Successful use of guanfacine in a patient with chronic refractory cough: A case report

Chronic idiopathic cough is a common and often frustrating complaint for patients as well as providers. When common etiologies of cough are ruled out and/or do not respond to usual treatments, neurogenic cough should be considered as a diagnosis of exclusion. Here, we report on a 58-year-old woman with an 8-year history of chronic, treatment-refractory cough of unknown etiology that we diagnosed as neurogenic cough and successfully treated with guanfacine monotherapy, with rapid and durable improvement in symptoms. This case was particularly challenging for a number of reasons, including a distant past smoking history and previous pneumonia, a significant psychiatric history, and a mildly deviated nasal septum and nasal osteophyte, all or some of which could have contributed to the etiology of the cough. This case illustrates that neurogenic cough should be a diagnostic consideration in patients presenting with chronic cough in whom other treatment modalities have failed, and also suggests that the therapeutic use of guanfacine in this clinical setting warrants future investigation

Obesity Contributes to Transformation of Myometrial Stem-Cell Niche to Leiomyoma via Inducing Oxidative Stress, DNA Damage, Proliferation, and Extracellular Matrix Deposition

Leiomyomas (fibroids) are monoclonal tumors in which myometrial stem cells (MSCs) turn tumorigenic after mutation, abnormal methylation, or aberrant signaling. Several factors contribute to metabolic dysfunction in obesity, including abnormal cellular proliferation, oxidative stress, and DNA damage. The present study aims to determine how adipocytes and adipocyte-secreted factors affect changes in MSCs in a manner that promotes the growth of uterine leiomyomas. Myometrial stem cells were isolated from the uteri of patients by fluorescence-activated cell sorting (FACS) using CD44/Stro1 antibodies. Enzyme-linked immunosorbent assay (ELISA), Western blot, and immunocytochemistry assays were performed on human adipocytes (SW872) co-cultured with MSCs and treated with leptin or adiponectin to examine the effects of proliferation, extracellular matrix (ECM) deposition, oxidative damage, and DNA damage. Co-culture with SW872 increased MSC proliferation compared to MSC culture alone, according to 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) results. The expressions of PCNA and COL1A increased significantly with SW872 co-culture. In addition, the expression of these markers was increased after leptin treatment and decreased after adiponectin treatment in MSCs. The Wnt/β-catenin and TGF-β/SMAD signaling pathways promote proliferation and ECM deposition in uterine leiomyomas. The expression of Wnt4, β-catenin, TGFβ3, and pSMAD2/3 of MSCs was increased when co-cultured with adipocytes. We found that the co-culture of MSCs with adipocytes resulted in increased NOX4 expression, reactive oxygen species production, and γ-H2AX expression. Leptin acts by binding to its receptor (LEP-R), leading to signal transduction, resulting in the transcription of genes involved in cellular proliferation, angiogenesis, and glycolysis. In MSCs, co-culture with adipocytes increased the expression of LEP-R, pSTAT3/STAT3, and pERK1/2/ERK/12. Based on the above results, we suggest that obesity may mediate MSC initiation of tumorigenesis, resulting in leiomyomas

Lateral dispersion is required for circuit integration of newly generated dentate granule cells

The process of circuit integration of newly-generated dentate granule cells of the hippocampus has been presumed to be a dynamic process. In fact, little is known regarding the initial development of newly generated neurons prior to circuit integration and the significance of this stage for circuit integration. Here, using advanced live imaging methods, we systematically analyze the dynamic dispersion of newly generated neurons in the neurogenic zone and observe that cells that are physically adjacent coordinate their lateral dispersion. Whole-cell recordings of adjacent newly generated neurons reveal that they are coupled via gap junctions. The dispersion of newly generated cells in the neurogenic zone is restricted when this coupling is disrupted, which severely impairs their subsequent integration into the hippocampal circuit. The results of this study reveal that the dynamic dispersion of newly generated dentate granule cells in the neurogenic zone is a required developmental stage for circuit integration

Uterine Transcriptome: Understanding Physiology and Disease Processes

In recent years, transcriptomics has enabled us to gain a deeper understanding of fundamental reproductive physiology, including the menstrual cycle, through a more precise molecular analysis. The endometrial mRNA transcript levels fluctuate during the normal menstrual cycle, indicating changes in the relative recruitment and abundance of inflammatory cells, as well as changes in the receptivity and remodeling of the endometrium. In addition to providing a more comprehensive understanding of the molecular underpinnings of pathological gynecological conditions such as endometriosis, leiomyomas, and adenomyosis through RNA sequencing, this has allowed researchers to create transcriptome profiles during both normal menstrual cycles and pathological gynecological conditions. Such insights could potentially lead to more targeted and personalized therapies for benign gynecological conditions. Here, we provide an overview of recent advances in transcriptome analysis of normal and pathological endometrium

Youth Screen Media Habits and Sleep: Sleep-Friendly Screen Behavior Recommendations for Clinicians, Educators, and Parents

With the widespread use of portable electronic devices and the normalization of screen media devices in the bedroom, insufficient sleep has become commonplace, affecting 30% of toddlers, preschoolers, and school-age children and the majority of adolescents.1,2 In a recent literature review of studies investigating the link between youth screen media use and sleep, 90% of included studies found an association between screen media use and delayed bedtime and/or decreased total sleep time.3 Proposed mechanisms include displacement of time that would have been spent sleeping, psychological stimulation and light exposure, and increased physiological alertness.3 This pervasive phenomenon of pediatric sleep loss has widespread implications due to the associations between insufficient sleep and increased risk of childhood obesity 4, disrupted psychological well-being 5 and impaired cognitive/academic functioning6. There is a clear need for more basic, translational, and clinical research examining the effects of screen media on sleep loss and health consequences in children and adolescents in order to educate and motivate clinicians, teachers, parents and youth themselves to foster healthy sleep habits

Genetic dissection of the neuro-glio-vascular machinery in the adult brain

Abstract The adult brain actively controls its metabolic homeostasis via the circulatory system at the blood brain barrier interface. The mechanisms underlying the functional coupling from neuron to vessel remain poorly understood. Here, we established a novel method to genetically isolate the individual components of this coupling machinery using a combination of viral vectors. We first discovered a surprising non-uniformity of the glio-vascular structure in different brain regions. We carried out a viral injection screen and found that intravenous Canine Adenovirus 2 (CAV2) preferentially targeted perivascular astrocytes throughout the adult brain, with sparing of the hippocampal hilus from infection. Using this new intravenous method to target astrocytes, we selectively ablated these cells and observed severe defects in hippocampus-dependent contextual memory and the metabolically regulated process of hippocampal neurogenesis. Combined with AAV9 targeting of neurons and endothelial cells, all components of the neuro-glio-vascular machinery can be simultaneously labeled for genetic manipulation. Together, we demonstrate a novel method, which we term CATNAP (CAV/AAV Targeting of Neurons and Astrocytes Perivascularly), to target and manipulate the neuro-glio-vascular machinery in the adult brain