Enlargement Of Ventricles Research Articles

Impact of Motile Ciliopathies on Human Development and Clinical Consequences in the Newborn.

Motile cilia are hairlike organelles that project outward from a tissue-restricted subset of cells to direct fluid flow. During human development motile cilia guide determination of the left-right axis in the embryo, and in the fetal and neonatal periods they have essential roles in airway clearance in the respiratory tract and regulating cerebral spinal fluid flow in the brain. Dysregulation of motile cilia is best understood through the lens of the genetic disorder primary ciliary dyskinesia (PCD). PCD encompasses all genetic motile ciliopathies resulting from over 60 known genetic mutations and has a unique but often underrecognized neonatal presentation. Neonatal respiratory distress is now known to occur in the majority of patients with PCD, laterality defects are common, and very rarely brain ventricle enlargement occurs. The developmental function of motile cilia and the effect and pathophysiology of motile ciliopathies are incompletely understood in humans. In this review, we will examine the current understanding of the role of motile cilia in human development and clinical considerations when assessing the newborn for suspected motile ciliopathies.

Iron Rims in Patients With Multiple Sclerosis as Neurodegenerative Marker? A 7-Tesla Magnetic Resonance Study.

Introduction: Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the central nervous system, characterized by inflammatory-driven demyelination. Symptoms in MS manifest as both physical and neuropsychological deficits. With time, inflammation is accompanied by neurodegeneration, indicated by brain volume loss on an MRI. Here, we combined clinical, imaging, and serum biomarkers in patients with iron rim lesions (IRLs), which lead to severe tissue destruction and thus contribute to the accumulation of clinical disability.Objectives: Subcortical atrophy and ventricular enlargement using an automatic segmentation pipeline for 7 Tesla (T) MRI, serum neurofilament light chain (sNfL) levels, and neuropsychological performance in patients with MS with IRLs and non-IRLs were assessed.Methods: In total 29 patients with MS [15 women, 24 relapsing-remitting multiple sclerosis (RRMS), and five secondary-progressive multiple sclerosis (SPMS)] aged 38 (22–69) years with an Expanded Disability Status Score of 2 (0–8) and a disease duration of 11 (5–40) years underwent neurological and neuropsychological examinations. Volumes of lesions, subcortical structures, and lateral ventricles on 7-T MRI (SWI, FLAIR, and MP2RAGE, 3D Segmentation Software) and sNfL concentrations using the Simoa SR-X Analyzer in IRL and non-IRL patients were assessed.Results: (1) Iron rim lesions patients had a higher FLAIR lesion count (p = 0.047). Patients with higher MP2Rage lesion volume exhibited more IRLs (p <0.014) and showed poorer performance in the information processing speed tested within 1 year using the Symbol Digit Modalities Test (SDMT) (p <0.047). (2) Within 3 years, patients showed atrophy of the thalamus (p = 0.021) and putamen (p = 0.043) and enlargement of the lateral ventricles (p = 0.012). At baseline and after 3 years, thalamic volumes were lower in IRLs than in non-IRL patients (p = 0.045). (3) At baseline, IRL patients had higher sNfL concentrations (p = 0.028). Higher sNfL concentrations were associated with poorer SDMT (p = 0.004), regardless of IRL presence. (4) IRL and non-IRL patients showed no significant difference in the neuropsychological performance within 1 year.Conclusions: Compared with non-IRL patients, IRL patients had higher FLAIR lesion counts, smaller thalamic volumes, and higher sNfL concentrations. Our pilot study combines IRL and sNfL, two biomarkers considered indicative for neurodegenerative processes. Our preliminary data underscore the reported destructive nature of IRLs.

97 An unusual combination of rare congenital heart defects in a 70 years old lady complaining worsening dyspnea

Abstract Methods and results A 70-year-old woman presented to our outpatient clinic complaining of worsening dyspnoea in the last 3 months. She had a medical history of hypertension, diabetes, dyslipidemia, and paroxysmal atrial fibrillation. We performed a comprehensive evaluation starting with a transthoracic echocardiogram that showed a dilatation of right ventricle with normal function, severe pulmonary regurgitation, and moderate tricuspid regurgitation with estimated pulmonary artery systolic pressure of 55 mmHg; the left ventricle had normal dimension and function, with mild aortic and mitral regurgitation, and a subaortic membrane which caused a mild obstruction (maximum gradient 17 mmHg). The cardiac magnetic resonance (CMR) confirmed the enlargement of the right ventricle and of the pulmonary artery trunk (51 mm) and the severity of pulmonary regurgitation (regurgitant fraction of 41%). CMR also clearly showed the VSD just below the subaortic membrane and the left to right shunt with a jet that appeared to proceed straight from the left ventricle through the pulmonary valve (Figure 1A). The estimated Qp/Qs was 1.6 and no intramyocardial late enhancement was present. Pulmonary pressures and pulmonary vascular resistance were normal at the right heart catheterization and the Qp/Qs ratio calculated invasively was 1.45. Considering patient high-risk profile for coronary artery disease, a coronary angiography was also performed showing an abnormal origin of the right coronary artery (RCA) from the mid-portion of the left anterior descending coronary artery (LAD) with two significant stenosis: one involving the bifurcation of RCA and the other the mid-portion of the LAD (Figure 1B). The coronary computed tomography angiography (CCTA) showed a benign course of the RCA anterior to the pulmonary artery towards the auriculoventricular groove (Figure 1C, D). Taking into account all these findings, multidisciplinary heart team decided to perform a cardiac surgery intervention of pulmonary valve and trunk replacement, closure of ventricular septal defect and two coronary bypass grafts on LAD and RCA. Conclusions This case represents a combination of some rare congenital heart abnormalities where multimodality cardiovascular imaging techniques were essential to establish a proper diagnosis and to plan an adequate surgical repair. We hypothesize that the peculiar orientation of the VSD jet may have caused the pulmonary trunk dilatation considering that neither the shunt, nor the pulmonary pressure appear to have been of sufficient magnitude to cause it. Pulmonary ectasia and the damage inflicted by the jet to the cusps of the valve have led to the severe valvular insufficiency. While aortic and tricuspid regurgitation are known to be associated with VSD, to the best of our knowledge this is the first report of pulmonary regurgitation secondary to VSD.

Carbonic anhydrase 2 and 3 as risk biomarkers for dilated cardiomyopathy associated heart failure.

Dilated cardiomyopathy (DCM) is a complex type of cardiomyopathy that is affected by both genetic and non-genetic factors. It is characterized by an enlargement of the left ventricle or bi-ventricle, and is often accompanied by cardiac systolic dysfunction. The main results include arrhythmia, heart failure (HF), and sudden death. The prognosis of this disease is usually poor, and the 5-year survival time is about 50%. Early diagnosis is very important for the treatment of DCM. Studies have shown that primary prevention after discovering the disease effectively reduces the mortality rate of the disease. However, there is currently no effective biomarker for the early diagnosis of DCM. The rapid development of omics in protein has promoted the "precise" study of modern medical research. In this article, the potential biomarkers for predicting and diagnosing DCM-related HF were studied by a plasma protein omics analysis. Tandem mass tag-labeled quantitative proteomic studies were performed in 20 patients, comprising 10 DCM-associated HF patients, and 10 control patients who without clinical HF events. Further validation research was conducted by enzyme-linked immunosorbent assay (ELISA) with an expanded cohort (control group =40; HF group =48). Among the 854 identified proteins, the expression of 86 proteins was significantly upregulated, while the expression of 21 proteins was downregulated (with an expression difference >1.5-fold; P<0.05) in the 2 groups. The Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and protein-protein interaction (PPI) networks analyses indicated that the bicarbonate transport process played a critical role in HF. Importantly, carbonic anhydrase 2 (CA2) and 3 (CA3), which play central roles in regulating the transport of bicarbonate, were highly expressed in the HF group. The ELISA validation results showed that the expression levels of CA2 and CA3 at admission were remarkably higher (P<0.0001 and P=0.0157) in the plasma of the HF patients than that of the control patients. The present study showed that two molecules (i.e., CA2 and CA3) are involved in the bicarbonate transport pathway, and are risk factors and potential biomarkers for the diagnosis of DCM patients with HF.

Adaptive neighbor constrained deviation sparse variant fuzzy c-means clustering for brain MRI of AD subject

Progression of Alzheimer’s disease (AD) bears close proximity with the tissue loss in the medial temporal lobe (MTL) and enlargement of lateral ventricle (LV). The early stage of AD, mild cognitive impairment (MCI), can be traced by diagnosing brain MRI scans with advanced fuzzy c-means clustering algorithm that helps to take an appropriate intervention. In this paper, firstly the sparsity is initiated in clustering method that too rician noise is also incorporated for brain MR scans of AD subject. Secondly, a novel neighbor pixel constrained fuzzy c-means clustering algorithm is designed where topoloty-based selection of parsimonious neighbor pixels is automated. The adaptability in choice of neighbor pixel class outliers more justified object edge boundary which outperforms a dynamic cluster output. The proposed adaptive neighbor constrained deviation sparse variant fuzzy c-means clustering (AN_DsFCM) can withhold imposed sparsity and withstands rician noise at imposed sparse environment. This novel algorithm is applied for MRI of AD subjects and normative data is acquired to analyse clustering accuracy. The data processing pipeline of theoretically plausible proposition is elaborated in detail. The experimental results are compared with state-of-the-art fuzzy clustering methods for test MRI scans. Visual evaluation and statistical measures are studied to meet both image processing and clinical neurophysiology standards. Overall the performance of proposed AN_DsFCM is significantly better than other methods.

Vision‐based gait analysis system utilizing deep learning algorithms in idiopathic normal‐pressure hydrocephalus patients

AbstractBackgroundIdiopathic normal‐pressure hydrocephalus (INPH) is a rare neurological disorder. It is an idiopathic adult‐onset syndrome involving nonobstructive enlargement of cerebral ventricles, and it is known by its symptoms of cognitive impairment, gait disturbance, and urinary dysfunction. While INPH can present with any of these classic clinical symptoms in varying degrees, the most frequent and important INPH clinical feature is gait disturbance. A vision‐based gait analysis method using monocular videos was proposed to estimate temporo‐spatial gait parameters by leveraging deep learning algorithms. This study aimed to validate vision‐based gait analysis using GAITRite as the reference system and analyze relationships between Frontal Assessment Battery (FAB) scores and gait variability measured by vision‐based gait analysis in INPH patients.MethodGait data from 46 patients were simultaneously collected from the vision‐based system utilizing deep learning algorithms and the GAITRite system.ResultThere was a strong correlation in 11 gait parameters between our vision‐based gait analysis method and the GAITRite gait analysis system. Our results also demonstrated excellent agreement between the two measurement systems for all parameters except stride time variability after the cerebrospinal fluid tap test. Our data showed that stride time and stride length variability measured by the vision‐based gait analysis system were correlated with FAB scores.ConclusionVision‐based gait analysis utilizing deep learning algorithms can provide comparable data to GAITRite when assessing gait dysfunction in INPH. Frontal lobe functions may be associated with gait variability measurements using vision‐based gait analysis for INPH patients.

PATHOHISTOLOGICAL CHANGES IN PIGS WITH MYCOPLASMOSIS

A pathological autopsy was performed on 6 corpses of piglets in the first week of life who died from mycoplasmosis. Examination of the visible mucous membranes revealed hyperemia of the mucous membrane of the nasal cavity and thymus. Simultaneous lesions of the pharyngeal, parotid, cervical, mandibular lymph nodes were noted. They were slightly enlarged, from dark pink to dark red. The heart is irregularly shaped due to the expansion of the right ventricle or the diffuse expansion of all departments. Lungs have doughy consistency, uneven color. In some cases, there are diffuse red areas covering the entire lobe of the lungs, in other cases, there is a defeat of small areas. The liver has a smooth surface, soft or pasty consistency, the parenchyma pattern is slightly smoothed in section. The color of the liver is different: dark red areas, without clear boundaries turn into creamy-clay. Flatulence was a characteristic feature of the stomach and intestines. Catarrhal enteritis was registered in animals, which manifested itself in the form of moderate hyperemia of the intestinal mucosa and serous membranes. Microscopically, there is a significant blood supply to the vessels in the lungs. Alveoli are half fall down, in the form of slit-like lumens. In areas of tissue infiltration by inflammatory infiltrate, the alveolar wall is thickened, alveocytes are in a state of turbid swelling and vacuolar dystrophy, they are impregnated with erythrocytes. Peribronchial pneumonia of lymphocytic character is observed. The liver is in a state of acute venous hyperemia. The central and intraparticle capillaries are sharply dilated and filled with blood in some lobes, and the hepatic beams are compressed accordingly. In the center of other lobes, diffuse infiltration of liver tissue by erythrocytes as a consequence of diapedesis is noted. Hepatocytes are in a state of granular dystrophy. Destructive changes are strongly expressed in the mucous membrane of the small intestine: desquamation of the epithelium, necrosis of epitheliocytes and villi, destruction of crypts. In the brain tissue, there is dilation of the lumens of large and small blood vessels, extracellular and perivascular edema, areas of reactive necrosis.

The plasma fraction GRF6019 slows brain atrophy in mild‐to‐moderate Alzheimer’s disease

AbstractBackgroundThe plasma fraction GRF6019 shows multiple benefits on age‐related changes in the mouse brain, including enhanced synaptic density and neurogenesis. In a trial of GRF6019 in mild‐to‐moderate Alzheimer’s disease (AD), cognition stabilized over a 24‐week period (Hannestad et al., 2020). Here we present the volumetric MRI data from that trial.MethodParticipants were 60‐90 years old with probable AD according to NIA‐AA criteria, and Mini Mental State Examination score 12‐24. They received 1 daily infusion of 100 mL or 250 mL of GRF6019 over 5 consecutive days at Week 1 and Week 13. MRIs were done at baseline at the end of the study using a MP‐RAGE or IR‐SPGR sequence. The 3D T1‐weighted scans were acquired sagittally over approximately 192 slices at a thickness of 1.0‐1.2. Images underwent the Freesurfer pipeline and hand editing to correct over‐ and under‐estimations of hippocampal volumes. Hippocampal and lateral ventricular volumes were extracted and normalized by the estimated total intracranial volume. Fold‐changes between baseline and 6 months were estimated and log2‐transformed to obtain a symmetrical distribution. MRI images from ADNI were analyzed in the same manner.ResultHippocampal volumes decreased from baseline by 2% (p&lt;0.001, one‐sample Wilcoxon test) in ADNI AD participants (n=75), while hippocampal volumes did not significantly change in ADNI control participants (n=82; 0.03%, p&gt;0.05) or in GRF6019‐treated AD trial participants (n=34; 0.3%, p&gt;0.05). Lateral ventricle volumes increased from baseline by 5.2% in ADNI AD but showed smaller increases in ADNI controls (2.7%) and in GRF6019‐treated individuals (3.1%). The difference in change from baseline between GRF6019 AD and ADNI AD was significant in the right lateral ventricle (p&lt;0.005, two‐samples Wilcoxon test) but not in the left lateral ventricle. There was no apparent difference in the change from baseline in MRI volumes between the 100 ml and 250 mL dose of GRF6019.ConclusionIn mild‐to‐moderate AD, the plasma fraction GRF6019 slowed hippocampal atrophy and lateral ventricle enlargement compared to matched individuals with AD in ADNI. The MRI data are consistent with the lack of cognitive worsening observed in these trial participants and supports continued clinical development of GRF6019 in AD.

Abstract 13156: Acute Myocardial Infarction With Biventricular Thrombi Due to Blunt Thoracic Trauma

To our knowledge, this is the first ever reported case of biventricular thrombi with acutemyocardial infarction following blunt thoracic wall trauma. We present a case of a man who presented with non-ST segment elevation myocardial infarction with left anterior descending artery (LAD) occlusion and biventricular thrombi after a blunt thoracic wall trauma. Clinical Vignette: A 56-year-old man with past medical history of diabetes mellitus and hypothyroidism presented to our ED with dizziness after motor vehicle collision. Initial workup revealed biventricular thrombi, pulmonary embolus, and dural sinus thrombosis. 2D echocardiogram showed decreased systolic function with ejection fraction of 15% and enlargement of both ventricles with biventricular thrombi. Serial troponin I levels consistently elevated from 0.3 to 0.6. After initiating cangrelor and heparin infusion, patient underwent coronary angiography which revealed LAD occlusion with a thrombus. Patient then successfully underwent mechanical thrombectomy with restoration of TIMI grade III blood flow. Discussion: Hence, we presented the first ever reported case of biventricular thrombi with LAD occlusion resulting from blunt thoracic wall trauma. While trauma induced musculoskeletal pain may mask symptoms of myocardial infarction, a high index of suspicion for acute coronary syndrome can lead to desirable outcomes in such patients.

Diagnostic Classification of Patients with Dilated Cardiomyopathy Using Ventricular Strain Analysis Algorithm.

Dilated cardiomyopathy (DCM) is a cardiomyopathy with left ventricle or double ventricle enlargement and systolic dysfunction. It is an important cause of sudden cardiac death and heart failure and is the leading indication for cardiac transplantation. Major heart diseases like heart muscle damage and valvular problems are diagnosed using cardiac MRI. However, it takes time for cardiologists to measure DCM-related parameters to decide whether patients have this disease. We have presented a method for automatic ventricular segmentation, parameter extraction, and diagnosing DCM. In this paper, left ventricle and right ventricle are segmented by parasternal short-axis cardiac MR image sequence; then, related parameters are extracted in the end-diastole and end-systole of the heart. Machine learning classifiers use extracted parameters as input to predict normal people and patients with DCM, among which Random forest classifier gives the highest accuracy. The results show that the proposed system can be effectively utilized to detect and diagnose DCM automatically. The experimental results suggest the capabilities and advantages of the proposed method to diagnose DCM. A small amount of sample input can generate results comparable to more complex methods.

Age-related neurodegeneration and cognitive impairments of NRMT1 knockout mice are preceded by misregulation of RB and abnormal neural stem cell development

N-terminal methylation is an important posttranslational modification that regulates protein/DNA interactions and plays a role in many cellular processes, including DNA damage repair, mitosis, and transcriptional regulation. Our generation of a constitutive knockout mouse for the N-terminal methyltransferase NRMT1 demonstrated its loss results in severe developmental abnormalities and premature aging phenotypes. As premature aging is often accompanied by neurodegeneration, we more specifically examined how NRMT1 loss affects neural pathology and cognitive behaviors. Here we find that Nrmt1−/− mice exhibit postnatal enlargement of the lateral ventricles, age-dependent striatal and hippocampal neurodegeneration, memory impairments, and hyperactivity. These morphological and behavior abnormalities are preceded by alterations in neural stem cell (NSC) development. Early expansion and differentiation of the quiescent NSC pool in Nrmt1−/− mice is followed by its subsequent depletion and many of the resulting neurons remain in the cell cycle and ultimately undergo apoptosis. These cell cycle phenotypes are reminiscent to those seen with loss of the NRMT1 target retinoblastoma protein (RB). Accordingly, we find misregulation of RB phosphorylation and degradation in Nrmt1−/− mice, and significant de-repression of RB target genes involved in cell cycle. We also identify novel de-repression of Noxa, an RB target gene that promotes apoptosis. These data identify Nα-methylation as a novel regulatory modification of RB transcriptional repression during neurogenesis and indicate that NRMT1 and RB work together to promote NSC quiescence and prevent neuronal apoptosis.

Advances in Chronic Obstructive Pulmonary Disease Imaging.

Chest computed tomography (CT) imaging is a useful tool that provides in vivo information regarding lung structure. Imaging has contributed to a better understanding of COPD, allowing for the detection of early structural changes and the quantification of extra-pulmonary structures. Novel CT imaging techniques have provided insight into the progression of the main COPD subtypes, such as emphysema and small airway disease. This article serves as a review of new information relevant to COPD imaging. CT abnormalities, such as emphysema and loss of airways, are present even in smokers who do not meet the criteria for COPD and in those with mild-to-moderate disease. Subjects with mild-to-moderate COPD, with the highest loss of airways, also experience the highest decline in lung function. Extra-pulmonary manifestations of COPD, such as right ventricle enlargement and low muscle mass measured on CT, are associated with increased risk for all-cause mortality. CT longitudinal data has also given insight into the progression of COPD. Mechanically affected areas of lung parenchyma adjacent to emphysematous areas are associated with a greater decline in FEV1. Subjects with the greatest percentage of small airway disease, as measured on matched inspiratory-expiratory CT scan, also present with the greatest decline in lung function.

Cognitive impairment caused by hypoxia: from clinical evidences to molecular mechanisms.

Hypoxia is a state of reduced oxygen supply and excessive oxygen consumption. According to the duration of hypoxic period, it can be classified as acute and chronic hypoxia. Both acute and chronic hypoxia could induce abundant neurological deficits. Although there have been significant advances in the pathophysiological injuries, few studies have focused on the cognitive dysfunction. In this review, we focused on the clinical evidences and molecular mechanisms of cognitive impairment under acute and chronic hypoxia. Hypoxia can impair several cognitive domains such as attention, learning and memory, procession speed and executive function, which are similar in acute and chronic hypoxia. The severity of cognitive deficit correlates with the duration and degree of hypoxia. Recovery can be achieved after acute hypoxia, while sequelae or even dementia can be observed after chronic hypoxia, perhaps due to the different molecular mechanisms. Cardiopulmonary compensatory response, glycolysis, oxidative stress, calcium overload, adenosine, mitochondrial disruption, inflammation and excitotoxicity contribute to the molecular mechanisms of cognitive deficit after acute hypoxia. During the chronic stage of hypoxia, different adaptive responses, impaired neurovascular coupling, apoptosis, transcription factors-mediated inflammation, as well as Aβ accumulation and tau phosphorylation account for the neurocognitive deficit. Moreover, brain structural changes with hippocampus and cortex atrophy, ventricle enlargement, senile plaque and neurofibrillary tangle deposition can be observed under chronic hypoxia rather than acute hypoxia.

Active hydrocephalus with aqueduct stenosis to an old woman

Introduction: Aqueduct stenosis (AS) in old people is a rare pathological entity. I report a case of a 66 years old woman with severe ataxia, cognitive deterioration, loss of sphincters control (gatism). Clinical, neuro-radiologic and therapeutic considerations are discussed.&#x0D; Case presentation: A 66 years old woman with a 6 months history of mild cerebral trauma by car accident without losing consciousness, present 2 months before hospitalization severe ataxia, cognitive disorders, gatism. At the time of trauma, brain scanner performed in another institution showed minimal fronto-basal cerebral contusions and blood collection around the brain stem. One month after a new unenhanced brain scan all previous lesions are gone. At admission, an abnormal enlargement of lateral and third ventricles are remarked both on unenhanced CT and MRI scan of the brain explained by cerebral aqueductal stenosis. Ventricular open pressure was 350 mm H2O. A ventriculoperitoneal shunt with a variable pressure valve was installed. The surgery went uneventful and the patient recovered as expected. 6-month follow-up visit the patient was symptom-free, with a fine intellectual recovery.

Diversity and function of motile ciliated cell types within ependymal lineages of the zebrafish brain.

SummaryMotile cilia defects impair cerebrospinal fluid (CSF) flow and can cause brain and spine disorders. The development of ciliated cells, their impact on CSF flow, and their function in brain and axial morphogenesis are not fully understood. We have characterized motile ciliated cells within the zebrafish brain ventricles. We show that the ventricles undergo restructuring through development, involving a transition from mono- to multiciliated cells (MCCs) driven by gmnc. MCCs co-exist with monociliated cells and generate directional flow patterns. These ciliated cells have different developmental origins and are genetically heterogenous with respect to expression of the Foxj1 family of ciliary master regulators. Finally, we show that cilia loss from the tela choroida and choroid plexus or global perturbation of multiciliation does not affect overall brain or spine morphogenesis but results in enlarged ventricles. Our findings establish that motile ciliated cells are generated by complementary and sequential transcriptional programs to support ventricular development.

Hyperthyroidism With Atrial Fibrillation in Children: A Case Report and Review of the Literature

Atrial fibrillation is exceedingly rare in children with structurally and functionally normal hearts. We present a novel case of a 15-year-old female with known hyperthyroidism who subsequently developed atrial fibrillation. She had been suffering from fatigue, heat intolerance and myalgias for 6 months. Her initial TSH was 0.01mU/L, and free T4 was 75.4 pmol/L, with a free T3 of >30.8 pmol/L. An electrocardiogram showed atrial fibrillation with a ventricular rate of 141 beats per minute. An echocardiogram demonstrated an enlarged left atrium and ventricle, with mild mitral regurgitation. She was treated with methimazole and underwent synchronized cardioversion. She subsequently returned to a euthyroid state and remained in normal sinus rhythm. In this case, we discuss the physiologic and arrhythmogenic properties of thyroid hormone, with a summary of the existing literature on atrial fibrillation in hyperthyroidism in children. Current guidelines for treatment of atrial fibrillation are also outlined.

Arrhythmogenic Right Ventricular Cardiomyopathy With Right Ventricular Thrombus Found Incidentally on a Trauma CT Scan

A 19-year-old patient with no prior medical history was involved in a medium speed motor vehicle accident. The patient could not recall if they had a syncopal event immediately prior or sustained any loss of consciousness after the accident. The patient underwent a trauma protocol computed tomography (CT) scan of their brain, neck, chest, abdomen, and pelvis. The CT chest identified an enlarged right ventricle (RV) with a filling defect that was concerning for a RV thrombus (Figure 1A). A single non-occlusive pulmonary embolus in a segmental branch of the pulmonary artery to the right lower lobe was also present (not pictured).

Abstract 403: FAM210A Maintains Cardiac Mitochondrial Homeostasis Through Regulating Letm1-dependent Ca 2+ Efflux

Mitochondria play fundamental roles in supporting healthy myocardium function. Disturbed cardiac mitochondrial homeostasis causes mitochondrial dysfunction associated with cardiomyopathy in humans and mice. Recent genome-wide association studies (GWAS) discovered that the mutations of FAM210A (family with sequence similarity 210 member A) are associated with sarcopenia and osteoporosis. Interestingly, Fam210a is most highly expressed in the heart and multiple omics analyses in mouse hearts reveal Fam210a as a hub gene in cardiac hypertrophy. However, the molecular function of FAM210A in the heart remains elusive. Here, we discover that FAM210A is critical for maintaining cardiac mitochondrial function and homeostasis. Cardiomyocyte (CM) specific knockout (KO) of Fam210a in adult mice leads to progressive heart failure with enlarged left ventricle chamber and ultimately causes mortality at ~70 days after Fam210a KO. The FAM210A deficient CMs exhibit myofilament disarray at ~9 weeks post Fam210a KO. Moreover, Fam210a KO results in a remarkably elevated mitochondrial ROS production, dramatically compromised mitochondrial membrane potential, and reduced expression of mitochondrial electron transport chain (ETC) complex genes. As a result, the mitochondrial respiratory activity is significantly reduced and the mitochondrial cristae are disrupted in Fam210a KO CMs. In contrast, at the early stage of ~5 weeks post tamoxifen-induced Fam210a KO, we observe increased mitochondrial ROS production, disturbed mitochondrial membrane potential, and reduced respiratory activity in CMs prior to heart failure. Transcriptomic and proteomic analyses from Fam210a KO hearts indicate that FAM210A deficiency causes chronic integrated stress response (ISR) in the heart. Mechanistically, Interactome analyses show that FAM210A binds to mitochondrial Ca 2+ /H + exchanger LETM1 (leucine zipper and EF-hand containing transmembrane protein 1) and regulates LETM1-mediated mitochondrial Ca 2+ efflux. Altogether, we discover a novel function of FAM210A in maintaining the cardiac mitochondrial homeostasis by regulating mitochondrial Ca 2+ efflux, and deficiency of FAM210A causes mitochondrial dysfunction and leads to heart failure.

DANDY WALKER MALFORMATION: A RARE CASE REPORT

Dandy-Walker malformation (DWM) or syndrome is a posterior fossa anomaly characterized by agenesis or hypoplasia of the vermis and cystic enlargement of the fourth ventricle causing upward displacement of tentorium and torcula. Most patients have hydrocephalus at the time of diagnosis. DMW is the most common posterior fossa malformation, and it typically occurs sporadically. This is a case report of male fetus that was diagnosed to have Dandy Walker Malformation during the antenatal obstetric scans.

Differences in clinical features of hypertrophic cardiomyopathy with or without left ventricular enlargement.

Few studies have focused on the clinical features of hypertrophic cardiomyopathy (HCM) with enlarged left ventricle (ELV). In this study, participants were patients with HCM (n=170), who were divided into two groups [ELV and normal left ventricle (NLV)] according to left ventricle size. Age at diagnosis, sex, complications, electrocardiogram (ECG), symptoms, drug treatment, and echocardiographic parameters were compared between the NLV (n=153) and ELV (n=17) groups. The incidence of end-stage HCM (ES-HCM) among all HCM patients was 5.29%, while that of ELV was 10.0%. For all patients with HCM and those with asymmetric septal HCM (ASHCM), there were more males with ELV than NLV. Of the patients with HCM and ASHCM, left ventricular ejection fraction (LVEF) was significantly lower in the ELV group than the NLV group; accordingly, the rates of diuretics use in the ELV group were higher than those in the NLV group. Among apical HCM (ApHCM) patients, the left atrial diameter (LAd), incidence of atrial fibrillation (Af) or ST-T change, and rate of angiotensin converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) use were all higher in the ELV group compared to the NLV group. These findings suggest that the prevalence of ES-HCM in HCM patients with ELV was higher than those with NLV. Additionally, ELV is more common in men than women and there are differences in the clinical features of different types of HCM with ELV.