Parasite manipulation of host phenotypes inferred from transcriptional analyses in a trematode-amphipod system.

Manipulation of host phenotypes by parasites is hypothesized to be an adaptive strategy enhancing parasite transmission across hosts and generations. Characterizing the molecular mechanisms of manipulation is important to advance our understanding of host-parasite coevolution. The trematode (Levinseniella byrdi) is known to alter the colour and behaviour of its amphipod host (Orchestia grillus) presumably increasing predation of amphipods which enhances trematode transmission through its life cycle.

Activity of Novel Topoisomerase Inhibitors against and .

Antimicrobial resistance is a global issue, and the investigation of alternative therapies that are not traditional antibiotics are warranted. Novel bacterial type II topoisomerase inhibitors (NBTIs) have recently emerged as a novel class of antibiotics with reduced potential for cross-resistance to fluoroquinolones due to their novel mechanism of action. This study investigated the activity of a series of cyclohexyl-oxazolidinone bacterial topoisomerase inhibitors against type strains of and .

Clinical Course of SARS-CoV-2 Infection in Adults with ESKD Receiving Outpatient Hemodialysis.

Background: Patients with ESKD on maintenance dialysis receive dialysis in common spaces with other patients and have a higher risk of severe SARS-CoV-2 infections. They may have persistently or intermittently positive SARS-CoV-2 RT-PCR tests after infection. We describe the clinical course of SARS-CoV-2 infection and the serologic response in a convenience sample of patients with ESKD to understand the duration of infectivity.

Discovery and structure-activity relationships of a novel oxazolidinone class of bacterial type II topoisomerase inhibitors.

There is an increasingly urgent and unmet medical need for novel antibiotic drugs that tackle infections caused by multidrug-resistant (MDR) pathogens. Novel bacterial type II topoisomerase inhibitors (NBTIs) are of high interest due to limited cross-resistance with fluoroquinolones, however analogues with Gram-negative activity often suffer from hERG channel inhibition. A novel series of bicyclic-oxazolidinone inhibitors of bacterial type II topoisomerase were identified which display potent broad-spectrum anti-bacterial activity, including against MDR strains, along with an encouraging in vitro safety profile.

Development and Validation of an Enzyme Immunoassay for Detection and Quantification of SARS-CoV-2 Salivary IgA and IgG.

Oral fluids offer a noninvasive sampling method for the detection of Abs. Quantification of IgA and IgG Abs in saliva allows studies of the mucosal and systemic immune response after natural infection or vaccination. We developed and validated an enzyme immunoassay (EIA) to detect and quantify salivary IgA and IgG Abs against the prefusion-stabilized form of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein expressed in suspension-adapted HEK-293 cells.

Factors influencing environmental sampling recovery of healthcare pathogens from non-porous surfaces with cellulose sponges.

Results from sampling healthcare surfaces for pathogens are difficult to interpret without understanding the factors that influence pathogen detection. We investigated the recovery of four healthcare-associated pathogens from three common surface materials, and how a body fluid simulant (artificial test soil, ATS), deposition method, and contamination levels influence the percent of organisms recovered (%R). Known quantities of carbapenemase-producing KPC+ Klebsiella pneumoniae (KPC), Acinetobacter baumannii, vancomycin-resistant Enterococcus faecalis, and Clostridioides difficile spores (CD) were suspended in Butterfield's buffer or ATS, deposited on 323cm2 steel, plastic, and laminate surfaces, allowed to dry 1h, then sampled with a cellulose sponge wipe.

Development and validation of an enzyme immunoassay for detection and quantification of SARS-CoV-2 salivary IgA and IgG.

Oral fluids offer a non-invasive sampling method for the detection of antibodies. Quantification of IgA and IgG antibodies in saliva allows studies of the mucosal and systemic immune response after natural infection or vaccination. We developed and validated an enzyme immunoassay (EIA) to detect and quantify salivary IgA and IgG antibodies against the prefusion-stabilized form of the SARS-CoV-2 spike protein.

Sampling efficiency of from healthcare surfaces: culture and nonculture detection methods.

Sponges and swabs were evaluated for their ability to recover dried 1 hour on steel and plastic surfaces. Culture recovery ranged from <0.1% (sponges) to 8.

A Comparison of Less Invasive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Diagnostic Specimens in Nursing Home Residents-Arkansas, June-August 2020.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing remains essential for early identification and clinical management of cases. We compared the diagnostic performance of 3 specimen types for characterizing SARS-CoV-2 in infected nursing home residents.

Methods: A convenience sample of 17 residents were enrolled within 15 days of first positive SARS-CoV-2 result by real-time reverse transcription polymerase chain reaction (RT-PCR) and prospectively followed for 42 days.

Infectious Period of Severe Acute Respiratory Syndrome Coronavirus 2 in 17 Nursing Home Residents-Arkansas, June-August 2020.

Background: To estimate the infectious period of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in older adults with underlying conditions, we assessed duration of coronavirus disease 2019 (COVID-19) symptoms, reverse-transcription polymerase chain reaction (RT-PCR) positivity, and culture positivity among nursing home residents.

Methods: We enrolled residents within 15 days of their first positive SARS-CoV-2 test (diagnosis) at an Arkansas facility from July 7 to 15, 2020 and instead them for 42 days. Every 3 days for 21 days and then weekly, we assessed COVID-19 symptoms, collected specimens (oropharyngeal, anterior nares, and saliva), and reviewed medical charts.

Recovery efficiency of two glove-sampling methods.

Two methods to sample pathogens from gloved hands were compared: direct imprint onto agar and a sponge-wipe method. The sponge method was significantly better at recovering Clostridiodes difficile spores, and no difference was observed between the methods at 101 inoculum for carbapenemase-producing KPC+ Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus, and Acinetobacter baumannii.

Episodic foresight and stroke.

Objective: Stroke is often associated with increased difficulty engaging in specific future-directed thoughts and behaviors, such as generating phenomenological characteristics of future events (a component of episodic foresight) and executing directed preparatory behaviors (a component of prospective memory). The objective of this study was to clarify whether this group also exhibits increased difficulties using episodic foresight to appropriately guide future-directed behaviors.

Method: Stroke patients (n = 26) and demographically matched healthy controls (n = 26) were administered a behavioral measure that met strict criteria for assessing episodic foresight.

Survival, Persistence, and Isolation of the Emerging Multidrug-Resistant Pathogenic Yeast Candida auris on a Plastic Health Care Surface.

The emerging multidrug-resistant pathogenic yeast represents a serious threat to global health. Unlike most other species, this organism appears to be commonly transmitted within health care facilities and causes health care-associated outbreaks. To better understand the epidemiology of this emerging pathogen, we investigated the ability of to persist on plastic surfaces common in health care settings compared with that of , a species known to colonize the skin and plastics.

Effects of Simulated Low Vision on Postural Adjustment to Changes in Center of Mass in Older Adults.

This study examined how instrumental activities of daily living (IADL) performed by older adults under low-vision simulation conditions affect postural adjustments to changes in center of mass (COM). Ten participants with normal vision performed seven activities under two conditions, normal vision, and simulated macular degeneration (MD). Postural adjustment to changes in COM and time to complete activities were recorded.

Acting with the future in mind is impaired in long-term opiate users.

Rationale: Episodic foresight is a fundamental human capacity. It refers to the ability to simulate future situations and organise current actions accordingly. While there is some evidence that opiate users have a reduced capacity to imagine themselves in future situations, no study to date has assessed whether opiate users show deficits in the ability to take steps in the present in anticipation of future needs.

Anilinoquinazoline inhibitors of the RET kinase domain-Elaboration of the 7-position.

We have previously reported a series of anilinoquinazoline derivatives as potent and selective biochemical inhibitors of the RET kinase domain. However, these derivatives displayed diminished cellular potency. Herein we describe further optimisation of the series through modification of their physicochemical properties, delivering improvements in cell potency.

The discovery of 2-substituted phenol quinazolines as potent RET kinase inhibitors with improved KDR selectivity.

Deregulation of the receptor tyrosine kinase RET has been implicated in medullary thyroid cancer, a small percentage of lung adenocarcinomas, endocrine-resistant breast cancer and pancreatic cancer. There are several clinically approved multi-kinase inhibitors that target RET as a secondary pharmacology but additional activities, most notably inhibition of KDR, lead to dose-limiting toxicities. There is, therefore, a clinical need for more specific RET kinase inhibitors.

Episodic foresight and schizophrenia.

Objective: People with schizophrenia have difficulty engaging in specific future-directed thoughts and behaviours, such as generating phenomenological characteristics of future events (a component of episodic foresight), and executing directed preparatory behaviours (a component of prospective memory). However, it remains unclear whether they also exhibit difficulties using episodic foresight to appropriately guide future-directed behaviours.

Method: People with schizophrenia and non-clinical controls were administered a behavioural measure that met strict criteria for assessing episodic foresight.

Characterization of major histocompatibility complex class I loci of the lark sparrow (Chondestes grammacus) and insights into avian MHC evolution.

The major histocompatibilty complex (MHC) has become increasingly important in the study of the immunocapabilities of non-model vertebrates due to its direct involvement in the immune response. The characterization of MHC class I loci in the lark sparrow (Chondestes grammacus) revealed multiple MHC class I loci with elevated genetic diversity at exon 3, evidence of differential selection between the peptide binding region (PBR) and non-PBR, and the presence of multiple pseudogenes with limited divergence. The minimum number of functional MHC class I loci was estimated at four.

Episodic foresight and aging.

Decline in episodic memory is one of the most prominent cognitive deficits seen in late adulthood. It is therefore surprising that few studies have examined how the related capacity for episodic foresight might also be affected in this age group. Preliminary evidence suggests that older adults show deficits in generating phenomenological characteristics of future events, but the critical question of whether such deficits extend to generating and executing appropriate future intentions remains to be addressed.

Distribution, prevalence and host specificity of avian malaria parasites across the breeding range of the migratory lark sparrow (Chondestes grammacus).

The lark sparrow (Chondestes grammacus) is a ground-nesting passerine that breeds across much of the central North American steppe and sand barrens. Through genotyping and sequencing of avian malaria parasites we examined levels of malaria prevalence and determined the distribution of Haemoproteus and Plasmodium lineages across the breeding range of the lark sparrow. Analysis of 365 birds collected from five breeding locations revealed relatively high levels of malaria prevalence in adults (80 %) and juveniles (46 %), with infections being primarily of Haemoproteus (91 % of sequenced samples).

Novel steroid inhibitors of glucose 6-phosphate dehydrogenase.

Novel derivatives of the steroid DHEA 1, a known uncompetitive inhibitor of G6PD, were designed, synthesized, and tested for their ability to inhibit this dehydrogenase enzyme. Several compounds with approximately 10-fold improved potency in an enzyme assay were identified, and this improved activity translated to efficacy in a cellular assay. The SAR for steroid inhibition of G6PD has been substantially developed; the 3β-alcohol can be replaced with 3β-H-bond donors such as sulfamide, sulfonamide, urea, and carbamate.

Optimisation of pharmacokinetic properties to afford an orally bioavailable and selective V1A receptor antagonist.

The previously described lead compound 5 is a potent and selective V(1A) antagonist with affinity at both the rat and human receptor, but displays poor oral bioavailability and moderate clearance. We report herein the successful optimisation of the pharmacokinetic (PK) properties to afford the potent, selective, orally bioavailable and CNS penetrant compound 15f. A custom optimisation approach was required which demonstrated the value of using early, rapid in vivo PK studies to show improvements in oral exposure.