Clinical Profile, Trends, and Management in Pediatric Patients with Audiovestibular Disorders: Can We Predict Emotional Disability in Pediatric Patients with Episodes of Vertigo and Dizziness?

Background: Audiovestibular disorders in childhood occur with considerable frequency. However, the difficulty of obtaining medical history, the nonspecificity of symptoms, and the lack of cooperation during complementary tests often contribute significantly to diagnostic biases, attributing clinical presentations to psychosomatic disorders. The objectives of this work are, firstly, to characterize, from an auditory and vestibular perspective, the most frequent causes of vertigo in childhood and a possible relationship with emotional symptoms.

Impact of prenatal THC exposure on lipid metabolism and microbiota composition in rat offspring.

Objective: Recent studies have demonstrated that prenatal exposure to the psychoactive ingredient of cannabis that is tetrahydrocannabinol (THC) disrupts fatty acid (FA) signaling pathways in the developing brain, potentially linking to psychopathologic consequences. Our research aims to investigate whether changes in midbrain FA metabolism are linked to modifications in peripheral metabolism of FAs and shifts in microbiota composition.

Methods: In order to model prenatal exposure to THC (PTE) in rats, Sprague Dawley dams were systemically administered with THC (2 mg/kg, s.

Maternal immune activation impairs endocannabinoid signaling in the mesolimbic system of adolescent male offspring.

Prenatal infections can increase the risk of developing psychiatric disorders such as schizophrenia in the offspring, especially when combined with other postnatal insults. Here, we tested, in a rat model of prenatal immune challenge by the viral mimic polyriboinosinic-polyribocytidilic acid, whether maternal immune activation (MIA) affects the endocannabinoid system and endocannabinoid-mediated modulation of dopamine functions. Experiments were performed during adolescence to assess i) the behavioral endophenotype (locomotor activity, plus maze, prepulse inhibition of startle reflex); ii) the locomotor activity in response to Δ9-Tetrahydrocannabinol (THC) and iii) the properties of ventral tegmental area (VTA) dopamine neurons in vivo and their response to THC; iv) endocannabinoid-mediated synaptic plasticity in VTA dopamine neurons; v) the expression of cannabinoid receptors and enzymes involved in endocannabinoid synthesis and catabolism in mesolimbic structures and vi) MIA-induced neuroinflammatory scenario evaluated by measurements of levels of cytokine and neuroinflammation markers.

COR758, a negative allosteric modulator of GABA receptors.

Allosteric modulators of G protein coupled receptors (GPCRs), including GABARs (GABARs), are promising therapeutic candidates. While several positive allosteric modulators (PAM) of GABARs have been characterized, only recently the first negative allosteric modulator (NAM) has been described. In the present study, we report the characterization of COR758, which acts as GABAR NAM in rat cortical membranes and CHO cells stably expressing GABARs (CHO-GABA).

Prenatal THC Does Not Affect Female Mesolimbic Dopaminergic System in Preadolescent Rats.

Cannabis use among pregnant women is increasing worldwide along with permissive sociocultural attitudes toward it. Prenatal cannabis exposure (PCE), however, is associated with adverse outcome among offspring, ranging from reduced birth weight to child psychopathology. We have previously shown that male rat offspring prenatally exposed to Δ9-tetrahydrocannabinol (THC), a rat model of PCE, exhibit extensive molecular, cellular, and synaptic changes in dopamine neurons of the ventral tegmental area (VTA), resulting in a susceptible mesolimbic dopamine system associated with a psychotic-like endophenotype.

Mesolimbic dopamine dysregulation as a signature of information processing deficits imposed by prenatal THC exposure.

Cannabis is the illicit drug most widely used by pregnant women worldwide. Its growing acceptance and legalization have markedly increased the risks of child psychopathology, including psychotic-like experiences, which lowers the age of onset for a first psychotic episode. As the majority of patients with schizophrenia go through a premorbid condition long before this occurs, understanding neurobiological underpinnings of the prodromal stage of the disease is critical to improving illness trajectories and therapeutic outcomes.

Mobile Health in Adherence to Oral Anticancer Drugs: A Scoping Review.

In oncology, adherence to oral antineoplastic medication is a key element of treatment, on which the success of any therapeutic intervention depends. Given their widespread use in clinical practice, it is important to identify tools that can facilitate the monitoring and self-management of the patient at home, to avoid the consequences of employing ineffective treatment. One of the tools available today to take action on this phenomenon is mobile health technology.

Prenatal THC exposure produces a hyperdopaminergic phenotype rescued by pregnenolone.

The increased legal availability of cannabis has led to a common misconception that it is a safe natural remedy for, among others, pregnancy-related ailments such as morning sickness. Emerging clinical evidence, however, indicates that prenatal cannabis exposure (PCE) predisposes offspring to various neuropsychiatric disorders linked to aberrant dopaminergic function. Yet, our knowledge of how cannabis exposure affects the maturation of this neuromodulatory system remains limited.

Qualitative study of patients with metastatic prostate cancer to adherence of hormone therapy.

Purpose: To explore adherence to oral hormone treatment in patients with metastatic prostate cancer (mCRPC) and to identify the factors that influence it.

Methods: A qualitative exploratory study was conducted at the National Cancer Institute of Rome. Patients aged >18 years with castration-resistant prostate cancer (mCRPC) and who were using oral hormone drugs were recruited.

Changes in stress-stimulated allopregnanolone levels induced by neonatal estradiol treatment are associated with enhanced dopamine release in adult female rats: reversal by progesterone administration.

Background: Allopregnanolone plays a role in the stress response and homeostasis. Alterations in the estrogen milieu during the perinatal period influence brain development in a manner that persists into adulthood. Accordingly, we showed that a single administration of estradiol benzoate (EB) on the day of birth decreases brain allopregnanolone concentrations in adult female rats.

OTX2 regulates the expression of TAp63 leading to macular and cochlear neuroepithelium development.

OTX proteins, homologs of the Drosophila orthodenticle (Otd), are important for the morphogenesis of the neuroectoderm, and for the central nervous system formation. OTX1 and OTX2 are important for the cochlea and macula development, indeed when OTX1 is knocked down, these organs undergo developmental failure. Moreover OTX2 transfection revert this effect in OTX1(-/-) mice.

The E3 ligase Itch knockout mice show hyperproliferation and wound healing alteration.

The HECT-type E3 ubiquitin ligase Itch is absent in the non-agouti-lethal 18H or Itchy mice, which develop a severe immunological disease. Several of the known Itch substrates are relevant for epidermal development and homeostasis, such as p63, Notch, c-Jun and JunB. By analysing Itchy mice before the onset of immunological alterations, we investigated the contribution of Itch in skin development and wound healing.

Role of p63 and the Notch pathway in cochlea development and sensorineural deafness.

The ectodermal dysplasias are a group of inherited autosomal dominant syndromes associated with heterozygous mutations in the Tumor Protein p63 (TRP63) gene. Here we show that, in addition to their epidermal pathology, a proportion of these patients have distinct levels of deafness. Accordingly, p63 null mouse embryos show marked cochlea abnormalities, and the transactivating isoform of p63 (TAp63) protein is normally found in the organ of Corti.

Exogenous nef induces proinflammatory signaling events in murine macrophages.

Despite the fact that murine cells are not permissive for human immunodeficiency virus type 1 (HIV-1) infection, several investigators have constructed transgenic (Tg) mice to model HIV-1-induced diseases to overcome this restriction. The generation of Tg mice expressing selected HIV-1 genes revealed that Nef harbors a major disease determinant. HIV-1 Nef protein is a molecular adapter able to interact with several cellular partners, interfering with cellular functions.

Functional characterization of a novel TP63 mutation in a family with overlapping features of Rapp-Hodgkin/AEC/ADULT syndromes.

Heterozygous mutations in TP63 cause a wide spectrum of autosomal dominant developmental disorders variably affecting skin, limbs, and face. TP63 encodes p63, a protein expressed in two main isoforms (Tap63 and ΔNp63) with critical roles in both cell differentiation and development. Some analyses suggest a relationship of the mutation site to the observed clinical picture, although this link is inconsistent.

Differential altered stability and transcriptional activity of ΔNp63 mutants in distinct ectodermal dysplasias.

Heterozygous mutations of p63, a key transcription factor in epithelial development, are causative in a variety of human ectodermal dysplasia disorders. Although the mutation spectrum of these disorders displays a striking genotype-phenotype association, the molecular basis for this association is only superficially known. Here, we characterize the transcriptional activity and protein stability of ΔNp63 mutants (that is, mutants of a p63 isoform that lacks the N-terminal transactivation domain) that are found in ectrodactyly-ectodermal dysplasia-cleft syndrome (EEC), ankyloblepharon-ectodermal dysplasia-clefting syndrome (AEC) and nonsyndromic split-hand/split-foot malformation (SHFM).

The mammary gland and the homeobox gene Otx1.

The mammary gland, the unique organ that primarily form at puberty, is an ideal model to study the functions of homeobox (HB) genes in both development and tumorigenesis. HB genes comprise a large family of developmental regulators that have a critical role in cell growth and differentiation. In the normal mammary gland, homeobox genes are involved in ductal formation, epithelial branching, and lobulo-alveolar development by regulating epithelial proliferation and differentiation.

Connexin 26 (GJB2) mutations as a cause of the KID syndrome with hearing loss.

KID syndrome (MIM 148210) is an ectodermal dysplasia characterized by the occurrence of localized erythematous scaly skin lesions, keratitis and severe bilateral sensorineural deafness. KID syndrome is inherited as an autosomic dominant disease, due to mutations in the gene encoding gap junction protein GJB2 (connexin 26, Cx26). Cx26 is a component of gap junction channels in the epidermis and in the stria vascularis of the cochlea.

Connexin 26 (GJB2) mutations, causing KID Syndrome, are associated with cell death due to calcium gating deregulation.

The autosomic dominant KID Syndrome (MIM 148210), due to mutations in GJB2 (connexin 26, Cx26), is an ectodermal dysplasia with erythematous scaly skin lesions, keratitis and severe bilateral sensorineural deafness. The Cx26 protein is a component of gap junction channels in epithelia, including the cochlea, which coordinates the exchange of molecules and ions. Here, we demonstrate that different Cx26 mutants (Cx26D50N and Cx26G11E) cause cell death in vitro by the alteration of intra-cellular calcium concentrations.

Knuckle pads, in an epidermal palmoplantar keratoderma patient with Keratin 9 R163W transgrediens expression.

Epidermolytic PalmoPlantar keratoderma (EPPK) Vörner-type is an autosomal dominantly inherited skin disease, characterized by severe thickening of the palms and soles, caused by mutations in the keratin K9 (KRT9) gene. To date, a number of KRT9 mutations have been detected, most of which affect the highly conserved 1A region of the central alpha-helical domain, important for keratin heterodimerization. The most common mutation is the substitution of the arginine in position 163 with a tryptophan (R163W), which has been reported in North American, European, and Japanese populations.