Bi-allelic NRXN1α deletion in microglia derived from iPSC of an autistic patient increases interleukin-6 production and impairs supporting function on neuronal networking.

Autism spectrum disorder (ASD) is a set of heterogeneous neurodevelopmental conditions, with a highly diverse genetic hereditary component, including altered neuronal circuits, that has an impact on communication skills and behaviours of the affected individuals. Beside the recognised role of neuronal alterations, perturbations of microglia and the associated neuroinflammatory processes have emerged as credible contributors to aetiology and physiopathology of ASD. Mutations in NRXN1, a member of the neurexin family of cell-surface receptors that bind neuroligin, have been associated to ASD.

Successful Percutaneous Closure of Gerbode Defect and Right Atrial-Aortic Fistula Following Infective Endocarditis.

We report a case of infective endocarditis with a septal abscess that was complicated with abnormal blood flow from the left ventricle to the right atrium (Gerbode defect) along with abnormal blood flow from the aorta to the right atrium (atrial-aortic fistula). This is the first reported case of successful correction of both defects by a percutaneous approach.

Sex Differences in Long-term Outcome of Prenatal Exposure to Excess Glucocorticoids-Implications for Development of Psychiatric Disorders.

Exposure to prenatal insults, such as excess glucocorticoids (GC), may lead to pathological outcomes, including neuropsychiatric disorders. The aim of the present study was to investigate the long-term effects of in utero exposure to the synthetic GC analog dexamethasone (Dex) in adult female offspring. We monitored spontaneous activity in the home cage under a constant 12 h/12 h light/dark cycle, as well as the changes following a 6-h advance of dark onset (phase shift).

The Threat Posed by Environmental Contaminants on Neurodevelopment: What Can We Learn from Neural Stem Cells?

Exposure to chemicals may pose a greater risk to vulnerable groups, including pregnant women, fetuses, and children, that may lead to diseases linked to the toxicants' target organs. Among chemical contaminants, methylmercury (MeHg), present in aquatic food, is one of the most harmful to the developing nervous system depending on time and level of exposure. Moreover, certain man-made PFAS, such as PFOS and PFOA, used in commercial and industrial products including liquid repellants for paper, packaging, textile, leather, and carpets, are developmental neurotoxicants.

Modeling Neurological Disorders in 3D Organoids Using Human-Derived Pluripotent Stem Cells.

Modeling neurological disorders is challenging because they often have both endogenous and exogenous causes. Brain organoids consist of three-dimensional (3D) self-organizing brain tissue which increasingly is being used to model various aspects of brain development and disorders, such as the generation of neurons, neuronal migration, and functional networks. These organoids have been recognized as important tools to model developmental features of the brain, including neurological disorders, which can provide insights into the molecular mechanisms involved in those disorders.

Mine sludge waste recycling as bio-stimulant for applications in anaerobic wastewater treatment.

This study examined the applicability of two mine sludge wastes, mine tailing sludge (MTS) and acid mine drainage sludge (AMDS) as iron-rich bio-stimulant for enhancing organic matter degradation in anaerobic process. Batch treatment of domestic sewage having 343 ± 10 mg/L chemical oxygen demand (COD) using MTS and AMDS as additives mixed with septic tank sludge as anaerobic inoculum produced lower start-up time, higher efficiency of COD removal, enhanced biomass retention, and higher acidogenic and methanogenic activity after stabilization. Biostimulation induced by mine sludge waste additives in anaerobic system were observed to have correlation with percentage of iron content in the additives, as well as difference in surface charge between biomass and the additives.

Sox2 is required for olfactory pit formation and olfactory neurogenesis through BMP restriction and upregulation.

The transcription factor Sox2 is necessary to maintain pluripotency of embryonic stem cells, and to regulate neural development. Neurogenesis in the vertebrate olfactory epithelium persists from embryonic stages through adulthood. The role plays for the development of the olfactory epithelium and neurogenesis within has, however, not been determined.

Perfluorooctane sulfonate induces neuronal and oligodendrocytic differentiation in neural stem cells and alters the expression of PPARγ in vitro and in vivo.

Perfluorinated compounds are ubiquitous chemicals of major concern for their potential adverse effects on the human population. We have used primary rat embryonic neural stem cells (NSCs) to study the effects of perfluorooctane sulfonate (PFOS) on the process of NSC spontaneous differentiation. Upon removal of basic fibroblast growth factor, NSCs were exposed to nanomolar concentrations of PFOS for 48 h, and then allowed to differentiate for additional 5 days.

Inherited effects of low-dose exposure to methylmercury in neural stem cells.

Methylmercury (MeHg) is an environmental contaminant with recognized neurotoxic effects, particularly to the developing nervous system. In the present study, we show that nanomolar concentrations of MeHg can induce long-lasting effects in neural stem cells (NSCs). We investigated short-term direct and long-term inherited effects of exposure to MeHg (2.

Dickkopf 1 mediates glucocorticoid-induced changes in human neural progenitor cell proliferation and differentiation.

Glucocorticoids (GC) are critical for normal development of the fetal brain, and alterations in their levels can induce neurotoxicity with detrimental consequences. Still, there is little information available on the effects of GC on human neural stem/progenitor cells (hNPC). In the present study, we have investigated the effects of the synthetic GC dexamethasone (Dex) on hNPC grown as neurospheres, with special focus on their proliferation and differentiation capacity and the underlying molecular mechanisms.

Neural stem cells for developmental neurotoxicity studies.

The developing nervous system is particularly susceptible to toxicants, and exposure during development may result in long-lasting neurological impairments. The damage can range from subtle to severe, and it may impose substantial burdens on affected individuals, their families, and society. Given the little information available on developmental neurotoxicity (DNT) and the growing number of chemicals that need to be tested, new testing strategies and approaches are necessary to identify developmental neurotoxic agents with speed, reliability, and respect for animal welfare.

Treatment of peripartum cardiomyopathy with mechanical assist devices and cardiac transplantation.

Background: Peripartum cardiomyopathy is a life threatening illness. If maximal medical therapy fails, patients may then be treated with mechanical circulatory support devices and (or) cardiac transplantation. Our purpose is to demonstrate the long-term efficacy of these surgical interventions.

Risk factor analysis for bridge to transplantation with the CardioWest total artificial heart.

Background: Safety and efficacy studies of various mechanical circulatory support devices are important, but may not be strictly comparable. Lacking prospective randomized studies for different devices, we believe that comparison of risk factor analyses may give the surgeon a tool more powerful than current studies for matching a patient with an appropriate device. In this paper, we report risk factor profiles for bridge to transplantation with the CardioWest total artificial heart and summarize reports for other devices.

Pediatric bridge to heart transplantation: application of the Berlin Heart, Medos and Thoratec ventricular assist devices.

Background: Bridge to transplantation (BTT) is an accepted option when a donor heart is not available. Extensive clinical study has been done with BTT in the adult population, but comparatively fewer data are available in the pediatric population with regard to pulsatile devices.

Methods: Ten pediatric patients are presented, all of whom underwent BTT or recovery with pneumatic paracorporeal systems.

CardioWest total artificial heart in a moribund adolescent with left ventricular thrombi.

Bridge to transplant is a well-known strategy to enable patients with congestive heart failure to live until transplant. A 15-year-old boy with Beckers' muscular dystrophy and cardiomyopathy was accepted for heart transplantation. He suffered a cardiac arrest and was placed on extracorporeal membrane oxygenator.

Total artificial heart bridge to transplantation: a 9-year experience with 62 patients.

Background: The SynCardia CardioWest total artificial heart (CardioWest TAH) is a biventricular, orthotopic, pneumatic, pulsatile blood pump driven by an external console. For each ventricle, the length of the blood-flow path is shorter and the inflow and outflow valves are larger than in any other bridge-to-transplant device, resulting in greater blood flow at smaller pre-load. Such a device should be optimal for bridging transplant candidates who have biventricular failure and for whom all other therapies have failed.

Successful management of empyema in a patient with a total artificial heart.

A description of successful management of a patient who developed an empyema as a postoperative complication following the insertion of a CardioWest total artificial heart (TAH) as a bridge to cardiac transplantation is presented. By using traditional methods of management, the patient recovered and went on to transplant.