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Growing evidence demonstrates that human mesenchymal stromal cells (MSCs) modify their in vivo anti-inflammatory actions depending on the specific inflammatory environment encountered. Understanding this better is crucial to refine MSC-based cell therapies for lung and other diseases. Using acute exacerbations of cystic fibrosis (CF) lung disease as a model, the effects of ex vivo MSC exposure to clinical bronchoalveolar lavage fluid (BALF) samples, as a surrogate for the in vivo clinical lung environment, on MSC viability, gene expression, secreted cytokines, and mitochondrial function was compared to effects of BALF collected from healthy volunteers. CF BALF samples which cultured positive for Aspergillus sp. (Asp) induced rapid MSC death, usually within several hours of exposure. Further analyses suggested the fungal toxin gliotoxin as a potential mediator contributing to CF BALF-induced MSC death. RNA sequencing analyses of MSCs exposed to either Asp+ or Asp- CF BALF samples identified a number of differentially expressed transcripts, including those involved in interferon-signaling, anti-microbial gene expression, and cell death. Toxicity did not correlate with bacterial lung infections. These results suggest that the potential use of MSC-based cell therapies for CF or other lung diseases may not be warranted in the presence of Aspergillus.

Overactive bladder (OAB) is a syndrome characterized by symptoms of urinary urgency with or without urgency urinary incontinence (UUI), usually with frequency and nocturia. OAB affects approximately 17% of women in the United States and Europe. The causes of OAB, as with many bladder disorders, are multifactorial and are not completely understood. The primary functions of the lower urinary tract (bladder and bladder outlet mechanism) are storage and evacuation of urine. The bladder and the micturition cycle are under complex neural control involving both the sympathetic and parasympathetic nervous systems. Micturition may occur in response to the activation of receptors in the bladder muscle and detection of chemical stimuli by receptors within the bladder lining. Neurogenic or myogenic bladder dysfunction can lead to the symptoms of urgency, frequency, and UUI that characterize OAB. The consequences of this condition are far-reaching and include direct medical consequences and coping strategies that adversely affect quality of life. Although the prevalence of OAB increases with age, it is not a normal consequence of aging. Antimuscarinic agents (e.g., oxybutynin, tolterodine, trospium, solifenacin, and darifenacin) have demonstrated efficacy for the treatment of OAB symptoms in multiple clinical trials. This review explores the physiological basis for OAB, the effects of OAB on health-related quality of life, and the pharmacotherapies that may provide relief to patients with this distressing condition.

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Conceptual frameworks in science have shifted from reductionism and its focus on ever-smaller parts to complexity, an outgrowth of chaos theory that views those parts in relation to one another, to the larger entity they form and to the environment in which that entity exists. Examples of this conceptual shift are occurring in many areas of science, but nowhere is it more germane than in the medical sciences that serve women. After a historical focus on reproduction and the development of obstetrics-gynecology, medicine has now gained a broader view of the woman using sex- and gender-based science, and a new field called "women's health" is evolving. Complexity science does not invalidate or eliminate the need for reductionist science, it simply makes a wider array of phenomena understandable. Its method allows going beyond the metaphor of the body as a machine and challenges the user to re-examine how health and illness are understood. This article explores how these changes in science must inform the development of an academic discipline in women's health. The conceptual framework of complexity science also advances the discussions about women's health from reproduction to a totally new and exciting exploration of the interactions between reproduction and all other organ functioning that occurs in women in the contexts of their lives.