Expression of the estrogen receptor-α (ERα) gene, ESR1, is a clinical biomarker used to predict therapeutic outcome of breast cancer. Hence, there is significant interest in understanding the mechanisms regulating ESR1 gene expression. Proteasome activity is increased in cancer and we previously showed that proteasome inhibition leads to loss of ESR1 gene expression in breast cancer cells. Expression of ESR1 mRNA in breast cancer cells is controlled predominantly through a proximal promoter within ∼400 base pair (bp) of the transcription start site (TSS). Here, we show that loss of ESR1 gene expression induced by the proteasome inhibitor bortezomib is associated with inactivation of a distal enhancer located 150 kilobases (kb) from the TSS. Chromatin immunoprecipitation assays reveal several bortezomib-induced changes at the distal site including decreased occupancy of three critical transcription factors, GATA3, FOXA1, and AP2γ. Bortezomib treatment also resulted in decreased histone H3 and H4 acetylation and decreased occupancy of histone acetyltransferase, p300. These data suggest a mechanism to explain proteasome inhibitor-induced loss of ESR1 mRNA expression that highlights the importance of the chromatin environment at the −150 kb distal enhancer in regulation of basal expression of ESR1 in breast cancer cells.

Background Currently, the evidence for exercise in maintaining health, well-being, and physical functioning is overwhelming. Despite these benefits, more than 50% of the population fails to meet the recommended exercise requirements for age and health status. In our study, we sought to provide a method to increase exercise adherence that was both effective and time-efficient for physicians and their patients. Methods The primary objective of this research study was to evaluate the effectiveness of a graded exercise protocol and biweekly monitoring on increasing the duration of aerobic exercise to 150 min per week in a population of elderly individuals with chronic disease. Secondarily, we evaluated for improvement in resting heart rate, blood pressure, body mass index (BMI), and cardiorespiratory fitness. The overall study design was a randomized, prospective cohort study with assessor blinding. Forty-five patients aged ≥60 years with multiple comorbidities were recruited from the Internal Medicine Clinic at Wright-Patterson AFB. Participants were randomized into a treatment or control arm and observed over a period of 34 weeks. Those in the treatment arm were given a graded walking protocol and received biweekly phone calls to evaluate compliance. Those in the control arm did not receive an intervention or biweekly monitoring. Measurements of heart rate, blood pressure, and BMI were taken quarterly in both groups. At the beginning and conclusion of the study, each participant completed a modified Balke treadmill test and Physical Activity Scale for the Elderly (PASE). Continuous variables were evaluated with the independent samples t-test, whereas categorical variables were evaluated with the chi-squared test. Results A greater percentage of the treatment group achieved the primary outcome (41.6% vs. 0%; p = 0.003). Those in the treatment group also had favorable improvements in heart rate response (− 2.4 beats/min vs. + 5.3 beats/min; p = 0.038) and PASE (+ 66 vs.-20; p < 0.001). No significant differences were observed between groups for mean change in heart rate, blood pressure, or BMI. Conclusion Guided, independent exercise and surveillance can be an effective tool in primary care practice to help patients reach the recommended levels of exercise for both age and health status.

Patient: Male, 72-year-old Final Diagnosis: Pneumoscrotum Symptoms: Dyspnea • facial swelling Medication: — Clinical Procedure: Chest tube Specialty: Critical Care Medicine • Urology Objective: Unusual clinical course Background: Pneumoscrotum is a rare clinical occurrence in which air accumulates in the scrotum. The origin of air is primarily from trauma, but spontaneous pneumoscrotum can develop from gastrointestinal or pulmonary sources. Physical examination of pneumoscrotum typically includes crepitus of the perineal region and scrotal swelling and associated findings depending on the origin of the free air. However, pneumoscrotum in the setting of a scrotal wound, which allows air to pass freely outside the body, has not been previously documented in the literature. Case Report: A 72-year-old man who recently underwent a scrotal incision and drainage for recurrent epididymitis presented to a local emergency room with chief concerns of “whistling scrotum” and dyspnea. The chest CT revealed bilateral pneumothoraces, pneumomediastinum, and excessive subcutaneous emphysema throughout his abdomen, perineum, and scrotum. His scrotum had a dehiscent wound without any gross edema or air trapping contained within the scrotum. He received bilateral chest tubes and subcutaneous air drains with complete resolution of his pneumothoraces. The pneumoscrotum and associated subcutaneous emphysema of the perineum and thighs resolved after a prolonged period, and necessitated additional scrotal surgery. Conclusions: Prompt evaluation for source control is necessary with pneumoscrotum, as the source likely requires immediate stabilization or surgical intervention. This case report describes a unique presentation of a common entity (pneumothorax) within pulmonology/critical care in a patient with an open scrotal wound from a recent scrotal procedure, which allowed the air to escape from his abdominal compartment, and resulted in his “scrotal whistling.” It is unclear how the air passing through the scrotum affected the patient’s presentation, such as allowing more air to build up in the subcutaneous tissues versus developing critical illness.