The risk of Alzheimer's disease (AD) is higher in women than in men, a sex difference that likely results from the effects of sex steroid hormones. To investigate this relationship, we first compared progression of β-amyloid (Aβ) pathology in male and female triple transgenic (3xTg-AD) mice. We found that female 3xTg-AD mice exhibit significantly greater Aβ burden and larger behavioral deficits than age-matched males. Next, we evaluated how the organizational effects of sex steroid hormones during postnatal development may affect adult vulnerability to Aβ pathology. We observed that male 3xTg-AD mice demasculinized during early development exhibit significantly increased Aβ accumulation in adulthood. In contrast, female mice defeminized during early development exhibit a more male-like pattern of Aβ pathology in adulthood. Taken together, these results demonstrate significant sex differences in pathology in 3xTg-AD mice and suggest that these differences may be mediated by organizational actions of sex steroid hormones during development.

Objective: Transmission of SARS-CoV-2 has significant implications for hospital infection prevention and control, discharge management, and public health. We reviewed available literature to reach an evidenced-based consensus on the expected duration of viral shedding. Design: We queried four scholarly repositories/search engines for studies reporting SARS-CoV-2 viral shedding dynamics by PCR and/or culture available through September 8, 2020. We calculated the pooled median duration of viral RNA shedding from respiratory and fecal sources. Results: Seventy-seven studies on SARS-CoV-2 were included. All studies reported PCR-based testing and 12 also included viral culture data. The overall pooled median duration of RNA shedding from respiratory sources was 18.4 days (95% CI: 15.5 days - 21.3 days; I2=98.87%, p<0.01) among 28 studies. When stratified by disease severity, the pooled median duration of viral RNA shedding from respiratory sources was 19.8 days (95% CI: 16.2 days – 23.5 days; I2=96.42%, p<0.01) among severely ill patients and 17.2 days (95% CI: 14.0 days - 20.5 days; I2=95.64%, p<0.01) in mild/moderate illness. Viral RNA was detected up to 92 days after symptom onset. Viable virus was isolated by culture from -6 days to 20 days relative to symptom onset. Conclusions: SARS-COV-2 RNA shedding can be prolonged, yet high heterogeneity exists. Detection of viral RNA may not correlate with infectivity since available viral culture data suggests shorter durations of shedding of viable virus. Additional data is needed to determine the duration of shedding of viable virus and the implications for risk of transmission.

Depletion of estrogens and progesterone at menopause has been linked to an increased risk for the development of Alzheimer's disease (AD) in women. A currently controversial literature indicates that although treatment of postmenopausal women with hormone therapy (HT) may reduce the risk of AD, several parameters of HT may limit its potential efficacy and perhaps, even exacerbate AD risk. One such parameter is continuous vs. cyclic delivery of the progestogen component of HT. Recent experimental evidence suggests that continuous progesterone can attenuate neural actions of estradiol (E(2)). In the present study, we compared the effects of continuous and cyclic progesterone treatment in the presence and absence of E(2) in ovariectomized 3xTg-AD mice, a transgenic mouse model of AD. We found that ovariectomy-induced hormone depletion increases AD-like pathology in female 3xTg-AD mice, including accumulation of beta-amyloid, tau hyperphosphorylation, and impaired hippocampal-dependent behavior. E(2) treatment alone prevents the increases in pathology. Continuous progesterone did not affect beta-amyloid levels when delivered alone but blocked the Abeta-lowering action of E(2). In contrast, cyclic progesterone significantly reduced beta-amyloid levels by itself and enhanced rather than inhibited the E(2) effects. These results provide new insight into the neural interactions between E(2) and progesterone that may prove valuable in optimizing HT regimens in postmenopausal women.

Introduction: The emergence of COVID-19 highlighted the critical importance of appropriate use of personal protective equipment (PPE) for the safety of patients and health care personnel. However, previously published survey data indicated that formal instruction on the correct utilization of PPE is uncommon in medical school curricula, and there is no published guidance about optimal instruction methods. The infectious disease (ID) simulation lab at Oregon Health & Science University filled this need. Methods: Second-through fourth-year medical students participated in the infection intersession, a 2-week didactic session that students were required to enroll in once during their clinical rotations. As part of the course, students completed the ID simulation lab, during which they were presented with common ID syndromes (suspected tuberculosis, C. difficile colitis, and neutropenic fever) and asked to select the proper PPE prior to interacting with standardized patients. ID physicians acted as the patients and then conducted feedback sessions, which focused on PPE choice, donning and doffing techniques, and ID diagnosis and management principles. Results: More than 500 medical students participated between 2016 and 2020, demonstrating the feasibility of the experience. The average exam scores were above 80%, and the average student evaluation score of the session was 8.9 out of 10, demonstrating acceptability. Discussion: The ID simulation lab allowed students to reinforce didactic teaching about PPE, dispel common misconceptions, and receive real-time feedback from ID clinicians. Availability of the lab and facilitators were limiting factors. Future work will focus on better understanding the efficacy of the sessions.

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