Exploring power and power sharing in participatory health research partnerships: A scoping review protocol.

Introduction: Participatory health research (PHR) as a research paradigm, guides the research process and strives to achieve positive change in society in the interest of people's health. In this scoping review, PHR will be used as an umbrella term considering a wide range of collaborative research approaches in the health context. PHR is conducted 'with' or 'by' those it intends to benefit, as opposed to 'on' and 'for' them.

Discovery and Optimization of a STING Agonist Platform for Application in Antibody Drug Conjugates.

While STING agonists have proven to be effective preclinically as anti-tumor agents, these promising results have yet to be translated in the clinic. A STING agonist antibody-drug conjugate (ADC) could overcome current limitations by improving tumor accessibility, allowing for systemic administration as well as tumor-localized activation of STING for greater anti-tumor activity and better tolerability. In line with this effort, a STING agonist ADC platform was identified through systematic optimization of the payload, linker, and scaffold based on multiple factors including potency and specificity in both in vitro and in vivo evaluations.

Discovery of novel polyamide-pyrrolobenzodiazepine hybrids for antibody-drug conjugates.

Pyrrolobenzodiazepine (PBD) dimers are well-known highly potent antibody drug conjugate (ADC) payloads. The corresponding PBD monomers, in contrast, have received much less attention from the ADC community. We prepared several novel polyamide-linked PBD monomers and evaluated their utility as ADC payloads.

Comprehension, Utility, and Acceptability of a Multidomain Physical Functioning Report for Systemic Lupus Erythematosus Patients and Their Providers.

Objective: Patient-provider discussions about functioning are often outside the scope of usual care for systemic lupus erythematosus (SLE), and tools to facilitate such discussions are lacking. The present study was undertaken to assess the comprehension, utility, and acceptability of a novel, individualized functioning report, the purpose of which is to facilitate patient-provider communication about functioning, in a predominantly Black SLE patient population.

Methods: Individualized reports (including sections with pictorial representations of participants' measured activities of daily living, falls, physical performance, perceived physical functioning, and community mobility from a previous pilot study visit) and surveys were emailed or mailed to 59 SLE patients.

The TechSAge Minimum Battery: A multidimensional and holistic assessment of individuals aging with long-term disabilities.

Background: People with disabilities acquired in early to mid-life are living longer, contributing to growing numbers of older adults who are aging with disability, an understudied population likely to be underserved.

Objectives: This paper demonstrates the usefulness of the TechSAge Minimum Battery as a holistic assessment of health for people aging with disabilities.

Methods: Survey data of socio-demographic and health characteristics were collected from 176 older adults with long-term vision, hearing, and/or mobility disabilities.

A web-based carepartner-integrated rehabilitation program for persons with stroke: study protocol for a pilot randomized controlled trial.

Background: Family carepartner management and support can improve stroke survivor recovery, yet research has placed little emphasis on how to integrate families into the rehabilitation process without increasing negative carepartner outcomes. Our group has developed creative approaches for engaging family carepartners in rehabilitation activities to improve physical and psychosocial health for both the carepartner and stroke survivor. The purpose of this study is to explore a novel, web-based intervention (Carepartner and Constraint-Induced Therapy; CARE-CITE) designed to facilitate positive carepartner involvement during a home-based application of constraint-induced movement therapy (CIMT) for the upper extremity.

A Modular, Tn7-Based System for Making Bioluminescent or Fluorescent Salmonella and Escherichia coli Strains.

Unlabelled: Our goal was to develop a robust tagging method that can be used to track bacterial strains in vivo To address this challenge, we adapted two existing systems: a modular plasmid-based reporter system (pCS26) that has been used for high-throughput gene expression studies in Salmonella and Escherichia coli and Tn7 transposition. We generated kanamycin- and chloramphenicol-resistant versions of pCS26 with bacterial luciferase, green fluorescent protein (GFP), and mCherry reporters under the control of σ(70)-dependent promoters to provide three different levels of constitutive expression. We improved upon the existing Tn7 system by modifying the delivery vector to accept pCS26 constructs and moving the transposase genes from a nonreplicating helper plasmid into a temperature-sensitive plasmid that can be conditionally maintained.

Synthesis and Evaluation of Oxyguanidine Analogues of the Cysteine Protease Inhibitor WRR-483 against Cruzain.

A series of oxyguanidine analogues of the cysteine protease inhibitor WRR-483 were synthesized and evaluated against cruzain, the major cysteine protease of the protozoan parasite Trypanosoma cruzi. Kinetic analyses of these analogues indicated that they have comparable potency to previously prepared vinyl sulfone cruzain inhibitors. Co-crystal structures of the oxyguanidine analogues WRR-666 (4) and WRR-669 (7) bound to cruzain demonstrated different binding interactions with the cysteine protease, depending on the aryl moiety of the P1' inhibitor subunit.

Periplasmic Acid Stress Increases Cell Division Asymmetry (Polar Aging) of Escherichia coli.

Under certain kinds of cytoplasmic stress, Escherichia coli selectively reproduce by distributing the newer cytoplasmic components to new-pole cells while sequestering older, damaged components in cells inheriting the old pole. This phenomenon is termed polar aging or cell division asymmetry. It is unknown whether cell division asymmetry can arise from a periplasmic stress, such as the stress of extracellular acid, which is mediated by the periplasm.

Older Adults' Use of and Attitudes toward Activity Monitoring Technologies.

Self-management of health is becoming increasingly important in today's healthcare climate. Activity monitoring technologies have the potential to support health self-management by tracking, storing, compiling, and providing feedback about an individual's engagement in movement activities. Older adults represent a fast growing segment of the population who may benefit from such technologies.

Spirohexenolide A targets human macrophage migration inhibitory factor (hMIF).

Spirohexenolides A and B comprise a unique family of spirotetronate natural products. We report on the identification of their binding to and modulation of human macrophage migration inhibitor factor (hMIF). Using an immunoaffinity-fluorescent labeling method, the properties of this interaction are detailed and evidence is provided that hMIF plays a key role in the cytostatic activity of the spirohexenolides.

New technology-based functional assessment tools should avoid the weaknesses and proliferation of manual functional assessments.

Background: Formal functional assessment tools for use with older adults have been in widespread use since the 1960s. Instruments have been designed to assess a wide range of different aspects of a person's everyday life. This article seeks to document the evolution of the tools used in such a way as to inform the development of the field.

Structure of FD-895 revealed through total synthesis.

The total synthesis of FD-895 was completed through a strategy that featured the use of a tandem esterification ring-closing metathesis (RCM) process to construct the 12-membered macrolide and a modified Stille coupling to append the side chain. These studies combined with detailed analysis of all four possible C16-C17 stereoisomers were used to confirm the structure of FD-895 and identify an analog with an enhanced subnanomolar bioactivity.

Comparison of radiation treatment delivery for pancreatic cancer: Linac intensity-modulated radiotherapy versus helical tomotherapy.

Introduction: Intensity-modulated radiotherapy (IMRT) has been shown to reduce dose to organs at risk (OAR) while adequately treating tumour volume. This study quantitatively compares the dosimetric differences from step-and-shoot IMRT compared with helical tomotherapy (HT) for pancreatic head cancer.

Methods: Twelve consecutive patients with non-metastatic, stage T3 or T4, unresectable pancreatic head cancer were planned for step-and-shoot IMRT as well as HT.

Convergent route to the spirohexenolide macrocycle.

Using key functional dissections, the synthesis of spirohexenolides is examined through a three-component strategy that features a 1,2-addition to couple tetronate and aldehyde components forming the C2-C3 bond and a Stille coupling to install the third sulfone-containing component. The macrocycle is completed by an intramolecular Julia-Kocienski reaction to form the C10-C11 trans-disubstituted olefin. Application of this strategy is described in progress toward the synthesis of (±)-spirohexenolide B.

Cytoplasmic acidification and the benzoate transcriptome in Bacillus subtilis.

Background: Bacillus subtilis encounters a wide range of environmental pH. The bacteria maintain cytoplasmic pH within a narrow range. Response to acid stress is a poorly understood function of external pH and of permeant acids that conduct protons into the cytoplasm.

Isolation, structure elucidation, and antitumor activity of spirohexenolides A and B.

In this report, we describe the discovery of a pair of bioactive spirotetronates, spirohexenolides A (1) and B (2), that arose from the application of mutagenesis, clonal selection techniques, and media optimization to strains of Streptomyces platensis. The structures of spirohexenolides A (1) and B (2) were elucidated through X-ray crystallography and confirmed by 1D and 2D NMR studies. Under all examined culture conditions, spirohexenolide A (1) was the major metabolite with traces of spirohexenolide B (2) arising in cultures containing increased loads of adsorbent resins.

Responsiveness of a Xenopus laevis cell line to the aryl hydrocarbon receptor ligands 6-formylindolo[3,2-b]carbazole (FICZ) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

The aryl hydrocarbon receptor (AHR) mediates the toxic effects of environmental contaminants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Frogs are very insensitive to TCDD toxicity, and AHRs from Xenopus laevis (African clawed frog) bind TCDD with >20-fold lower affinity than mouse AHR(b-1). Frog AHRs may nonetheless be highly responsive to structurally distinct compounds, especially putative endogenous ligands.

Acid and base stress and transcriptomic responses in Bacillus subtilis.

Acid and base environmental stress responses were investigated in Bacillus subtilis. B. subtilis AG174 cultures in buffered potassium-modified Luria broth were switched from pH 8.

Rapid acid treatment of Escherichia coli: transcriptomic response and recovery.

Background: Many E. coli genes show pH-dependent expression during logarithmic growth in acid (pH 5-6) or in base (pH 8-9). The effect of rapid pH change, however, has rarely been tested.

A synthetic entry to pladienolide B and FD-895.

Presented within are syntheses of the pladienolide B and FD-895 side-chains, as well as models of the essential ring-closing metathesis and Stille coupling that will be used to complete their total syntheses. Several analogs of the pladienolide B side-chain were also prepared in order to evaluate the scope of the methodology and to create a library of structures that could be used for stereochemical and SAR analyses.

Oxygen limitation modulates pH regulation of catabolism and hydrogenases, multidrug transporters, and envelope composition in Escherichia coli K-12.

Background: In Escherichia coli, pH regulates genes for amino-acid and sugar catabolism, electron transport, oxidative stress, periplasmic and envelope proteins. Many pH-dependent genes are co-regulated by anaerobiosis, but the overall intersection of pH stress and oxygen limitation has not been investigated.

Results: The pH dependence of gene expression was analyzed in oxygen-limited cultures of E.

Evaluation of redox indicators for determining sulfate-reducing and dechlorinating conditions.

An in situ methodology based on covalently bonded redox indicators has been developed for determining when sulfate-reducing conditions exist in environmental samples. Three immobilized redox indicators [thionine (Thi, formal potential at pH 7 (E(0')7) equals 52 mV), cresyl violet (CV, E(0')7 = -81 mV), and phenosafranine (PSaf, E(0')7 = -267 mV)] were tested for their response to sulfide in synthetic solutions and under sulfate-reducing conditions in wastewater slurries. The byproduct of the sulfate-reducing process, sulfide, was found to couple well to CV in the concentration range of 1-100 microM total sulfide ([S(-II)]) and the pH range of 6-8.