Defects In Adulthood Research Articles

Neonatal Exposure to Polystyrene Nanoplastics Impairs Microglia-Mediated Synaptic Pruning and Causes Social Behavioral Defects in Adulthood.

The increasing prevalence and persistence of nanoplastics (NPs) have become critical environmental concerns. These particles have the potential to enter the food chain and accumulate in living organisms, which exerts their adverse effects on human health. The release of nanoparticles from feeding bottles raises concerns about potential health issues, especially for newborns exposed to NPs at the neonatal stage. In this study, we examined the impacts of neonatal exposure to polystyrene nanoplastics (PS-NPs) on neurodevelopment. Our study demonstrates that exposure to PS-NPs in newborn mice impairs microglial autophagic function and energy metabolism, leading to the disruption of microglia-mediated synaptic pruning during early neurodevelopment. These mice subsequently develop social behavioral defects in adulthood, suggesting the long-lasting effects of neonatal PS-NP exposure on brain development and behavior. Together, these data provide insights into the mechanism by which PS-NPs affect early neurodevelopment, thus emphasizing the crucial need to address plastic pollution globally.

Surgical treatment of congenital heart defects in adulthood

Surgical treatment of congenital heart defects in adulthood

Novel insights into minipuberty and GnRH: Implications on neurodevelopment, cognition, and COVID-19 therapeutics.

In humans, the first 1000 days of life are pivotal for brain and organism development. Shortly after birth, gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus are activated, a phenomenon known as minipuberty. This phenomenon, observed in all mammals studied, influences the postnatal development of the hypothalamic-pituitary-gonadal (HPG) axis and reproductive function. This review will put into perspective the results of recent studies showing that the impact of minipuberty extends beyond reproductive function, influencing sensory and cognitive maturation. Studies in mice have revealed the role of nitric oxide (NO) in regulating minipuberty amplitude, with NO deficiency linked to cognitive and olfactory deficits. Additionally, findings indicate that cognitive and sensory defects in adulthood in a mouse model of Down syndrome are associated with an age-dependent decline of GnRH production, whose origin can be traced back to minipuberty, and point to the potential therapeutic role of pulsatile GnRH administration in cognitive disorders. Furthermore, this review delves into the repercussions of COVID-19 on GnRH production, emphasizing potential consequences for neurodevelopment and cognitive function in infected individuals. Notably, GnRH neurons appear susceptible to SARS-CoV-2 infection, raising concerns about potential long-term effects on brain development and function. In conclusion, the intricate interplay between GnRH neurons, GnRH release, and the activity of various extrahypothalamic brain circuits reveals an unexpected role for these neuroendocrine neurons in the development and maintenance of sensory and cognitive functions, supplementing their established function in reproduction. Therapeutic interventions targeting the HPG axis, such as inhaled NO therapy in infancy and pulsatile GnRH administration in adults, emerge as promising approaches for addressing neurodevelopmental cognitive disorders and pathological aging.

Carrier State of Chronic Granulomatous Disease Presented at Middle Age: A Case Report

Introduction: Chronic granulomatous disease (CGD) is the most common inherited defect of phagocytes. Although most female carriers of X-linked CGD have been considered to be unaffected, they may have similar problems to those of CGD patients. This study suggests that the CGD carrier state might be more complex than it was previously appreciated. Case Presentation: A sixty-year-old woman visited our hospital in June 2021 due to pneumonia and pleural effusion. Chest computed tomography scan revealed left lower lobe pneumonia and mediastinal lymphadenopathies. In July 2021, her symptoms (high-grade fever, chills, and hemoptysis) were initially attributed to a hydatid cyst. Therefore, she underwent a lobectomy, resulting in purulent drainage on the excision site on the skin, refractory to local and systemic treatments. The refractory and recurrent nature of the lesions led to the immunological evaluation, which was completely normal with a 100% nitroblue tetrazolium (NBT) and a dihydrorhodamine (DHR) of 278 (normal > 100). Further DHR123 flow cytometry investigations with multiple stimulants revealed a carrier state of CGD, which was relevant to her history of chronic complications. Conclusions: Adult patients with unusual manifestations suggestive of neutrophil function defects in adulthood should be evaluated for the CGD carrier state. In these cases, NBT alone may miss the diagnosis of CGD. In such cases, DHR testing with multiple stimulants may establish a robust diagnosis.

Unruptured Sinus of Valsalva Aneurysm Coexisting with Ventricular Septal Defect

Unruptured sinus of valsalva aneursym is an incidental, relatively rare finding on cardiac imaging and is often found in association with other cardiac defects with ventricular septal defect as the commonest. It presents a diagnostic challenge on transthoracic echocardiography in coexistence with ventricular septal defect in adulthood, mimicking other cardiac defects. Unruptured sinus of valsalva aneurysm coexisting with ventricular septal defect usually presents with symptoms of rupture—a surgical emergency in the third and fourth decade of life. We report a case of a 24-year-old single mother referred to the Cardiology Clinic of the University of Nigeria Teaching Hospital with 5 months symptoms of heart failure. Investigations showed cardiomegaly, prominent pulmonary conus, and upper lobe vessel diversion on chest x-ray. There were bigeminal premature ventricular contractions, left atrial abnormality, biventricular hypertrophy with a right strain on electrocardiogram, and bidirectional membranous ventricular septal defect with right sinus of valsalva aneurysm on transthoracic echocardiography.

The effect of single-cell knockout of Fragile X Messenger Ribonucleoprotein on synaptic structural plasticity.

Fragile X Syndrome (FXS) is the best-known form of inherited intellectual disability caused by the loss-of-function mutation in a single gene. The FMR1 gene mutation abolishes the expression of Fragile X Messenger Ribonucleoprotein (FMRP), which regulates the expression of many synaptic proteins. Cortical pyramidal neurons in postmortem FXS patient brains show abnormally high density and immature morphology of dendritic spines; this phenotype is replicated in the Fmr1 knockout (KO) mouse. While FMRP is well-positioned in the dendrite to regulate synaptic plasticity, intriguing in vitro and in vivo data show that wild type neurons embedded in a network of Fmr1 KO neurons or glia exhibit spine abnormalities just as neurons in Fmr1 global KO mice. This raises the question: does FMRP regulate synaptic morphology and dynamics in a cell-autonomous manner, or do the synaptic phenotypes arise from abnormal pre-synaptic inputs? To address this question, we combined viral and mouse genetic approaches to delete FMRP from a very sparse subset of cortical layer 5 pyramidal neurons (L5 PyrNs) either during early postnatal development or in adulthood. We then followed the structural dynamics of dendritic spines on these Fmr1 KO neurons by in vivo two-photon microscopy. We found that, while L5 PyrNs in adult Fmr1 global KO mice have abnormally high density of thin spines, single-cell Fmr1 KO in adulthood does not affect spine density, morphology, or dynamics. On the contrary, neurons with neonatal FMRP deletion have normal spine density but elevated spine formation at 1 month of age, replicating the phenotype in Fmr1 global KO mice. Interestingly, these neurons exhibit elevated thin spine density, but normal total spine density, by adulthood. Together, our data reveal cell-autonomous FMRP regulation of cortical synaptic dynamics during adolescence, but spine defects in adulthood also implicate non-cell-autonomous factors.

The ETS transcription factor Spi2 regulates hematopoietic cell development in zebrafish.

The E26 transformation-specific or E-twenty-six (ETS) genes encode a superfamily of transcription factors involved in diverse biological processes. Here, we report the identification and characterization of a previously unidentified member of the ETS transcription factors, Spi2, that is found exclusively in the ray-finned fish kingdom. We show that the expression of spi2 is restricted to hemogenic endothelial cells (HECs) and to hematopoietic stem and progenitor cells (HSPCs) in zebrafish. Using bacteria artificial chromosome transgenesis, we generate a spi2 reporter line, TgBAC(spi2:P2a-GFP), which manifests the GFP pattern recapitulating the endogenous spi2 expression. Genetic ablation of spi2 has little effect on HEC formation and the endothelial-to-hematopoietic transition, but results in compromised proliferation of HSPCs in the caudal hematopoietic tissue (CHT) during early development and in severe myeloid lineage defect in adulthood. Epistatic analysis shows that spi2 acts downstream of runx1 in regulating HSPC development in the CHT. Our study identifies Spi2 as an essential regulator for definitive hematopoietic cell development and creates a TgBAC(spi2:P2a-GFP) reporter line for tracking HECs, HSPCs, myeloid cells and thrombocytes from early development to adulthood.

Innocent Murmur since Childhood: Elderly Patient with Undiagnosed Interventricular Septal Defect

Ventricular septal defects in adulthood only account for 10 per cent of congenital heart defects, In patients with evidence of LV volume overload and no Pulmonary Arterial Hypertension (no non-invasive signs of Pulmonary artery pressure elevation or invasive confirmation of Pulmonary Vascular Resistance <3 Woods Units in case of such signs), VSD closure is recommended regardless of symptoms. “Maladie de Rogers” is referred to as a VSD with a small left-to-right shunt, the pulmonary vascular resistance is not significantly elevated and the left-to-right shunt is small (Qp: Qs <1.5:1), in the absence of aortic valve prolapse and regurgitation or Infective endocarditis, may be managed by observation without need for operative intervention.

Fetal exposure to anti-mullerian hormone triggers a transgenerational epigenetic transmission of polycystic ovary syndrome (PCOS) defects in adulthood

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Risk Factors for Coronary Artery Aneurysm in Children with Kawasaki Disease: A Case-control Study

Coronary artery aneurysms (CAA) are common in children with Kawasaki disease (KD) who have delayed diagnosis. This can increase the high cardiovascular burden and cause acquired heart defects in adulthood. This study aims to investigate the risk factors for CAA in children with KD. An observational retrospective case-control study was carried out in Surabaya Tertiary Hospital. We collected the medical records in the child care installation, Pediatrics ward, from 2016 to 2019. The research participants were pediatric patients who were treated with KD. The exclusion criteria were incomplete medical record data regarding the risk factors studied. The risk factors studied included age, sex, duration of fever, haemoglobin, leukocytes levels, platelets levels, C-reactive protein (CRP), and albumin levels. Twenty-eight medical records of children with KD were collected in this study; only 17 eligible patients were observed. The confirmed CAA was found in 8 patients, while 9 patients were non-CAA aged ranging from 3-124 months. Almost 60% of patients had fever duration > 7 days, and 47.1% of patients had hemoglobin <10 g/dL. Platelets were the only risk factor that had a significant correlation for developing CAA in children with KD, with a p-value of 0.015 at a 95% confidence interval (CI), odds ratio (OR) of 24 (1.785 – 336.227). Almost half of KD patients in this study were at risk for developing CAA; platelet value was a risk factor that we could consider in the administration of aspirin and IVIG therapy, providing the follow-up results and evaluating aneurysm progression or regression after IVIG administration is needed to prevent poor long-term outcomes.

English

The aim is to report an Ivorian experience of the surgical management of atrial septal defects in adulthood. Our retrospective study included 19 patients over 18 years old operated on for atrial septal defects (ASD) between January 2005 and December 2015 at the Abidjan Heart Institute (AHI). 13 women and 6 men with a mean age of 26±9.07 years were included. For each patient we noted the clinical and para-clinical signs as well as the operative result and the short and long term follow-up data. Patients were symptomatic in 73.7% of cases. Two patients had atrial flutter. On cardiac echo-Doppler, the right ventricle measured 43.5 ±4.2 mm. The systolic pulmonary artery pressure was 45 ± 14.7 mmHg. There were 3 cases of grade III tricuspid insufficiency and 1 case of abnormal venous return. Closure of the septal defect was performed with an autologous pericardial patch in 18 cases. Operative mortality was nil. The average length of stay in the surgical intensive care unit was 2.5 days. Eleven patients presented immediate postoperative complications, including 2 cardiac and 9 extracardiac. The total postoperative hospital stay was 14.7 days. After a mean follow-up of 8.25 ± 4 years, all patients had functional improvement with a significant decrease in right ventricular size and pulmonary arterial pressure. Surgical management of atrial septal defects in adulthood is associated with low mortality with a satisfactory functional outcome. Key words: Atrial septal defect, surgical closure, adult.

Atrial septal defect in adulthood: a new paradigm for congenital heart disease

Atrial septal defects (ASDs) represent the most common congenital heart defect diagnosed in adulthood. Although considered a simple defect, challenges in optimal diagnostic and treatment options still exist due to great heterogeneity in terms of anatomy and time-related complications primarily arrhythmias, thromboembolism, right heart failure and, in a subset of patients, pulmonary arterial hypertension (PAH). Atrial septal defects call for tertiary expertise where all options may be considered, namely catheter vs. surgical closure, consideration of pre-closure ablation for patients with atrial tachycardia and suitability for closure or/and targeted therapy for patients with PAH. This review serves to update the clinician on the latest evidence, the nuances of optimal diagnostics, treatment options, and long-term follow-up care for patients with an ASD.

Effect of Neonatal Treatment With the NMDA Receptor Antagonist, MK-801, During Different Temporal Windows of Postnatal Period in Adult Prefrontal Cortical and Hippocampal Function.

The neonatal MK-801 model of schizophrenia has been developed based on the neurodevelopmental and NMDA receptor hypofunction hypotheses of schizophrenia. This animal model is generated with the use of the NMDA receptor antagonist, MK-801, during different temporal windows of postnatal life of rodents leading to behavioral defects in adulthood. However, no studies have examined the role of specific postnatal time periods in the neonatal MK-801 (nMK-801) rodent model and the resulting behavioral and neurobiological effects. Thus, the goal of this study is to systematically investigate the role of NMDA hypofunction, during specific temporal windows in postnatal life on different cognitive and social behavioral paradigms, as well as various neurobiological effects during adulthood. Both female and male mice were injected intraperitoneally (i.p.) with MK-801 during postnatal days 7–14 (p7–14) or 11–15 (p11–15). Control mice were injected with saline during the respective time period. In adulthood, mice were tested in various cognitive and social behavioral tasks. Mice nMK-801-treated on p7–14 show impaired performance in the novel object, object-to-place, and temporal order object recognition (TOR) tasks, the sociability test, and contextual fear extinction. Mice nMK-801-treated on p11–15 only affects performance in the TOR task, the social memory test, and contextual fear extinction. No differences were identified in the expression of NMDA receptor subunits, the synapsin or PSD-95 proteins, either in the prefrontal cortex (PFC) or the hippocampus (HPC), brain regions significantly affected in schizophrenia. The number of parvalbumin (PV)-expressing cells is significantly reduced in the PFC, but not in the HPC, of nMK-801-treated mice on p7–14 compared to their controls. No differences in PV-expressing cells (PFC or HPC) were identified in nMK-801-treated mice on p11–15. We further examined PFC function by recording spontaneous activity in a solution that allows up state generation. We find that the frequency of up states is significantly reduced in both nMK-801-treated mice on p7–14 and p11–15 compared to saline-treated mice. Furthermore, we find adaptations in the gamma and high gamma activity in nMK-801-treated mice. In conclusion, our results show that MK-801 treatment during specific postnatal temporal windows has differential effects on cognitive and social behaviors, as well as on underlying neurobiological substrates.

The role of Niemann-Pick type C2 in zebrafish embryonic development.

Niemann-Pick disease type C (NPC) is a rare, fatal, neurodegenerative lysosomal disease caused by mutations of either NPC1 or NPC2. NPC2 is a soluble lysosomal protein that functions in coordination with NPC1 to efflux cholesterol from the lysosomal compartment. Mutations of either gene result in the accumulation of unesterified cholesterol and other lipids in the late endosome/lysosome, and reduction of cellular cholesterol bioavailability. Zygotic null npc2m/m zebrafish showed significant unesterified cholesterol accumulation at larval stages, a reduction in body size, and motor and balance defects in adulthood. However, the phenotype at embryonic stages was milder than expected, suggesting a possible role of maternal Npc2 in embryonic development. Maternal-zygotic npc2m/m zebrafish exhibited significant developmental defects, including defective otic vesicle development/absent otoliths, abnormal head/brain development, curved/twisted body axes and no circulating blood cells, and died by 72 hpf. RNA-seq analysis conducted on 30 hpf npc2+/m and MZnpc2m/m embryos revealed a significant reduction in the expression of notch3 and other downstream genes in the Notch signaling pathway, suggesting that impaired Notch3 signaling underlies aspects of the developmental defects observed in MZnpc2m/m zebrafish.

Evolving Paradigms in the Treatment of Atrial Septal Defects With Pulmonary Arterial Hypertension.

Atrial septal defects are one of the most frequently diagnosed congenital heart defects in adulthood. The presence of concurrent moderate or severe pulmonary arterial hypertension without Eisenmenger syndrome at the time of diagnosis can make for a challenging clinical scenario. There is continually evolving literature to determine the ideal approach to this subset of patients. Here we aim to review the clinical presentation, history, medical therapy, and closure options for atrial septal defects-pulmonary arterial hypertension with predominant left-to-right shunting, in the absence of Eisenmenger syndrome.

Common arterial trunk: pathomorphological changes of unoperated cardiac defect in adulthood

Congenital heart defects in adulthood constitute the sufficient proportion of cardiac pathology. The common arterial trunk (CAT) is one of the сongenital cardiac defects that is described in the adult population. Without surgical intervention, patients who survived become inoperable quickly due to the development of early congestive heart insufficiency and pulmonary hypertension. The purpose of the research is to analyze the autopsy case of unoperated congenital cardiac defects in adulthood. Materials and methods. The pathomorphological analysis of the case of death of a 33-year-old male with untreated complex congenital heart defect – CAT, ventricular septal defect, Eisenmenger's syndrome was made using standard and elective histological techniques. Results. In the forensic examination of the body of the deceased 33-year-old male, congenital heart defect was diagnosed as CAT and ventricular septal defect. Coronary, pulmonary and major arteries of a large circle of blood circulate from the CAT. Congenital heart defect has been complicated by the development of cardiomegaly (heart weight 1500 g) with myocardial hypertrophy of both ventricles and led to decompensation of cardiac activity. During the pathohistological examination of the valve of the CAT we determined the foci of fibrinoid necrosis, myxomatosis, single accumulation of lymphocytes, focal fibrosis. In the myocardium of the right and left ventricles we observed hypertrophy, focal contraction and fragmentation of cardiomyocytes, expressed intramuscular edema, sclerosis of the walls of the small intramural arteries with perifocal areas of vacuolar degeneration of cardiomyocytes, stromal cardiosclerosis, isolated interstitial infiltration of lymphocytes, dilatation of lymphatic vessels. In the pulmonary tissue diffuse hemosiderosis, multiple intravalveolar hemorrhages, sclerosis of the small pulmonary arteries with the formation of two- and three-sided lumen, sclerosis of interalveolar membranes were detected. Morphological changes in the myocardium and lungs confirm prolonged congestive heart failure and pulmonary hypertension. Conclusions . We describe a unique case of long-term survival of a patient with CAT without surgical intervention. The complex of pathomorphological changes of the described case testifies to cardiovascular remodeling, which is the base of hemodynamic evolution of complex congenital heart disease and allowed the man to live up to 33 years without surgical intervention.

OP-80 - Atrial Septal Defect in Adulthood: About 392 Patients

Introduction: Inter atrial septal defect (ASD) are common and account for 10% of heart disease diagnosed at birth and 30 to 40% in adulthood with an estimated prevalence of 14 to 24/ 10 000.

Optic Disk Drusen: Historical and Up-To-Date Aspects

Optic disc drusen are an important differential diagnosis in the diagnostic evaluation of a prominent optic nerve head. Drusen of the optic disc occur in 0.34 to 2.4 % of human individuals and manifest themselves bilaterally in three of four cases. Drusen are found six times more often within histological sections than on funduscopic examination. It is known that optic disc drusen can occur in familial clusters without any other pathological ophthalmic findings. They can also be associated with retinitis pigmentosa, or with the Joubert or Alagille syndromes. Non-invasive diagnostic tools include fundus-autofluorescence (AF), optical coherence tomography (OCT) and ultrasound. Drusen of the optic nerve head are asymptomatic in most cases, though transient ischemia can lead to transient visual impairment. In particular, superficial drusen can lead to profound visual field defects in adulthood. Regular ophthalmological follow-up examinations with tonometry and perimetry are recommended for the early detection of visual field defects. Radial optic neurotomy (RON) seems to be a therapeutic option in patients with acute deterioration of the visual field.

Clinical course and potential complications of small ventricular septal defects in adulthood: Late development of left ventricular dysfunction justifies lifelong care

BackgroundPatients with small ventricular septal defects (VSDs) are thought to have excellent long-term survival, although complications may not be uncommon. MethodsWe identified all patients aged ≥16years with native isolated VSD between January 2000 and September 2013. Clinical outcomes were retrospectively reviewed. Transthoracic echocardiograms performed within 2years of last assessment were reviewed for hemodynamic sequelae. ResultsTwo-hundred-and-thirty-one patients, 100 (43%) male, mean age at last follow-up 34±13years were studied. During the recorded period there were no deaths. The majority (224/231; 97%) were asymptomatic. Documented arrhythmias occurred in 7 patients (3%), double-chamber right ventricle (DCRV) in 29 (13%), more than mild aortic regurgitation in 6 (3%) and infective endocarditis in 24 (10%) patients.Surgery due to complications associated with VSD was performed in 26 (11%) patients at a median age of 27.6years (IQR: 16.1–38.7) due to DCRV (n=17, 65%), infective endocarditis (n=6, 23%), progression of left–right shunt (n=2, 8%) and aortic regurgitation (n=1, 4%).At most recent echocardiography (n=164), 10 (6%), had reduced LVEF, 34 (21%) had increased LVEDD and 17 (10%) had LVESD >4.0cm. Thirty-two patients (25%) with normal LV dimensions had LA enlargement suggesting LV diastolic dysfunction. ConclusionsWe report a non-negligible incidence of major complications or clinical events during late follow-up of adult patients with restrictive VSDs. Furthermore, we show co-existing LV dysfunction, systolic or diastolic in a subset of patients. Indication for VSD closure in childhood may be recognized, whereas lifelong follow-up for adult with restrictive VSDs is clearly warranted.

Effect of Early Intervention on Language Development in Hearing-Impaired Children.

Hearing loss from birth up to the age of 3 years has a negative effect on speech/language development and results in sensory, cognitive, emotional, and academic defects in adulthood by causing delayed development of communicative-linguistic abilities. The present study was performed in order to assess the effect of early intervention on language development in Persian children aged 6-7 years with severe sensorineural hearing loss. Thirty boys and girls aged 6-7 years participated in this study, all of them had severe congenital sensorineural hearing loss in both ears. All children were using bilateral behind-the-ear hearing aid, and had similar economic/socio-cultural backgrounds. Subjects were categorized into two groups based on the age of identification/intervention of hearing loss (3-6 and 12-15 months of age). The Persian TOLD-P3 test was used to evaluate language development in all subjects. Data collection was accomplished by observation, completion of questionnaires, and speech recording. There was a significant difference in language development in 11 sub-tests and five lingual gains on the Persian TOLD-P3 test between early (3-6 months of age) and late identified/intervened (12-15 months of age) hearing-impaired children (P[Formula: see text]0.05). Early identified/intervened hearing-impaired children had a notable preference in all assessed sub-tests and lingual gains. Early identification/intervention of hearing loss before the age of 6 months has a significant positive effect on a child's language development in terms of picture/relational/oral vocabulary, grammatical comprehension, sentence combining, grammatical completion, phonologic analysis, word differentiation, word production, semantics, and syntax. Moreover, early identification/ intervention of hearing loss develops the hearing-impaired child's lingual gains in visual vocabulary, grammatical completion, word differentiation, phonologic analysis, and word production.