PCRX-201, a novel IL-1Ra gene therapy treatment approach for low back pain resulting from intervertebral disc degeneration.

Low back pain is the leading cause of global disability with intervertebral disc (IVD) degeneration a major cause. However, no current treatments target the underlying pathophysiological causes. PCRX-201 presents a novel gene therapy approach that addresses this issue.

Rare connective tissue diseases in patients with C1-inhibitor deficiency hereditary angioedema: first evidence on prevalence and distribution from a large Italian cohort study.

Introduction: In patients with Hereditary Angioedema (HAE) related to primary C1 inhibitor deficiency (C1INH), the defective clearance of immune complexes and apoptotic materials along with impairment of normal humoral response potentially leads to autoimmunity. Few studies report evidence on autoimmune diseases in C1INH-HAE, but no large population studies focus on rare connective tissue diseases (RCTDs). We aim at evaluating for the first time prevalence and distribution of RCTDs - Systemic Lupus Erytematosus (SLE), primary Sjogren Syndrome (SjS), primary antiphospholipid syndrome (APS), Systemic Sclerosis (SSc), and mixed connective tissue diseases (MCTD) in a large Italian cohort of C1INH-HAE patients.

Comorbidities in Angioedema Due to C1-Inhibitor Deficiency: An Italian Survey.

Background: Hereditary angioedema (HAE) due to C1-inhibitor (C1-INH) deficiency is characterized by unpredictable recurrent episodes of swelling affecting the skin and the mucosa tissues, including gastrointestinal tract and/or oropharyngeal-laryngeal mucosae. Long-term prophylaxis (LTP) is used to prevent attacks.

Objective: Because C1-INH plays a pivotal role in several biological pathways, we investigated the possible association of comorbidities with C1-INH deficiency and the use of LTP with attenuated androgens (AA) or tranexamic acid (TXA).

A Mixed-Methods Analysis of Speech-Language Pathologists' Executive Function Services.

Purpose: The purpose of this study was to examine school-based speech-language pathologists' (SLPs') implementation of services to address students' executive function (EF) needs, with particular emphasis on the prevalence and characteristics of EF interventions and the factors and barriers that influence service provision for students with EF needs.

Method: We applied an explanatory sequential mixed-methods research design, beginning with a quantitative survey followed by a series of qualitative interviews. We analyzed the survey results using descriptive data and binary logistic regressions and used the emergent trends to inform our interview protocol, so that we could explore those trends in greater detail and context.

The impact of puberty on the onset, frequency, location, and severity of attacks in hereditary angioedema due to C1-inhibitor deficiency: A survey from the Italian Network for Hereditary and Acquired Angioedema (ITACA).

Introduction: Hereditary angioedema due to C1-inhibitor deficiency is influenced by hormonal factors, with a more severe course of disease in women. Our study aims to deepen the impact of puberty on onset, frequency, location and severity of attacks.

Methods: Retrospective data were collected through a semi-structured questionnaire and shared by 10 Italian reference centers of the Italian Network for Hereditary and Acquired Angioedema (ITACA).

Multicentric Observational Study on Safety and Tolerability of COVID-19 Vaccines in Patients with Angioedema with C1 Inhibitor Deficiency: Data from Italian Network on Hereditary and Acquired Angioedema (ITACA).

Angioedema due to C1 inhibitor deficiency (AE-C1-INH) is a rare disease characterized by recurrent and unpredictable attacks of angioedema. Multiple trigger factors, including trauma, emotional stress, infectious diseases, and drugs, could elicit angioedema attacks. The aim of this study was to collect data on the safety and tolerability of COVID-19 vaccines in a population of patients affected by AE-C1-INH.

Speech-Language Pathology Interventions for Children With Executive Function Deficits: A Systematic Literature Review.

Purpose: The purpose of this synthesis was to systematically review the research and guidance for school-based speech-language pathologists (SLPs) who provide intervention to children with developmental executive function (EF) deficits, particularly those children with co-occurring developmental language disorder (DLD).

Method: We conducted a structured search of four major electronic databases, as well as a manual review of references and journals, which yielded 4,571 nonduplicate articles. We screened first titles and abstracts and then full texts to identify peer-reviewed articles, dissertations, and theses containing research or guidance for SLPs' interventions for children with co-occurring DLD and EF deficits; this process yielded 27 articles for analysis.

Pregnancy in women with Hereditary Angioedema due to C1-inhibitor deficiency: Results from the ITACA cohort study on outcome of mothers and children with exposure to plasma-derived C1-inhibitor.

Background: In women with Hereditary Angioedema (HAE) due to C1-inhibitor (C1INH) deficiency (C1INH-HAE), pregnancy counseling and treatment can be challenging. Despite the evidence of the immediate favorable outcome and safety of plasma-derived (pd)C1INH concentrate, there are no data regarding any difference among women who underwent or not pdC1INH during pregnancy or on children with exposure to pdC1INH. The present interview study aimed at analyzing outcome of C1INH-HAE mothers and children according to pdC1INH-exposure during pregnancies.

Differential activity of mGlu allosteric modulators provides evidence for mGlu heterodimers at hippocampal Schaffer collateral-CA1 synapses.

Glutamate acts at eight metabotropic glutamate (mGlu) receptor subtypes expressed in a partially overlapping fashion in distinct brain circuits. Recent evidence indicates that specific mGlu receptor protomers can heterodimerize and that these heterodimers can exhibit different pharmacology when compared to their homodimeric counterparts. Group III mGlu agonist-induced suppression of evoked excitatory potentials and induction of long-term potentiation at Schaffer collateral-CA1 (SC-CA1) synapses in the rodent hippocampus can be blocked by the selective mGlu negative allosteric modulator (NAM), ADX71743.

Transactions between Problem Behaviors and Academic Performance in Early Childhood.

This study aimed to further the understanding of transactional relationships that exist between problem behaviors and academic performance in early childhood. Early academic and behavior difficulties increase the risk of school disengagement, academic failure, and dropout. Although children's academic and behavioral difficulties have been shown to be intercorrelated, little research has focused on how the relationship reciprocates and progresses in early childhood.

A Systematic Review and Meta-Analysis of the Language Skills of Youth Offenders.

Purpose: This systematic review and meta-analysis estimates the overall language skills of youth offenders involved with the juvenile justice system. Given the importance of this population, identifying avenues through which we can increase the likelihood of successful interventions is a necessary societal effort.

Method: Eighteen studies, representing data from 3,304 individuals, contributed 82 effect sizes to the current analytic sample.

Efficacy and Safety of FX201, a Novel Intra-Articular IL-1Ra Gene Therapy for Osteoarthritis Treatment, in a Rat Model.

Osteoarthritis (OA) is a disabling, degenerative disease characterized by progressive cartilage and bone damage. There remains a need for local therapies that, following a single injection, can provide long-term pain relief and functional improvement and potentially delay disease progression. FX201 is a novel, intra-articular (IA), interleukin-1 receptor antagonist (IL-1Ra) gene therapy in development for the treatment of OA.

mGluR5 Negative Modulators for Fragile X: Treatment Resistance and Persistence.

Fragile X syndrome (FXS) is caused by silencing of the human gene and is the leading monogenic cause of intellectual disability and autism. Abundant preclinical data indicated that negative allosteric modulators (NAMs) of metabotropic glutamate receptor 5 (mGluR5) might be efficacious in treating FXS in humans. Initial attempts to translate these findings in clinical trials have failed, but these failures provide the opportunity for new discoveries that will improve future trials.

Psychological processes in the experience of hereditary angioedema in adult patients: an observational study.

Background: Hereditary angioedema associated to C1 inhibitor deficiency (C1-INH-HAE) is a pathological condition characterized by episodes of subcutaneous swelling and it is frequently associated with discomfort and social impairment of the patients, due to the anxiety experienced for an unpreventable manifestation of an attack during daily life. In children increased level of stress and alexithymia have been associated to C1-INH-HAE, and the latter correlated also with the severity of the disease. We hypothesized that the involvement of psychological issues may impact on the severity of C1-INH-HAE in adult patients as well, interfering with their ability to engage with the management of the disease.

The experience of living with a chronic disease in pediatrics from the mothers' narratives: The Clinical Interview on Parental Sense of Grip on the Disease.

The Clinical Interview on the Sense of Grip on Chronic Disease has been administered to 68 mothers of children affected by Hereditary Angioedema (C1-Inh HAE), Type 1 Diabetes (T1D), Juvenile Rheumatoid Arthritis (JRA). The objectives are to detect general features of the experience of parenting children with chronic illness as well as the specificities of this experience related to the different conditions. Four Profiles of Sense of Grip were identified: Adempitive, Controlling, Reactive, Dynamic.

Tailoring Effective Behavior Management Strategies for Speech-Language Pathologists.

Purpose Many speech-language pathologists (SLPs) experience challenging behaviors during service delivery and also report minimal training in effective behavior management strategies. The purpose of this tutorial is to present low-effort behavior management strategies that SLPs can adopt, adapt, and implement. Method After providing an overall rationale for effective behavior management strategies, we present two evidence-based behavior management strategies aimed at improving positive behavior and engagement.

Selective inhibition of glycogen synthase kinase 3α corrects pathophysiology in a mouse model of fragile X syndrome.

Fragile X syndrome is caused by gene silencing and loss of the encoded fragile X mental retardation protein (FMRP), which binds to mRNA and regulates translation. Studies in the mouse model of fragile X syndrome indicate that aberrant cerebral protein synthesis downstream of metabotropic glutamate receptor 5 (mGluR5) signaling contributes to disease pathogenesis, but clinical trials using mGluR5 inhibitors were not successful. Animal studies suggested that treatment with lithium might be an alternative approach.

The central role of endothelium in hereditary angioedema due to C1 inhibitor deficiency.

An impairment of the endothelial barrier function underlies a wide spectrum of pathological conditions. Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) can be considered the "pathophysiological and clinical paradigm" of Paroxysmal Permeability Diseases (PPDs), conditions characterized by recurrent transient primitively functional alteration of the endothelial sieving properties, not due to inflammatory-ischemic-degenerative injury and completely reversible after the acute flare. It is a rare yet probably still underdiagnosed disease which presents with localized, non-pitting swelling of the skin and submucosal tissues of the upper respiratory and gastrointestinal tracts, without significant wheals or pruritus.

Pediatric angioedema: Essential features and preliminary results from the Hereditary Angioedema Global Registry in Italy.

Isolated angioedema, which is a localized, non-pitting, and transient swelling of the subcutaneous or submucosal tissue not associated with pruritus, urticaria, or anaphylaxis, may be classified, based on genetic pattern and mediators, respectively, as acquired or hereditary and histamine- or non-histamine-induced. The pediatric population with C1-INH-HAE (Hereditary angioedema due to C1-inhibitor deficiency) is mostly symptomatic. The frequency of symptoms in such a population compared to adults seems to be lower, but we need more prospective data to conclude on this point.

Lanadelumab for the prevention of attacks in hereditary angioedema.

: Hereditary angioedema (HAE) with C1 esterase inhibitor deficiency (C1-INH-HAE) is a rare disease that manifests with cutaneous and/or submucosal swellings due to uncontrolled activation of the contact/kinin system. Attacks recur with unpredictable frequency and severity, laryngeal edema is potentially lethal, and the disease burden may severely disrupt patients' lives.: This review provides an overview of lanadelumab, a human monoclonal antibody targeted against plasma kallikrein that was recently approved for prevention of symptoms in C1-INH-HAE.

Lanadelumab Injection Treatment For The Prevention Of Hereditary Angioedema (HAE): Design, Development And Place In Therapy.

Despite the efficacy of the on-demand treatment for the control of acute attacks of Hereditary Angioedema due to C1-Inhibitor Deficiency (C1-INH-HAE), the number and severity of attacks and the impairment in the quality of life of the affected patients have led to the development of a new monoclonal antibody, lanadelumab, directly addressed to the blockage of bradykinin, the principal mediator of vasodilation during angioedema attacks. It is indicated for the prophylactic treatment, it is easy to administer, highly effective and with known limited side effects. The current review summarizes the development of the drug, its clinical background and its perspectives.

Melkersson-Rosenthal syndrome: a case report of a rare disease with overlapping features.

Background: Melkersson-Rosenthal syndrome (MRS) is a rare, neuro-mucocutaneous disease which presents as orofacial swelling, facial palsy and fissured tongue. These symptoms may occur simultaneously or, more frequently, with a oligosymptomatic or monosymptomatic pattern. Swelling, that is the most common initial finding, may mimic hereditary or acquired angioedema, a disorder caused by histamine or bradykinin-mediated plasma-leakage affecting subcutaneous and/or submucosal tissue.