Tissue Loss Research Articles

The influence of tobacco smoking on the outcomes achieved by root coverage procedures: An updated systematic review.

This updated version of a systematic review (SR) originally published in 2009 evaluated the effect of smoking on the clinical outcomes achieved with root coverage (RC) procedures in the treatment of gingival recession (GR) defects. This SR includes randomized controlled trials, controlled clinical trials, and case series with a minimum follow-up of 6 months. Eligible studies involved GR defects without interproximal tissue loss submitted to RC procedures, as well as outcome measures from smokers (i.e., those smoking 10 or more cigarettes per day at baseline) and nonsmokers, recorded separately. Three electronic databases were searched up to March 31, 2024. Random effects meta-analyses were conducted thoroughly. A total of 12 studies reporting on 181 smokers and 162 nonsmokers, submitted to different RC procedures, were included. Half of these trials were originally included in the 2009 SR, whereas the other half (six studies) were included in this update. Nonsmokers experienced greater reductions in GR and gains in clinical attachment level compared to smokers. Pooled estimates comparing smokers and nonsmokers who received coronally advanced flap (CAF) alone and subepithelial connective tissue graft (SCTG) + CAF showed that nonsmokers achieved greater mean root coverage (MRC) in both treatments. Significant differences in MRC of 10.85% (95% CI, 1.92 to 19.77) and 22.04 (95% CI, 14.25 to 29.83), favoring nonsmokers, were identified for CAF and SCTG + CAF, respectively. Similarly, nonsmokers treated with SCTG + CAF displayed superior number of sites exhibiting complete root coverage (CRF) when compared with smokers (risk ratio, 4.12; 95% CI, 1.73 to 9.80). Smoking negatively impacts the outcomes of RC procedures, particularly those achieved by SCTG-based procedures. Smoking was linked to poorer RC outcomes. These outcomes highlight the critical need to integrate smoking cessation into periodontal treatment plans.

Comparative Study between Mechanical Rotational Atherectomy Combined with Drug-Coated Balloon versus Drug-Coated Balloon Alone for Treatment of In-Stent Restenosis during Peripheral Endovascular Interventions: A Multicentric Trial

Purpose: To compare the efficacy and safety of percutaneous mechanical debulking (PMD) using mechanical rotational atherectomy combined with paclitaxel drug-coated balloon (DCB) versus using paclitaxel DCB alone in the treatment of in-stent restenosis. Material and Methods: This is a multicentric retrospective observational study conducted over a period of 2 years from 2020 to 2022. The study included 49 patients presented with chronic limb-threatening ischemia (CLTI) associated with in-stent restenosis, either acute (<14 days), subacute (<3 months) or chronic (>3 months). The enrolled patients underwent endovascular revascularization using either PMD combined with paclitaxel DCB or paclitaxel DCB only. They were followed up for 6 months after the intervention clinically and by duplex evaluation. Results: The lesion length was about 14.2 mm in the group treated by PMD+ DCB and 9.3 mm in the group treated by DCB alone. The technical success rate was the same between the two groups. However, the follow-up after 6 months showed that patencies for PMD + DCB and DCB alone were 15 (68.2%) patients and 15 (55.6%) patients, respectively (significant p value = 0.028). Procedural-related complications for PMD + DCB are distal embolization (9%) of cases and no vessel perforation. Regarding the candidates who were treated by DCB alone, there were minor groin hematomas (11.1%), distal arterial thrombosis (11.1%) and contrast-induced nephropathy (CIN) (11.1%) cases. Conclusion: The endovascular management of in-stent restenosis using percutaneous mechanical debulking (PMD) in conjunction with paclitaxel drug-coated balloon (DCB) showed that PMD combined with DCB is a safe and effective modality for achieving recanalization. It gives a satisfactory outcome in terms of technical success, freedom from clinically driven target lesion revascularization rate (CD-TLR) and mortality. Despite these promising results, further research with a large enrolled population may be required to determine the cost/benefit.

Gata6 functions in zebrafish endoderm to regulate late differentiating arterial pole cardiogenesis.

Mutations in GATA6 are associated with congenital heart disease, most notably conotruncal structural defects. However, how GATA6 regulates cardiac morphology during embryogenesis is undefined. We used knockout and conditional mutant zebrafish alleles to investigate the spatiotemporal role of gata6 during cardiogenesis. Loss of gata6 specifically impacts atrioventricular valve formation and recruitment of epicardium, with a prominent loss of arterial pole cardiac cells, including those of the ventricle and outflow tract. However, there are no obvious defects in cardiac progenitor cell specification, proliferation or death. Conditional loss of gata6 starting at 24 h is sufficient to disrupt the addition of late differentiating cardiomyocytes at the arterial pole, with decreased expression levels of anterior secondary heart field (SHF) markers spry4 and mef2cb. Conditional loss of gata6 in the endoderm is sufficient to phenocopy the straight knockout, resulting in a significant loss of ventricular and outflow tract tissue. Exposure to a Dusp6 inhibitor largely rescues the loss of ventricular cells in gata6-/- larvae. Thus, gata6 functions in endoderm are mediated by FGF signaling to regulate the addition of anterior SHF progenitor derivatives during heart formation.

Advancing Myocardial Infarction Treatment: Harnessing Multi-Layered Recellularized Cardiac Patches with Fetal Myocardial Scaffolds and Acellular Amniotic Membrane.

Myocardial infarction (MI) is a leading cause of irreversible functional cardiac tissue loss, requiring novel regenerative strategies. This study assessed the potential therapeutic efficacy of recellularized cardiac patches, incorporating fetal myocardial scaffolds with rat fetal cardiomyocytes and acellular human amniotic membrane, in adult Wistar rat models of MI. Decellularized myocardial tissue was obtained from 14 to 16 week-old human fetuses that had been aborted. Chemical detergents (0.1% EDTA and 0.2% sodium dodecyl sulfate) were used to prepare the fetal extracellular matrix (ECM), which was characterized for bio-scaffold microstructure and biocompatibility via scanning electron microscopy (SEM) and MTT assay, respectively. Neonatal cardiomyocytes were extracted from the ventricles of one-day-old Wistar rats' littermates and characterized through immunostaining against Connexin-43 and α-smooth muscle actin. The isolated cells were seeded onto decellularized tissues and covered with decellularized amniotic membrane. Sixteen healthy adult Wistar rats were systematically allocated to control and MI groups. MI was induced via arterial ligation. Fourteen days post-operation, the MI group was received the engineered patches. Following a two-week post-implantation period, the animals were euthanized, and the hearts were harvested for the graft evaluation. Histological analysis, DAPI staining, and ultra-structural examination corroborated the successful depletion of cellular elements, while maintaining the integrity of the fetal ECM and architecture. Subsequent histological and immunohistochemichal (IHC) evaluations confirmed effective cardiomyocyte seeding on the scaffolds. The application of these engineered patches in MI models resulted in increased angiogenesis, reduced fibrosis, and restricted scar tissue formation, with the implanted cardiomyocytes remaining viable at graft sites, indicating prospective in vivo cell viability. This study suggests that multi-layered recellularized cardiac patches are a promising surgical intervention for myocardial infarction, showcasing significant potential by promoting angiogenesis, mitigating fibrosis, and minimizing scar tissue formation in MI models. These features are pivotal for enhancing the therapeutic outcomes in MI patients, focusing on the restoration of the myocardial structure and function post-infarction.

Outcomes of Noncompliant Balloons in the Treatment of Lower Extremity Chronic Limb Threatening Ischemia: A Prospective Study.

This is a prospective study to investigate the clinical outcomes of using noncompliant balloons in lower limb angioplasty for chronic limb threatening ischemia (CLTI). This is a prospective single-center cohort study performed at a local tertiary hospital in Singapore. Consecutive patients who underwent lower limb angioplasty for CLTI using a noncompliant balloon catheter were enrolled if they were aged 40 years and above, presented with CLTI Rutherford grade 4 to 6, and had TASC C or D lesions in the lower limb vessels that were at least 100mm in length. Patient demographics, Rutherford grading, lesion characteristics, complications, and follow-up data were collected and analyzed. The primary outcomes were 30-day freedom from major adverse events, amputation-free survival (AFS) at 12 months, and freedom from clinically driven target lesion revascularization (cdTLR) at 12 months. Secondary outcomes included clinical success and target lesion primary patency (TLPP) at 12 months. Amputation-free survival, freedom from cdTLR, and TLPP were calculated by Kaplan-Meier analysis. From May 2020 to December 2021, 50 patients (50 limbs) were enrolled. 43 (86%) patients had diabetes mellitus, while 12 patients (24%) had end-stage renal failure. 85 lesions were treated, including 59 (69.4%) below-the-knee (BTK) lesions. All the lesions were TASC C (n=45, 52.9%) or TASC D (n=40, 47.1%) lesions. Mean lesion length was 231.4±116.2mm. Technical success rate was 96.5%. No patients were lost to follow-up. Median follow-up duration was 282 days (IQR: 31-390 days). One patient died on day 26 due to an acute myocardial infarction. Two patients had groin hematomas postprocedure, both of which were treated conservatively. AFS, freedom from cdTLR, and TLPP at 12 months postprocedure was 70.0% (95% confidence interval [CI]: 58.4%-83.9%), 90.1% (95% CI: 83.4%-97.4%), and 61.1% (95% CI: 50.7%-73.6%), respectively. Early results have shown that the use of a high-pressure, noncompliant balloon is effective in lower limb angioplasty for CLTI in a highly challenging group of patients with a high prevalence of long BTK disease. Good vessel patency and limb salvage rates can be achieved, with a low complication rate. We await more long-term outcomes on vessel patency. There are many devices in the market for use in lower limb angioplasty. However, many of them come with an increased financial cost, procedural time and procedural difficulty. We report our prospective results with the exclusive use of a high pressure, non-compliant balloon, in a challening group of patients with a high prevalence of diabetes and end stage renal failure, achieving amputation free surival at 6 and 12 months post-procedure of 84.0% and 70.0% respectively. The use of non-compliant balloon is technically easy and does not add additional steps compared to a standard POBA procedure, thus limiting costs. We believe this article can be a push factor for clinicians to consider the use of these high pressure, non-compliant balloons in their patient care.

A Systematic Review and Meta-Analysis of Management Options for Empty Nose Syndrome: A Proposed Management Algorithm.

Empty nose syndrome (ENS) is an acquired condition characterized by paradoxical nasal obstruction and sensation of nasal dryness often accompanied by psychological disorders such as depression or anxiety, typically occurring after the loss of inferior turbinate tissue or volume in the setting of prior sinonasal surgery. This review aims to identify and evaluate the reported management options. PubMed, Scopus, and Web of Science. The terms "empty nose syndrome" OR "atrophic rhinitis" were used in a systematic search of original articles since the year 1990, yielding 1432 individual studies. These were screened on the Covidence platform for inclusion if any intervention was reported for the treatment of ENS. A pooled analysis of standardized mean differences (SMDs) combined with a random effects model was employed to report outcomes in Empty Nose 6-Item Questionnaire (ENS6Q), Sino-Nasal Outcome Test (SNOT), anxiety, and depression scores. A total of 35 articles were included, comprising 957 individual ENS patients. Surgical interventions mostly in the form of meatus augmentation implants accounted for 26 out of the 36 articles. The remaining ten articles included medical and psychological management options. SMD in SNOT, ENS6Q, anxiety, and depression scores were reported and demonstrated statistically significant improvements in follow-up periods of up to 1 year. All articles reported favorable outcomes following their chosen interventions. There is a paucity of evidence on the management of ENS and an absence of randomized controlled trials. Surgical intervention appears to be the current mainstay of treatment, but there is a potential role for psychological and medical management.

Concurrent plate fixation and pedicled flap coverage for open fractures complicated by soft tissue loss of the tibia in pediatric cohort: a clinical series.

The optimal treatment of open fractures complicated by soft tissue loss of pediatric tibial fractures remains inconclusive. The author described a protocol of concurrent plate fixation and pedicled flap coverage and retrospectively reviewed the outcomes of such injuries. A total of 25 pediatric cases with Gustilo lllB open tibial fracture were treated by single-stage plate fixation and pedicled flap reconstruction. The reviewed information consisted of time to fix and flap, type of plate, type of pedicled flap, fracture union time, postoperative complication and the clinical outcomes by objective scoring system. Fix and flap was undergone between 7 and 12days after injury with the average time of 8.2days. Regarding the type of plate, narrow LCP was applied in 8, 3.5mm precontoured LCP in 10, 5.0mm precontoured in 2 and double LCP in 5. According to soft tissue reconstruction, the medial gastrocnemius flap was selected in 6 cases, myocutaneous medial gastrocnemius flap in 2, soleus flap in 3, hemisoleus flap in 5, reverse sural flap in 6 and combined medial gastrocnemius and hemisoleus flaps in 3. No flap-related complication was demonstrated. All cases established fracture union in between 12 and 24weeks with an average time to union of 17.7weeks. According to postoperative complications, infected plate occurred in 2 cases and implant irritation in 5. According to Puno functional score, excellent results were presented in 7 cases and good results in 18 cases. Single-stage plate fixation and pedicled flap coverage are a reliable regimen for pediatric open fractures complicated by soft tissue loss of the tibia.

Integrated single-cell RNA-seq analysis reveals mitochondrial calcium signaling as a modulator of endothelial-to-mesenchymal transition.

Endothelial cells (ECs) are highly plastic, capable of differentiating into various cell types. Endothelial-to-mesenchymal transition (EndMT) is crucial during embryonic development and contributes substantially to vascular dysfunction in many cardiovascular diseases (CVDs). While targeting EndMT holds therapeutic promise, understanding its mechanisms and modulating its pathways remain challenging. Using single-cell RNA sequencing on three in vitro EndMT models, we identified conserved gene signatures. We validated original regulators in vitro and in vivo during embryonic heart development and peripheral artery disease. EndMT induction led to global expression changes in all EC subtypes rather than in mesenchymal clusters. We identified mitochondrial calcium uptake as a key driver of EndMT; inhibiting mitochondrial calcium uniporter (MCU) prevented EndMT in vitro, and conditional Mcu deletion in ECs blocked mesenchymal activation in a hind limb ischemia model. Tissues from patients with critical limb ischemia with EndMT features exhibited significantly elevated endothelial MCU. These findings highlight MCU as a regulator of EndMT and a potential therapeutic target.

Impact of Peripheral Angioplasty on Wound Oxygenation and Healing in Patients with Chronic Limb-Threatening Ischemia Measured by Near-Infrared Spectroscopy.

Managing chronic limb-threatening ischemia (CLTI) is challenging due to difficulties in assessing tissue oxygen saturation in ulcers. Near-infrared spectroscopy (NIRS) is a non-invasive method for measuring tissue oxygen saturation (StO2). This study evaluated the effects of endovascular treatment (EVT) on StO2 and wound healing in CLTI patients, comparing NIRS to standard ankle-brachial index (ABI) measurements. Using the Duesseldorf PTA Registry, 43 CLTI patients were analyzed: 27 underwent EVT, and 16 received conservative treatment. ABI assessed macrocirculation, while NIRS measured wound, wound area, and mean foot StO2 at baseline, post-EVT, and four-month follow-up. Wound severity was classified by wound area and wound, ischemia, and foot infection (WIfI) score. Wound StO2 increased significantly (median (interquartile range (IQR)), 38 (49.3) to 60 (34.5)%, p = 0.004), as did wound area StO2 (median (IQR), 70.9 (21.6) to 72.8 (18.3)%, p < 0.001), with no significant changes in the control group by four-month follow-up. Wound area decreased significantly after EVT (mean ± SD, 343.1 ± 267.8 to 178.1 ± 268.5 mm2, p = 0.01) but not in the control group. Changes in wound StO2, wound area StO2, and WIfI score correlated with wound area reduction, unlike ABI. This small exploratory study shows that NIRS-measured StO2 improvements after EVT correlate with reduced wound area and WIfI scores, highlighting NIRS as a potential enhancement for CLTI wound management in addition to ABI.

Necrotizing Fasciitis in Iv Drug Abuser by Oil Injection: A Case Report

Necrotizing fasciitis (NF) is a necrotizing soft tissue infection that can result in fast tissue loss, necrosis, and potentially fatal acute sepsis. Diabetes, cancer, alcohol abuse, and chronic liver and renal disease are all risk factors for NF. Our case was a 50 years old male with IV drug abuse that inject oil in his arms and admitted by diagnosis of Necrotizing Fasciitis and perform serial surgery and antibiotic therapy for him to save his life and his arm. NF is a rare bacterial inflammation (infection) that can destroy the skin and underlying tissues (connective tissue, subcutaneous fat, muscles, and muscle membranes). The disease can be very dramatic, with shock and damage to internal organs. In this case report, serial debridement with adequate antibiotherapy followed by reconstructive surgeries were made. An early diagnosis remains challenging and crucial for salvaging the affected area. Necrotizing fasciitis is a life-threatening soft tissue infection characterized by a rapid spreading infection of the subcutaneous tissue and in particular the fascia. The management of infected tissues requires a rapid diagnosis, immediate aggressive surgical management and an extended debridement. In some cases, early amputations of the affected tissues and maximum intensive care treatment, in case of sepsis, are required. Due to a rising number of cases we aimed to report this case.

Protective effects of mesenchymal stem cells-derived extracellular vesicles against ischemia-reperfusion injury of hearts donated after circulatory death: Preliminary study in a pig model

IntroductionInsufficient supply of cardiac grafts represents a severe obstacle in heart transplantation. Donation after Circulatory Death (DCD), in addition to conventional donation after brain death, is one promising option to overcome the organ shortage. However, DCD organs undergo an inevitable more extended period of warm unprotected ischemia between circulatory arrest and graft procurement. Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) have shown remarkable protective effects against ischemia-reperfusion injury. Thus, we aimed to enhance grafts preservation from DCD donors, through treatment with MSC-EVs. MethodsFemale pigs were euthanized by barbiturate overdose and after 20 min of a flat EKG, the chest was opened, the heart harvested and subsequently connected to an extracorporeal perfusion machine. MSC-EVs, isolated by ion exchange chromatography, were added to the perfusion solution (1×1011 particles) and the heart was perfused for 2 h. Then, heart tissue biopsies were taken to assess histological changes, mitochondrial morphology, antioxidant enzyme activity and inflammation mediators’ expression. Biochemical parameters of myocardial viability were assessed in the perfusate. ResultsThe treatment with MSC-EVs significantly prevented mitochondria swelling, mitochondrial cristae loss and oxidative stress in cardiac tissue. The protective effect of MSC-EVs was confirmed by the delayed increase of the cardiac-specific enzymes CK and TnC in the perfusate and the reduction of caspase-3+ cells in tissue sections. ConclusionMSC-EVs improve graft quality by preserving the mitochondrial ultrastructure protecting the myocardium against oxidative stress, reducing apoptosis of cardiac cells and preventing the increase of pro-inflammatory cytokines.

Erythrocyte Oxidative Status in People with Obesity: Relation to Tissue Losses, Glucose Levels, and Weight Reduction.

This study aimed to investigate the impact of reductions in various body mass components on the erythrocyte oxidative status and glycemic state of people with obesity (PWO). A total of 53 PWO followed a six-month individualized low-calorie diet with exercise, during which anthropometric, biochemical, and oxidative parameters were measured. The participants were divided into groups based on weight (W), visceral fat area (VFA), total body water (TBW), and skeletal muscle mass (SMM) losses, as well as normoglycemia (NG) and hyperglycemia (HG). Weight reduction normalized glycemia and influenced erythrocyte enzyme activity. Regardless of the tissue type lost (VFA, TBW, or SMM), glutathione peroxidase activity decreased in all groups, accompanied by an increase in glutathione reductase activity. Lipofuscin (LPS) and malondialdehyde (MDA) concentrations decreased regardless of the type of tissue lost. The α-/γ-tocopherol ratio increased in those losing >10% body weight, >15% VFA, and >5% TBW. In the NG group, compared to the HG group, there was a decrease in glutathione peroxidase and an increase in glutathione reductase, with these changes being stronger in the HG group. The LPS and MDA concentrations decreased in both groups. Significant correlations were observed between glucose reduction and changes in catalase, retinol, and α-tocopherol, as well as between VFA reduction and changes in vitamin E, L-LPS, and the activities of L-GR and L-GST. This analysis highlights the complex interactions between glucose metabolism, oxidative state, and erythrocyte membrane integrity, crucial for understanding diabetes and its management. This study shows the significant metabolic adaptability of erythrocytes in response to systemic changes induced by obesity and hyperglycemia, suggesting potential therapeutic targets to improve metabolic health in obese individuals.

Novel metagenomics analysis of stony coral tissue loss disease.

Stony coral tissue loss disease (SCTLD) has devastated coral reefs off the coast of Florida and continues to spread throughout the Caribbean. Although a number of bacterial taxa have consistently been associated with SCTLD, no pathogen has been definitively implicated in the etiology of SCTLD. Previous studies have predominantly focused on the prokaryotic community through 16S rRNA sequencing of healthy and affected tissues. Here, we provide a different analytical approach by applying a bioinformatics pipeline to publicly available metagenomic sequencing samples of SCTLD lesions and healthy tissues from 4 stony coral species. To compensate for the lack of coral reference genomes, we used data from apparently healthy coral samples to approximate a host genome and healthy microbiome reference. These reads were then used as a reference to which we matched and removed reads from diseased lesion tissue samples, and the remaining reads associated only with disease lesions were taxonomically classified at the DNA and protein levels. For DNA classifications, we used a pathogen identification protocol originally designed to identify pathogens in human tissue samples, and for protein classifications, we used a fast protein sequence aligner. To assess the utility of our pipeline, a species-level analysis of a candidate genus, Vibrio, was used to demonstrate the pipeline's effectiveness. Our approach revealed both complementary and unique coral microbiome members compared with a prior metagenome analysis of the same dataset.

Meta-analysis of the association between chronic periodontitis and chronic kidney disease.

Many scholars have performed several clinical studies have investigated the association between chronic periodontitis (CP) and chronic kidney disease (CKD). However, there are still differences between these research results, and there is no unified conclusion. Therefore, a systematic review is required to understand this issue fully. To explore the correlation between CP and CKD. Literature on the correlation between CP and CKD, as well as the clinical attachment level (CAL) and pocket probing depth (PPD) of CKD and non-CKD, were retrieved from PubMed, Embase, the Cochrane Library, and Web of Science repositories until January 2024. After the effective data were extracted, data processing and statistics were performed using Stata 12.0. Of the 22 studies, 13 were related to CP and CKD, and 9 reported CAL and PPD in patients with CKD and healthy controls. Meta-analysis of the correlation between CP and CKD revealed that CKD probability in people with CP was 1. 54 times that of healthy individuals [relative risk = 1.54, 95% confidence interval (CI): 1.40-1.70], and CP incidence in patients with CKD was 1. 98 times that of healthy individuals [overall risk (OR) = 1.98, 95%CI: 1.53-2.57]. Meta-analysis of CAL and PPD evaluations between CKD patients and healthy individuals showed that CAL and PPD levels were higher in CKD patients [standard mean difference (SMD) of CAL = 0.65, 95%CI: 0.29-1.01; SMD of PPD = 0.33, 95%CI: 0.02-0.63]. A bidirectional association exists between CP and CKD. CKD risk is increased in CP patients and vice versa. Periodontal tissue or tooth loss risks increase over time in CKD patients.

Below-the-Ankle Antegrade Teleferic Technique: New Approach for Below-the-Ankle Revascularization in Challenging Cases of Chronic Limb-Threatening Ischemia.

To describe a novel bailout technique to approach below-the-ankle (BTA) chronic total occlusions or plantar-arch severe disease where the balloon/catheter is unable to follow the crossing guidewire and no other described recanalization approach is feasible. When facing a complex BTA revascularization, if the guidewire crosses but the balloon cannot progress due to a lack of pushability, an antegrade puncture of the infrapopliteal vessel where the tip of the guidewire lays is performed. The guidewire is then carefully navigated through this distal BTA vessel into the needle to achieve its rendezvous and externalization. A low-profile balloon is inserted through the femoral access and advanced till the non-crossable point of the BTA vessels. A torque device is then attached to the proximal hub of the balloon, and the through-and-through guidewire is subsequently pulled from the new distal access, allowing the balloon to be dragged across the lesion together with the wire. The below-the-ankle antegrade teleferic (BAT) technique may be considered for highly complex BTA revascularization procedures where the wire crosses the lesion, but no other device can be tracked over it. The clinical impact of this article lies in the description of a bailout technique for BTA revascularization where the guidewire crosses, but no device can be advanced. This technique can be helpful in scenarios where failure to achieve success could result in limb loss. The BAT technique provides a solution in extremely challenging cases, enhancing technical success, improving outcomes and potentially preserving the limbs of patients who would otherwise face amputation, if not revascularized.The video shows the BAT technique performed with a support catheter under fluoroscopy: antegrate puncture of the DP, advancement of the support catheter over the wire, rendezvous of the guidewire in the catheter and subsequent externalization of the wire.

Fully Automated Hippocampus Segmentation using T2-informed Deep Convolutional Neural Networks

Hippocampal atrophy (tissue loss) has become a fundamental outcome parameter in clinical trials on Alzheimer's disease. To accurately estimate hippocampus volume and track its volume loss, a robust and reliable segmentation is essential. Manual hippocampus segmentation is considered the gold standard but is extensive, time-consuming, and prone to rater bias. Therefore, it is often replaced by automated programs like FreeSurfer, one of the most commonly used tools in clinical research. Recently, deep learning-based methods have also been successfully applied to hippocampus segmentation. The basis of all approaches are clinically used T1-weighted whole-brain MR images with approximately 1 mm isotropic resolution. However, such T1 images show low contrast-to-noise ratios (CNRs), particularly for many hippocampal substructures, limiting delineation reliability. To overcome these limitations, high-resolution T2-weighted scans are suggested for better visualization and delineation, as they show higher CNRs and usually allow for higher resolutions. Unfortunately, such time-consuming T2-weighted sequences are not feasible in a clinical routine.We propose an automated hippocampus segmentation pipeline leveraging deep learning with T2-weighted MR images for enhanced hippocampus segmentation of clinical T1-weighted images based on a series of 3D convolutional neural networks and a specifically acquired multi-contrast dataset. This dataset consists of corresponding pairs of T1- and high-resolution T2-weighted images, with the T2 images only used to create more accurate manual ground truth annotations and to train the segmentation network. The T2-based ground truth labels were also used to evaluate all experiments by comparing the masks visually and by various quantitative measures.We compared our approach with four established state-of-the-art hippocampus segmentation algorithms (FreeSurfer, ASHS, HippoDeep, HippMapp3r) and demonstrated a superior segmentation performance. Moreover, we found that the automated segmentation of T1-weighted images benefits from the T2-based ground truth data.In conclusion, this work showed the beneficial use of high-resolution, T2-based ground truth data for training an automated, deep learning-based hippocampus segmentation and provides the basis for a reliable estimation of hippocampal atrophy in clinical studies.

Abstract Tu023: The VEGF-A splice variants as a mechanism of impaired Inflammatory Angiogenesis in the context of advanced aging.

Background and Objectives: Aging and age-related diseases like peripheral artery disease (PAD) is associated with impairment of angiogenesis responses to injury. Critical ischemic limb and wound injury animal models have shown impact of monocytes/macrophages as a major source of angiogenic mediators leading to new arterial growth. Aging has also been associated with impairment of blood flow recovery and reduced VEGF-A expression in animals. However, recombinant VEGF-A administration or clinical trials involving VEGF-A have not fully overcome the foot perfusion and prevent limb/leg amputation. We sought to understand molecular mechanisms of reduced VEGF-A expression which remain incomplete in the context of advanced aging. Results: Firstly, in hindlimb ischemia mouse model, our data from liposomes containing-clodronate treated mice (12-weeks C57Bl6 with macrophage depletion model ) ( Fig. 1a ) demonstrate impairment of blood flow recovery compared to Control group. On day 3 post-surgery, VEGF-A and VEGF-A isoforms expression (VEGF-A 165 a and VEGF-A 165 b, respectively) were reduced in ischemic muscle. Fluorescence staining showed a reduction of macrophages (CD68 + ) was also associated with reduced endothelial cells (CD31 + ). Using a myeloid-specific and inducible deleted VEGF fl/fl mice, we then have shown a key role of early inflammatory macrophages stage as a major source of VEGF-A required for angiogenesis in young mice (Fig. 1b). Secondly, bone marrow-derived-macrophages (BMDMs) from C57Bl6 104-weeks mice also demonstrate reduced VEGF-A expression. Aged BMDMs demonstrate reduced VEGF-A 165 a while VEGF-A 165 b was highly increased. Polarized BMDMs from 12-weeks demonstrate increased VEGFR1 in “M2" macrophages while VEGFR2 was increased in “M1” macrophages. On the other hand, BMDMs from 104-weeks demonstrate reduced VEGFR2 expression while VEGFR1 was unaffected compared to young. Lastly, 104-weeks mice also demonstrate severe impairment of blood flow recovery ( Fig. 2 ) after surgery and reduced VEGF-A and VEGF-A 165 a in ischemic muscle tissue. VEGF-A 165 b was increased and both receptors, VEGF-R1/R2 levels ( Fig. 3 ) were also reduced. Fluorescence staining on day 3 post ligation demonstrates reduced endothelial cells recruitment in muscle tissue while macrophage (CD68+) number was similar. Conclusion: Our investigations will contribute to define mechanisms whereby vascular injury is associated with VEGF-A isoforms specific switch in the context of advanced aging.

Microbial and transcriptional response of Acropora valida and Turbinaria peltata to Vibrio coralliilyticus challenge: insights into corals disease resistance

BackgroundCoral diseases are significant drivers of global coral reef degradation, with pathogens dominated by Vibrio coralliilyticus playing a prominent role in the development of coral diseases. Coral phenotype, symbiotic microbial communities, and host transcriptional regulation have been well-established as factors involved in determining coral disease resistance, but the underlying mechanisms remain incompletely understood.MethodsThis study employs high-throughput sequencing to analyse the symbiotic microbial and transcriptional response of the hosts in order to evaluate the disease resistance of Acropora valida and Turbinaria peltata exposed to Vibrio coralliilyticus.ResultsA. valida exhibited pronounced bleaching and tissue loss within 7 h of pathogen infection, whereas T. peltata showed no signs of disease throughout the experiment. Microbial diversity analyses revealed that T. peltata had a more flexible microbial community and a higher relative abundance of potential beneficial bacteria compared to A. valida. Although Vibrio inoculation resulted in a more significant decrease in the Symbiodiniaceae density of A. valida compared to that of T. peltata, it did not lead to recombination of the coral host and Symbiodiniaceae in either coral species. RNA-seq analysis revealed that the interspecific differences in the transcriptional regulation of hosts after Vibrio inoculation. Differentially expressed genes in A. valida were mainly enriched in the pathways associated with energy supply and immune response, such as G protein-coupled receptor signaling, toll-like receptor signaling, regulation of TOR signaling, while these genes in T. peltata were mainly involved in the pathway related to immune homeostasis and ion transport, such as JAK-STAT signaling pathway and regulation of ion transport.ConclusionsPathogenic challenges elicit different microbial and transcriptional shifts across coral species. This study offers novel insights into molecular mechanisms of coral resistance to disease.

DPHC from Ishige okamurae mitigates oxidative stress-induced myopathy by regulating MuRF-1/MAFbx signaling in C2C12 cells

This study investigated the potential protective effects of diphlorethohydroxycarmalol (DPHC), which was isolated from Ishige okamurae, on oxidative stress-induced myopathy both in vitro and in vivo. DPHC did not exhibit any toxic effects and exerted preventive actions against hydrogen peroxide (H2O2)-induced cell toxicity and scavenged intracellular reactive oxygen species in C2C12 myocytes. Furthermore, the DPHC markedly attenuated H2O2-induced myopathy in C2C12 cells by downregulating MuRF-1/MAFbx, which is a key factor in myopathy. The in vivo study revealed that the DPHC improved the endurance capacity and inhibited oxidative stress induced myopathy through the regulation of MuRF-1/MAFbx protein expressions via the NF-κB and p38 MAPK pathways in muscle tissue based on a H2O2-induced zebrafish model. Further, histological analysis indicated that the DPHC treatment significantly improved H2O2-induced muscle tissue loss and myopathy in vivo. Thus, our findings confirmed the viability of DPHC as a potential candidate for the treatment of oxidative stress-induced myopathy.

Histopathological and phylogenetic description of an Amazonian cnidaria microparasite Myxobolus rousseauxii n. sp. infecting the gill arches of Brachyplatystoma rousseauxii (Siluriformes)

From genus Myxobolus, cnidarians of Myxozoa class, is well known for infecting economically important fish species and, as result, relevant losses in aquaculture production can be observed. They are present in a big range of fish in its natural habitat, including the migratory Brachyplatystoma rousseauxii catfish. This study aimed is to develop an integrative characterization of a new species of Myxobolus, located in B. rousseauxii's gills. To accomplish this, 30 specimens of B. rousseauxii catfish were collected from Mosqueiro Island in Pará, Brazil; necropsied and analyzed for morphology, histology and molecular characteristics. Cysts with conjunctival capsule development made up of fibroblasts were observed at the gill arches; such proliferation caused bone tissue loss and cartilage compression. The cysts contained Myxobolus myxospores measuring 9.9 μm of length and 9.6 μm of width, whereas polar capsules were 5.4 μm long and 3.4 μm wide, with 8 to 9 coils of polar tubules. Phylogenetic analyses revealed that new species were included in a subclade alongside species from the same geographic location and infection site that infect Siluriformes fish. Morphological and molecular differences revealed that Myxobolus spp. parasite-host associations through histopathology supporting the designation of a new M. rousseauxii n. sp. species in B. rousseauxii, a commercially important fish.