Heart Specimens Research Articles

High-resolution three-dimensional atlas of congenital heart defects based on micro-CT images of human postmortem wax-infiltrated heart specimens

IntroductionPostmortem heart specimens are essential for education and research on the anatomy, morphology, and pathology of congenital heart defects. However, such specimens are rarely obtained these days, and the specimens stored in formalin are inexorably deteriorating. This study aimed to develop methods to archive three-dimensional data of rare human heart specimens and to publish the data. MethodsAll wax-infiltrated human postmortem heart specimens stored in the Cardiac Registry, Boston Children's Hospital were scanned using microfocus computed tomography (X-Tek HMXST225, Nikon Metrology, Inc.), and reproduced using a three-dimensional printer (Form 3B, Formlabs Inc.). The digital models were published as an interactive three-dimensional online atlas. The resolution of the three-dimensional data was evaluated. ResultsThe primary diagnoses in the 88 specimens included in the study include normal cardiac anatomy (11 cases), transposition of the great arteries {S,D,D} (11 cases), ventricular septal defect (10 cases), double-outlet right ventricle (9 cases), hypoplastic left heart syndrome (9 cases), and common atrioventricular canal (7 cases). Twenty-five cases (28%) underwent previous surgical or percutaneous interventions to the heart, including Mustard procedure (1 case), Senning procedure (2 cases, one was performed on a postmortem heart specimen). The median voxel size of the three-dimensional data was 40.5 um (IQR, 32.8–64.2). All intracardiac structures were precisely reproduced as digital and physical three-dimensional models. ConclusionsThe methods and resultant models were considered useful for archiving and furthering the utilization of these invaluable specimens. The atlas is available at https://www.sketchfab.com/heartmodels/collections.

Targeting Cyclophilin A in the Cardiac Microenvironment Preserves Heart Function and Structure in Failing Hearts.

Cardiac hypertrophy is characterized by remodeling of the myocardium, which involves alterations in the ECM (extracellular matrix) and cardiomyocyte structure. These alterations critically contribute to impaired contractility and relaxation, ultimately leading to heart failure. Emerging evidence implicates that extracellular signaling molecules are critically involved in the pathogenesis of cardiac hypertrophy and remodeling. The immunophilin CyPA (cyclophilin A) has been identified as a potential culprit. In this study, we aimed to unravel the interplay between eCyPA (extracellular CyPA) and myocardial dysfunction and evaluate the therapeutic potential of inhibiting its extracellular accumulation to improve heart function. Employing a multidisciplinary approach encompassing in silico, in vitro, in vivo, and ex vivo experiments we studied a mouse model of cardiac hypertrophy and human heart specimen to decipher the interaction of CyPA and the cardiac microenvironment in highly relevant pre-/clinical settings. Myocardial expression of CyPA (immunohistology) and the inflammatory transcriptome (NanoString) was analyzed in human cardiac tissue derived from patients with nonischemic, noninflammatory congestive heart failure (n=187). These analyses were paralleled by a mouse model of Ang (angiotensin) II-induced heart failure, which was assessed by functional (echocardiography), structural (immunohistology, atomic force microscopy), and biomolecular (Raman spectroscopy) analyses. The effect of inhibiting eCyPA in the cardiac microenvironment was evaluated using a newly developed neutralizing anti-eCyPA monoclonal antibody. We observed a significant accumulation of eCyPA in both human and murine-failing hearts. Importantly, higher eCyPA expression was associated with poor clinical outcomes in patients (P=0.043) and contractile dysfunction in mice (Pearson correlation coefficient, -0.73). Further, myocardial expression of eCyPA was critically associated with an increase in myocardial hypertrophy, inflammation, fibrosis, stiffness, and cardiac dysfunction in vivo. Antibody-based inhibition of eCyPA prevented (Ang II)-induced myocardial remodeling and dysfunction in mice. Our study provides strong evidence of the pathogenic role of eCyPA in remodeling, myocardial stiffening, and dysfunction in heart failure. The findings suggest that antibody-based inhibition of eCyPA may offer a novel therapeutic strategy for nonischemic heart failure. Further research is needed to evaluate the translational potential of these interventions in human patients with cardiac hypertrophy.

Distinctive Deposition Patterns of Sporadic Transthyretin-Derived Amyloidosis in the Atria: A Forensic Autopsy-Based Study.

Left-to-right differences in the histopathologic patterns of transthyretin-derived amyloid (ATTR) deposition in the atria of older adults have not yet been investigated. Hence, this study evaluated heart specimens from 325 serial autopsy subjects. The amount of ATTR deposits in the seven cardiac regions, including both sides of atria and atrial appendages, was evaluated semiquantitatively. Using digital pathology, we quantitatively evaluated the immunohistochemical deposition burden of ATTR in the myocardium. We identified 20 sporadic ATTR cardiac amyloidosis cases (nine males). All patients had ATTR deposition in the left atrial regions of the myocardium. In the semiquantitative analysis, 14 of the 20 cases showed more severe ATTR deposition on the left atrial regions than on the right side, with statistically significant differences in the pathology grading (p < 0.01 for both the atrium and atrial appendage). Quantitative analysis further supported the difference. Moreover, six had ATTR deposition in the epineurium and/or neural fibers of the atria. Cluster analysis revealed that ATTR deposition in the myocardium was significantly more severe in males than in females. The heterogeneous distribution of amyloid deposits between atria revealed in this study may impair the orderly transmission of the cardiac conduction system and induce arrhythmias, which may be further aggravated by additional neuropathy in the advanced phase. This impairment could be more severe among males. These findings emphasize that atrial evaluation is important for individuals with sporadic ATTR cardiac amyloidosis, particularly for early detection.

Innovative Mitral Valve Repair Using a Novel Automated Suturing System: Preliminary Data.

(1) Background and Objectives: Mitral regurgitation is a common valve disease requiring surgical repair. Even with satisfactory results, repair techniques may underlie subjectivity and variability and require long learning curves. A novel approach, the "Roman Arch" technique, may ease the technical burden. This study assessed an automated suturing device's feasibility and time efficiency for a proposed simplified technique. (2) Materials and Methods: Using the MiStitch™ and MiKnot™ devices (LSI Solutions, Inc., Victor, NY, USA), the suture pattern was performed in a cadaver model. Three surgeons with different expertise levels conducted the procedures. Repair and suture placement times were recorded and analyzed. (3) Results: The modified "Roman Arch" repair was completed on all ten human heart specimens with an average total repair time of 3:01 ± 00:59 min and a trend toward reduced times as experience increased. The study confirmed the technical feasibility with 90% of the attempts rated as rather satisfactory or very satisfactory. (4) Conclusions: The MiStitch™ system effectively facilitated the modified "Roman Arch" repair in an ex vivo setting, suggesting its potential to reduce the technical complexity of mitral valve repairs. Further studies are needed to confirm its efficacy and safety in clinical practice.

Heart proteomic profiling discovers MYH6 and COX5B as biomarkers for sudden unexplained death

Sudden unexplained death (SUD) is not uncommon in forensic pathology. Yet, diagnosis of SUD remains challenging due to lack of specific biomarkers. This study aimed to screen differentially expressed proteins (DEPs) and validate their usefulness as diagnostic biomarkers for SUD cases. We designed a three-phase investigation, where in the discovery phase, formalin-fixed paraffin-embedded (FFPE) heart specimens were screened through label-free proteomic analysis of cases dying from SUD, mechanical injury and carbon monoxide (CO) intoxication. A total of 26 proteins were identified to be DEPs for the SUD cases after rigorous criterion. Bioinformatics and Adaboost-recursive feature elimination (RFE) analysis further revealed that three of the 26 proteins (MYH6, COX5B and TNNT2) were potential discriminative biomarkers. In the training phase, MYH6 and COX5B were verified to be true DEPs in cardiac tissues from 29 independent SUD cases as compared with a serial of control cases (n = 42). Receiver operating characteristic (ROC) analysis illustrated that combination of MYH6 and COX5B achieved optimal diagnostic sensitivity (89.7 %) and specificity (84.4 %), with area under the curve (AUC) being 0.91. A diagnostic software based on the logistic regression formula derived from the training phase was then constructed. In the validation phase, the diagnostic software was applied to eight authentic SUD cases, seven (87.5 %) of which were accurately recognized. Our study provides a valid strategy towards practical diagnosis of SUD by integrating cardiac MYH6 and COX5B as dual diagnostic biomarkers.

A modifiable valve-sparing pediatric cardiac dissection technique promotes specimen longevity and optimizes advanced image analysis postpathological examination.

This paper illustrates a valve-sparing cardiac dissection technique that keeps the atrioventricular and semilunar valves and other important cardiac structures intact. The technique minimizes disruption in heart specimens, so they remain suitable for teaching, demonstration, and further research. When performed following the perfusion-distension method of fixation, as our group previously described, this technique could optimize the preservation of heart specimens for teaching and digital archiving postdissection.

Pathology of explanted pediatric hearts: An 11-year study. Population characteristics and implications for outcomes.

As more pediatric patients become candidates for heart transplantation (HT), understanding pathological predictors of outcome and the accuracy of the pretransplantation evaluation are important to optimize utilization of scarce donor organs and improve outcomes. The authors aimed to investigate explanted heart specimens to identify pathologic predictors that may affect cardiac allograft survival after HT. Explanted pediatric hearts obtained over an 11-year period were analyzed to understand the patient demographics, indications for transplant, and the clinical-pathological factors. In this study, 149 explanted hearts, 46% congenital heart defects (CHD), were studied. CHD patients were younger and mean pulmonary artery pressure and resistance were significantly lower than in cardiomyopathy patients. Twenty-one died or underwent retransplantation (14.1%). Survival was significantly higher in the cardiomyopathy group at all follow-up intervals. There were more deaths and the 1-, 5- and 7-year survival was lower in patients ≤10 years of age at HT. Early rejection was significantly higher in CHD patients exposed to homograft tissue, but not late rejection. Mortality/retransplantation rate was significantly higher and allograft survival lower in CHD hearts with excessive fibrosis of one or both ventricles. Anatomic diagnosis at pathologic examination differed from the clinical diagnosis in eight cases. Survival was better for the cardiomyopathy group and patients >10 years at HT. Prior homograft use was associated with a higher prevalence of early rejection. Ventricular fibrosis (of explant) was a strong predictor of outcome in the CHD group. We presented several pathologic findings in explanted pediatric hearts.

Curcumin attenuates doxorubicin-induced cardiotoxicity via suppressing oxidative Stress, preventing inflammation and apoptosis: Ultrastructural and computational approaches

Currently, doxorubicin (DOX) is one of the medications commonly used in chemotherapy to treat different types of tumors.Nonetheless, despite being effective in multiple tumors, yet its use is limited owing to its cytotoxic effects, the therapeutic use of DOX has been limited. This work aimed to explore whether curcumin (CMN) can prevents DOX-induced cardiotoxicity in rats. Four groups of rats were created, with the first functioning as a control, while the second group received CMN. DOX alone was administered to the third group, whereas CMN and DOX were administered to the fourth group. Lipid peroxidation assessed as Malondialdehyde (MDA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), oxidative stress markers as catalase (CAT), superoxide dismutase (SOD), and inflammatory markers as tumor necrosis factor-alpha (TNF-α) in heart homogenates, each one was assessed. Heart specimens was investigated histologically and ultrastructurally. Increased, AST, and ALT serum levels, increased MDA levels, decreased SOD and CAT levels, and increased TNF-α concentrations in heart homogenates were all signs of DOX-induced myocardial injury. Histological and ultrastructural examinations revealed vacuoles and larger, swollen mitochondria in the cytoplasm. Furthermore, DOX caused significant changes in the myocardium, most notably nuclei disintegration, myofibrillar loss, and myocyte vacuolization. Using CMN with DOX reduced the harmful consequences of DOX on the myocardium by returning the increased AST and ALT levels to their original levels as compared to the control and reducing them. In cardiac tissue, CMN significantly increased the concentrations of SOD and CAT and significantly decreased the concentrations of MDA and TNF-α. Biochemical and histological studies have demonstrated that CMN has a heart-protective effect that might be related to its antioxidant and anti-inflammatory capabilities.

Impact of Anemia on Cardiovascular Events and All-Cause Death Among Participants Who Received Intense Blood Pressure Treatment: A Secondary Analysis of SPRINT.

To investigate whether anemia is associated with incident cardiovascular events and all-cause death among participants who received intensive blood pressure (BP) treatment in the Systolic Blood Pressure Intervention Trial (SPRINT). A total of 4394 participants who received intensive BP control (systolic BP 120 mmHg) in SPRINT were included. Anemia status was self-reported. Our primary outcome was a composite of cardiovascular events, and the secondary outcome was all-cause death. Cox regression was used to compare the incidence of outcomes between participants with anemia and non-anemia. In order to balance the baseline characteristics between the 2 groups, inverse probability of treatment weighting (IPTW) was applied. Hazard ratios (HRs), along with 95% confidence intervals (CIs), were then calculated. There were 4394 participants who received intensive BP control (537 participants with anemia). Participants with anemia were older (mean age 68.86 versus 67.75, p = 0.01) and more likely to be female (64.8% versus 31.8%, p 0.001). The presence of anemia was strongly associated with composite cardiovascular events after adjusting for potential confounders (HR 1.66, 95% CI 1.18-2.34, p = 0.004). The association remained statistically significant even in the population after IPTW (HR 1.55, 95% CI 1.06-2.27, p = 0.024). The secondary outcome revealed that participants with anemia had a higher rate of all-cause death compared to those without anemia. The HR of all-cause death for participants with anemia was 1.61 (95% CI 1.00-2.57, p = 0.049) in the population after IPTW. Anemia appears to be an independent risk factor for composite cardiovascular events and all-cause death among participants who received intensive BP control in SPRINT. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01206062. All SPRINT anonymized data can be found at the National Heart, Lung and Blood Institute (NHLBI) Biologic Specimen and Data Repository (https://biolincc.nhlbi.nih.gov/home/).

Histological and ultrastructural analysis of biopsy specimens of donor heart under conditions of extended period of pharmaco-cold ischaemia

At the histological and ultramicroscopic level, compare biopsy specimens of donor heart under standard (up to 240 min) and extended (more than 240 min) periods of pharmaco-cold preservation. Biopsy specimens of the left atrium of donor hearts: group 1 - 8 samples after transportation with pharmaco-cold preservation of the graft in Bretschneider solution (Dr. Franz Köhler Chemie GmbH, Germany) up to 240 min, (Me 140), and group 2 - 5 samples after an extended pharmaco-cold period (more than 240 min; Me 375) were examined using light microscopy of semi-thin sections and transmission electron microscopy, followed by stereological and statistical analysis. A comparative study of the myocardium of donor hearts revealed stereotypical dystrophic changes in cardiomyocytes. Semi-thin sections demonstrated a mosaic pattern of myocardial parenchyma in both groups, caused by contracture and less pronounced lytic changes in myocytes, which were accompanied by stromal edema without statistically significant differences according to stereological studies. Ultrathin sections of the perinuclear zones of cardiomyocytes visualized reduction and focal damage to myofibrils and mitochondria in combination with pronounced autophagy; at the same time, with a shorter duration of the pharmaco-cold period, the stereological indicators of cardiomyocyte organelles indicated a relatively better supply of myofibrils with mitochondria. The results obtained suggest a sufficiently high degree of preservation of the tissue and ultrastructural organization of donor hearts with prolonged (more than 240 min) pharmaco-cold ischemia to restore adequate cardiac activity after heart transplantation.

Histopathological study of heart and cardiac vessels in autopsy cases from tertiary health-care center

Background: Atherosclerosis is a chronic inflammatory disease causing more morbidity and mortality in developed as well as in developing countries. Among Indians, atherosclerotic lesions occur 10–15 years earlier, and the lesions are formed in the advanced stage. It is difficult and expensive to evaluate the atherosclerotic lesions in living subjects. Atherosclerosis of cardiac vessels and myocardial infarction are the most common fatal cardiac diseases discovered in autopsies. The incidence of coronary artery diseases is increasing worldwide as well as in India, which carries a huge challenge in diagnosing the same. Aims and Objectives: The aims and objectives are to study the spectrum of histopathological findings in heart and atherosclerotic lesions in cardiac vessels in autopsy cases. Materials and Methods: This is a retrospective study done in the Department of Pathology at Government Kilpauk Medical College and Hospital over a period of 1 year (March 2022–December 2022). In this study, a total of 100 autopsy cases were taken to study the pathology of the heart and the grading of atherosclerotic lesions in cardiac vessels. Heart specimens were received from the Forensic Medicine Department. The atherosclerotic lesions of cardiac vessels were graded according to the American Heart Association (AHA) classification. Results: Among 100 cases studied during a period of 1 year, most of the cases were in the age group of 30–41 years. Male preponderance was noted when compared to females. Out of 100 cases, 79 cases had histopathological evidence of atherosclerosis, and other findings were as follows: one case of giant cell myocarditis, one case of pericarditis, and one case of adenocarcinoma of the lung extending into the coronary vessels. The most common type of atherosclerotic lesion seen was type 7 AHA, most frequently involving the aorta, followed by both coronary ostia and the left anterior descending artery. Conclusion: In this study, atherosclerotic lesions were observed very frequently in younger individuals. It is an indication for the implementation of antiatherogenic preventive measures in young populations. It highlights the importance of screening for cardiovascular risk factors at an early age.

Multi-scale study on the electrochemical behavior and corrosion mechanism of 5083 aluminum alloy with different microstructures in a NaCl environment.

We conducted electrochemical experiments on 5083 aluminum alloy with different microstructures and measured the samples before and after corrosion by SEM and EBSD. At the same time, density functional theory was used to calculate the chloride ion adsorption behavior of the Mg2Al3 phase, which explained the corrosion mechanism on a multi-scale. The results indicated that edge and heart specimens with varying grain sizes exhibited different trends post heat treatment. Specifically, increasing temperature led to larger grain sizes in the heart region, while smaller grain sizes were observed at the edge. Furthermore, the quantity of the second phase was higher after heat treatment at 550 °C compared to 520 °C. The grain size affects the densification of the passivation film and the potential difference between the second phase and the substrate, leading to variations in corrosivity. Density functional theory calculation demonstrates that the Mg2Al3 (001)MgAl and (001)Al surfaces exhibit higher susceptibility to Cl- adsorption, showing the lowest adsorption energies of Cl- at the Mg-top of (001)MgAl and Al-top sites of (001)Al. A stronger bond between Cl- and Mg atoms leads to intergranular corrosion in different directions.

Efficacy of cryodehydration technique in preserving the gross and histoarchitectural details of goat visceral and musculoskeletal specimens.

This study sought to determine the effectiveness of the cryodehydration technique in preserving the morphologic and morphometric attributes of the anatomical specimens of goats. Different anatomical parts of a goat, i.e., heart, lungs, spleen, liver, kidney, and musculoskeletal specimens, were collected and fixed in 15% formalin. Later on, the fixed specimens were cryodehydrated by fast freezing (burning process) and repeated freezing-thawing sessions, followed by wood glue coating. Finally, the macroscopic (i.e., weight, color, texture, odor, and durability) and microscopic characteristics (by routine hematoxylin and eosin staining) of the cryodehydrated specimens were studied. The resultant specimens produced excellent color and texture and were lightweight (60%-80% weight loss), soft, dry, odorless, durable, and easy to handle. The histoarchitectural details of the heart and skeletal muscle were well preserved, while some distinctive alterations were observed in the parenchymatous organs, i.e., breach in cellular integrity, loss of cell cytoplasm, loss of cytoplasmic and nuclear clarity, increased sinusoidal space, dilatation of the renal tubules, and reduction in glomerular size. Nevertheless, the basic histoarchitecture of each specimen was yet to be distinctly identifiable. The current study findings suggest that the cryodehydration technique can preserve gross anatomical features as well as histoarchitectural details and can be an effective tool for facilitating veterinary education and research.

A Study on Variations in Size and Shape of Left Atrial Appendage from Formalin-fixed Cadavers

Introduction: Atrial appendages were once considered vestigial structures with no significant role in atrial function. However, they are now recognized as significantly impacting various pathophysiological conditions, including cardiac thromboembolism and arrhythmias. The left atrial appendage (LAA), in particular, has been found to have significant variations in shape and size, and its relationship with nearby structures, such as the pulmonary veins (PVs), is crucial in planning interventional and surgical procedures in and around the LAA. Although most studies examining variations in the LAA are image-based, few have focused on anatomical studies. Materials and Methods: In this study, we examined heart specimens from 54 cadavers for anatomical dissection at a tertiary care teaching hospital. After removing the heart from the pericardial cavity, we opened the left atrium and examined its interior. Observations were made regarding the LAA orifice and PV orifices, and measurements were taken. Subsequently, we removed the LAA along with a portion of the left atrial wall, observed its shape and number of lobes, and took measurements. To classify the shape, we used a system proposed by Wang et al. based on resemblance to familiar objects. Categorical variables were expressed as percentages and continuous as mean and standard deviation. The institutional research committee and the institutional ethics committee approved the study. Results: The most common shape variant observed was the Chicken Wing type, followed closely by the Windsock type. Specimens with Cauliflower or Cactus morphology were rare, with the Cactus variant being the least common. The LAA orifice was round or oval shaped in most cases. In most cases, the LAA orifice was at the same or lower level as the left superior PV orifice, with a prominent ridge between the two orifices in most patients. We observed most of the appendages to be trilobed, with considerable variations in length and diameter. We found two specimens with unusual morphologies but no specimens with accessory appendages. Conclusions: Based on our study, there are significant differences in findings compared to some of the previous studies reporting the shape variations of LAA. However, our findings are matching with those of some other earlier studies. The variations in the shape and size of LAA orifices and their relationship to PV orifices are similar to those reported in earlier studies. The distribution of variations in the size of LAA was also similar to those reported in earlier studies. Conducting larger studies to explore these variations could aid in designing and developing therapeutic interventions in the LAA.

Study of the Histopathological Changes in the Heart in Postmortem/Autopsy Cases in Tertiary Care Center.

There has been a significant increase in global cardiac-related fatalities, particularly over the last five decades. In India, cardiovascular diseases have emerged as a prevalent condition. Moreover, the incidence of sudden cardiac death has shown a steady rise worldwide. The aim of this study was to research how frequently cardiac disease was found during postmortem/autopsy cases and how it affects sudden death. The research was conducted at the Department of Pathology, SRTR, GMC, Ambajogai, India. One hundred and eighty cardiac specimens were examined from October 2019 to October 2021. Formalin-fixed heart specimens had multiple sections cut out of them at 4-5 mm intervals. The tissues underwent preparation, followed by sectioning into 4 μm thickness using paraffin. The standard staining method of hematoxylin and eosin was used to stain the samples. Different cardiac histomorphological alterations were assessed. The study included 180 autopsy cases. The highest numbers of cases were observed in the age group of 31-40 years (20.2%). Triple-vessel involvement was seen in the majority of 61.5% of cases, out of 180 cases, 52.7% of cases were of hypertrophy. The research highlights the prevalence of cardiovascular diseases, particularly atherosclerosis and hypertrophy. Notably, sudden death cases showed a distinct distribution across the study years, with males being predominantly affected. This underscores the urgent need for preventive measures and interventions to prevalent cardiovascular conditions effectively.

MORPHOMETRIC ANALYSIS OF CORONARY ARTERIES IN HARYANVI POPULATION

Objective: The present study aimed to record the length of coronary arteries was carried out for better anatomical knowledge about the branches of coronary arteries and its variation is essential for cardiologists and interpretation of coronary angiograms by radiologists. Methods: The study group was comprised 60 human cadaveric hearts retrieved from the dead bodies of the age group 18–50 years brought for medicolegal autopsy. Results: In 60 heart specimen’s length of right coronary artery (RCA)-I (34.4–128.8 mm, 81.5±18.1), RCA-II (6.2–43.4 mm, 20.3±9.9), RCA-III (9.6–69 mm, 38.2±18.7), length of left coronary artery (3.4–19 mm, 12.6±3.74 mm), length of left circumflex artery (31.9–144.5 mm, 79.2±26.2 mm), and length of left anterior descending artery (33.4–154.4 mm, 105.3±27 mm). Conclusion: The name and nature of a coronary artery or a branch define that vessel’s vascularization pattern or territory, rather than its origin. Better anatomical knowledge about the branches of the coronary artery and its variation is essential for cardiologists and interpretation of coronary angiograms by radiologists.

Causes of Post-Mortem Carcass and Organ Condemnations and Economic Loss Assessment in a Cattle Slaughterhouse.

The study was undertaken to investigate the main causes of carcass and organ condemnations, as well as to estimate the financial losses suffered by a cattle slaughterhouse. In this regard, an active abattoir survey, based on standard post-mortem inspection procedures for meat, was conducted on 151,741 cattle, from January 2021 to December 2022. Overall, 13.27% (n = 20,125) of the carcasses expressed lesions or pathological conditions and, out of them, 1.15% (n = 1738) were totally confiscated, while another 12.12% (n = 18,387) were partially admitted for human consumption. In the case of organs, the general inspection data reveal that 12.28% (n = 18,630), 7.56% (n = 11,477), 1.89% (n = 2862), and 0.27% (n = 412) of the examined liver, lung, heart, and kidney specimens presented one or more types of abnormalities. In addition, regarding the types of specific pathological findings, dystrophies/anomalies (69.8%), circulatory disorders (40.6%), fecal contamination (60.9%), and suspected bacterial/viral infections showed a dominant occurrence in the liver, lung, heart, and kidneys, respectively. Consequently, the total direct financial losses resulting from edible part condemnation over the two years was estimated at EUR 4,021,717.3, which represents 1.17% of the total achievable net revenue without carcass and organ condemnation. Of this, EUR 3,661,400.4 (1.07%) and EUR 360,316.9 (8.73%) was related to carcass and organ condemnation, respectively. The study results demonstrate that the post-mortem inspection of meat at the slaughterhouse level plays a crucial role in identifying pathological lesions, in addition to some other issues, such as fecal contamination or non-compliant laboratory results, relevant to both public health and economic factors.

BBLN triggers CAMK2D pathology in mice under cardiac pressure overload and potentially in unrepaired hearts with tetralogy of Fallot

Tetralogy of Fallot (TOF) is one of the most prevalent congenital heart defects, with adverse cardiac remodeling and long-term cardiac complications. Here, searching for pathomechanisms, we find upregulated bublin coiled-coil protein (BBLN) in heart specimens of TOF patients with cyanosis, which positively correlates with cardiac remodeling pathways. Human BBLN, a protein with largely unknown function, promoted heart failure features, with increased mortality when overexpressed in mice, in a protein dosage-dependent manner. BBLN enhanced cardiac inflammation, fibrosis and necroptosis by calcium/calmodulin-dependent protein kinase II delta (CAMK2D) activation, whereas a BBLN mutant with impaired CAMK2D binding was inert. Downregulation of CAMK2D by an interfering RNA retarded BBLN-induced symptoms of heart failure. Endogenous BBLN was induced by hypoxia as a major TOF feature in human patients and by chronic pressure overload in mice, and its downregulation decreased CAMK2D hyperactivity, necroptosis and cardiovascular dysfunction. Thus, BBLN promotes CAMK2D-induced pathways to pathological cardiac remodeling, which are triggered by hypoxia in TOF.

Cytoprotective effects of cinnamaldehyde and adipoRon against cyclophosphamide‐induced cardio-renal toxicity in rats: Insights into oxidative stress, inflammation, and apoptosis

Cyclophosphamide is an alkylating agent used in the treatment of various types of tumors and autoimmune diseases. Unfortunately, cyclophosphamide usage is limited in clinical situations due to its cardio-renal toxicity. The current study investigates the protective effects of cinnamaldehyde and adipoRon against cyclophosphamide-induced cardio-renal toxicity. 24 adult male Sprague-Dawley rats were assorted in a random manner into 4 groups; control, cyclophosphamide, cyclophosphamide+cinnamaldehyde (90 mg/kg) and cyclophosphamide+adipoRon (25 mg/kg), rats treated with cinnamaldehyde and adipoRon for 10 days and on the 7th day of the experiment, rats were given a single I.P. injection of cyclophosphamide (200 mg/kg). Thereafter, specimens of heart and kidney tissues were used for biochemical, immunohistochemical and histopathological analysis. Cinnamaldehyde and adipoRon attenuated the cardio-renal intoxication induced by cyclophosphamide which was manifested by a marked decrease in cardiac-renal injury markers (CK-MB, LDH, cTnI, serum creatinine and blood urea nitrogen) accompanied with normalization of histopathological changes. Moreover, cinnamaldehyde and adipoRon reversed cardio-renal oxidative stress, inflammation, and apoptosis as they have significantly decreased 8-OHdG levels, MDA contents, NF-κB, TNF-α and caspase-3 expression. On the other hand, cinnamaldehyde and adipoRon have upregulated antioxidant biomarkers; GSH concentration, Nrf2 expression as well as the anti-inflammatory cytokine; IL-10 and the antiapoptotic; BCL2. In conclusion, these cytoprotective effects of cinnamaldehyde and adipoRon suggesting the possibility of using them in combination with cyclophosphamide treatment protocols to minimize their unwanted side effects.

Genetic and morphological characterization of a new genotype of nervous necrosis virus circulating among Nile tilapia in the south of Egypt.

Nervous necrosis virus (NNV) is the causative agent of viral nervous necrosis in freshwater and marine fishes. In this study, NNV circulating among wild and farmed Nile tilapia (Oreochromis niloticus) was genetically and morphologically characterized using reverse transcription polymerase chain reaction (RT-PCR), sequencing analysis, and transmission electron microscopy (TEM). Brain, eye, and other organ (spleen, kidney, heart, and liver) specimens were collected from 87 wild (66) and farmed (21) Nile tilapia fish during their adult or juvenile stage at different localities in Qena and Sohag governorates in southern Egypt. Among them, 57/87 fish showed suspected NNV clinical signs, and 30/87 were healthy. The results revealed that NNV was detected in 66 out of 87 fish (58.62% in the wild and 17.24% in farmed Nile tilapia by RT-PCR), and the prevalence was higher among diseased (55.17%) than in healthy (20.69%) fish. NNV was detected in the brain, eye, and other organs. Using TEM, virion size variations based on the infected organs were observed. Nucleotide sequence similarity indicated that NNVs had a divergence of 75% from other fish nodaviruses sequenced in Egypt and worldwide. Phylogenetic analysis distinguished them from other NNV genotypes, revealing the emergence of a new NNV genotype in southern Egypt. In conclusion, NNV is circulating among diseased and healthy Nile tilapia, and a new NNV genotype has emerged in southern Egypt.