External Tissue Research Articles

Estimating nonlinear anisotropic properties of healthy and aneurysm ascending aortas using magnetic resonance imaging.

An ascending aortic aneurysm is an often asymptomatic localized dilatation of the aorta. Aortic rupture is a life-threatening event that occurs when the stress on the aortic wall exceeds its mechanical strength. Therefore, patient-specific finite element models could play an important role in estimating the risk of rupture. This requires not only the geometry of the aorta but also the nonlinear anisotropic properties of the tissue. In this study, we presented a methodology to estimate the mechanical properties of the aorta from magnetic resonance imaging (MRI). As a theoretical framework, we used finite element models to which we added noise to simulate clinical data from real patient geometry and different properties of healthy and aneurysmal aortic tissues collected from the literature. The proposed methodology considered the nonlinear properties, the zero pressure geometry, the heart motion, and the external tissue support. In addition, we analyzed the aorta as a homogeneous material and as a heterogeneous model with different properties for the ascending and descending parts. The methodology was also applied to pre-surgical,in vivo MRI data of a patient who underwent surgery during which an aortic wall sample was obtained. The results were compared with those obtained from ex vivo biaxial test of the patient's tissue sample. The methodology showed promising results after successfully recovering the nonlinear anisotropic material properties of all analyzed cases. This study demonstrates that the variable used during the optimization process can affect the result. In particular, variables such as principal strains were found to obtain more realistic materials than the displacement field.

Behavioural Monitoring Underlines Habituation to Repeated Stressor Stimuli in Farmed Gilthead Sea Bream (Sparus aurata) Reared at a High Stocking Density.

A confinement stress test with 75% tank space reduction and behavioural monitoring through tri-axial accelerometers externally attached to the operculum was designed. This procedure was validated by demonstrating the less pronounced stress response in gilthead sea bream than in European sea bass (950-1200 g). Our study aimed to assess habituation to high stocking densities with such procedure in gilthead sea bream. Animals (420-450 g) were reared (June-August) in a flow-through system at two stocking densities (CTRL: 10-15 kg/m3; HD: 18-24 kg/m3), with natural photoperiod and temperature (21-29 °C), and oxygen levels at 5.2-4.2 (CTRL) and 4.2-3.2 ppm (HD). At the end, blood and muscle were sampled for haematology and transcriptomic analyses, and external tissue damage was assessed by image-based scoring. Four days later, fish underwent a 45 min confinement stress test over two consecutive days. HD fish showed reduced feed intake, growth rates and haematopoietic activity. Muscle transcriptome changes indicated a shift from systemic to local growth regulation and a primed muscle regeneration over protein accretion in HD animals with slight external injuries. After stress testing, HD fish exhibited a decreased recovery time in activity and respiration rates, which was shorter after a second stressor exposure, confirming habituation to high densities.

Antioxidant hydrogels for the treatment of osteoarthritis: mechanisms and recent advances.

Articular cartilage has limited self-healing ability, resulting in injuries often evolving into osteoarthritis (OA), which poses a significant challenge in the medical field. Although some treatments exist to reduce pain and damage, there is a lack of effective means to promote cartilage regeneration. Reactive Oxygen Species (ROS) have been found to increase significantly in the OA micro-environment. They play a key role in biological systems by participating in cell signaling and maintaining cellular homeostasis. Abnormal ROS expression, caused by internal and external stimuli and tissue damage, leads to elevated levels of oxidative stress, inflammatory responses, cell damage, and impaired tissue repair. To prevent excessive ROS accumulation at injury sites, biological materials can be engineered to respond to the damaged microenvironment, release active components in an orderly manner, regulate ROS levels, reduce oxidative stress, and promote tissue regeneration. Hydrogels have garnered significant attention due to their excellent biocompatibility, tunable physicochemical properties, and drug delivery capabilities. Numerous antioxidant hydrogels have been developed and proven effective in alleviating oxidative stress. This paper discusses a comprehensive treatment strategy that combines antioxidant hydrogels with existing treatments for OA and explores the potential applications of antioxidant hydrogels in cartilage tissue engineering.

Deep Learning Artificial Intelligence Predicts Homologous Recombination Deficiency and Platinum Response From Histologic Slides.

Cancers with homologous recombination deficiency (HRD) can benefit from platinum salts and poly(ADP-ribose) polymerase inhibitors. Standard diagnostic tests for detecting HRD require molecular profiling, which is not universally available. We trained DeepHRD, a deep learning platform for predicting HRD from hematoxylin and eosin (H&E)-stained histopathological slides, using primary breast (n = 1,008) and ovarian (n = 459) cancers from The Cancer Genome Atlas (TCGA). DeepHRD was compared with four standard HRD molecular tests using breast (n = 349) and ovarian (n = 141) cancers from multiple independent data sets, including platinum-treated clinical cohorts with RECIST progression-free survival (PFS), complete response (CR), and overall survival (OS) endpoints. DeepHRD predicted HRD from held-out H&E-stained breast cancer slides in TCGA with an AUC of 0.81 (95% CI, 0.77 to 0.85). This performance was confirmed in two independent primary breast cancer cohorts (AUC, 0.76 [95% CI, 0.71 to 0.82]). In an external platinum-treated metastatic breast cancer cohort, samples predicted as HRD had higher complete CR (AUC, 0.76 [95% CI, 0.54 to 0.93]) with 3.7-fold increase in median PFS (14.4 v 3.9 months; P = .0019) and hazard ratio (HR) of 0.45 (P = .0047). There were no significant differences in nonplatinum treatment outcome by predicted HRD status in three breast cancer cohorts, including CR (AUC, 0.39) and PFS (HR, 0.98, P = .95) in taxane-treated metastatic breast cancer. Through transfer learning to high-grade serous ovarian cancer, DeepHRD-predicted HRD samples had better OS after first-line (HR, 0.46; P = .030) and neoadjuvant (HR, 0.49; P = .015) platinum therapy in two cohorts. DeepHRD can predict HRD in breast and ovarian cancers directly from routine H&E slides across multiple external cohorts, slide scanners, and tissue fixation variables. When compared with molecular testing, DeepHRD classified 1.8- to 3.1-fold more patients with HRD, which exhibited better OS in high-grade serous ovarian cancer and platinum-specific PFS in metastatic breast cancer.

#1387 Comprehensive evaluation of clinical consequences in diverse forms of fistula elevation procedure

Abstract Background and Aims Arteriovenous fistula (AVF) superficialization is a recommended alternative autologous vascular access (VA) in patients for whom conventional AVF creation is not possible because of insufficient forearm vessels. This procedure utilizes a deeply located vein as an outflow conduit in AVF creation and makes the vein accessible for cannulation. Tunnel transposition (TT) is employed in a standard manner as a venous superficialization technique. This is accomplished by tunneling the transected vein through a subcutaneous tunnel. However, TT is frequently associated with stenosis at the area of transposition because the transposed vein is torsed, kinked, or compressed by external tissue. Thus, TT tends to be exclusively applied to the basilic vein in the upper arm considering both the anatomic positional relation and the inherent limitations of this procedure. We recently reported that elevation transposition (ET) can serve as a practical substitute for TT (Contrib Nephrol. 2019:198:1-11). ET is a simplified minimally invasive superficialization approach in which the vein is elevated and positioned in a subcutaneous pocket immediately beneath the incision. In AVF superficialization employing ET (i.e., fistula elevation procedure [FEP]), three potential outflow veins are available in the upper arm: the cephalic, basilic, and brachial veins. This study was performed to comprehensively evaluate the clinical consequences of three valid FEP techniques to ascertain whether they are reasonable alternatives to autologous VA and which, if any, have superior performance. Method The demographic and outcome data of 111 patients who underwent the FEP from April 2016 to June 2023 were retrospectively collected and analyzed. The outcomes of the three fistula techniques were assessed and compared in terms of patency rates, requirements for VA intervention therapy (VAIVT), and complication rates. Results The mean follow-up period was 36.2 ± 20.1 (range, 1.3-80.8) months. The basilic, cephalic, and brachial vein-based FEP was performed in 63.1%, 23.4%, and 13.5% of cases, respectively. The overall cumulative primary and secondary patency rates were 76.2% and 98.2% at 1 year and 70.7% and 97.0% at 2 years, respectively. VAIVT was required in 32.4% of cases, and the patency rates at 1 and 2 years after VAIVT were 65.3% and 62.0%, respectively. There were no significant differences in these patency rates among the three FEP types. Minor complications such as lymphorrhea or epidermolysis occurred in only 4.5% of cases. Conclusion Our results suggest that the FEP provides three equivalently reliable options to accommodate the deeply located venous anatomy of the upper arm on individual-patient basis. The diversity of the FEP may contribute to avoiding prosthetic VA and central venous catheter-based dialysis, at least in part, by expanding the applicability of the autologous VA.

Seahorse-Tail-Inspired Soft Pneumatic Actuator: Development and Experimental Characterization.

The study of bio-inspired structures and their reproduction has always fascinated humans. The advent of soft robotics, thanks to soft materials, has enabled considerable progress in this field. Over the years, polyps, worms, cockroaches, jellyfish, and multiple anthropomorphic structures such as hands or limbs have been reproduced. These structures have often been used for gripping and handling delicate objects or those with complex unknown a priori shapes. Several studies have also been conducted on grippers inspired by the seahorse tail. In this paper, a novel biomimetic soft pneumatic actuator inspired by the tail of the seahorse Hippocampus reidi is presented. The actuator has been developed to make a leg to sustain a multi-legged robot. The prototyping of the actuator was possible by combining a 3D-printed reinforcement in thermoplastic polyurethane, mimicking the skeletal apparatus, within a silicone rubber structure, replicating the functions of the external epithelial tissue. The latter has an internal channel for pneumatic actuation that acts as the inner muscle. The study on the anatomy and kinematic behaviour of the seahorse tail suggested the mechanical design of the actuator. Through a test campaign, the actuator prototype was characterized by isotonic tests with an external null load, isometric tests, and activation/deactivation times. Specifically, the full actuator distension of 154.5 mm occurs at 1.8 bar, exerting a maximum force of 11.9 N, with an activation and deactivation time of 74.9 and 94.5 ms, respectively.

Evaluation of the External Soft Tissue Changes Following the Correction of Class II Skeletal Malocclusion in the Adolescence Period Using Removable and Fixed Functional Appliances: A Systematic Review and Meta-Analysis.

In this systematic review, we aimed to assess the current evidence regarding the effectiveness of functional treatment with both removable and fixed appliances to normalize the external soft tissue for skeletal class II adolescent individuals. We performed a broad electronic search to retrieve relevant studies from nine databases to identify randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that investigated soft tissue changes following functional treatment and evaluated the changes using 2D lateral cephalometric radiographsand 3D-optical surface laser scanning. A total of three RCTs and eight CCTs were included. Ages ranged from 11 to 16 years with the fixed functional appliances, and from eight to 12 years with the removable ones, including 689 skeletal class II patients. Version 2 of Cochran's risk-of-bias (RoB2), and the risk of bias in non-randomized studies of interventions (ROBIN-I) were used to assess the risk of bias for the included papers. Of the 11 eligible studies, three studies were included in the meta-analysis to assess the upper and lower lip position in relation to the E-line (Ricketts's aesthetic line) in addition to the nasolabial angle. The meta-analysis showed that the upper lip retracted after functional treatment with Twin-block in relation to E-line (mean difference (MD) = -1.93; 95% CI: -2.37, -1.50; p < 0.00001; χ² = 5.43; p = 0.07; I2 = 63%), while the lower lip position did not change after functional treatment with Twin-block in relation to E-line (MD = 0.03; 95% CI: -0.56, 0.61; p = 0.92; χ² = 1.74; p = 0.42; I2 = 0%). The nasolabial angle increased after Twin-block treatment (MD = 5.75; 95% CI: 4.57, 6.93;p < 0.00001; χ² = 6.77; p = 0.03; I2 = 70%). The mentolabial angle and Z-angle also increased after functional therapy, where the facial convexity angle decreased, regardless of the functional devices used. On the other hand, using the 3D-optical surface laser scanning showed that the upper lip length and the commissural width did not change following therapy, but the lower lip increased in length, as well as the total face height. More high-quality RCTs are required to obtain accurate evidence in this field.

The Effects of Negative Pressure Therapy on Hair Growth of Mouse Models.

Negative pressure therapy (NPT) has been shown to facilitate wound healing and promote hair growth in a porcine model. However, there is a paucity of research on the impact of negative pressure on hair growth in murine models. Despite the ability of nude mice to develop hair follicles, the hair they produce is often flawed towing to genetically induced keratin disorders, rendering them a pertinent animal model for assessing hair regeneration. Therefore, this study aims to investigate the effects of negative pressure on hair follicle growth in a nude mouse model. To achieve this, a customized external tissue expansion device was developed to apply negative pressure to the dorsum of nude mice. The mice were subjected to several treatment courses consisting of 15 and 30 min of continuous negative pressure at 10 mmHg, which were repeated 5 and 10 times every other day until sacrifice. Dorsal skin samples were subsequently extracted from the suction and nonsuction areas. The sections were stained with various antibodies to assess the expression of SOX-9, LHX-2, Keratin-15, β-catenin, CD31, and vascular endothelial growth factor-A, and a TUNEL assay was used to analyze cell apoptosis. The results showed that the number of hair follicles and angiogenesis were significantly higher in the suction area than in the nonsuction area in all groups. Moreover, mice that received NPT for 15 min for 10 times had a higher hair follicle density than the other three groups. Immunofluorescence staining for LHX-2 and Keratin 15 further validated the results of these findings. In conclusion, this study demonstrated that negative pressure effectively promotes hair follicle growth and angiogenesis in nude mice through SOX-9- and LHX-2-mediated follicular regeneration and β-catenin-mediated hair follicle morphogenesis. Impact Statement The results of this study indicate that negative pressure therapy (NPT) is effective in promoting hair growth in nude mice, as evidenced by increased hair follicle density and angiogenesis in the treated areas. Using a custom external tissue expansion device (ETED) device, 15-min NPT treatment conducted over 10 sessions demonstrated the highest follicle density. This suggest that developing a regimen for NPT may offer to create innovative treatment approaches for hair loss, ultimately benefiting individuals suffering from hair loss disorders.

Correlation analysis of disulfidptosis-related gene signatures with clinical prognosis and immunotherapy response in sarcoma

Disulfidptosis, a newly discovered type of programmed cell death, could be a mechanism of cell death controlled by SLC7A11. This could be closely associated with tumor development and advancement. Nevertheless, the biological mechanism behind disulfidptosis-related genes (DRGs) in sarcoma (SARC) is uncertain. This study identified three valuable genes (SLC7A11, RPN1, GYS1) associated with disulfidptosis in sarcoma (SARC) and developed a prognostic model. The multiple databases and RT-qPCR data confirmed the upregulated expression of prognostic DRGs in SARC. The TCGA internal and ICGC external validation cohorts were utilized to validate the predictive model capacity. Our analysis of DRG riskscores revealed that the low-risk group exhibited a more favorable prognosis than the high-risk group. Furthermore, we observed a significant association between DRG riskscores and different clinical features, immune cell infiltration, immune therapeutic sensitivity, drug sensitivity, and RNA modification regulators. In addition, two external independent immunetherapy datasets and clinical tissue samples were collected, validating the value of the DRGs risk model in predicting immunotherapy response. Finally, the SLC7A11/hsa-miR-29c-3p/LINC00511, and RPN1/hsa-miR-143-3p/LINC00511 regulatory axes were constructed. This study provided DRG riskscore signatures to predict prognosis and response to immunotherapy in SARC, guiding personalized treatment decisions.

Continuous External Tissue Expansion for Closure of Forehead Flap Donor Site.

Continuous external tissue expansion has been shown to be effective in the management of craniofacial wounds resulting from tumor resection, trauma, and wound dehiscence. Forehead flap donor sites are typically managed with secondary intention healing. However, this can create esthetic problems in pigmented skin because of the tendency to form thick scars. Here, the authors describe the use of continuous external tissue expansion for the management of a paramedian forehead flap donor site. A Dermaclose device was used at the time of forehead flap elevation and removed at the pedicle division and inset. Sufficient skin expansion was achieved for primary closure. The final scar was esthetically pleasing. External tissue expansion is ideal for forehead flap donor sites as the second stage of the operation provides an opportunity for expander removal and wound closure.

Tissue-resident macrophages specifically express Lactotransferrin and Vegfc during ear pinna regeneration in spiny mice

The details of how macrophages control different healing trajectories (regeneration vs. scar formation) remain poorly defined. Spiny mice (Acomys spp.) can regenerate external ear pinnae tissue, whereas lab mice (Mus musculus) form scar tissue in response to an identical injury. Here, we used this dual species system to dissect macrophage phenotypes between healing modes. We identified secreted factors from activated Acomys macrophages that induce a pro-regenerative phenotype in fibroblasts from both species. Transcriptional profiling of Acomys macrophages and subsequent invitro tests identified VEGFC, PDGFA, and Lactotransferrin (LTF) as potential pro-regenerative modulators. Examining macrophages invivo, we found that Acomys-resident macrophages secreted VEGFC and LTF, whereas Mus macrophages do not. Lastly, we demonstrate the requirement for VEGFC during regeneration and find that interrupting lymphangiogenesis delays blastema and new tissue formation. Together, our results demonstrate that cell-autonomous mechanisms govern how macrophages react to the same stimuli to differentially produce factors that facilitate regeneration.

A disulfidptosis-related lncRNAs signature in hepatocellular carcinoma: prognostic prediction, tumor immune microenvironment and drug susceptibility

Disulfidptosis, a novel type of programmed cell death, has attracted researchers’ attention worldwide. However, the role of disulfidptosis-related lncRNAs (DRLs) in liver hepatocellular carcinoma (LIHC) not yet been studied. We aimed to establish and validate a prognostic signature of DRLs and analyze tumor microenvironment (TME) and drug susceptibility in LIHC patients. RNA sequencing data, mutation data, and clinical data were obtained from the Cancer Genome Atlas Database (TCGA). Lasso algorithm and cox regression analysis were performed to identify a prognostic DRLs signature. Kaplan–Meier curves, principal component analysis (PCA), nomogram and calibration curve, function enrichment, TME, immune dysfunction and exclusion (TIDE), tumor mutation burden (TMB), and drug sensitivity analyses were analyzed. External datasets were used to validate the predictive value of DRLs. qRT-PCR was also used to validate the differential expression of the target lncRNAs in tissue samples and cell lines. We established a prognostic signature for the DRLs (MKLN1-AS and TMCC1-AS1) in LIHC. The signature could divide the LIHC patients into low- and high-risk groups, with the high-risk subgroup associated with a worse prognosis. We observed discrepancies in tumor-infiltrating immune cells, immune function, function enrichment, and TIDE between two risk groups. LIHC patients in the high-risk group were more sensitive to several chemotherapeutic drugs. External datasets, clinical tissue, and cell lines confirmed the expression of MKLN1-AS and TMCC1-AS1 were upregulated in LIHC and associated with a worse prognosis. The novel signature based on the two DRLs provide new insight into LIHC prognostic prediction, TME, and potential therapeutic strategies.

External Volume Expansion: Timing and Effects on the Rate of Fat Graft Retention in BALB/c Nude Mice.

Fat grafting has been widely used for soft-tissue augmentation. External volume expansion (EVE) is a favorable tool for improvement in the rate of fat graft retention. However, few studies have focused on the most appropriate time for its implementation. In this study, BALB/c nude mice were used to investigate the effective time for the implementation of external volume expansion to improve the rate of fat retention. Sixteen mice were divided into four groups, and EVE was performed at different time points before or both before and after fat grafting. Fat tissue from a human donor was injected into the mice following EVE. Visual assessment, micro-computed tomography analysis, and histopathological evaluation were used to assess fat retention. After 10 weeks, the group that underwent EVE 5 days before fat grafting demonstrated a significantly higher preserved fat volume, as determined by micro-computed tomography (p<0.05). Moreover, the group that received additional EVE after fat grafting exhibited a higher retention rate compared to the groups receiving EVE only before grafting (p<0.05). Histopathological analysis indicated that swelling, edema, and inflammation were more pronounced in the group with EVE immediately before grafting, while angiogenesis and lipogenesis were more active in the group with additional EVE after grafting. EVE is a safe and effective approach for improving the rate of fat graft retentions. Furthermore, the timing of external tissue expansion plays a crucial role in fat retention. Based on our animal study, performing EVE immediately before and after fat grafting may be an effective strategy for enhancing the rate of fat graft retentions.

Survey of Surgeon-reported Postoperative Protocols for Deep Inferior Epigastric Perforator Flap in Breast Reconstruction.

The use of deep inferior epigastric perforator (DIEP) flaps is a well-established breast reconstruction technique. A 29-question survey was e-mailed to 3186 active American Society of Plastic Surgeons members, aiming to describe postoperative monitoring practice patterns among surgeons performing DIEP flaps. From 255 responses (8%), 79% performing DIEP surgery were analyzed. Among them, 34.8% practiced for more than 20 years, 34.3% for 10-20 years, and 30.9% for less than 10 years. Initial 24-hour post-DIEP monitoring: intensive care unit (39%) and floor (36%). Flap monitoring: external Doppler (71%), tissue oximetry (41%), and implantable Doppler (32%). Postoperative analgesia: acetaminophen (74%), non-steroidal anti-inflammatory drugs (69%), neuromodulators (52%), and opioids (4.4%) were administered on a scheduled basis. On postoperative day 1, 61% halt intravenous fluids, 67% allow ambulation, 70% remove Foley catheter, and 71% start diet. Most surgeons discharged patients from the hospital on postoperative day 3+. Regardless of experience, patients were commonly discharged on day 3. Half of the surgeons are in academic/nonacademic settings and discharge on/after day 3. This study reveals significant heterogeneity among the practice patterns of DIEP surgeons. In light of these findings, it is recommended that a task force be convened to establish standardized monitoring protocols for DIEP flaps. Such protocols have the potential to reduce both the length of hospital stays and overall care costs all while ensuring optimal pain management and vigilant flap monitoring.

Understanding how high stocking densities and concurrent limited oxygen availability drive social cohesion and adaptive features in regulatory growth, antioxidant defense and lipid metabolism in farmed gilthead sea bream (Sparus aurata).

The study combined the use of biometric, behavioral, physiological and external tissue damage scoring systems to better understand how high stocking densities drive schooling behavior and other adaptive features during the finishing growing phase of farmed gilthead sea bream in the Western Mediterranean. Fish were grown at three different final stocking densities (LD, 8.5kg/m3; MD, 17kg/m3; HD, 25kg/m3). Water oxygen concentration varied between 5 and 6ppm in LD fish to 3-4ppm in HD fish with the summer rise of water temperature from 19°C to 26°C (May-July). HD fish showed a reduction of feed intake and growth rates, but they also showed a reinforced social cohesion with a well-defined endogenous swimming activity rhythm with feeding time as a main synchronization factor. The monitored decrease of the breathing/swimming activity ratio by means of the AEFishBIT data-logger also indicated a decreased energy partitioning for growth in the HD environment with a limited oxygen availability. Plasma glucose and cortisol levels increased with the rise of stocking density, and the close association of glycaemia with the expression level of antioxidant enzymes (mn-sod, gpx4, prdx5) in liver and molecular chaperones (grp170, grp75) in skeletal muscle highlighted the involvement of glucose in redox processes via rerouting in the pentose-phosphate-pathway. Other adaptive features included the depletion of oxidative metabolism that favored lipid storage rather than fatty acid oxidation to decrease the oxygen demand as last electron acceptor in the mitochondrial respiratory chain. This was coincident with the metabolic readjustment of the Gh/Igf endocrine-growth cascade that promoted the regulation of muscle growth at the local level rather than a systemic action via the liver Gh/Igf axis. Moreover, correlation analyses within HD fish displayed negative correlations of hepatic transcripts of igf1 and igf2 with the data-logger measurements of activity and respiration, whereas the opposite was found for muscle igf2, ghr1 and ghr2. This was indicative of a growth-regulatory transition that supported a proactive instead of a reactive behavior in HD fish, which was considered adaptive to preserve an active and synchronized feeding behavior with a minimized risk of oxidative stress and epidermal skin damage.

Autophagy and Inflammation: Regulatory Roles in Viral Infections.

Autophagy is a highly conserved intracellular degradation pathway in eukaryotic organisms, playing an adaptive role in various pathophysiological processes throughout evolution. Inflammation is the immune system's response to external stimuli and tissue damage. However, persistent inflammatory reactions can lead to a range of inflammatory diseases and cancers. The interaction between autophagy and inflammation is particularly evident during viral infections. As a crucial regulator of inflammation, autophagy can either promote or inhibit the occurrence of inflammatory responses. In turn, inflammation can establish negative feedback loops by modulating autophagy to suppress excessive inflammatory reactions. This interaction is pivotal in the pathogenesis of viral diseases. Therefore, elucidating the regulatory roles of autophagy and inflammation in viral infections will significantly enhance our understanding of the mechanisms underlying related diseases. Furthermore, it will provide new insights and theoretical foundations for disease prevention, treatment, and drug development.

Klippel–Trenaunay–Weber Syndrome—Case Report: Diagnostic Role of Fetal Autopsy and Histopathology

Abstract Objectives The aim of this study was to evaluate a case of Klippel–Trenaunay–Weber Syndrome (KTWS) diagnosed at 15 weeks of gestation. Materials and Methods A 30-year-old G4P1L1A2 at 15 weeks gestation was detected with abnormal fetal right lower limb thickness and hypervascularity in both thighs. Multiseptated hypoechoic areas were detected involving skin and subcutaneous tissue of the left shoulder region, axilla, chest wall, and lower back region posteriorly extending into both lower limbs associated with cortical thickening of long bones of the lower limb. Significant subcutaneous thickening was present in the right foot along with a slow flow vascular malformation. The couple did not opt for any prenatal testing and continued the pregnancy. Results The patient received routine antenatal care and at 27 weeks of gestation there was polyhydramnios with fetal demise. She delivered a macerated stillborn baby girl weighing 2.5 kg (&gt;99th centile). Consent was obtained for external autopsy, fetal photographs, and tissue biopsy. The fetus was grossly macerated. The skin was hypertrophied and subcutaneous tissue along with bluish discoloration was present over the affected areas. Histopathology of fetal thigh tissue was suggestive of arteriovenous malformation compatible with a diagnosis of KTWS. Conclusions KTWS has unique sonographic features. Confirmation can be done by clinical exome sequencing of amniotic fluid or fetal tissue.

Early Clues in Diagnosing Fournier’s Gangrene

Necrotizing Fasciitis has a high mortality if not managed early, yet early diagnosis is inherently difficult. The external tissue is initially unaffected, therefore we rely on secondary signs of toxicity, which often represent an already established systemic infection. It typically effects immunocompromised patients, who are slow to manifest these secondary signs, complicating the diagnosis further. We present a case of an immunocompromised patient, who did not manifest typical signs of systemic infection. Atrial Fibrillation was the first clue to an underlying infection, and initially the only localising infective source was a hydrocele. Cutaneous features in keeping with a Fournier’s Gangrene occurred forty-eight hours later. This case highlights the difficulty in diagnosing Fournier’s Gangrene, and the possibility that a hydrocele in a septic patient may be reactive to a more sinister underlying necrotizing infection.

Facial Soft Tissue Characteristics Among Sagittal and Vertical Skeletal Patterns: A Cone-Beam Computed Tomography Study.

Background Facial esthetics depend on the skeletal and dental structures underlying variable facial soft tissue thickness. In this social context, determining the relationship between external soft tissue and underlying skeletal and dental hard tissue is essential for detailed orthodontic diagnosis and treatment planning. Objective This study aims to measure facial soft tissue thickness in different sagittal and vertical skeletal patterns. Methodology This is an observational study utilizing pre-existing cone-beam computed tomography (CBCT) images of 170 subjects (110 females and 60 males) with a mean age group of 37.45 ± 13.83 years. CBCT images were then classified sagittally based on the point A-Nasion-point B (ANB) angle from Steiner's analysis into skeletal Class I, Class II, and Class III. Furthermore, vertical patterns were grouped based on the Frankfort-mandibular plane angle (FMA) from Tweed's analysis into hyperdivergent, hypodivergent, and normodivergent facial types. One-way ANOVA was used to compare the means of facial soft tissue thickness between the skeletal groups, followed by Tukey's post-hoc test for individual comparison. Multinomial logistic regression analysis was used to test the association between gender, age, and skeletal groups. The significance level was 0.05. Results One-way ANOVA revealed statistically significant differences in both sagittal and vertical groups (p≤0.05).Tukey's post hoc analysis showed that the skeletal Class III group has increased soft tissue thickness in the subnasale, upper lip, and mention compared to Class I and Class II subjects. Moreover, the hypodivergent group demonstrated increased soft tissue thickness in gnathion and mentioned landmarks in relation to the other groups. Multinomial logistic regression analysis showed significant differences between groups according to both gender and sagittal skeleton patterns (p≤0.05), with males less likely to be in Class II. Conclusions Skeletal Class III and hypodivergent groups have thicker soft tissue in specific facial landmarks. Sexual dimorphism was marked in soft tissue measurements.

Infection dynamic of Micropterus salmoides rhabdovirus and response analysis of largemouth bass after immersion infection.

Largemouth bass (Micropterus salmoides) is an important economic freshwater aquaculture fish originating from North America. However, the frequent outbreaks of Micropterus salmoides rhabdovirus (MSRV) have seriously limited the healthy development of Micropterus salmoides farming industry. In the present study, a strain of MSRV was isolated and identified from infected largemouth bass by PCR, transmission electron micrograph observation and genome sequences analysis, and tentatively named MSRV-HZ01 strain. Phylogenetic analyses showed that the MSRV-HZ01 presented the highest similarity to MSRV-2021, followed by MSRV-FJ985 and MSRV-YH01. The various tissues of juvenile largemouth bass exhibited significant pathological damage following MSRV-HZ01 immersion infection, and the mortality reached 90%. We also found that intestine was the key organ for MSRV to enter the fish body initially by dynamic analysis of viral infection, and the head kidney was the susceptible tissue of virus. Moreover, the MSRV was also transferred to the external mucosal tissue in later stage of viral infection to achieve horizontal transmission. In addition, the genes of IFN γ and IFN I-C were significantly up-regulated after MSRV infection to exert antiviral functions. The genes of cGAS and Sting might play an important role in the regulation of interferon expression. In conclusion, we investigated the virus infection dynamics and fish response following MSRV immersion infection, which would promote our understanding of the interaction between MSRV and largemouth bass under natural infection.