Membranous Sac Research Articles

EPAC inhibitor suppresses angiogenesis and tumor growth of triple-negative breast cancer

AimsExchange protein directly activated by cAMP 1 (EPAC1), a major isoform of guanine nucleotide exchange factors, is highly expressed in vascular endothelia cells and regulates angiogenesis in the retina. High intratumor microvascular densities (MVD) resulting from angiogenesis is responsible for breast cancer development. Downregulation of EPAC1 in tumor cell reduces triple-negative breast cancer (TNBC)-induced angiogenesis. However, whether Epac1 expressed in vascular endothelial cells contributes to angiogenesis and tumor development of TNBC remains elusive. Main methodsWe employed NY0123, a previously identified potent EPAC inhibitor, to explore the anti-angiogenic biological role of EPAC1 in vitro and in vivo through vascular endothelial cells, rat aortic ring, Matrigel plug, and chick embryo chorioallantoic membrane (CAM) and yolk sac membrane (YSM) assays, as well as the in vivo xenograft tumor models of TNBC in both chick embryo and mice. Key findingsInhibiting EPAC1 in vascular endothelial cells by NY0123 significantly suppresses angiogenesis and tumor growth of TNBC. In addition, NY0123 possesses a better inhibitory efficacy than ESI-09, a reported specific EPAC inhibitor tool compound. Importantly, inhibiting EPAC1 in vascular endothelia cells regulates the typical angiogenic signaling network, which is associated with not only vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor-2 (VEGFR2) signaling, but also PI3K/AKT, MEK/ERK and Notch pathway. ConclusionsOur findings support that EPAC1 may serve as an effective anti-angiogenic therapeutic target of TNBC, and EPAC inhibitor NY0123 has the therapeutic potential to be developed for the treatment of TNBC.

A case series of successfully managing exomphalos major with awake graduated compression dressing and early enteral feeding.

Exomphalos anomaly is defined as the herniation of abdominal viscera into the base of the umbilical cord, with only a membranous sac covering these contents. It has an incidence of approximately 1 in 4000-6000 births. Management of exomphalos major (EM) remains controversial and limited, with very few studies to guide decision-making. This is a case series of four neonates with EM treated at a tertiary paediatric referral centre between 2018 and 2021 with a gradual compression dressing technique. Four neonates were diagnosed with EM. The average gestational age was 38 + 5 (range 38 + 2 - 39 + 2), and the average birth weight was 3.1kg (range 2.56 - 3.49kg). The defect size ranged between 5 and 7cm. All patients were commenced on gradual compression dressing between days 1 and 3 of life. Dressings were applied at the bedside in the general neonatal ward. The average time taken to reach full feeds was 1week; only one patient required parenteral nutrition. Three underwent surgical repair at two and 16weeks of age; one had delayed repair at the age of 1year because of the COVID-19 pandemic. None required patch repair. None required prolonged ventilation after repair. This case series describes a successful compression dressing technique that reduces sac content without the need for general anaesthetic or respiratory compromise, whereby simultaneous enteral feeding is tolerated.

Hydranencephaly Associated with Bilateral Megalocornea and Bilateral Cleft Lip in an Infant of Mother with Gestational Diabetes Mellitus

Abstract Background: Hydranencephaly is a rare congenital disorder of the central nervous system, in which the cerebrum is replaced by a membranous sac of cerebrospinal fluid. Clinical Description: A 2-month-old baby girl presented with abnormal body movements. She was born to a mother with gestational diabetes and had been diagnosed with hydrocephalus antenatally. The baby had features of facial dysmorphism such as bilateral megalocornea, bilateral cleft lip, and cleft palate. A magnetic resonance imaging (MRI) brain revealed the absence of cerebral hemispheres with remnants of parenchyma in the orbitofrontal area that had been replaced by cerebrospinal fluid, diagnostic of hydranencephaly. Karyotyping and echocardiography findings were normal. Management and Outcome: The prognosis was explained to parents, who opted for no therapeutic intervention. The thus patient kept on supportive care and she succumbed at the age of 6 months. Conclusion: Our case creates awareness regarding a possible association between gestational diabetes and hydranencephaly. Furthermore, the hydranencephaly in this case was unique due to its association with bilateral megalocornea and cleft lip. The case reiterates the fact that a hydrocephalus diagnosed antenatally may actually be a hydranencephaly, which is confirmed in MRI brain imaging postnatally.

Омфалоцеле - щодо тактики ведення та лікування

An omphalocele is an abdominal defect covered by a membranous sac consisting of three layers: peritoneum, jelly of the ventricle and amnion as the outer layer. The vessels of the umbilical cord flow into the top of the pouch, which usually contains the herniated abdominal contents: intestines, liver, spleen, bladder and/or gonads. The pouch covers and protects the herniated organs from harmful external influences. Purpose - to improve care for patients with omphalocele, improve their life quality by updating treatment standards using the experience of other countries around the world. A literature review is provided and personal experience is highlighted - 2 clinical cases with a diagnosis of omphalocele. Both underwent operative treatment. All children recovered and were discharged from the clinic. Depending on the clinical manifestations, the size of the defect and the content of the hernia sac, the term and tactics of treatment differ. Conclusions. The discussion about the tactics of omphalocele treatment depending on the size is still relevant. Clinical recommendations for the management of omphalocele remain only recommendations, and in each individual case, the decision regarding the terms and methods of treatment remains with the surgeon. It is necessary to remember the possibility of entrapment, which forces the surgeon to perform urgent surgical intervention. No conflict of interests was declared by the authors.

Volumetric Reconstruction of a Human Retinal Pigment Epithelial Cell Reveals Specialized Membranes and Polarized Distribution of Organelles.

Despite the centrality of the retinal pigment epithelium (RPE) in vision and retinopathy our picture of RPE morphology is incomplete. With a volumetric reconstruction of human RPE ultrastructure, we aim to characterize major membranous features including apical processes and their interactions with photoreceptor outer segments, basolateral infoldings, and the distribution of intracellular organelles. A parafoveal retinal sample was acquired from a 21-year-old male organ donor. With serial block-face scanning electron microscopy, a tissue volume from the inner-outer segment junction to basal RPE was captured. Surface membranes and complete internal ultrastructure of an individual RPE cell were achieved with a combination of manual and automated segmentation methods. In one RPE cell, apical processes constitute 69% of the total cell surface area, through a dense network of over 3000 terminal branches. Single processes contact several photoreceptors. Basolateral infoldings facing the choriocapillaris resemble elongated filopodia and comprise 22% of the cell surface area. Membranous tubules and sacs of endoplasmic reticulum represent 20% of the cell body volume. A dense basal layer of mitochondria extends apically to partly overlap electron-dense pigment granules. Pores in the nuclear envelope form a distinct pattern of rows aligned with chromatin. Specialized membranes at the apical and basal side of the RPE cell body involved in intercellular uptake and transport represent over 90% of the total surface area. Together with the polarized distribution of organelles within the cell body, these findings are relevant for retinal clinical imaging, therapeutic approaches, and disease pathomechanisms.

Development of long-acting injectable suspensions by continuous antisolvent crystallization: An integrated bottom-up process

Our present work elucidated the operational feasibility of direct generation and stabilization of long-acting injectable (LAI) suspensions of a practically insoluble drug, itraconazole (ITZ), by combining continuous liquid antisolvent crystallization with downstream processing (i.e., centrifugal filtration and reconstitution). A novel microchannel reactor-based bottom-up crystallization setup was assembled and optimized for the continuous production of micro-suspension. Based upon the solvent screening and solubility study, N-methyl pyrrolidone (NMP) was selected as the optimal solvent and an impinging jet Y-shaped microchannel reactor (MCR) was selected as the fluidic device to provide a reproducible homogenous mixing environment. Operating parameters such as solvent to antisolvent ratio (S/AS), total jet liquid flow rates (TFRs), ITZ feed solution concentration and the maturation time in spiral tubing were tailored to 1:9 v/v, 50 mL/min, 10 g/100 g solution, and 96 h, respectively. Vitamin E TPGS (0.5% w/w) was found to be the most suitable excipient to stabilize ITZ particles amongst 14 commonly used stabilizers screened. The effect of scaling up from 25 mL to 15 L was evaluated effectively with in situ monitoring of particle size distribution (PSD) and solid-state form. Thereafter, the suspension was subjected to centrifugal filtration to remove excess solvent and increase ITZ solid fraction. As an alternative, an even more concentrated wet pellet was reconstituted with an aqueous solution of 0.5% w/w Vitamin E TPGS as resuspending agent. The ITZ LAI suspension (of 300 mg/mL solid concentration) has the optimal PSD with a D10 of 1.1 ± 0.3 µm, a D50 of 3.53 ± 0.4 µm and a D90 of 6.5 ± 0.8 µm, corroborated by scanning electron microscopy (SEM), as remained stable after 548 days of storage at 25 °C. Finally, in vitro release methods using Dialyzer, dialysis membrane sac were investigated for evaluation of dissolution of ITZ LAI suspensions. The framework presented in this manuscript provides a useful guidance for development of LAI suspensions by an integrated bottom-up approach using ITZ as model API.

Combination of Phenethyl Isothiocyanate and Dasatinib Inhibits Hepatocellular Carcinoma Metastatic Potential through FAK/STAT3/Cadherin Signalling and Reduction of VEGF Secretion.

Cancerous cells are characterised by their ability to invade, metastasise, and induce angiogenesis. Tumour cells use various molecules that can be targeted to reverse these processes. Dasatinib, a potent Src inhibitor, has shown promising results in treating hepatocellular carcinoma (HCC) in vitro and in vivo. However, its effectiveness is limited by focal adhesion kinase (FAK) activation. Isothiocyanates, on the other hand, are phytochemicals with broad anticancer activity and FAK inhibition capabilities. This study evaluated the synergistic effect of dasatinib and phenethyl isothiocyanate (PEITC) on HCC. The combination was tested using various assays, including MTT, adhesion, scratch, Boyden chamber, chorioallantoic membrane (CAM), and yolk sac membrane (YSM) assays to evaluate the effect of the drug combination on HCC metastatic potential and angiogenesis in vitro and in vivo. The results showed that the combination inhibited the adhesion, migration, and invasion of HepG2 cells and reduced xenograft volume in the CAM assay. Additionally, the combination reduced angiogenesis in vitro, diminishing the growth of vessels in the tube formation assay. The inhibition of FAK/STAT3 signalling led to increased E-cadherin expression and reduced VEGF secretion, reducing HCC metastatic potential. Therefore, a combination of PEITC and dasatinib could be a potential therapeutic strategy for the treatment of HCC.

CYD0281, a Bcl-2 BH4 domain antagonist, inhibits tumor angiogenesis and breast cancer tumor growth

BackgroundB-cell lymphoma 2 (Bcl-2) family proteins are key regulators of apoptosis, which possess four conserved Bcl-2 homologies (BH) domains. Among the BH domains, the BH3 domain is considered as a potent ‘death domain’ while the BH4 domain is required for anti-apoptotic activity. Bcl-2 can be converted to a pro-apoptotic molecule through the removal or mutation of the BH4 domain. Bcl-2 is considered as an inducer of angiogenesis, which can promote tumor vascular network formation and further afford nutrients and oxygen to promote tumor progression. However, whether disrupting the function of the BH4 domain to convert Bcl-2 into a pro-apoptotic molecule could make Bcl-2 possess the potential for anti-angiogenic therapy remains to be defined.MethodsCYD0281 was designed and synthesized according to the lead structure of BDA-366, and its function on inducing a conformational change of Bcl-2 was further evaluated via immunoprecipitation (IP) and immunofluorescence (IF) assays. Moreover, the function of CYD0281 on apoptosis of endothelial cells was analyzed via cell viability, flow cytometry, and western blotting assays. Additionally, the role of CYD0281 on angiogenesis in vitro was determined via endothelial cell migration and tube formation assays and rat aortic ring assay. Chick embryo chorioallantoic membrane (CAM) and yolk sac membrane (YSM) models, breast cancer cell xenograft tumor on CAM and in mouse models as well as the Matrigel plug angiogenesis assay were used to explore the effects of CYD0281 on angiogenesis in vivo.ResultsWe identified a novel potent small-molecule Bcl-2-BH4 domain antagonist, CYD0281, which exhibited significant anti-angiogenic effects both in vitro and in vivo, and further inhibited breast cancer tumor growth. CYD0281 was found to induce conformational changes in Bcl-2 through the exposure of the BH3 domain and convert Bcl-2 from an anti-apoptotic molecule into a cell death inducer, thereby resulting in the apoptosis of vascular endothelial cells.ConclusionsThis study has revealed CYD0281 as a novel Bcl-2-BH4 antagonist that induces conformational changes of Bcl-2 to convert to a pro-apoptotic molecule. Our findings indicate that CYD0281 plays a crucial role in anti-angiogenesis and may be further developed as a potential anti-tumor drug candidate for breast cancer. This work also provides a potential anti-angiogenic strategy for breast cancer treatment.

Hemihydranencephaly of Premature Infant - Case Report

Abstract Hydranencephaly represents a rare anomaly of the central nervous system and is characterized by the parenchymal absence which is replaced with a membranous sac filled with cerebrospinal liquid, glial tissue and ependyma. When it is manifested as hemihydranencephaly, the patient’s prognosis is better. We presented a case of a premature infant with hemihydranencephaly in twin pregnancy that had a fatal outcome. A premature infant in a controlled pregnancy was delivered at 31 weeks of gestational age. The mother of the newborn was hospitalized in the Clinic for Infective Diseases since she had tested positive for SARS-Covid- 19. Following an urgent Caesarean section, the newborn was tested for Covid 19 using the rapid antigen and PCR test and the results were negative. In the delivery room, the tactile stimulation, aspiration, positive pressure ventilation of the infant were applied, after which it was intubated. After the intubation, a manual heart massage was performed, after which the cardiac activity and agonal breathing movements were detected.” Three hours later, cardiorespiratory arrest happened, following unsuccessful resuscitation. The other twin was born with no anomalies, but showed signs of respiratory distress syndrome. Autopsy revealed that there was a thin-walled cavity filled with clear, yellowish liquid in the right hemisphere. Documenting cases of newborns with hydranencephaly is of a great importance for counseling parents regarding length of survival, successful management of pregnancy, and performance of prenatal diagnostic procedures.

Fatal Bowel Obstruction Due to Paraduodenal Hernia: A Case Report.

A paraduodenal hernia is a rare type of hernia, however it is the most common type of internal hernias. It can develop after surgery, trauma, or be congenital. Paraduodenal hernias are rare in children. Clinical presentation is nonspecific. Patients range from being asymptomatic to presenting with clinical symptoms associated with small bowel obstructions. Diagnostic tools such as X-ray, plain abdominal radiography, and computed tomography may be used to diagnose paraduodenal hernias. Described is the case of a 5-year-old female who died suddenly of a bowel obstruction due to a paraduodenal hernia found at postmortem examination. In the hours prior to death, she reported stomach pain, vomiting, and later developed a fever. Postmortem CT study showed free fluid in the abdomen and bowel distention. Internal examination showed an obstructed bowel with ischemic sections extending from the distal portions of the small bowel up to the proximal portions of the transverse colon. The ischemic portions were entrapped within a clear membranous sac within the abdominal cavity. The sac was concluded to be a paraduodenal hernia. Paraduodenal hernias are rare and difficult to diagnose but they must be considered in the diagnostic process, as without surgical intervention the mortality rate can be high.

Agronomic Practices Alter Regulated Effects of Easily Extractable Glomalin-Related Soil Protein on Fruit Quality and Soil Properties of Satsuma Mandarin

Easily extractable glomalin-related soil protein (EEG) released from arbuscular mycorrhizal fungi exhibits many roles in soil and plants, while it is not clear whether the biostimulator alone or in combination with agronomic practices can improve soil characteristics and fruit quality in citrus. The objective of this study was to analyze the effects of foliar sprays of EEG, singly or in combination with fruit bagging (FB), reflective film mulching (RF), and grass-proof cloth mulching (GPC) on root mycorrhizal colonization rate, fruit internal and external quality, and soil structure and fertility on an early-ripening Satsuma mandarin “Oita 4” (Citrus unshiu cv. Oita 4). Exogenous EEG application increased root mycorrhizal colonization, while agronomic practices dramatically inhibited root mycorrhizal colonization in EEG-treated trees. Foliar EEG application significantly improved the internal and external quality of fruits, but the combination of three agronomic practices with EEG did not further enlarge the improved effect on the external quality of fruit and even produced an inhibitory effect. Also, the addition of RF further amplified the improved effect of EEG on the contents of fruit vitamin C and soluble solids. EEG application also significantly elevated sucrose in the fruit pith and juice sac, fructose in the fruit peel, fruit pith, segment membrane, and juice sac, and glucose in the fruit pith, segment membrane, and juice sac. Additional RF treatment could increase sucrose in the fruit peel and juice sac as well as glucose in the fruit peel to varying degrees in EEG-treated trees. EEG application also significantly increased soil organic carbon, mean weight diameter, nitrate nitrogen, ammonium nitrogen, available phosphorus, and available potassium levels, with additional agronomic practices almost reducing the promoting effect of EEG on these soil variables. It has been summarized that a single EEG application had positive effects on fruit quality and soil fertility, while the additional agronomic practices resulted in little change or even suppressed the positive effects of EEG.

Fossilized soft tissues in Palaeozoic bryozoans

AbstractThin sections of three Palaeozoic bryozoans reveal fossilized soft tissues that show the position of organic cuticle and internal structures such as the membranous sac and gut. The fossilization occurred apparently due to fast burial under anoxic conditions. The position of a membranous sac in the Permian trepostome Rhombotrypella superangustata is indicative of a progressive polypide cycle. The position of the polypide in the Ordovician Graptodictya delicata behind the superior and interior hemisepta suggests a protective function of the hemisepta.

New Therapeutics for Extracellular Vesicles: Delivering CRISPR for Cancer Treatment

Cancers are defined by genetic defects, which underlines the prospect of using gene therapy in patient care. During the past decade, CRISPR technology has rapidly evolved into a powerful gene editing tool with high fidelity and precision. However, one of the impediments slowing down the clinical translation of CRISPR-based gene therapy concerns the lack of ideal delivery vectors. Extracellular vesicles (EVs) are nano-sized membrane sacs naturally released from nearly all types of cells. Although EVs are secreted for bio-information conveyance among cells or tissues, they have been recognized as superior vectors for drug or gene delivery. Recently, emerging evidence has spotlighted EVs in CRISPR delivery towards cancer treatment. In this review, we briefly introduce the biology and function of the CRISPR system and follow this with a summary of current delivery methods for CRISPR applications. We emphasize the recent progress in EV-mediated CRISPR editing for various cancer types and target genes. The reported strategies for constructing EV-CRISPR vectors, as well as their limitations, are discussed in detail. The review aims to throw light on the clinical potential of engineered EVs and encourage the expansion of our available toolkit to defeat cancer.

Silver sulfadiazine as the topical treatment for giant omphalocele: a case report

Background: Major omphalocele is defined as an abdominal defect greater than 5 cm with the presence of the liver and most parts of the bowel in the sac. The management remains challenging for pediatricians and surgeons with remarkably high mortality. Reports about topical agents/dressing used as escharotic therapy, such as silver sulfadiazine, povidone-iodine, topical antibiotics, or honey, have been published with different results. Continued application of a thick layer of silver sulfadiazine on the omphalocele surface is needed to promote eschar formation and neo-epithelialization. Case description: A term, 2700-gram newborn male infant presented with abdominal defect and herniated abdominal contents covered by a membranous sac containing liver that is widely known as omphalocele. A thick layer of silver sulfadiazine was applied repeatedly onto the omphalocele sac to promote epithelialization and successfully reduce the sac diameter. The patient showed a positive outcome as it reduced the omphalocele size after nine days. The patient family has been educated about the continued application of silver sulfadiazine. Although non-operative delayed treatment has lower mortality rates and better clinical outcomes, the patients should wait for the reconstruction surgery for a long time. Conclusion: Conservative treatment with silver sulfadiazine is safe and shows satisfying results to the giant omphalocele.

Case Report: Hydranencephaly in a female newborn with congenital cytomegalovirus infection

Background: Hydranencephaly is a congenital abnormality of the central nervous system characterized by massive hemispheric necrosis and ventricular dilatation with most of the cerebral hemispheres being replaced by membranous sacs filled with cerebrospinal fluid (CSF). Cytomegalovirus (CMV) infection can be one of the causes of hydranencephaly. The choice of therapy for hydranencephaly is a challenge because of poor prognosis, but now neural stem cell (NSC) transplantation may give new hope. Case report: We report a case of a female newborn born at term by cesarean section from a gravida 5, para 3, abortus 1 (G5P3A1) mother with suspected hydrocephalus. Head circumference was 35 cm at birth. The baby was born crying immediately, looked active, and did not appear cyanotic, but on the second day, the baby looked less active, moaned, showed acral cyanosis, and had a large fontanelle that was dilated and soft. Signs of hydrocephalus such as Macewen’s sign, setting sun phenomenon, and transillumination were found to be positive. Echocardiographic examination showed floppy interatrial septum and mild mitral regurgitation. Non-contrast computerized tomography (CT) scan of the head showed hydranencephaly. The toxoplasmosis, rubella, CMV, and herpes simplex virus (TORCH) screening showed positive anti-CMV immunoglobulin G (IgG). The baby underwent a ventriculoperitoneal (VP) shunt procedure with a head circumference of 36 cm before surgery. VP shunt was performed with an opening pressure of 15 cmH2O. Conclusions: After the VP shunt procedure, the baby's general condition improved with the head circumference within normal limits. The baby was discharged from the hospital after 16 days of treatment.

Intrathoracic mass in a 5-month-old infant: fetus in fetu—a case report

BackgroundThe fetu in fetu (FIF) is an extremely rare congenital condition characterized by a 2nd fetus that grows into the body of the healthy twin. Its thoracic location is more exceptional.Case presentationWe report a case of intrathoracic mass in a 5-month-old female infant, diagnosed after an assessment for respiratory distress. She underwent an emergency left thoracotomy which allowed for the removal of a large thoraco-mediastinal mass inside a membranous sac containing a clear liquid mixed with vernix caseosa. The mass was completely covered with normal skin, three lobes similar to rudimentary outline of the head and limb. It was attached to a single large vascular pedicle. The pathological examination concluded that there was a high possibility of FIF. The postoperative follow-up was uncomplicated, and the child is still in good clinical condition after the 5-month follow-up.ConclusionThe assessment of the respiratory distress in an infant with a mass centered by an axial skeleton on the chest x-ray and thoracic CT scan may suggest a diagnosis of intrathoracic FIF.

Non-clinical studies indicating lack of interactions between iron/calcium ions and linzagolix, an orally available GnRH antagonist

Linzagolix is an orally available gonadotropin-releasing hormone antagonist used to treat sex-hormone-dependent diseases in women. This study aimed to investigate drug-drug interactions between linzagolix and iron/calcium ions in the intended clinical setting by conducting pharmacokinetic studies in vitro and in rats. Insoluble precipitate formation with metal ions was evaluated by measuring linzagolix concentrations in four types of bio-relevant dissolution media (fasted/fed state simulated gastric fluid and fasted/fed state simulated gastric fluid version 2), and chelate complex formation with metal ions was evaluated by release of linzagolix from a cellulose membrane sac. In these in vitro studies, linzagolix showed no potential for insoluble precipitate formation under fasted/fed conditions and no chelate complex formation in the presence of metal ions. In rats, the plasma concentration-time profiles of linzagolix and iron ion were similar regardless of whether they were administered with or without ferrous sulfate and linzagolix choline at clinically relevant doses. Thus, linzagolix and iron ion had no effect on each other’s absorption in vivo. In conclusion, linzagolix is unlikely to cause clinically relevant drug-drug interactions by chelating metal ions according to the results of in vitro and in vivo studies.

Visualizing intra-Golgi localization and transport by side-averaging Golgi ministacks.

The mammalian Golgi comprises tightly adjacent and flattened membrane sacs called cisternae. We still do not understand the molecular organization of the Golgi and intra-Golgi transport of cargos. One of the most significant challenges to studying the Golgi is resolving Golgi proteins at the cisternal level under light microscopy. We have developed a side-averaging approach to visualize the cisternal organization and intra-Golgi transport in nocodazole-induced Golgi ministacks. Side-view images of ministacks acquired from Airyscan microscopy are transformed and aligned before intensity normalization and averaging. From side-average images of >30 Golgi proteins, we uncovered the organization of the pre-Golgi, cis, medial, trans, and trans-Golgi network membrane with an unprecedented spatial resolution. We observed the progressive transition of a synchronized cargo wave from the cis to the trans-side of the Golgi. Our data support our previous finding, in which constitutive cargos exit at the trans-Golgi while the secretory targeting to the trans-Golgi network is signal dependent.

Assessment of the epi-pericardial fibrotic substrate by collagen-targeted probes

The identification of the fibrotic arrhythmogenic substrate as a means of improving the diagnosis and prediction of atrial fibrillation has been a focus of research for many years. The relationship between the degree of atrial fibrosis as a major component of atrial cardiomyopathy and the recurrence of arrhythmia after AF ablation can correlate. While the focus in identification and characterisation of this substrate has been centred on the atrial wall and the evaluation of atrial scar and extracellular matrix (ECM) expansion by late gadolinium-enhancement (LGE) on cardiac magnetic resonance imaging (CMRI), LGE cannot visualise diffuse fibrosis and diffuse extravasation of gadolinium. The atrial pericardium is a fine avascular fibrous membranous sac that encloses the atrial wall, which can undergo remodelling leading to atrial disease and AF. Nevertheless, little attention has been given to the detection of its fibrocalcification, impact on arrhythmogenesis and, most importantly, on the potential prothrombotic role of epi-pericardial remodelling in generation of emboli. We have recently reported that tracers against collagen I and IV can provide a direct assessment of the ECM, and thus can estimate fibrotic burden with high sensitivity. Here, we show the ability of these optical tracers to identify epi-pericardial fibrosis, as well as to demonstrate subtle interstitial fibrosis of the atrial wall in a mouse model of beta-2-adrenergic receptor (β2-AR) cardiac overexpression.

Case Report: Hydranencephaly in a female newborn with congenital cytomegalovirus infection

Background: Hydranencephaly is a congenital abnormality of the central nervous system characterized by massive hemispheric necrosis and ventricular dilatation with most of the cerebral hemispheres being replaced by membranous sacs filled with cerebrospinal fluid (CSF). Cytomegalovirus (CMV) infection can be one of the causes of hydranencephaly. The choice of therapy for hydranencephaly is a challenge because of poor prognosis, but now neural stem cell (NSC) transplantation may give new hope. Case report: We report a case of a female newborn born at term by cesarean section from a gravida 5, para 3, abortus 1 (G5P3A1) mother with suspected hydrocephalus. Head circumference was 35 cm at birth. The baby was born crying immediately, looked active, and did not appear cyanotic, but on the second day, the baby looked less active, moaned, showed acral cyanosis, and had a large fontanelle that was dilated and soft. Signs of hydrocephalus such as Macewen’s sign, setting sun phenomenon, and transillumination were found to be positive. Echocardiographic examination showed floppy interatrial septum and mild mitral regurgitation. Non-contrast computerized tomography (CT) scan of the head showed hydranencephaly. The toxoplasmosis, rubella, CMV, and herpes simplex virus (TORCH) screening showed positive anti-CMV immunoglobulin G (IgG). The baby underwent a ventriculoperitoneal (VP) shunt procedure with a head circumference of 36 cm before surgery. VP shunt was performed with an opening pressure of 15 cmH2O. Conclusions: After the VP shunt procedure, the baby's general condition improved with the head circumference within normal limits. The baby was discharged from the hospital after 16 days of treatment.