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Polycystic ovarian syndrome (PCOS) is a complex disorder with multiple abnormalities, including hyperandrogenism, ovulatory dysfunction, and altered gonadotropin secretion. The majority of patients have elevated LH levels in plasma and a persistent rapid frequency of LH (GnRH) pulse secretion, the mechanisms of which are unclear. Earlier work has suggested that the sensitivity of the GnRH pulse generator to inhibition by ovarian steroids is impaired. We performed a study to determine whether antiandrogen therapy with flutamide could enhance feedback inhibition by estradiol (E2) and progesterone (P) in women with PCOS. Ten anovulatory women with PCOS and nine normal controls (days 8-10 of the cycle) were studied on three occasions. During each admission, LH and FSH were determined every 10 min and E2, P, and testosterone (T) every 2 h for 13 h. After 12 h, GnRH (25 ng/kg) was given iv. After the first admission, patients were started on flutamide (250 mg twice daily), which was continued for the entire study. The second admission occurred on days 8-10 of the next menstrual cycle for normal controls and on study day 28 for PCOS patients. Subjects were then given E2 transdermally (mean plasma E2, 106+/-18 pg/mL) and P by vaginal suppository to obtain varied plasma concentrations of P (mean P, 4.4+/-0.5 ng/mL; range, 0.6-9.0 ng/mL), and a third study was performed 7 days later. At baseline women with PCOS had higher LH pulse amplitude, response to GnRH, T, androstenedione, and insulin and lower sex hormone-binding globulin concentrations (P < 0.05). Most hormonal parameters were not altered by 4 weeks of flutamide, except T in controls and E2 and FSH in PCOS patients, which were lower. Of note, flutamide alone had no effect on LH pulse frequency or amplitude, mean plasma LH, or LH responsiveness to exogenous GnRH. After the addition of E2 and P for 7 days, both PCOS patients and normal controls had similar reductions in LH pulse frequency (4.0+/-0.7 and 5.8+/-0.7 pulses/12 h, respectively). This contrasts with our earlier results in the absence of flutamide, where a plasma P level of less than 10 ng/mL had minimal effects on LH pulse frequency in women with PCOS, but was effective in controls. These results suggest that although the elevated LH pulse frequency in PCOS may in part reflect impaired sensitivity to E2 and P, continuing actions of hyperandrogenemia are important for sustaining the abnormal hypothalamic sensitivity to feedback inhibition by ovarian steroids.

PURPOSE COVID-19 has infected more than 94 million people worldwide and caused more than 2 million deaths. Patients with cancer are at significantly increased risk compared with the general population. Telemedicine represents a common strategy to prevent viral spread. We sought to evaluate patient with cancer and physician perceptions of telemedicine during the COVID-19 pandemic. METHODS A 16-question survey was e-mailed to 1,843 active e-mails of patients presenting to one of the six cancer clinics at a comprehensive cancer care center from January 1, 2020, to June 1, 2020. A six-question survey was e-mailed to attending physicians of those clinics. Specialties included Medical Oncology, Hematology-Oncology, Surgical Oncology, Urological Oncology, and Gynecologic Oncology. RESULTS Three hundred seventy-four patients (20.3%) and 14 physicians (66.7%) responded. Most (68.2%) currently prefer in-person visits, and 80.4% prefer in-person visits following pandemic resolution. More than half (52.2%) of patients preferring virtual visits do so because of convenience. Most (63.1%) patients with cancer are comfortable with a complete physical examination. Surgical patients are more likely to prefer a complete examination ( P = .0476). Physicians prefer in-person visits (64.2%) and believe that virtual visits maybe or probably do not provide comparable care (64.2%). 71.4% believe that virtual visits help prevent the spread of infectious disease. CONCLUSION Given preferences for in-person visits, cancer care teams should be prepared to continue providing in-person visits for many of their patients. The discrepancy between patient and provider concern for spread of infectious disease represents an area where patients may benefit from increased education. Providers should feel comfortable performing physical examinations at their own discretion.

Adherence to National Comprehensive Cancer Network guidelines for pancreatic cancer patients improves survival. Compliance nationwide is low, especially for older patients and minorities and those treated outside academic centers. More studies will need to be performed to identify factors that hinder compliance.

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Alzheimer’s disease (AD), a multifactorial complex neural disorder, is categorized with progressive memory loss and cognitive impairment as main clinical features. The multitarget directed ligand (MTDL) strategy is explored for the treatment of multifactorial diseases such as cancer and AD. Herein, we report the synthesis and screening of 24 N-propargyl-substituted diphenylpyrimidine derivatives as MTDLs against acetylcholine/butyrylcholine esterases and monoamine oxidase enzymes. In this series, VP1 showed the most potent MAO-B inhibitory activity with an IC50 value of 0.04 ± 0.002 μM. VP15 with an IC50 value of 0.04 ± 0.003 μM and a selectivity index of 626 (over BuChE) displayed the most potent AChE inhibitory activity in this series. In the reactive oxygen species (ROS) inhibition studies, VP1 reduced intercellular ROS levels in SH-SY5Y cells by 36%. This series of compounds also exhibited potent neuroprotective potential against 6-hydroxydopamine-induced neuronal damage in SH-SY5Y cells with up to 90% recovery. In the in vivo studies in the rats, the hydrochloride salt of VP15 was orally administered and found to cross the blood–brain barrier and reach the target site. VP15·HCl significantly attenuated the spatial memory impairment and improved the cognitive deficits in the mice. This series of compounds were found to be irreversible inhibitors and showed no cytotoxicity against neuronal cells. In in silico studies, the compounds attained thermodynamically stable orientation with complete occupancy at the active site of the receptors. Thus, N-propargyl-substituted diphenylpyrimidines displayed drug-like characteristics and have the potential to be developed as MTDLs for the effective treatment of AD.

Studies have shown high-volume institutions have decreased mortality and increased survival for pancreatectomy. However, not all patients can travel to high-volume centers. Socioeconomic factors may influence treatment decisions. The goal of this study is to examine socioeconomic factors that determine where a patient is treated and how that location affects outcome. This is a retrospective study of the National Cancer Database of patients diagnosed with pancreatic cancer from 2004 to 2014. The primary outcome was to examine socioeconomic factors that predicted where a patient underwent their pancreatectomy. Patients treated at academic programs (APs) had to travel a mean distance of 80.9 miles, whereas patients treated at community programs (CPs) had to travel 31.7 miles ( P < 0.0001). Spanish and Hispanic patients were less likely to travel to an AP (69% had surgery at an AP versus 76% of non-Hispanic patients, P < 0.001). Patients with higher comorbidities were also more likely to have care at CPs. Patients who had pancreatic cancer surgery at CPs were more likely to be Hispanic or with higher medical comorbidities. Those who had surgery at AP traveled further distances but had better perioperative outcomes and had an improvement in overall survival.