Concurrent Validity of Performance-Based Measures of Daily Functioning with Cognitive Measures and Informant Reported Everyday Functioning.

Objective: Despite the substantial need for reliable and valid assessment of functional ability in older adults, there is currently limited research on the emergence of early functional declines during prodromal dementia stages, such as subjective cognitive decline (SCD) and mild cognitive impairment (MCI). This study uses novel performance-based assessments to characterize subtle, yet clinically meaningful, changes in functional ability.

Method: A sample of 93 older adults classified as cognitively unimpaired (CU; n = 30, Mage = 73.

Oral pharmacokinetics and efficacy of oral phospholipid remdesivir nucleoside prodrugs against SARS-CoV-2 in mice.

Oral broad-spectrum antivirals are urgently needed for the treatment of many emerging and contemporary RNA viruses. We previously synthesized 1--octadecyl-2--benzyl--glyceryl-P-RVn (ODBG-P-RVn, V2043), a phospholipid prodrug of GS-441524 (remdesivir nucleoside, RVn), and demonstrated its efficacy in a SARS-CoV-2 mouse model. Structure-activity relationship studies focusing on the prodrug scaffold identified two modifications, 3-fluoro-4-methoxy-benzyl (V2053) and 4-cyano-benzyl (V2067), that significantly enhanced the broad-spectrum antiviral activity against multiple RNA viruses when compared to V2043.

Biopsy-based transcriptomics in the diagnosis of kidney transplant rejection.

Purpose Of Review: The last year has seen considerable progress in translational research exploring the clinical utility of biopsy-based transcriptomics of kidney transplant biopsies to enhance the diagnosis of rejection. This review will summarize recent findings with a focus on different platforms, potential clinical applications, and barriers to clinical adoption.

Recent Findings: Recent literature has focussed on using biopsy-based transcriptomics to improve diagnosis of rejection, in particular antibody-mediated rejection.

Perceptions of older and younger adults who wear hearing aids.

Objective: To investigate older and younger adults' perceptions of older and younger adults who wear hearing aids.

Design: Participants completed two Implicit Association Tests: One with images of older adults (OA-IAT) and one with images of younger adults (YA-IAT), either wearing or not wearing hearing aids. Participants also rated age, attractiveness, and intelligence of younger and older adults pictured with or without a hearing aid.

An investigation of temperature and fever burdens in patients with sepsis admitted from the emergency department to the hospital.

Aim: We sought to collect granular data on temperature burden to further explore existing conflicting information on the relationship between temperature alterations and outcomes in patients with sepsis requiring hospital admission.

Methods: This was a prospective cohort study that enrolled a convenience sample of patients with sepsis or septic shock admitted to the hospital from the emergency department (ED). A "unit of temperature burden (UTB)" was defined as >1°C (1.

Enhanced broad spectrum in vitro antiviral efficacy of 3-F-4-MeO-Bn, 3-CN, and 4-CN derivatives of lipid remdesivir nucleoside monophosphate prodrugs.

Broad spectrum oral antivirals are urgently needed for the early treatment of many RNA viruses of clinical concern. We previously described the synthesis of 1-O-octadecyl-2-O-benzyl-glycero-3-phospho-RVn (V2043), an orally bioavailable lipid prodrug of remdesivir nucleoside (RVn, GS-441524) with broad spectrum antiviral activity against viruses with pandemic potential. Here we compared the relative activity of V2043 with new RVn lipid prodrugs containing sn-1 alkyl ether or sn-2 glycerol modifications.

Application of the Banff Human Organ Transplant Panel to kidney transplant biopsies with features suspicious for antibody-mediated rejection.

The Banff Classification for Allograft Pathology includes the use of gene expression in the diagnosis of antibody-mediated rejection (AMR) of kidney transplants, but a predictive set of genes for classifying biopsies with 'incomplete' phenotypes has not yet been studied. Here, we developed and assessed a gene score that, when applied to biopsies with features of AMR, would identify cases with a higher risk of allograft loss. To do this, RNA was extracted from a continuous retrospective cohort of 349 biopsies randomized 2:1 to include 220 biopsies in a discovery cohort and 129 biopsies in a validation cohort.

A Simple Molecular Tool for the Assessment of Kidney Transplant Biopsies.

Background: The Banff Classification for Allograft Pathology recommendations for the diagnosis of kidney transplant rejection includes molecular assessment of the transplant biopsy. However, implementation of molecular tools in clinical practice is still limited, partly due to the required expertise and financial investment. The reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA) assay is a simple, rapid, and inexpensive assay that permits simultaneous evaluation of a restricted gene panel using paraffin-embedded tissue blocks.

Visual Speech Improves Older and Younger Adults' Response Time and Accuracy for Speech Comprehension in Noise.

Past research suggests that older adults expend more cognitive resources when processing visual speech than younger adults. If so, given resource limitations, older adults may not get as large a visual speech benefit as younger ones on a resource-demanding speech processing task. We tested this using a speech comprehension task that required attention across two talkers and a simple response (i.

Developing a Real-Time Test to Investigate Conversational Speech Understanding.

Purpose: This study aimed to develop and test a measure of real-time continuous speech understanding to be used with natural dialogues.

Method: The measure was based on a category monitoring paradigm and employed five existing recordings of natural dialogues from which the different test categories and associated target words were derived. For each dialogue, a listener was first given a semantic category and asked to press a button as quickly as possible whenever they heard an instance of the category.

Ring-opening reactions for the solid-phase synthesis of nisin lipopeptide analogues.

Three lipopeptide analogues of the lantibiotic nisin A have been synthesised on-resin using Fmoc-SPPS techniques to investigate the structure-activity relationship of the A and B ring of these types of lanthipeptides. Lanthionine and methyllanthionine macrocycles were incorporated using orthogonally protected residues for on-resin cyclisation. Unsaturated dehydroalanine and, for the first time, dehydrobutyrine were synthesised on-resin from their cysteine derivatives.

Response of phytoplankton community composition to physicochemical and meteorological factors under different hydrological conditions in Lake Diefenbaker.

Changes in hydro-meteorological conditions due to warming climate and the operation of reservoirs may support algal blooms. Lake Diefenbaker is a large reservoir on the Canadian Prairies. Annual flow volume from its major tributary, the South Saskatchewan River (SSR), varies with precipitation and temperature in the Rocky Mountains.

Amygdala but not hippocampal damage associated with smaller social network size.

Social network size has been associated with complex socio-cognitive processes (e.g., memory, perspective taking).

A Narrative Review of Loneliness and Brain Health in Older Adults: Implications of COVID-19.

Purpose Of Review: This narrative review highlights important factors contributing to loneliness in older adults prior to and during the COVID-19 pandemic and effects on brain health.

Recent Findings: We characterize risk factors for loneliness in older adulthood and the impact of COVID-19. Furthermore, we discuss the implications of loneliness for older adults' brain health.

Investigating the role of involuntary retrieval in music-evoked autobiographical memories.

Music is a particularly salient autobiographical memory cue. Prior work has indicated that autobiographical memories evoked by music are more episodically rich than those evoked by other sensory cues. One explanation for this effect could be that music evokes autobiographical memories in a more involuntary manner than other cues.

Broad-Spectrum Antiviral Activity of ODBG-P-RVn: An Orally-Available, Lipid-Modified Monophosphate Prodrug of Remdesivir Parent Nucleoside (GS-441524).

The necessity for intravenous administration of remdesivir confines its utility for treatment of coronavirus disease 2019 (COVID-19) to hospitalized patients. We evaluated the broad-spectrum antiviral activity of ODBG-P-RVn, an orally available, lipid-modified monophosphate prodrug of the remdesivir parent nucleoside (GS-441524), against viruses that cause diseases of human public health concern, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ODBG-P-RVn showed 20-fold greater antiviral activity than GS-441524 and had activity nearly equivalent to that of remdesivir in primary-like human small airway epithelial cells.

Effects of Age and Uncertainty on the Visual Speech Benefit in Noise.

Purpose: Listeners understand significantly more speech in noise when the talker's face can be seen (visual speech) in comparison to an auditory-only baseline (a visual speech benefit). This study investigated whether the visual speech benefit is reduced when the correspondence between auditory and visual speech is uncertain and whether any reduction is affected by listener age (older vs. younger) and how severe the auditory signal is masked.

Slow acoustic surface modes through the use of hidden geometry.

The acoustic surface modes supported by a partly covered periodic meander groove structure formed in an assumed perfectly rigid plate are investigated. This allows one to create a slower acoustic surface wave than can be achieved with the same uncovered meander structure. By changing the size of the uncovered section the phase and group speeds can be tuned.

Decarboxylative Radical Addition to Methylideneoxazolidinones for Stereocontrolled Synthesis of Selectively Protected Diamino Diacids.

Syntheses of stereochemically pure and selectively protected diamino diacids can be achieved by redox decarboxylation of distal -hydroxyphthalimide esters of protected aspartic, glutamic or α-aminoadipic acids via radical addition to methylideneoxazolidinones. The products are useful for solid-supported syntheses of robust bioactive carbocyclic peptide analogs. Yields of reactive primary radical addition are superior to those of more stabilized radicals, and the reaction fails if the alkylideneoxazolidinone has a methyl substituent on its terminus (i.

Broad-spectrum in vitro antiviral activity of ODBG-P-RVn: an orally-available, lipid-modified monophosphate prodrug of remdesivir parent nucleoside (GS-441524).

The intravenous administration of remdesivir for COVID-19 confines its utility to hospitalized patients. We evaluated the broad-spectrum antiviral activity of ODBG-P-RVn, an orally available, lipid-modified monophosphate prodrug of the remdesivir parent nucleoside (GS-441524) against viruses that cause diseases of human public health concern, including SARS-CoV-2. ODBG-P-RVn showed 20-fold greater antiviral activity than GS-441524 and had near-equivalent activity to remdesivir in primary-like human small airway epithelial cells.

Diagnostic application of transcripts associated with antibody-mediated rejection in kidney transplant biopsies.

Background: The diagnosis of antibody-mediated rejection (AMR) is reached using the Banff Classification for Allograft Pathology, which now includes gene expression analysis. In this study, we investigate the application of 'increased expression of thoroughly validated gene transcripts/classifiers strongly associated with AMR' as diagnostic criteria.

Method: We used quantitative real-time polymerase chain reaction for 10 genes associated with AMR in a retrospective cohort of 297 transplant biopsies, including biopsies that met the full diagnostic criteria for AMR, even without molecular data (AMR, n = 27), biopsies that showed features of AMR, but that would only meet criteria for AMR with increased transcripts [suspicious for AMR (AMRsusp), n = 49] and biopsies that would never meet criteria for AMR (No-AMR, n = 221).

Rethinking Remdesivir: Synthesis, Antiviral Activity, and Pharmacokinetics of Oral Lipid Prodrugs.

Remdesivir (RDV; GS-5734) is currently the only FDA-approved antiviral drug for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The drug is approved for use in adults or children 12 years or older who are hospitalized for the treatment of COVID-19 on the basis of an acceleration of clinical recovery for inpatients with this disease. Unfortunately, the drug must be administered intravenously, restricting its use to those requiring hospitalization for relatively advanced disease.

A Narrative Review Examining the Utility of Interpersonal Synchrony for the Caregiver-Care Recipient Relationship in Alzheimer's Disease and Related Dementias.

The stressful nature of caring for an older adult with a chronic disease, such as Alzheimer's disease (AD), can create barriers between the caregiver-care recipient, as they try to navigate their continuously changing social relationship. Interpersonal synchrony (i.e.