The Impact of Estrogen-Suppressing Contraceptives on Behavioral and Functional Difficulties in Borderline Personality Disorder.

Borderline Personality Disorder (BPD) is characterized by rapidly shifting emotional, interpersonal, and behavioral symptoms, and is often co-morbid with mood and anxiety disorders. Females are more likely to be diagnosed with BPD than males and exhibit greater functional impairment. Hormonal fluctuations, particularly in estrogen levels, may influence the manifestation of BPD symptoms. Here we investigated the influence of estrogen-suppressing contraceptives on behavioral and functional difficulties in BPD. The analytical sample included 348 females ages 18-50 undergoing residential treatment for psychiatric disorders, with 131 having a BPD diagnosis. Patients were categorized based on their contraceptive method: 1) Estrogen-suppressing contraceptives (N=145) and 2) Naturally cycling (N=203). Interaction models tested the impact of estrogen-suppressing contraceptives on the relationship between BPD diagnosis and behavioral and functional difficulties at admission and discharge, assessed by the four Behavior and Symptom Identification Scale (BASIS-32) domains: difficulties in relationships, daily living, depression/anxiety, and impulsivity. Females with a BPD diagnosis were more likely to use estrogen-suppressing contraceptives compared to those without BPD (p=0.04). However, estrogen-suppressing contraceptive use was not associated with behavioral and functional difficulties at admission, discharge, or over time. Estrogen-suppressing contraceptives moderated the association between BPD diagnosis and difficulties in relationships (p=0.004), difficulties in daily living (p=0.01), and depression/anxiety symptoms (p=0.004). Patients with BPD expressed increased behavioral and functional difficulties at admission, discharge, and over time only if naturally cycling (p<0.003). Our findings suggest that estrogen-suppressing contraceptives may help to regulate the rapidly shifting emotional, interpersonal, and behavioral symptoms in females with BPD by stabilizing estrogen levels.

Supervised Machine Learning Approach to Identify Early Predictors of Poor Outcome in Patients with COVID-19 Presenting to a Large Quaternary Care Hospital in New York City.

BACKGROUND: The progression of clinical manifestations in patients with coronavirus disease 2019 (COVID-19) highlights the need to account for symptom duration at the time of hospital presentation in decision-making algorithms. METHODS: We performed a nested case-control analysis of 4103 adult patients with COVID-19 and at least 28 days of follow-up who presented to a New York City medical center. Multivariable logistic regression and classification and regression tree (CART) analysis were used to identify predictors of poor outcome. RESULTS: Patients presenting to the hospital earlier in their disease course were older, had more comorbidities, and a greater proportion decompensated (<4 days, 41%; 4-8 days, 31%; >8 days, 26%). The first recorded oxygen delivery method was the most important predictor of decompensation overall in CART analysis. In patients with symptoms for <4, 4-8, and >8 days, requiring at least non-rebreather, age ≥ 63 years, and neutrophil/lymphocyte ratio ≥ 5.1; requiring at least non-rebreather, IL-6 ≥ 24.7 pg/mL, and D-dimer ≥ 2.4 µg/mL; and IL-6 ≥ 64.3 pg/mL, requiring non-rebreather, and CRP ≥ 152.5 mg/mL in predictive models were independently associated with poor outcome, respectively. CONCLUSION: Symptom duration in tandem with initial clinical and laboratory markers can be used to identify patients with COVID-19 at increased risk for poor outcomes.

Cell-Free Total Biosynthesis of Plant Terpene Natural Products using an Orthogonal Cofactor Regeneration System.

Here we report the one-pot, cell-free enzymatic synthesis of the plant monoterpene nepetalactol starting from the readily available geraniol. A pair of orthogonal cofactor regeneration systems permitted NAD+-dependent geraniol oxidation followed by NADPH-dependent reductive cyclization without isolation of intermediates. The orthogonal cofactor regeneration system maintained a high ratio of NAD+ to NADH and a low ratio of NADP+ to NADPH. The overall reaction contains four biosynthetic enzymes, including a soluble P450; and five accessory and cofactor regeneration enzymes. Furthermore, addition of a NAD+-dependent dehydrogenase to the one-pot mixture led to ~1 g/L of nepetalactone, the active cat- attractant in catnip.

Iterative Catalysis in the Biosynthesis of Mitochondrial Complex II Inhibitors Harzianopyridone and Atpenin B.

The pentasubstituted pyridine natural products harzianopyridone and atpenins are potent inhibitors of mitochondrial complex II. We identified the pathways of these compounds from their fungal producers and uncovered that the biosynthetic steps require multiple iterative enzymes. In particular, a methyltransferase and a flavin-dependent monooxygenase are used iteratively to introduce C5 and C6 methoxy groups. The pathway unexpectedly requires the installation and removal of an N-methoxy group, which is proposed to be a directing group that tunes the reactivity of the pyridone ring, possibly through the alpha effect.