of therapeutic proteins in complex biological samples, owing to its high sensitivity, specificity, and throughput. Accordingly, its application as an essential analytical tool is continuously expanded in pharmaceutical R&D processes. Proper sample preparation is also important since clean samples can minimize the interference from co-existing substances and improve the specificity and sensitivity of LC-MS/MS assays. A combination of different methods can be utilized to improve bioanalytical performance and ensure more accurate quantification. This review provides an overview of various protein assays and sample preparation methods, with particular emphasis on quantitative protein analysis by LC-MS/MS. [ABSTRACT FROM AUTHOR]

Pediatric gastrointestinal motility disorders represent some of the most challenging clinical conditions with largely undefined pathogenetic pathways and therefore limited therapeutic options. Herein, we provide an overview of the recent advances in treatment options for these disorders and their clinical impact. PubMed and Medline databases were searched for relevant articles related to the treatment of achalasia, esophageal atresia, gastroparesis, PIPO and constipation published between 2017 and 2022. In this article, we review and summarize recent advances in management of gastrointestinal motility disorders in children with a particular focus on emerging therapies as well as novel diagnostic modalities that help guide their application or develop new, more targeted treatments. Gastrointestinal motility disorders represent one of the most challenging conundrums in pediatric age and despite significant advances in investigative tools, the palette of treatment options remain limited. Overall, while pharmacological options have failed to bring a curative solution, recent advances in minimal invasive therapeutic and diagnostic techniques have emerged as potential keys to symptom and quality of life improvement, such as ENDOFLIP, POEM, cine-MRI, fecal microbiota transplantation. [ABSTRACT FROM AUTHOR]

Autologous vascular arterial or venous graft are not available in 10-40% of patients, due to vascular pathologies, and the utility of decellularized biological scaffolds would be a solution for those cases. The purpose of this research was to obtain a functional acellular xenograft, prior to in-vivo testing as a vascular graft in an experimental animal. Two batches of carotid vasculo-nervous bundles were collected from porcine models from a local slaughterhouse. The arterial grafts were dissected and isolated, obtaining carotid arteries with a caliber of 5–6 mm and a length of approximately 10–12 cm. Two decellularization protocols were used, immersion (n = 10) and perfusion (n = 9). The resulting grafts underwent histological examination, DNA analysis, electrophoresis and spectrophotometry. Due to severe tissue damage and friability, the batch that was decellularized using perfusion was not examined. The histological examination of grafts stained with hematoxylin-eosin and DAPI highlighted the absence of nuclei. Spectrophotometry revealed a 90% decellularization, and electrophoresis of revealed the migration band of the material extracted from the fresh tissue, as well as the absence of migration bands in the case of the material extracted from decellularized tissues. We successfully used the immersion protocol to obtain a functional acellular vascular graft, in contrast to perfusion decellularization, where intraluminal high pressures damage the extracellular matrix. [ABSTRACT FROM AUTHOR]

Simple Summary: SARS-CoV-2 infects humans and several animals, but infection of companion and zoo animals occurs mainly from humans through the aerosol route. Constant monitoring of the infection in animals is essential because of their close contact with humans, which increases the risk of infection and the potential for a surge of new viral variants. Therefore, it is of relevance to develop economical, fast, and effective diagnostic tests that are able to detect previous infections in multiple animal species. This study aimed to produce a double-antigen sandwich enzyme-linked immunosorbent assay (ELISA) using N and RBD proteins. The results show that this assay is able to detect antibodies against SARS-CoV-2 in serum samples from cats, dogs, guinea pigs, rats, tigers, and humans. SARS-CoV-2 infects humans and a broad spectrum of animal species, such as pets, zoo animals, and nondomestic animals. Monitoring infection in animals is important in terms of the risk of interspecies transmission and the emergence of new viral variants. Economical, fast, efficient, and sensitive diagnostic tests are needed to analyze animal infection. Double-antigen sandwich ELISA has the advantage of being multispecies and can be used for detecting infections caused by pathogens that infect several animal hosts. This study aimed to develop a double-antigen sandwich ELISA using two SARS-CoV-2 proteins, N and RBD. We compared its performance, when using these proteins separately, with an indirect ELISA and with a surrogate virus neutralization test. Positive and negative controls from a cat population (n = 31) were evaluated to compare all of the tests. After confirming that double-antigen sandwich ELISA with both RBD and N proteins had the best performance (AUC= 88%), the cutoff was adjusted using positive and negative samples from cats, humans (n = 32) and guinea pigs (n = 3). The use of samples from tigers (n = 2) and rats (n = 51) showed good agreement with the results previously obtained using the microneutralization test. Additionally, a cohort of samples from dogs with unknown infection status was evaluated. These results show that using two SARS-CoV-2 proteins in the double-antigen sandwich ELISA increases its performance and turns it into a valuable assay with which to monitor previous infection caused by SARS-CoV-2 in different animal species. [ABSTRACT FROM AUTHOR]

In tissue engineering, the decellularization of organs and tissues as a biological scaffold plays a critical role in the repair of neurodegenerative diseases. Various protocols for cell removal can distinguish the effects of treatment ability, tissue structure, and extracellular matrix (ECM) ability. Despite considerable progress in nerve regeneration and functional recovery, the slow regeneration and recovery potential of the central nervous system (CNS) remains a challenge. The success of neural tissue engineering is primarily influenced by composition, microstructure, and mechanical properties. The primary objective of restorative techniques is to guide existing axons properly toward the distal end of the damaged nerve and the target organs. However, due to the limitations of nerve autografts, researchers are seeking alternative methods with high therapeutic efficiency and without the limitations of autograft transplantation. Decellularization scaffolds, due to their lack of immunogenicity and the preservation of essential factors in the ECM and high angiogenic ability, provide a suitable three-dimensional (3D) substrate for the adhesion and growth of axons being repaired toward the target organs. This study focuses on mentioning the types of scaffolds used in nerve regeneration, and the methods of tissue decellularization, and specifically explores the use of decellularized nerve tissues (DNT) for nerve transplantation. [ABSTRACT FROM AUTHOR]

Recent years have seen the emergence of tissue engineering strategies as a means to overcome some of the limits of conventional medical treatment. A biomaterial with tailored physio-chemical characteristics is used in this sophisticated method to transport stem cells and growth factors/bioactive substances, or to attract local endogenous cells, enabling new tissue formation. Biomaterials might serve as a biomimetic structure inspired by the natural milieu, assisting the cells in establishing their natural relationships. Such a method would benefit from having ready access to an abundant reservoir of stem cells with strong tissue regeneration capacity, in addition to using biological compatible material to promote new tissue creation. Teeth may have a plethora of self-renewing, multipotent mesenchymal stem cell (MSC) populations. Recent advancements and promising directions for cell transplantation and homing techniques using dental MSCs for tissue regeneration are discussed in this review paper. Overall, this research paints a picture of the present landscape of new approaches to using tooth-derived MSCs in conjunction with biomaterials and bioactive substances for tissue regeneration. [ABSTRACT FROM AUTHOR]

Background: Several strategies have been implemented to better identify the course of the ureters intra-operatively due of the morbidity associated with ureteric injuries especially during gynaecological surgery. We described our experience with pre-operative ureteric catherisation in women who underwent major endoscopic gynaecological surgery. Methods: A case-controlled study of 862 women who underwent major endoscopic gynaecological surgery sourced from two health institutions were conducted. Two groups were compared: those who had pre-operative prophylactic ureteric catherisation (study group) and those who had routine cystoscopy performed immediately post surgery (control group). Results: There were no intra-operative ureteric injuries or associated complications noted in the study group. When compared to the control group, length of hospital stay (2 days vs 5 days; p < 0.05) and overall mean time for cystoscopy (11 min vs 35 min; p < 0.05) was significantly shorter in the study group. There was no long-term morbidity recorded in the study group. Conclusion: Our experiences with prophylactic pre-operative bilateral ureteric catheterisation for major endoscopic gynaecological surgeries were favourable and are associated with low complication rates. Routine or adjunct use before major gynaecological and pelvic surgery combined with meticulous surgical technique can help reduce iatrogenic and unintentional ureteric injuries. [ABSTRACT FROM AUTHOR]

Objective: To determine the maximum uterine diameter threshold associated with an elevated risk of complications following laparoscopic supracervical hysterectomy (LSH)., Methods: This was a retrospective cohort study from a single tertiary referral center. We enrolled patients who underwent LSH for benign indications at our hospital between January 2013 and June 2023. The primary outcome was the occurrence of surgical complications within the 30-day timeframe of hysterectomy. The covariate included the year of the procedure, patient age, body mass index, parity, American Society of Anesthesiologists classification, comorbidities, history of previous abdominal and pelvic surgery, and preoperative anemia, blood loss, surgical time, hospital stay and pathology. The exclusion criteria comprised those who underwent hysterectomy for malignancy, individuals who underwent total vaginal hysterectomy or laparoscopically assisted vaginal hysterectomy, and those with missing data on uterine maximum diameter, study outcomes, or covariates., Results: We included a final sample of 120 patients, revealing a median uterine diameter of 9.12 cm, with 9.2% experiencing complications. The median uterine weight among 40 patients was 275 g. Receiver operating characteristic (ROC) curve analysis suggested a potential cutoff of 11.55 cm for predicting complications, with an area under the ROC curve of 0.67. Multivariate logistic regression confirmed a significant association between uterine diameter exceeding the cutoff and increased complication risk (OR 33.925, 95% CI: 2.294-501.690, P = 0.0103). A correlation (r = 0.762, P < 0.001) between uterine weight and diameter indicated the latter's suitability for preoperative assessment of uterine weight., Conclusion: The maximum uterine diameter with an optimal cutoff of 11.55 cm was associated with increased complication risk., (© 2024 International Federation of Gynecology and Obstetrics.)

The process of tissue regeneration requires the utilization of a scaffold, which serves as a structural framework facilitating cellular adhesion, proliferation, and migration within a physical environment. The primary aim of scaffolds in tissue engineering is to mimic the structural and functional properties of the extracellular matrix (ECM) in the target tissue. The construction of scaffolds that accurately mimic the architecture of the extracellular matrix (ECM) is a challenging task, primarily due to the intricate structural nature and complex composition of the ECM. The technique of decellularization has gained significant attention in the field of tissue regeneration because of its ability to produce natural scaffolds by removing cellular and genetic components from the extracellular matrix (ECM) while preserving its structural integrity. The present study aims to investigate the various decellularization techniques employed for the purpose of isolating the extracellular matrix (ECM) from its native tissue. Additionally, a comprehensive comparison of these methods will be presented, highlighting their respective advantages and disadvantages. The primary objective of this study is to gain a comprehensive understanding of the anatomical and functional features of the native liver, as well as the prevalence and impact of liver diseases. Additionally, this study aims to identify the limitations and difficulties associated with existing therapeutic methods for liver diseases. Furthermore, the study explores the potential of tissue engineering techniques in addressing these challenges and enhancing liver performance. By investigating these aspects, this research field aims to contribute to the advancement of liver disease treatment and management. [ABSTRACT FROM AUTHOR]

Biomaterial templates play a critical role in establishing and bioinstructing three-dimensional cellular growth, proliferation and spatial morphogenetic processes that culminate in the development of physiologically relevant in vitro liver models. Various natural and synthetic polymeric biomaterials are currently available to construct biomimetic cell culture environments to investigate hepatic cell–matrix interactions, drug response assessment, toxicity, and disease mechanisms. One specific class of natural biomaterials consists of the decellularized liver extracellular matrix (dECM) derived from xenogeneic or allogeneic sources, which is rich in bioconstituents essential for the ultrastructural stability, function, repair, and regeneration of tissues/organs. Considering the significance of the key design blueprints of organ-specific acellular substrates for physiologically active graft reconstruction, herein we showcased the latest updates in the field of liver decellularization–recellularization technologies. Overall, this review highlights the potential of acellular matrix as a promising biomaterial in light of recent advances in the preparation of liver-specific whole organ scaffolds. The review concludes with a discussion of the challenges and future prospects of liver-specific decellularized materials in the direction of translational research. [ABSTRACT FROM AUTHOR]

OBJECTIVES: We aimed to evaluate the clinical features and treatment strategies applied to the patients with ectopic pregnancy admitted to our tertiary care center before and during the pandemic. METHODS: Women aged 18-45 years, who were admitted to the hospital with a diagnosis of ectopic pregnancy in the pre- and postpandemic periods, were included in this case-control study. RESULTS: A total of 173 patients, 116 patients before the pandemic and 57 patients during the pandemic, were included in the study. The rate of admissions from the emergency department was higher during the pandemic than before the pandemic (P = 0.003). The rupture was detected significantly higher during the outbreak (13/116 [11.2%]) than before the pandemic (16/57 [28.1%]) (P = 0.009). While conservative treatment was applied more frequently in the prepandemic period, it was observed that patients were treated surgically more frequently during the pandemic period (P = 0.003). While laparoscopic surgery was preferred before the pandemic, laparotomy was applied to all patients during the pandemic (P < 0.001). CONCLUSIONS: In the first wave of the outbreak, there were delays in the diagnosis of ectopic pregnancies, and these patients presented with ruptures more frequently than before the pandemic. Furthermore, surgical treatment methods were used more than conservative therapies during the outbreak. [ABSTRACT FROM AUTHOR]

Purpose: Multiple regional nerve blocks proved no additional benefit in total laparoscopic hysterectomy in multimodal analgesia, as postoperative pain may mainly originate from the vaginal cuff. Theoretically, caudal block can relieve pain from the vaginal cuff by a sacral spinal nerve block. We aimed to verify whether a caudal block with ropivacaine and morphine can achieve an analgesic effect without additional adverse effects after a total laparoscopic hysterectomy.Patients and Methods: Forty-eight patients undergoing total laparoscopic hysterectomy were randomly allocated to receive preoperative caudal block with 20 mL of mixture including 0.25% ropivacaine and 2 mg morphine (caudal block group) or sham block (sham group). The primary outcome was the postoperative 24 h cumulative sufentanil consumption.Results: Median (IQR) sufentanil consumption in the first 24 postoperative hours of the caudal block group and the sham group was 0.00 (0.00 to 0.05) μg/kg vs 0.13 (0.04 to 0.21) μg/kg, respectively, p < 0.001. The majority of patients felt that visceral pain was more intense than incisional pain at 1, 6, 12, and 24 h post-surgery in the sham group (95.8% at 1 h, 95.8% at 6 h, 95.8% at 12 h, and 75% at 24 h post-surgery). Compared to the sham group, the caudal block reduced visceral pain scores at rest and during movement at 1 h (p < 0.001), 6 h (p < 0.001), 12 h (p < 0.001), and 24 h (p < 0.001) post-surgery. Intraoperative remifentanil consumption was significantly lower in the caudal block group than in the sham group (p = 0.004). There were no significant differences in other secondary outcomes between the two groups.Conclusion: A caudal block with ropivacaine and morphine could provide a satisfactory analgesic effect for 24 h postoperatively without additional adverse effects after total laparoscopic hysterectomy. [ABSTRACT FROM AUTHOR]

Recombinant antibodies specific to kanamycin were obtained using a sheep display library of scFv fragments (Griffin.1) and the possibility of their use for the determination of kanamycin by dot-immunoassay was demonstrated. The minimum detectable concentration of kanamycin was 1 μg/mL (distinguishable label binding other than background). It has been shown that anti-kanamycin phage antibodies are specific for kanamycin and do not interact with other antibiotics (neomycin, tetracycline, ampicillin, and gentamicin). Anti-kanamycin phage antibodies are a promising alternative to monoclonal antibodies for use in the determination of kanamycin. [ABSTRACT FROM AUTHOR]

Healing of dense regular connective tissue, due to a high fiber-to-cell ratio and low metabolic activity and regeneration potential, frequently requires surgical implantation or reconstruction with high risk of reinjury. An alternative to synthetic implants is using bioscaffolds obtained through decellularization, a process where the aim is to extract cells from the tissue while preserving the tissue-specific native molecular structure of the ECM. Proteins, lipids, nucleic acids and other various extracellular molecules are largely involved in differentiation, proliferation, vascularization and collagen fibers deposit, making them the crucial processes in tissue regeneration. Because of the multiple possible forms of cell extraction, there is no standardized protocol in dense regular connective tissue (DRCT). Many modifications of the structure, shape and composition of the bioscaffold have also been described to improve the therapeutic result following the implantation of decellularized connective tissue. The available data provide a valuable source of crucial information. However, the wide spectrum of decellularization makes it important to understand the key aspects of bioscaffolds relative to their potential use in tissue regeneration. [ABSTRACT FROM AUTHOR]

The presence of drug residues in food products has become a growing concern because of the adverse health risks and regulatory implications. Drug residues in food refer to the presence of pharmaceutical compounds or their metabolites in products such as meat, fish, eggs, poultry and ready-to-eat foods, which are intended for human consumption. These residues can come from the use of drugs in the field of veterinary medicine, such as antibiotics, antiparasitic agents, growth promoters and other veterinary drugs given to livestock and aquaculture with the aim of providing them as prophylaxis, therapy and for promoting growth. Various analytical techniques are used for this purpose to control the maximum residue limit. Compliance with the maximum residue limit is very important for food manufacturers according to the Food and Drug Administration (FDA) or European Union (EU) regulations. Effective monitoring and control of drug residues in food requires continuous advances in analytical techniques. Few studies have been reviewed on sample extraction and preparation techniques as well as challenges and future directions for the determination of veterinary drug residues in food. This current review focuses on the overview of regulations, classifications and types of food, as well as the latest analytical methods that have been used in recent years (2020–2023) for the determination of drug residues in food so that appropriate methods and accurate results can be used. The results show that chromatography is still a widely used technique for the determination of drug residue in food. Other approaches have been developed including immunoassay, biosensors, electrophoresis and molecular-based methods. This review provides a new development method that has been used to control veterinary drug residue limit in food. [ABSTRACT FROM AUTHOR]

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Surgery has long been an important treatment for limiting optic nerve damage and minimising visual loss in patients with glaucoma. Numerous improvements, modifications, and innovations in glaucoma surgery over recent decades have improved surgical safety, and have led to earlier and more frequent surgical intervention in glaucoma patients at risk of vision loss. This review summarises the latest advancements in trabeculectomy surgery, glaucoma drainage device (GDD) implantation, and minimally invasive glaucoma surgery (MIGS). A comprehensive search of MEDLINE, EMBASE, and CENTRAL databases, alongside subsequent hand searches—limited to the past 10 years for trabeculectomy and GDDs, and the past 5 years for MIGS—yielded 2283 results, 58 of which were included in the final review (8 trabeculectomy, 27 GDD, and 23 MIGS). Advancements in trabeculectomy are described in terms of adjunctive incisions, Tenon's layer management, and novel suturing techniques. Advancements in GDD implantation pertain to modifications of surgical techniques and devices, novel methods to deal with postoperative complications and surgical failure, and the invention of new GDDs. Finally, the popularity of MIGS has recently promoted modifications to current surgical techniques and the development of novel MIGS devices. [ABSTRACT FROM AUTHOR]

Background Free tissue transfer to cover complex wounds with exposed critical structures results in donor-site morbidity. Perfusion decellularization and recellularization of vascularized composite tissues is an active area of research to fabricate complex constructs without a donor site. Sodium dodecyl sulfate (SDS)-based protocols remain the predominant choice for decellularization despite the deleterious effects on tissue ultrastructure and capillary networks. We aimed to develop an automated decellularization process and compare different SDS perfusion times to optimize the protocol. Methods A three-dimensional-printed closed-system bioreactor capable of continuously perfusing fluid through the vasculature was used for decellularization. The artery and vein of rat epigastric fasciocutaneous free flaps were cannulated and connected to the bioreactor. Protocols had varying durations of 1% SDS solution (3, 5, and 10 days) followed by 1 day of 1% Triton X-100 and 1 day of 1x phosphate-buffered saline. The residual DNA was quantified. Microarchitecture of the constructs was assessed with histology, and the vascular network was visualized for qualitative assessment. Results The structural integrity and the microarchitecture of the extracellular matrix was preserved in the 3- and 5-day SDS perfusion groups; however, the subcutaneous tissue of the 10-day protocol lost its structure. Collagen and elastin structures of the pedicle vessels were not compromised by the decellularization process. Five-day SDS exposure group had the least residual DNA content (p < 0.001). Across all protocols, skin consistently had twice as much residual DNA over the subcutaneous tissues. Conclusion A compact and integrated bioreactor can automate decellularization of free flaps to bioengineer regenerative constructs for future use in reconstruction of complex defects. A decellularization protocol with 5 days of 1% SDS exposure was the most successful to keep the residual DNA content at a minimum while preserving the structural integrity of the tissues. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study was to develop a clinically applicable prediction tool to early seek for postoperative major complications after laparoscopic surgery for benign pathologies. Design: Retrospective analysis of prospectively collected data was performed. Setting: The study was conducted at Tertiary Care University Hospital. Participants: The participants of this study were reproductive-aged women undergoing laparoscopy for benign conditions. Methods: Anamnestic, intraoperative, and postoperative characteristics from January 2019 to December 2021 were retrospectively reviewed. Patients with postoperative complications (reintervention or postoperative bleeding) were matched in a 1:2 ratio with women with same surgical indications without complications. Cases and controls were matched for preoperative hemoglobin, hematocrit, weight, height, body mass index, age, and blood volume. A prediction model was created by inserting multiple independent modifying factors through logistic regression. The receiver operating characteristic (ROC) curve was used to evaluate the predictive accuracy of the model, and the Hosmer-Lemeshow (H-L) test was carried out to evaluate the goodness-of-fit, and a calibration curve was drawn to confirm the predictive performance. A nomogram was depicted to visualize the prediction model. Results: Thirty-nine complicated procedures were matched with 78 uncomplicated controls. According to the multivariate logistic regression analysis findings, the prediction model was developed using C-reactive protein (CRP), intraoperative blood loss, and 24 h postoperative urinary volume, therefore a nomogram was generated. The area under the ROC curve of the prediction model was 0.879, depicting good accuracy, the sensitivity was 60.00%, while specificity reached 93.59%. The H-L test (χ2 = 4.45, p = 0.931) and the calibration curve indicated a good goodness-of-fit and prediction stability. Limitations: The retrospective design, moderate sensitivity, and study population limit the generalization of the findings, requiring additional research. Conclusions: This prediction model based on CRP, intraoperative blood loss, and 24 h postoperative urinary volume might be a potentially useful tool for predicting reintervention and postoperative bleeding in patients undergoing planned gynecological laparoscopy. [ABSTRACT FROM AUTHOR]

Background: Tramadol (TRA) is an analgesic prescribed for treating mild to moderate pains, the abuse of which has increased in recent years. Chronic tramadol consumption produces neurotoxicity, although the mechanisms are unclear. The present study investigated the involvement of apoptosis and autophagy signaling pathways and the mitochondrial system in TRA-induced neurotoxicity. Materials and methods: Sixty adult male Wistar rats were divided into five groups that received standard saline or TRA in doses of 25, 50, 75, 100, or 150 mg/kg intraperitoneally for 21 days. On the 22nd day, the Open Field Test (OFT) was conducted. Jun N-Terminal Kinase (JNK), B-cell lymphoma-2 (Bcl-2), Beclin1, and Bcl-2-like protein 4 (Bax) proteins and tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) were measured in rat hippocampal tissue. Results: TRA at doses 75, 100, and 150 mg/kg caused locomotor dysfunction in rats and increased total and phosphorylated forms of JNK and Beclin-1, Bax, and Caspase-3. TRA at the three higher doses also increased the phosphorylated (inactive) form of Bcl-2 level while decreasing the unphosphorylated (active) form of Bcl-2. Similarly, the protein levels of TNF-α and IL-1β were increased dose-dependently. The mitochondrial respiratory chain enzymes were reduced at the three higher doses of TRA. Conclusion: TRA activated apoptosis and autophagy via modulation of TNF-α or IL-1β/JNK/Bcl-2/Beclin1 and Bcl-2/Bax signaling pathways and dysfunction of mitochondrial respiratory chain enzymes. [ABSTRACT FROM AUTHOR]

Tramadol (TRA) causes neurotoxicity whereas trimetazidine (TMZ) is neuroprotective. The potential involvement of the PI3K/Akt/mTOR signaling pathway in the neuroprotection of TMZ against TRA-induced neurotoxicity was evaluated. Seventy male Wistar rats were divided into groups. Groups 1 and 2 received saline or TRA (50 mg/kg). Groups 3, 4, and 5 received TRA (50 mg/kg) and TMZ (40, 80, or 160 mg/kg) for 14 days. Group 6 received TMZ (160 mg/kg). Hippocampal neurodegenerative, mitochondrial quadruple complex enzymes, phosphatidylinositol-3-kinases (PI3Ks)/protein kinase B levels, oxidative stress, inflammatory, apoptosis, autophagy, and histopathology were evaluated. TMZ decreased anxiety and depressive-like behavior induced by TRA. TMZ in tramadol-treated animals inhibited lipid peroxidation, GSSG, TNF-α, and IL-1β while increasing GSH, SOD, GPx, GR, and mitochondrial quadruple complex enzymes in the hippocampus. TRA inhibited Glial fibrillary acidic protein expression and increased pyruvate dehydrogenase levels. TMZ reduced these changes. TRA decreased the level of JNK and increased Beclin-1 and Bax. TMZ decreased phosphorylated Bcl-2 while increasing the unphosphorylated form in tramadol-treated rats. TMZ activated phosphorylated PI3Ks, Akt, and mTOR proteins. TMZ inhibited tramadol-induced neurotoxicity by modulating the PI3K/Akt/mTOR signaling pathways and its downstream inflammatory, apoptosis, and autophagy-related cascades. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the procurement, efficacy, and applications of different acellular matrices (AMs) on rat esophagi. Sixteen rats were used. Following tissue harvesting from donor rats, AMs were obtained by detergent-enzymatic treatment (DET) from the esophagus, jejunum, and trachea. Fifteen rats were allocated into groups defined by implemented AM types: esophageal (EAM), intestinal (IAM), and tracheal (TAM). According to groups, 5 × 5 mm esophageal wall defect repair was performed with AMs. Samples were examined for hyperemia, edema, inflammatory cells, and neovascularization by scoring. The existence of muscle cells was investigated with immunohistochemical assessment. The procurement of AM in vitro and its implementation on the damaged esophageal wall was achieved successfully. There was a significant difference between groups regarding hyperemia, inflammatory cells, and neovascularization (p < 0.05). Hyperemia and cell infiltration were higher, and neovascularization was poorer in TAM than in others (p < 0.05). The neovascularization was significantly higher in the EAM group (p < 0.05). Increased edema was detected in the IAM group than others, albeit with no significant difference. Staining with Masson's trichrome and desmin antibodies, showing increased inflammatory response on the matrix site, was not detected to regenerate muscle cells. Our DET approaches provided that AMs with potential for regeneration have been obtained from different tissues. Grafting by TAM caused higher grades of inflammation with poor angiogenesis and existing chondrocytes. Decreased inflammatory response of EAM was thought to be due to the native tissue-derived matrix. These results suggest that promoting self-regeneration with native tissue-derived AM can be improved and more convenient in damaged tissue repair. [ABSTRACT FROM AUTHOR]

titania (titanium dioxide, TiO2) is known to induce neurotoxicity and CNS dysfunctions. Numerous studies have explored the neuroprotective effects of melatonin against neurotoxicity. This study evaluates the potential of melatonin to protect against titania-induced neurotoxicity and the role of the Keap1/Nrf2/ARE signaling pathway. One group of animals were treated with Titania (0.045 and 0.075 g/rat) alone while the other with added melatonin (1 mg/kg and 3 mg/kg) and behavioral alterations were assessed using OFT (open field test). Neurochemical and histopathological changes were also studied in the hippocampus by analyzing kelch ECH associating protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), and antioxidant response element (ARE). It was seen that the animals with added Melatonin had improved behavioral scores in the OFT, like anxiety and motor dysfunction triggered by TiO2. Melatonin also reduced lipid peroxidation, ROS, GSSG, IL1β, TNFα, Bax, and Keap1 levels, but boosted GSH, GPx, GR, SOD,IL10,IL4, Bcl2, Nrf2, and ARE levels and improved quadruple mitochondrial enzyme complex activity in titania-treated animals. Histopathological examination showed melatonin induced cytoprotection against vacuolization and necrosis in granular cells of DG and pyramidal cells of CA1 area of the hippocampus. In our study, pretreatment with melatonin reduced titania-induced neurotoxicity in the hippocampus through a mechanism potentially mediated by the Keap-1/Nrf2/ARE pathway. [ABSTRACT FROM AUTHOR]

Uterine fibroids and adenomyosis are prevalent benign neoplasms that can lead to serious deleterious health effects including life-threatening anemia, prolonged menses, and pelvic pain; however, up to 40% of women remain undiagnosed. Traditional treatment options such as myomectomy or hysterectomy can effectively manage symptoms but may entail longer hospital stays and hinder future fertility. Endovascular treatment, such as uterine artery embolization (UAE), is a minimally invasive procedure that has emerged as a well-validated alternative to surgical options while preserving the uterus and offering shorter hospital stays. Careful patient selection and appropriate techniques are crucial to achieving optimal outcomes. There have been advancements in recent times that encompass pre- and postprocedural care aimed at enhancing results and alleviating discomfort prior to, during, and after UAE. Furthermore, success and reintervention rates may also depend on the size and location of the fibroids. This article reviews the current state of endovascular treatments of uterine fibroids and adenomyosis. [ABSTRACT FROM AUTHOR]

Using a naïve human scFv phage library, affinity selection of miniantibodies specific to heat shock proteins isolated from MH22a hepatoma cells and Sp2/0-Ag14 plasmacytoma cells was carried out. By using the obtained phage antibodies, the dynamics of the concentration of heat shock proteins in the blood sera of mice with implanted MH22a tumors were examined by dot immunoassay and enzyme-linked immunosorbent assay. Starting from the 14th day after xenotransplantation there was a gradual increase in the level of heat shock proteins in the blood serum. It was found that after implantation of tumor cells, tumor growth was accompanied by a significant increase in the accumulation of heat shock proteins in the blood serum. It has been shown that miniantibodies specific to heat shock proteins are an effective tool for determining and monitoring the accumulation of heat shock proteins in the blood serum of animals. [ABSTRACT FROM AUTHOR]

Aim: To investigate the vascularization capacity of a decellularized dental pulp matrix (DDP) of bovine origin seeded with human dental pulp stem cells (hDPSCs) in vitro and to present preliminary in vivo findings., Methodology: Bovine dental pulps were decellularized and then analysed using histological staining and DNA quantification. The resultant DDPs were characterized using immunohistochemical staining for the retention of vascular endothelial growth factor A (VEGF-A) and fibroblast growth factor 2 (FGF-2). Furthermore, DDPs were recellularized with hDPSCs and analysed histologically. The expression of markers involved in angiogenesis by hDPSCs colonizing the DDPs was assessed in vitro. A preliminary in vivo study was then conducted in which hDPSCs-seeded and unseeded DDPs were inserted in debrided human premolars root slices and implanted subcutaneously in immunodeficient mice. Samples were retrieved after 30 days and analysed using histological and immunohistochemical staining. The independent samples t-test, analysis of variance and a Kruskal-Wallis test were used to analyse the quantitative data statistically depending on the group numbers and normality of data distribution. The difference between the groups was considered significant when the P-value was less than 0.05., Results: Acellular dental pulp matrices were generated following bovine dental pulp decellularization. Evaluation of the developed DDPs revealed a significant DNA reduction (P < 0.0001) with preservation of the native histoarchitecture and vasculature and retention of VEGF-A and FGF-2. Upon recellularization of the DDPs with hDPSCs, the in vitro analyses revealed cell engraftment with progressive repopulation of DDPs' matrices and vasculature and with enhanced expression of markers involved in angiogenesis. In vivo implantation of root slices with hDPSCs-seeded DDPs revealed apparent vascularization enhancement as compared to the unseeded DDP group (P < 0.0001)., Conclusions: The developed decellularized dental pulp matrix had pro-angiogenic properties characterized by the retention of native vasculature and angiogenic growth factors. Seeding of hDPSCs into the DDP led to progressive repopulation of the vasculature, enhanced expression of markers involved in angiogenesis in hDPSCs and improved in vivo vascularization capacity. The se suggest that a combination of DDP and hDPSCs have the potential to provide a promising vascularization promoting strategy for dental pulp regeneration., (© 2021 The Authors. International Endodontic Journal published by John Wiley & Sons Ltd on behalf of British Endodontic Society.)

Acellular scaffolds from decellularized donor organs are showing promising clinical results in tissue and organ repair and regeneration. A successful decellularization process is determined by (a) its capability to decellularize complete organs of large animals, (b) retention of the extracellular matrix (ECM) structures and morphologies, and (c) minimal loss of ECM proteins. In this study, porcine esophagi were perfused in full thickness with 0.25% w/v sodium dodecyl sulfate at perfusion rates 0.1-0.2 ml/min for up to 5 days. Decellularized tissues were characterized for their residual DNA, histological staining for their matrix structures, immunohistochemical staining for collagen type IV and laminin, and scanning electron microscopy for structural integrity. Our results showed that full thickness esophageal tissues treated using the horizontal perfusion setup were decellularized with good structural and biochemical integrity in the ECM. Residual DNA content in decellularized tissues was found to be 36 ± 12 ng/mg of tissues (n = 6) which was significantly lower than that of native tissues (p = .00022). Our study showed that the organ must be decellularized in full thickness and perfusion pressure must be controlled to minimize radial expansion. These factors were found to be critical in preserving the folded mucosa in the decellularized tissues., (© 2020 Wiley Periodicals LLC.)

Background: Postoperative pain is a major concern after total abdominal hysterectomy (TAH). We suggest that the use of intraoperative superior hypogastric plexus block (SHPB) could be a viable and safe alternative for managing postoperative pain in patients who have undergone TAH. Materials and Methods: After receiving ethical approval, 54 patients who were scheduled for TAH were divided equally into two groups: Group A and Group B. Following the procedure, patients in Group A (n = 27) were injected with 20 ml of 0.25% bupivacaine, whereas patients in Group B (n = 27) were injected with 20 ml of 0.9% saline into the superior hypogastric plexus’s (SHPs) anatomical position. After the surgery and recovery from anesthesia, all patients were administered intravenous morphine at a dosage of 0.1 mg/kg for postoperative pain relief. The Visual Analog Pain Scale was used to evaluate the postoperative pain. The quantity of morphine consumed within 24 h was also recorded. The data collected from the study were analyzed using IBM SPSS version 23.0. Results: The pain score measured in the postanesthesia care unit and at 1, 2, and 4 h after surgery was significantly lower in Group A when compared to Group B, with P < 0.05. There were no significant differences observed in the Visual Analog Scale scores at 12 and 24 h postsurgery between the two groups, with P > 0.05. The amount of morphine consumed in the 24 h following surgery was found to be significantly lower in Group A when compared to Group B. This difference was statistically significant, with P < 0.001. Conclusion: Intraoperative SHPB block after abdominal hysterectomy provides effective postoperative analgesia and reduces postoperative morphine consumption compared to placebo, with fewer incidences of opioid adverse effects. [ABSTRACT FROM AUTHOR]

Human schistosomiasis is one of the most prevalent parasitic diseases worldwide. Various host factors can affect the host–parasite interactions. Therefore, the aim of the present work was to determine the parasitological, histopathological, biochemical, and immunological status of Schistosoma mansoni-infected hosts with metabolic disorders to identify the underlying possible mechanisms of these comorbidities. The study animals were divided into four groups. Group I represented the control groups, namely, the normal control group, the S. mansoni-infected control group, and the noninfected type 1 diabetes (T1DM), type 2 diabetes (T2DM), and obesity groups. The mice of the other three groups underwent induction of T1DM (Group II), T2DM (Group III) and obesity (Group IV) before being infected with S. mansoni. All mice were subjected to body weight measurement, blood glucose and insulin assessment, parasitological evaluation of adult worm count, tissue egg count and intestinal oogram. Histopathological and immunohistochemical study using anti-glial fibrillary acidic protein (GFAP) in hepatic stellate cells (HSCs) and image analysis of Masson's trichrome-stained liver sections using ImageJ (Fiji) software were carried out. Additionally, immunological analysis of tumour necrosis factor (TNF) beta, interleukin-5 (IL-5), IL-10, Forkhead box P3 (FOXP3) and pentraxin 3 (PTX3) levels besides biochemical study of total lipid profile were evaluated. The present study revealed a significant increase in the adult worm count and tissue egg output in the obesity group compared to the infected control group. The oogram of counted eggs showed prevalence of immature eggs in T1DM group, while T2DM and obese groups showed prevalence of mature eggs. The fibrosis area percentage showed significant increase in T2DM and obese groups while it was decreased in T1DM group in comparison to infected control group. Our data also showed significant increase in the levels of TNF-β, IL-5, PTX3 in T1DM, T2DM and obesity groups in comparison to infected control group, whilst the levels of FOXP3 and IL-10 were increased in the infected groups in comparison to their noninfected controls. Moreover, infected T1DM, T2DM and obesity groups showed higher blood glucose and lipid profile in comparison to the infected control group. However, these parameters were improved in comparison to their noninfected controls. In sum, induction of T2DM and obesity increased tissue egg counts, mature egg percentage, and fibrosis density, while schistosome infection induced changes in the lipid profile and blood glucose levels in infected diabetic and obese groups and impacted favorably insulin levels in obese mice. By better understanding the complexities of host–parasite interactions, efforts to reduce the burden of these debilitating diseases can be improved. [ABSTRACT FROM AUTHOR]

Drug-induced liver injury (DILI) is a major contributor to high attrition rates among candidate and market drugs and a key regulatory, industry, and global health concern. While acute and dose-dependent DILI, namely, intrinsic DILI, is predictable and often reproducible in preclinical models, the nature of idiosyncratic DILI (iDILI) limits its mechanistic understanding due to the complex disease pathogenesis, and recapitulation using in vitro and in vivo models is extremely challenging. However, hepatic inflammation is a key feature of iDILI primarily orchestrated by the innate and adaptive immune system. This review summarizes the in vitro co-culture models that exploit the role of the immune system to investigate iDILI. Particularly, this review focuses on advancements in human-based 3D multicellular models attempting to supplement in vivo models that often lack predictability and display interspecies variations. Exploiting the immune-mediated mechanisms of iDILI, the inclusion of non-parenchymal cells in these hepatoxicity models, namely, Kupffer cells, stellate cells, dendritic cells, and liver sinusoidal endothelial cells, introduces heterotypic cell–cell interactions and mimics the hepatic microenvironment. Additionally, drugs recalled from the market in the US between 1996–2010 that were studies in these various models highlight the necessity for further harmonization and comparison of model characteristics. Challenges regarding disease-related endpoints, mimicking 3D architecture with different cell–cell contact, cell source, and the underlying multi-cellular and multi-stage mechanisms are described. It is our belief that progressing our understanding of the underlying pathogenesis of iDILI will provide mechanistic clues and a method for drug safety screening to better predict liver injury in clinical trials and post-marketing. [ABSTRACT FROM AUTHOR]

The limited regenerative capacity of the human body, in conjunction with a shortage of healthy autologous tissue, has created an urgent need for alternative grafting materials. A potential solution is a tissue-engineered graft, a construct which supports and integrates with host tissue. One of the key challenges in fabricating a tissue-engineered graft is achieving mechanical compatibility with the graft site; a disparity in these properties can shape the behaviour of the surrounding native tissue, contributing to the likelihood of graft failure. The purpose of this review is to examine the means by which researchers have altered the mechanical properties of tissue-engineered constructs via hybrid material usage, multi-layer scaffold designs, and surface modifications. A subset of these studies which has investigated the function of their constructs in vivo is also presented, followed by an examination of various tissue-engineered designs which have been clinically translated. [ABSTRACT FROM AUTHOR]

Over 40,000 patients in the United States are estimated to suffer from end-stage liver disease and acute hepatic failure, for which liver transplantation is the only available therapy. Human primary hepatocytes (HPH) have not been employed as a therapeutic tool due to the difficulty in growing and expanding them in vitro, their sensitivity to cold temperatures, and tendency to dedifferentiate following two-dimensional culture. The differentiation of human-induced pluripotent stem cells (hiPSCs) into liver organoids (LO) has emerged as a potential alternative to orthotropic liver transplantation (OLT). However, several factors limit the efficiency of liver differentiation from hiPSCs, including a low proportion of differentiated cells capable of reaching a mature phenotype, the poor reproducibility of existing differentiation protocols, and insufficient long-term viability in vitro and in vivo. This review will analyze various methodologies being developed to improve hepatic differentiation from hiPSCs into liver organoids, paying particular attention to the use of endothelial cells as supportive cells for their further maturation. Here, we demonstrate why differentiated liver organoids can be used as a research tool for drug testing and disease modeling, or employed as a bridge for liver transplantation following liver failure. [ABSTRACT FROM AUTHOR]

Early diagnosis and monitoring are essential for the effective treatment and survival of patients with different types of malignancy. To this end, the accurate and sensitive determination of substances in human biological fluids related to cancer diagnosis and/or prognosis, i.e., cancer biomarkers, is of ultimate importance. Advancements in the field of immunodetection and nanomaterials have enabled the application of new transduction approaches for the sensitive detection of single or multiple cancer biomarkers in biological fluids. Immunosensors based on surface-enhanced Raman spectroscopy (SERS) are examples where the special properties of nanostructured materials and immunoreagents are combined to develop analytical tools that hold promise for point-of-care applications. In this frame, the subject of this review article is to present the advancements made so far regarding the immunochemical determination of cancer biomarkers by SERS. Thus, after a short introduction about the principles of both immunoassays and SERS, an extended presentation of up-to-date works regarding both single and multi-analyte determination of cancer biomarkers is presented. Finally, future perspectives on the field of SERS immunosensors for cancer markers detection are briefly discussed. [ABSTRACT FROM AUTHOR]

Tracheal replacement with a bioengineered tracheal substitute has been developed for long-segment tracheal diseases. The decellularized tracheal scaffold is an alternative for cell seeding. It is not defined if the storage scaffold produces changes in the scaffold's biomechanical properties. We tested three protocols for porcine tracheal scaffold preservation immersed in PBS and alcohol 70%, in the fridge and under cryopreservation. Ninety-six porcine tracheas (12 in natura, 84 decellularized) were divided into three groups (PBS, alcohol, and cryopreservation). Twelve tracheas were analyzed after three and six months. The assessment included residual DNA, cytotoxicity, collagen contents, and mechanical properties. Decellularization increased the maximum load and stress in the longitudinal axis and decreased the maximum load in the transverse axis. The decellularization of the porcine trachea produced structurally viable scaffolds, with a preserved collagen matrix suitable for further bioengineering. Despite the cyclic washings, the scaffolds remained cytotoxic. The comparison of the storage protocols (PBS at 4 °C, alcohol at 4 °C, and slow cooling cryopreservation with cryoprotectants) showed no significant differences in the amount of collagen and in the biomechanical properties of the scaffolds. Storage in PBS solution at 4 °C for six months did not change the scaffold mechanics. [ABSTRACT FROM AUTHOR]

Background and Objectives: Abdominal hysterectomy is a major surgery that is often associated with pronounced postsurgical pain. The objective of this research is to conduct a systematic review and meta-analysis of all randomized controlled trials (RCTs) and nonrandomized comparative trials (NCTs) that have surveyed the analgesic benefits and morbidity of intraoperative superior hypogastric plexus (SHP) block (intervention) compared with no SHP block (control) during abdominal hysterectomy. Materials and Methods: The Cochrane Central Register of Controlled Trials (CENTRAL), Google Scholar, Web of Science, PubMed, Scopus, and Embase were searched from inception until 8 May 2022. The Cochrane Collaboration tool and Newcastle–Ottawa Scale were used to evaluate the risk of bias of RCTs and NCTs, respectively. In a random effects mode, the data were pooled as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI). Results: Five studies (four RCTs and one NCT) comprising 210 patients (SHP block = 107 and control = 103) were analyzed. The overall postsurgical pain score (n = 5 studies, MD = −1.08, 95% CI [−1.41, −0.75], p < 0.001), postsurgical opioid consumption (n = 4 studies, MD = −18.90 morphine milligram equivalent, 95% CI, [−22.19, −15.61], p < 0.001), and mean time to mobilization (n = 2 studies, MD = −1.33 h, 95% CI [−1.98, −0.68], p < 0.001) were significantly decreased in the SHP block group contrasted with the control arm. Nevertheless, there was no significant variance between both arms regarding operation time, intraoperative blood loss, postsurgical NSAID consumption, and hospital stay. There were no major side effects or sympathetic block-related aftermaths in both groups. Conclusions: During abdominal hysterectomy and receiving perioperative multimodal analgesia, the administration of intraoperative SHP block is largely safe and exhibits better analgesic effects compared to cases without administration of SHP block. [ABSTRACT FROM AUTHOR]