Impact of age, race, and medication use on efficacy endpoints in a randomized controlled trial of topical sildenafil cream for the treatment of female sexual arousal disorder.

Background: A study of topical Sildenafil Cream 3.6% was completed among healthy premenopausal women with female sexual arousal disorder.

Aims: To compare efficacy endpoints based on product use in pre-planned and post-hoc subsets of age, race, and medication use.

mTORC1 signaling and diabetic kidney disease.

Diabetic kidney disease (DKD) represents the most lethal complication in both type 1 and type 2 diabetes. The disease progresses without obvious symptoms and is often refractory when apparent symptoms have emerged. Although the molecular mechanisms underlying the onset/progression of DKD have been extensively studied, only a few effective therapies are currently available.

IL-13 induces loss of CFTR in ionocytes and reduces airway epithelial fluid absorption.

The airway surface liquid (ASL) plays a crucial role in lung defense mechanisms, and its composition and volume are regulated by the airway epithelium. The cystic fibrosis transmembrane conductance regulator (CFTR) is abundantly expressed in a rare airway epithelial cell type called an ionocyte. Recently, we demonstrated that ionocytes can increase liquid absorption through apical CFTR and basolateral barttin/chloride channels, while airway secretory cells mediate liquid secretion through apical CFTR channels and basolateral NKCC1 transporters.

Specific EEG resting state biomarkers in FXS and ASD.

Background: Fragile X syndrome (FXS) and autism spectrum disorder (ASD) are neurodevelopmental conditions that often have a substantial impact on daily functioning and quality of life. FXS is the most common cause of inherited intellectual disability (ID) and the most common monogenetic cause of ASD. Previous literature has shown that electrophysiological activity measured by electroencephalogram (EEG) during resting state is perturbated in FXS and ASD.

Short-term and Long-term Stability of the Autism Diagnostic Observation Schedule (ADOS-2) Calibrated Comparison Scores (CCS) and Classification Scores in Youth with Down Syndrome or Fragile X Syndrome with Intellectual Disability.

Autism diagnosis in individuals with fragile X syndrome (FXS) or Down syndrome (DS) with co-occurring intellectual disability is complex since clinicians often must consider other co-occurring behavioral features. Understanding how best to assess the features of autism in individuals with these conditions is crucial. In this study, we consider the short-term and long-term psychometric consistency of the Autism Diagnostic Observation Schedule-2 (ADOS-2) calibrated comparison scores (CCSs) and ASD classifications in individuals with FXS or DS.

Description and predictors of self-determination in males and females with fragile X syndrome on the verge of adulthood.

Background: Self-determination refers to setting goals and making decisions regarding one's own life with support from others as needed. Research on people with intellectual and developmental disabilities has established the importance of self-determination for quality of life outcomes, such as increased independence and life satisfaction. However, self-determination has not been characterised specifically in fragile X syndrome (FXS), the leading inherited cause of intellectual disability.

Laboratory-based measures of executive function and daily living skills in young children with Down syndrome: informing future interventions.

Background: Adaptive behaviour refers to the practical skills necessary for independence and is considered a high-priority intervention target for children with neurogenetic conditions associated with intellectual disability, like Down syndrome (DS). Daily living skills (DLS) are a critical aspect of adaptive behaviour, but they have received little intervention attention, possibly because they involve a wide variety of skills across many settings. The present study aimed to advance DLS intervention science by examining the concurrent and longitudinal association between DLS performances and a cognitive skillset hypothesised to support DLS skill acquisition, executive function (EF).

Safety of topical sildenafil cream, 3.6% in a randomized, placebo-controlled trial for the treatment of female sexual arousal disorder.

Background: There are currently no Food and Drug Administration-approved treatments for female sexual arousal disorder (FSAD), which is physiologically analogous to male erectile dysfunction.

Aims: The study sought to test the systemic and local genital safety of topical sildenafil cream, 3.6% (sildenafil cream) among healthy premenopausal women with FSAD and their sexual partners over a 12-week treatment period.

IL-13 decreases susceptibility to airway epithelial SARS-CoV-2 infection but increases disease severity in vivo.

Treatments available to prevent progression of virus-induced lung diseases, including coronavirus disease 2019 (COVID-19) are of limited benefit once respiratory failure occurs. The efficacy of approved and emerging cytokine signaling-modulating antibodies is variable and is affected by disease course and patient-specific inflammation patterns. Therefore, understanding the role of inflammation on the viral infectious cycle is critical for effective use of cytokine-modulating agents.

Longitudinal follow-up of metformin treatment in Fragile X Syndrome.

Introduction: Metformin has been used as a targeted treatment to potentially improve cognition and slow the typical IQ decline that occurs during development among individuals with fragile X syndrome (FXS). In this follow-up study, we are following the trajectory of IQ and adaptive behavior changes over 1 to 3 years in individuals with FXS who are clinically treated with metformin in an open label trial.

Method: Individuals with FXS ages 6 to 25 years (mean 13.

Preliminary Efficacy of Topical Sildenafil Cream for the Treatment of Female Sexual Arousal Disorder: A Randomized Controlled Trial.

Objective: To assess the efficacy of topical sildenafil cream, 3.6% among healthy premenopausal women with female sexual arousal disorder.

Methods: We conducted a phase 2b, exploratory, randomized, placebo-controlled, double-blind study of sildenafil cream.

Epithelial responses to CFTR modulators are improved by inflammatory cytokines and impaired by antiinflammatory drugs.

Cystic fibrosis (CF) is a genetic disorder that disrupts CF transmembrane conductance regulator (CFTR) anion channels and impairs airway host defenses. Airway inflammation is ubiquitous in CF, and suppressing it has generally been considered to improve outcomes. However, the role of inflammation in people taking CFTR modulators, small-molecule drugs that restore CFTR function, is not well understood.

Long-COVID improves in 50% of patients after a year in a Midwestern cohort.

Background: Many of those infected with COVID-19 experience long-term disability due to persistent symptoms known as Long-COVID, which include ongoing respiratory issues, loss of taste and smell, and impaired daily functioning.

Research Question: This study aims to better understand the chronology of long-COVID symptoms.

Study Design And Methods: We prospectively enrolled 403 adults from the University of Iowa long-COVID clinic (June 2020 to February 2022).

Safety testing of Ovaprene: An investigational nonhormonal monthly vaginal contraceptive.

Objectives: Evaluate the safety of Ovaprene, an investigational nonhormonal vaginal contraceptive designed for monthly use.

Study Design: Open-label, multicenter study enrolling heterosexually-active women with previous permanent contraception who underwent assessments during five menstrual cycles: baseline postcoital test cycle, diaphragm postcoital test cycle, Ovaprene safety cycle, and two Ovaprene postcoital test cycles. Safety outcomes included treatment-emergent adverse events, systemic laboratory findings, pelvic examinations, colposcopies, Nugent scores, determination of community state types of vaginal microbiota, and anti-Escherichia coli activity and inflammatory markers in cervicovaginal fluids.

Eosinophil expression of triggering receptor expressed on myeloid cells 1 (TREM-1) restricts type 2 lung inflammation.

Asthma affects 25 million Americans, and recent advances in treatment are effective for only a portion of severe asthma patients. TREM-1, an innate receptor that canonically amplifies inflammatory signaling in neutrophils and monocytes, plays a central role in regulating lung inflammation. It is unknown how TREM-1 contributes to allergic asthma pathology.

SAS: Split antibiotic selection for identifying chaperones that improve protein solubility.

Background: Heterologous expression of active, native-folded protein in is critical in both academic research and biotechnology settings. When expressing non-native recombinant proteins in , obtaining soluble and active protein can be challenging. Numerous techniques can be used to enhance a proteins solubility, and largely focus on either altering the expression strain, plasmid vector features, growth conditions, or the protein coding sequence itself.

Characterising the social interaction style of autism in young adult males with fragile X syndrome.

Background: The characterisation of autism in fragile X syndrome (FXS) has been a source of controversy due to the complexity of disentangling autism traits from common features of the FXS phenotype. Autism in FXS is significantly underdiagnosed in the community, which may be partly due to insufficient clinical description of the social interaction profile of autism within the FXS phenotype. In this study, we applied a classic framework for characterising social interaction styles in autism to a sample of young adult males with FXS and co-occurring autism to enhance understanding of how the social challenges associated with autism manifest within FXS.

Successful postcoital testing of Ovaprene: An investigational non-hormonal monthly vaginal contraceptive.

Objective: Evaluate reduction in progressively motile sperm per high power field (HPF) in midcycle cervical mucus after intercourse with Ovaprene: an investigational monthly non-hormonal vaginal contraceptive consisting of a vaginal ring and mechanical barrier, releasing spermiostatic ferrous gluconate.

Study Design: Open-label, multicenter study enrolling heterosexually-active women with previous permanent contraception. Participants underwent a baseline postcoital test cycle with no device to confirm the presence of sperm, followed by one diaphragm postcoital test cycle, one Ovaprene safety cycle, and two Ovaprene postcoital test cycles.

Increased ENaC-mediated liquid absorption across vitamin-D deficient human airway epithelia.

Vitamin D deficiency is a risk factor for exacerbation of obstructive airway disease, a hallmark of which is mucus dehydration and plugging. Calcitriol (the active form of vitamin D) deficiency in cultured human airway epithelia resulted in increased and mRNAs encoding subunits of ENaC and the Na-K pump compared with supplemented epithelia. These drive the absorption of airway surface liquid.

Preliminary psychometric properties of an inhibition task in young children with Down syndrome.

Executive function (EF) skills are important treatment targets for people with Down syndrome (DS); however, few EF measures have been evaluated for use with young children in this population. : The present study evaluated preliminary psychometric properties of a measure of the EF component of inhibition. Participants were 73 children with DS between 2.