Novel MYH10 heterozygous variants associated to a syndrome combining mainly ptosis and ocular coloboma expand the MYH10 related phenotypes.

Syndromes associating both eyeball and periocular developmental anomalies, combining iris chorioretinal (ocular) coloboma and ptosis, are described in very rare clinical entities such as Baraitser-Winter cerebrofrontofacial syndrome (BWCFF). We report on six individuals from 3 unrelated families presenting with autosomal dominant eye malformations, including ocular coloboma, ptosis and craniofacial features suggesting BWCFF. However, no neurodevelopmental disorders (NDD) as usually observed in this syndrome were detected.

Animal models of chronic obstructive pulmonary disease and their role in drug discovery and development: a critical review.

Introduction: The use of laboratory animals is essential to understand the mechanisms underlying COPD and to discover and evaluate new drugs. However, the complex changes associated with the disease in humans are difficult to fully replicate in animal models.

Areas Covered: This review examines the most recent literature on animal models of COPD and their implications for drug discovery and development.

Late Hepatocellular Carcinoma Occurrence in Patients Achieving Sustained Virological Response After Direct-Acting Antiviral Therapy: A Matter of Follow-Up or Something Else?

: Despite achieving a sustained virological response (SVR) with direct-acting antivirals (DAAs), an unexpected increase in the occurrence rate of hepatocellular carcinoma (HCC) has been observed among HCV-treated patients. This study aims to assess the long-term follow-up of HCV patients treated with DAAs who achieved an SVR to investigate the potential for late-onset HCC. : In this prospective multicenter study, we enrolled consecutive HCV patients treated with DAAs following Italian ministerial guidelines between 2015 and 2018.

Biallelic NEXN variants and fetal onset dilated cardiomyopathy: two independent case reports and revision of literature.

Background: Dilated cardiomyopathy (DCM) is an etiologically heterogeneous group of diseases of the myocardium. With the rapid evolution in laboratory investigations, genetic background is increasingly determined including many genes with variable penetrance and expressivity. Biallelic NEXN variants are rare in humans and associated with poor prognosis: fetal and perinatal death or severe DCMs in infants.

The pharmacological management of asthma in adults: 2023 update.

Introduction: The pharmacotherapy of asthma is a dynamic process that changes as our knowledge of the underlying pathophysiology and treatment of this disease continues to evolve. This implies the need for continuous revision of the recommendations of asthma guidelines and strategies.

Areas Covered: This review summarizes the latest key practical information on the pharmacological management of asthma in adults.

The effect of combining an inhaled corticosteroid and a long-acting muscarinic antagonist on human airway epithelial cells in vitro.

Background: Airway epithelial cells (AECs) are a major component of local airway immune responses. Direct effects of type 2 cytokines on AECs are implicated in type 2 asthma, which is driven by epithelial-derived cytokines and leads to airway obstruction. However, evidence suggests that restoring epithelial health may attenuate asthmatic features.

Low-grade parental gonosomal mosaicism in CHD2 siblings with Smith-Magenis-like syndrome.

Loss-of-function CHD2 (chromodomain helicase DNA-binding protein 2) mutations are associated with a spectrum of neurodevelopmental disorders often including early-onset generalized seizures, photosensitivity, and epileptic encephalopathies. Patients show psychomotor delay/intellectual disability (ID), autistic features, and behavior disorders, such as aggression and impulsivity. Most reported cases are sporadic with description of germline mosaicism only in two families.

Breast density in NF1 women: a retrospective study.

Neurofibromatosis type 1 (NF1) is an autosomal dominant condition caused by neurofibromin haploinsufficiency due to pathogenic variants in the NF1 gene. Tumor predisposition has long been associated with NF1, and an increased breast cancer (BC) incidence and reduced survival have been reported in recent years for women with NF1. As breast density is another known independent risk factor for BC, this study aims to evaluate the variability of breast density in patients with NF1 compared to the general population.

Gain-of-function and loss-of-function variants in GRIA3 lead to distinct neurodevelopmental phenotypes.

AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors (AMPARs) mediate fast excitatory neurotransmission in the brain. AMPARs form by homo- or heteromeric assembly of subunits encoded by the GRIA1-GRIA4 genes, of which only GRIA3 is X-chromosomal. Increasing numbers of GRIA3 missense variants are reported in patients with neurodevelopmental disorders (NDD), but only a few have been examined functionally.

Advances in adrenergic receptors for the treatment of chronic obstructive pulmonary disease: 2023 update.

Introduction: Strong scientific evidence and large experience support the use of β-agonists for the symptomatic alleviation of COPD. Therefore, there is considerable effort in discovering highly potent and selective β-agonists.

Areas Covered: Recent research on novel β-agonists for the treatment of COPD.

Is it preferable to administer a bronchodilator once- or twice-daily when treating COPD?

Nocturnal and early morning symptoms are common and uncomfortable in many patients with COPD, and are likely to affect their long-term outcomes. However, it is still debated whether it is better to give long-acting bronchodilators once- or twice-daily to symptomatic COPD patients. The functional link between circadian rhythms of autonomic tone and airway calibre explains why the timing of administration of bronchodilators in chronic airway diseases can induce different effects when taken at different biological (circadian) times.

Strategies for overcoming the biological barriers associated with the administration of inhaled monoclonal antibodies for lung diseases.

Introduction: Monoclonal antibodies (mAbs) should be administered by inhalation rather than parenterally to improve their efficiency in lung diseases. However, the pulmonary administration of mAbs in terms of aerosol technology and the formulation for inhalation is difficult.

Areas Covered: The feasible or suitable strategies for overcoming the barriers associated with administering mAbs are described.

Ocular features in Williams-Beuren syndrome: a review of the literature.

Purpose Of Review: The current review will discuss the pathophysiology, work-up and clinical relevance of the ocular phenotype in Williams-Beuren syndrome in detail.

Recent Findings: Few case reports, case series and retrospective studies reported the ophthalmic features in Williams-Beuren syndrome, focusing on specific aspects of the ocular involvement. Recently, novel retinal findings have been described in association with the disease.

Pharmacokinetic considerations surrounding triple therapy for uncontrolled asthma.

Introduction: Solid pharmacological rationale and clinical evidence support the use of a combination of an inhaled corticosteroid (ICS), a long-acting β-agonist, and a long-acting muscarinic antagonist in severe asthma, which clinically results in increased lung function, improved symptoms, and decreased exacerbation rates.

Areas Covered: We examined the pharmacokinetic issues associated with triple therapy for uncontrolled asthma. We considered the pharmacokinetic characteristics of the three drug classes, the role of inhalers in influencing their pharmacokinetic behavior, and the impact of severe asthma on the pharmacokinetics of inhaled drugs.

The long-term exercise after traumatic brain injury: Reharmonizing brain by sound body.

Traumatic brain injuries (TBI) refer to multiple acquired dysfunctions arising from damage to the brain caused by an external force, including rapid acceleration/deceleration and concussion. Among them, mild TBI (mTBI) accounts for most cases (up to 90%) of injuries. It is responsible for a variety of symptoms, including anxiety, depression, and cognitive impairments that remain difficult to be treated.

Early pathological changes of peri-coronal tissue in the distal area of erupted or partially impacted lower third molars.

Aim: This study was performed to histologically evaluate peri-coronal tissues of partially impacted and erupted third molars that did not exhibit pathologic peri-coronal radiolucency.

Materials And Methods: Healthy patients with erupted or partially erupted (with part or all of the dental crown present in the oral cavity) mandibular third molars (classified as IA and IIA according to the Pell and Gregory classification) and vertically positioned (according to the Winter classification or erupted third molars) associated with peri coronal radiolucency of equal to or less than 2.5 mm.

SMARCE1-related meningiomas: A clear example of cancer predisposing syndrome.

We report the case of a 16-year-old girl presenting with spinal clear-cell multiple meningiomas (CCMs). In view of this presentation, we sequenced a bioinformatic panel of genes associated with susceptibility to meningioma, identifying a germline heterozygous variant in SMARCE1. Somatic DNA investigations in the CCM demonstrated the deletion of the wild-type allele (loss of heterozygosity, LOH), supporting the causative role of this variant.

Identification of bi-allelic LFNG variants in three patients and further clinical and molecular refinement of spondylocostal dysostosis 3.

Spondylocostal dysostosis (SCD), a condition characterized by multiple segmentation defects of the vertebrae and rib malformations, is caused by bi-allelic variants in one of the genes involved in the Notch signaling pathway that tunes the "segmentation clock" of somitogenesis: DLL3, HES7, LFNG, MESP2, RIPPLY2, and TBX6. To date, seven individuals with LFNG variants have been reported in the literature. In this study we describe two newborns and one fetus with SCD, who were found by trio-based exome sequencing (trio-ES) to carry homozygous (c.

Comparative study of the anaesthetic efficacy of 4% articaine versus 2% mepivacaine in mandibular third molar germectomy using different anaesthetic techniques: a split-mouth clinical trial.

Background: Currently, one of the most discouraging aspects for many patients undergoing dental procedures is the administration of local anaesthesia. Therefore, there is a constant search for new techniques to avoid the invasive and painful nature of the injection. This study aimed to compare the clinical efficacy of local anaesthetics with articaine 4% or mepivacaine 2% (both with epinephrine 1:100.

Chung-Jansen syndrome can mimic Cornelia de Lange syndrome: Another player among chromatinopathies?

Cornelia de Lange syndrome (CdLS) is a rare multisystem congenital neurodevelopmental disorder (NDD) characterized by distinctive facial anomalies, short stature, developmental delay, hirsutism, gastrointestinal abnormalities and upper limb reduction defects. CdLS syndrome is associated with causative variants in genes encoding for the cohesin complex, a cellular machinery involved in chromatid pairing, DNA repair and gene-expression regulation. In this report, we describe a familial case of a syndromic presentation in a 4-year-old patient (P1) and in his mother (P2).