Unprecedented Packing Polymorphism of Oxindole: An Exploration Inspired by Crystal Structure Prediction.

Crystal polymorphism, characterized by different packing arrangements of the same compound, strongly ties to the physical properties of a molecule. Determining the polymorphic landscape is complex and time-consuming, with the number of experimentally observed polymorphs varying widely from molecule to molecule. Furthermore, disappearing polymorphs, the phenomenon whereby experimentally observed forms cannot be reproduced, pose a significant challenge for the pharmaceutical industry. Herein, we focused on oxindole (OX), a small rigid molecule with four known polymorphs, including a reported disappearing form. Using crystal structure prediction (CSP), we assessed OX solid-state landscape and thermodynamic stability by comparing predicted structures with experimentally known forms. We then performed melt and solution crystallization in bulk and nanoconfinement to validate our predictions. These experiments successfully reproduced the known forms and led to the discovery of four novel polymorphs. Our approach provided insights into reconstructing disappearing polymorphs and building more comprehensive polymorph landscapes. These results also establish a new record of packing polymorphism for rigid molecules.

Malakoplakia of the Endometrium: A Rare Unexpected Disease Raising Clinical Concern for Malignancy.

Malakoplakia is a rare disease that manifests as a histiocytic inflammatory process and most often occurs in the urinary bladder. It is caused by an impaired capacity of histiocytes to kill and digest bacteria. The typical histopathologic findings are sheets of histiocytes with granular eosinophilic cytoplasm and characteristic Michaelis-Gutmann bodies, spherical bodies with a targetoid appearance. Malakoplakia is even rarer in the gynecologic tract, and our literature search found only 21 published patients of malakoplakia involving the endometrium. Here we report a 60-year-old female patient who presented with recurrent pelvic infections and postmenopausal bleeding, which raised concern for an endometrial malignancy. Hysterectomy with salpingo-oophorectomy revealed malakoplakia involving the endometrium and also the right ovary. Michaelis-Gutmann bodies were visible on the intraoperative frozen section that was performed to rule out an endometrial malignancy. We summarize the clinicopathologic findings of the published patients of endometrial malakoplakia.

Hardiness predicts mental health recovery during the COVID-19 pandemic.

OBJECTIVE: The COVID-19 pandemic has elicited wide-scale general psychological distress; however, longitudinal investigations are required to identify the critical resources that support individuals' adaptation to this type of unique situation over time. Hardiness, a cognitive trait that facilitates adaptation in the context of adversity and possible posttraumatic growth, may be particularly influential on mental health recovery during health disasters when other resources are not available or effective. METHOD: We tested the hypothesis that greater psychological hardiness prior to the pandemic would predict lower traumatic stress symptoms (TSSs) and loneliness early into the pandemic and decreases in TSSs and loneliness between early 2020 and late 2021. Predominantly ethnic minority (77% Latina/o/x or Asian American) female young adults (N = 80; Mage = 25 years; 88% female) attending a minority-serving public university completed a measure of hardiness in January 2020 as well as measures of pandemic-related TSSs and loneliness in April 2020, October 2020, and December 2021. RESULTS: Latent growth curve analyses indicated that hardiness was associated with lower initial loneliness as well as decreases in TSSs and loneliness over time. CONCLUSIONS: Consistent with previous research on adaptation to other potentially traumatic stressors, the current findings suggest that psychological hardiness may play a critical protective role during a global health disaster, both in terms of initial distress and changes in distress over time. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Cephalosporin resistance, tolerance, and approaches to improve their activities.

Cephalosporins comprise a ß-lactam antibiotic class whose first members were discovered in 1945 from the fungus Cephalosporium acremonium. Their clinical use for Gram-negative bacterial infections is widespread due to their ability to traverse outer membranes through porins to gain access to the periplasm and disrupt peptidoglycan synthesis. More recent members of the cephalosporin class are administered as last resort treatments for complicated urinary tract infections, MRSA, and other multi-drug resistant pathogens, such as Neisseria gonorrhoeae. Unfortunately, there has been a global increase in cephalosporin-resistant strains, heteroresistance to this drug class has been a topic of increasing concern, and tolerance and persistence are recognized as potential causes of cephalosporin treatment failure. In this review, we summarize the cephalosporin antibiotic class from discovery to their mechanisms of action, and discuss the causes of cephalosporin treatment failure, which include resistance, tolerance, and phenomena when those qualities are exhibited by only small subpopulations of bacterial cultures (heteroresistance and persistence). Further, we discuss how recent efforts with cephalosporin conjugates and combination treatments aim to reinvigorate this antibiotic class.

Effectiveness of an Advance Care Planning Intervention in Adults Receiving Dialysis and Their Families: A Cluster Randomized Clinical Trial.

Importance: Evidence of effectiveness of advance care planning (ACP) strategies for patients receiving dialysis and their families is needed. Objectives: To test the effectiveness of an ACP intervention to prepare patients and their surrogates for end-of-life (EOL) decision-making and to improve surrogate bereavement outcomes. Design, Setting, and Participants: This cluster randomized clinical trial, An Effectiveness-Implementation Trial of SPIRIT (Sharing Patients' Illness Representations to Increase Trust) in ESRD, was conducted from December 2017 to March 2023 and included 42 dialysis clinics in 5 US states (Georgia, New Mexico, North Carolina, Pennsylvania, and Virginia) randomized to provide intervention or usual care. Recruitment was from February 15, 2018, to January 31, 2022, and patient-surrogate dyads were followed up for 21 months (until January 17, 2023) or until patient death. Intervention: Each clinic selected 1 or 2 health care workers (eg, nurse practitioner, registered nurse, or social worker) to conduct 45- to 60-minute ACP discussions with dyads in the clinic or remotely. After March 13, 2020 (commencement of the COVID-19 emergency declaration), all discussions were conducted remotely. An ACP summary was placed in patients' medical records. Main Outcomes and Measures: The primary, 2-week preparedness outcomes were dyad congruence on EOL goals of care, patient decisional conflict, surrogate decision-making confidence, and a composite of dyad congruence and surrogate decision-making confidence. Secondary bereavement outcomes were anxiety, depression, and posttraumatic distress 3 months after patient death. To adjust for COVID-19 pandemic effects on bereavement outcomes, a variable to indicate the timing of baseline and 3-month assessment relative to the COVID-19 emergency declaration was created. Results: Of the 426 dyads enrolled, 231 were in the intervention clinics, and 195 were in the control clinics. Among all dyads, the mean (SD) patient age was 61.9 (12.7) years, and the mean (SD) surrogate age was 53.7 (15.4) years. At 2 weeks, after adjusting for baseline values, dyad congruence (odds ratio [OR], 1.61; 95% CI, 1.12-2.31; P = .001), decisional conflict scores (ß, -0.10; 95% CI, -0.13 to -0.07; P < .001), and the composite (OR, 1.57; 95% CI, 1.06-2.34; P = .03) were higher in the intervention group than in the control group. Surrogate decision-making confidence was similar between groups (ß, 0.06; 95% CI, -0.01 to 0.13; P = .12). Among 77 bereaved surrogates, after adjusting for baseline values and assessment timing, intervention group anxiety was lower than control group anxiety (ß, -1.55; 95% CI, -3.08 to -0.01; P = .05); however, depression (ß, -0.18; 95% CI, -2.09 to 1.73; P = .84) and posttraumatic distress (ß, -0.96; 95% CI, -7.39 to 5.46; P = .75) were similar. Conclusions and Relevance: In this randomized clinical trial, the ACP intervention implemented by health care workers at dialysis centers improved preparation for EOL decision-making but showed mixed effectiveness on bereavement outcomes. The ACP intervention implemented in dialysis centers may be an effective strategy to the dyad preparation for end-of-life care as opposed to the current focus on advance directives. Trial Registration: ClinicalTrials.gov Identifier: NCT03138564.