The Wnt signaling pathway is intricately connected with bone mass regulation in humans and rodent models. We designed an antibody-based platform that generates potent and selective Wnt mimetics. Using this platform, we engineer bi-specific Wnt mimetics that target Frizzled and low-density lipoprotein receptor-related proteins and evaluate their effects on bone accrual in murine models. These synthetic Wnt agonists induce rapid and robust bone building effects, and correct bone mass deficiency and bone defects in various disease models, including osteoporosis, aging, and long bone fracture. Furthermore, when these Wnt agonists are combined with antiresorptive bisphosphonates or anti-sclerostin antibody therapies, additional bone accrual/maintenance effects are observed compared to monotherapy, which could benefit individuals with severe and/or acute bone-building deficiencies. Our data support the continued development of Wnt mimetics for the treatment of diseases of low bone mineral density, including osteoporosis.

Uterine leiomyosarcoma (uLMS) is a rare and aggressive cancer with few effective therapeutics. The Notch signaling pathway is evolutionarily conserved with oncogenic properties, but it has not been well studied in uLMS. The purpose of our study was to determine expression of Notch family genes and proteins and to investigate the therapeutic effect of γ-secretase inhibitors (GSIs), indirect inhibitors of Notch signaling, in uLMS. We determined expression of Notch genes and proteins in benign uterine smooth muscle tissue, fibroids, and uLMS samples by immunostaining and in two uLMS cell lines, SK-UT-1B (uterine primary) and SK-LMS-1 (vulvar metastasis) by RT-PCR, Western blot and immunostaining. We exposed our cell lines to GSIs, DAPT and MK-0752, and measured expression of HES1, a downstream effector of Notch. Notch proteins were differentially expressed in uLMS. Expression of NOTCH3 and NOTCH4 was higher in uLMS samples than in benign uterine smooth muscle and fibroids. Expression of NOTCH4 was higher in SK-LMS-1 compared to SK-UT-1B. Exposure of SK-UT-1B and SK-LMS-1 to DAPT and MK-0752 decreased expression of HES1 and decreased uLMS cell viability in a dose- and time-dependent manner that was unique to each GSI. Our findings suggest that GSIs are potential therapeutics for uLMS, albeit with limited efficacy.

Objective. Dysphagia after pneumonectomy is uncommon but concerning. The purpose of this paper is to present a case of dysphonia secondary to postpneumonectomy syndrome. Case Report. A 66-year-old female with stage IIIa adenocarcinoma of the lung was treated with a left pneumonectomy. Three years later, she presented with severe dysphagia, dyspnea, and dysphonia. Esophagram demonstrated severely deviated esophagus to the left of midline, attributed to prior left-sided pneumonectomy, without clear evidence of any external compression. Chest CT scan showed associated leftward mediastinal shift. This patient was treated with voice therapy and an exclusion diet, as the patient elected not to have surgery. Conclusion. This is the first reported case of dysphonia accompanying severe dysphagia following left pneumonectomy. While postpneumonectomy syndrome is rare, a high degree of clinical suspicion is recommended when treating patients with history of pneumonectomy.

Trends in abortion care in the United States are changing quickly, affected by many epidemiological factors as well as a varying political climate. Surgical abortions are the more common method of conducting abortion care. Recent CDC National Surveillance Data has shown an increase in second-trimester abortion, correlating to an increased need for providers experienced in surgical abortions and cervical preparation agents, such as misoprostol, mifepristone, and laminaria. Furthermore, recent studies have shown an increase in long-acting reversible contraceptive options including post-abortion contraceptive use. We hoped to compare the trends in abortion of pregnancy in our low-resource urban environment against the national trends to better understand what demographic factors might influence decision-making. We identified a need for studies on trends in abortions of pregnancy in a low-resource urban setting which can become applicable across similar neighborhoods, some of which might not participate in CDC abortion surveillance reports. Our study shows an increase in dilation and evacuation procedures, correlating with an increase in the use of misoprostol and laminaria for cervical preparation as well as digoxin for induction of fetal demise, both of which would occur at higher frequency in the second trimester. We also found a preference towards no contraception after abortion, which slightly differs from national trends in recent years. Our study aims to evaluate these trends and identify the need for further quality assurance and improvement in this care.

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