Complications from “Stem Cell Tourism” in Neurology

“Stem cell tourism,” the practice of offering unproven cellular preparations to patients as approved therapy, is rising in neurology. Currently, the experiences of patients and reported complications from these procedures are unknown in the United States. We evaluate academic neurologists' experiences with stem cell tourism and assess perceived competency on discussing this topic with patients. We found a lack of neurologist preparedness to discuss stem cell therapies with patients and an alarming list of unreported complications from these unregulated procedures. We also identified an urgent need for neurologist education and the creation of a national registry for reporting patient complications resulting from experimental stem cell interventions. ANN NEUROL 2020;88:661–668     

Photofunctionalizable Hydrogel for Fabricating Volume Optical Diffractive Sensors

Volume amplitude gratings made of mesoporous hydrogels are beneficial for sensing, but are difficult to fabricate because they involve creating high aspect ratio features in soft materials. A novel photofunctionalizable hydrogel is reported and its suitability for fabricating grating sensors is demonstrated comprising of features with an aspect ratio of ≈3.2. To make a photofunctionalizable hydrogel with high optical quality that can be patterned using widely available light sources, a water‐soluble photoactive monomer and sensitizer are synthesized. A transmission amplitude grating is subsequently fabricated in a ≈100 µm thick photofunctionalizable hydrogel film by reaction of the free amines generated in the photoexposed regions with pH‐responsive fluorescein isothiocyanate. The volume hydrogel grating described herein is shown to be suitable for real‐time sensing of pH as an exemplar analyte. This work will have a significant impact on the fabrication of diffractive optical structures in thick films of hydrogels that are highly promising for biomolecular sensing in disease diagnosis and healthcare monitoring.     

Health-related lifestyles and obesity among adults with and without disability in Australia: Implication for mental health care

Background

Numerous studies have reported people with disabilities are more likely to be obese and engaged in unhealthy lifestyles. Few studies explored the mechanism of health-related lifestyles and obesity among people with disabilities.

Co-targeting bromodomain and extra-terminal proteins and MCL1 induces synergistic cell death in melanoma

The treatment of melanoma has been markedly improved by the introduction of targeted therapies and checkpoint blockade immunotherapy. Unfortunately, resistance to these therapies remains a limitation. Novel anticancer therapeutics targeting the MCL1 anti-apoptotic protein have shown impressive responses in haematological cancers but are yet to be evaluated in melanoma. To assess the sensitivity of melanoma to new MCL1 inhibitors, we measured the response of 51 melanoma cell lines to the novel MCL1 inhibitor, S63845. Additionally, we assessed combination of this drug with inhibitors of the bromodomain and extra-terminal (BET) protein family of epigenetic readers, which we postulated would assist MCL1 inhibition by downregulating anti-apoptotic targets regulated by NF-kB such as BCLXL, BCL2A1 and XIAP, and by upregulating pro-apoptotic proteins including BIM and NOXA. Only 14% of melanoma cell lines showed sensitivity to S63845, however, combination of S63845 and I-BET151 induced highly synergistic apoptotic cell death in all melanoma lines tested and in an in vivo xenograft model. Cell death was dependent on caspases and BAX/BAK. Although the combination of drugs increased the BH3-only protein, BIM, and downregulated anti-apoptotic proteins such as BCL2A1, the importance of these proteins in inducing cell death varied between cell lines. ABT-199 or ABT-263 inhibitors against BCL2 or BCL2 and BCLXL, respectively, induced further cell death when combined with S63845 and I-BET151. The combination of MCL1 and BET inhibition appears to be a promising therapeutic approach for metastatic melanoma, and presents opportunities to add further BCL2 family inhibitors to overcome treatment resistance.     

Prediction modelling using routine clinical parameters to stratify survival in Malignant Pleural Mesothelioma patients undergoing cytoreductive surgery

Introduction

Malignant pleural mesothelioma (MPM) is an uncommon cancer with a poor prognosis and heterogeneous survival. Surgery for MPM is offered in some specialist centers to highly selected patients. A previously described classification and regression tree (CART) model stratified survival in unselected MPM patients using routinely collected clinical data. This study aimed to examine the performance of this CART model on a highly selected surgical population.

Dioxane-Linked Amide Derivatives as Novel Bacterial Topoisomerase Inhibitors against Gram-Positive Staphylococcus aureus

In recent years, novel bacterial topoisomerase inhibitors (NBTIs) have been developed as future antibacterials for treating multidrug-resistant bacterial infections. A series of dioxane-linked NBTIs with an amide moiety has been synthesized and evaluated. Compound 3 inhibits DNA gyrase, induces the formation of single strand breaks to bacterial DNA, and achieves potent antibacterial activity against a variety of Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Optimization of this series of analogues led to the discovery of a subseries of compounds (22–25) with more potent anti-MRSA activity, dual inhibition of DNA gyrase and topoisomerase IV, and the ability to induce double strand breaks through inhibition of S. aureus DNA gyrase.     

Where Have All the Emergencies Gone? The Impact of the COVID-19 Pandemic on Obstetric and Gynecologic Procedures and Consults at a New York City Hospital

Study ObjectiveThe purpose of this study was to assess the impact of the coronavirus disease 2019 (COVID-19) pandemic on surgical volume and emergency department (ED) consults across obstetrics-gynecology (OB-GYN) services at a New York City hospital.DesignRetrospective cohort study.SettingTertiary care academic medical center in New York City.PatientsWomen undergoing OB-GYN ED consults or surgeries between February 1, 2020 and April 15, 2020.InterventionsMarch 16 institutional moratorium on elective surgeries.Measurements and Main ResultsThe volume and types of surgeries and ED consults were compared before and after the COVID-19 moratorium. During the pandemic, the average weekly volume of ED consults and gynecology (GYN) surgeries decreased, whereas obstetric (OB) surgeries remained stable. The proportions of OB-GYN ED consults, GYN surgeries, and OB surgeries relative to all ED consults, all surgeries, and all labor and delivery patients were 1.87%, 13.8%, 54.6% in the pre–COVID-19 time frame (February 1–March 15) vs 1.53%, 21.3%, 79.7% in the COVID-19 time frame (March 16–April 15), representing no significant difference in proportions of OB-GYN ED consults (p = .464) and GYN surgeries (p = .310) before and during COVID-19, with a proportionate increase in OB surgeries (p <.002). The distribution of GYN surgical case types changed significantly during the pandemic with higher proportions of emergent surgeries for ectopic pregnancies, miscarriages, and concern for cancer (p <.001). Alternatively, the OB surgery distribution of case types remained relatively constant.ConclusionThis study highlights how the pandemic has affected the ways that patients in OB-GYN access and receive care. Institutional policies suspending elective surgeries during the pandemic decreased GYN surgical volume and affected the types of cases performed. This decrease was not appreciated for OB surgical volume, reflecting the nonelective and time-sensitive nature of obstetric care. A decrease in ED consults was noted during the pandemic begging the question “Where have all the emergencies gone?” Although the moratorium on elective procedures was necessary, “elective” GYN surgeries remain medically indicated to address symptoms such as pain and bleeding and to prevent serious medical sequelae such as severe anemia requiring transfusion. As we continue to battle COVID-19, we must not lose sight of those patients whose care has been deferred.