Selective Deuteration and Tritiation of Pharmaceutically Relevant Sulfoximines.

Pharmaceutical-aligned research endeavors continue to diversify, including via the installation of new chemical functionality and non-classical bioisosteres within drug design. With this, an equally high demand emerges for the direct installation of isotopic substituents into these scaffolds within drug discovery programmes, as isotopologues are essential for the elucidation of the biological efficacy and metabolic fate of the active pharmaceutical ingredient (API). The sulfoximine functional group has recently become established as a high-value unit in this context; however, general and effective methods for the synthesis of deuterium (H, D) and tritium (H, T) labelled analogues have remained elusive.

Sigma Receptor Ligands Prevent COVID Mortality In Vivo: Implications for Future Therapeutics.

The emergence of lethal coronaviruses follows a periodic pattern which suggests a recurring cycle of outbreaks. It remains uncertain as to when the next lethal coronavirus will emerge, though its eventual emergence appears to be inevitable. New mutations in evolving SARS-CoV-2 variants have provided resistance to current antiviral drugs, monoclonal antibodies, and vaccines, reducing their therapeutic efficacy.

An immunomodulating peptide to counteract solar radiation-induced immunosuppression and DNA damage.

Ultraviolet radiation (UVR) induces immunosuppression and DNA damage, both of which contribute to the rising global incidence of skin cancer including melanoma. Nucleotide excision repair, which is activated upon UVR-induced DNA damage, is linked to expression of interleukin-12 (IL-12) which serves to limit immunosuppression and augment the DNA repair process. Herein, we report an immunomodulating peptide, designated IK14800, that not only elicits secretion of IL-12, interleukin-2 (IL-2) and interferon-gamma (IFN-γ) but also reduces DNA damage in the skin following exposure to UVR.

Digital Inclusion for Farmworkers in a Pandemic: The North Carolina Farmworker Health Program Internet Connectivity Project, 2020‒2021.

The North Carolina Farmworker Health Program (NCFHP) implemented an emergency program in response to North Carolina migrant and seasonal farmworkers' urgent need for Internet access for health information, family connections, and telehealth services during COVID-19 isolation and quarantine. This article describes the NCFHP Internet Connectivity Project implementation and evaluation from June 2020 to December 2021. The project placed 448 devices across the state and provided Internet access to more than 3184 farmworkers during the 2021 peak farming season.

A novel lipidic peptide with potential to promote balanced effector-regulatory T cell responses.

T cell-dendritic cell (DC) interactions contribute to reciprocal stimulation leading to DC maturation that results in production of interleukin-12 (IL-12) and interferon-gamma (IFN-γ). Both cytokines have been implicated in autoimmune diseases while being necessary for effective immune responses against foreign antigens. We describe a lipidic peptide, designated IK14004, that modifies crosstalk between T cells and DCs resulting in suppression of IL-12p40/IFN-γ production.

Risks of mining to salmonid-bearing watersheds.

Mining provides resources for people but can pose risks to ecosystems that support cultural keystone species. Our synthesis reviews relevant aspects of mining operations, describes the ecology of salmonid-bearing watersheds in northwestern North America, and compiles the impacts of metal and coal extraction on salmonids and their habitat. We conservatively estimate that this region encompasses nearly 4000 past producing mines, with present-day operations ranging from small placer sites to massive open-pit projects that annually mine more than 118 million metric tons of earth.

Effect of a valgus brace on medial tibiofemoral joint contact force in knee osteoarthritis with varus malalignment: A within-participant cross-over randomised study with an uncontrolled observational longitudinal follow-up.

Background: Previous investigations on valgus knee bracing have mostly used the external knee adduction moment. This is a critical limitation, as the external knee adduction moment does not account for muscle forces that contribute substantially to the medial tibiofemoral contact force (MTCF) during walking. The aims of this pilot study were to: 1) determine the effect of a valgus knee brace on MTCF; 2) determine whether the effect is more pronounced after 8 weeks of brace use; 3) assess the feasibility of an 8-week brace intervention.

Tibiofemoral contact force differences between flat flexible and stable supportive walking shoes in people with varus-malaligned medial knee osteoarthritis: A randomized cross-over study.

Objective: To compare the effect of stable supportive to flat flexible walking shoes on medial tibiofemoral contact force (MTCF) in people with medial knee osteoarthritis and varus malalignment.

Design: This was a randomized cross-over study. Twenty-eight participants aged ≥50 years with medial knee osteoarthritis and varus malalignment were recruited from the community.

Muscle Forces during Weight-Bearing Exercises in Medial Knee Osteoarthritis and Varus Malalignment: A Cross-Sectional Study.

Purpose: This study aimed to test the hypothesis that common weight-bearing exercises generate higher lower-limb muscle forces but do not increase medial tibiofemoral contact force (MTCF) when compared with walking in people with medial knee osteoarthritis and varus malalignment.

Methods: Twenty-eight participants 50 yr or older with medial knee osteoarthritis and varus malalignment were recruited from the community. Three-dimensional lower-body motion, ground reaction forces, and surface EMG from 12 lower-limb muscles were acquired during five squat, lunge, single-leg heel raise, and walking trials, performed at self-selected speeds.

Effects of adding aerobic physical activity to strengthening exercise on hip osteoarthritis symptoms: protocol for the PHOENIX randomised controlled trial.

Background: Hip osteoarthritis (OA) is a leading cause of musculoskeletal pain. Exercise is a core recommended treatment. Most evidence is based on muscle-strengthening exercise, but aerobic physical activity has potential to enhance clinical benefits.

A Pd-H/Isothiourea Cooperative Catalysis Approach to anti-Aldol Motifs: Enantioselective α-Alkylation of Esters with Oxyallenes.

The biological and therapeutic significance of natural products is a powerful impetus for the development of efficient methods to facilitate their construction. Accordingly, and reflecting the prevalence of β-oxy-carbonyl motifs, a sophisticated arsenal of aldol-based strategies has evolved that is contingent on the generation of single enolate isomers. Since this has the potential to compromise efficiency in reagent-based paradigms, direct catalysis-based solutions would be enabling.

Effects of adding a diet intervention to exercise on hip osteoarthritis pain: protocol for the ECHO randomized controlled trial.

Background: Hip osteoarthritis (OA) is a leading cause of musculoskeletal pain. Exercise is a core recommended treatment. Despite some clinical guidelines also recommending weight loss for hip OA, there is no evidence from randomised controlled trials (RCT) to substantiate these recommendations.

Expert-Moderated Peer-to-Peer Online Support Group for People With Knee Osteoarthritis: Mixed Methods Randomized Controlled Pilot and Feasibility Study.

Background: Osteoarthritis (OA) is a major problem globally. First-line management comprises education and self-management strategies. Online support groups may be a low-cost method of facilitating self-management.

Emerging mutation patterns in SARS-CoV-2 variants.

There is an urgent need to understand the functional effects of mutations in emerging variants of SARS-CoV-2. Variants of concern (alpha, beta, gamma and delta) acquired four patterns of spike glycoprotein mutations that enhance transmissibility and immune evasion: 1) mutations in the N-terminal domain (NTD), 2) mutations in the Receptor Binding Domain (RBD), 3) mutations at interchain contacts of the spike trimer, and 4) furin cleavage site mutations. Most distinguishing mutations among variants of concern are exhibited in the NTD, localized to sites of high structural flexibility.

Impact of Foliar Application of Acibenzolar-S-Methyl on Rose Rosette Disease and Rose Plant Quality.

Rose rosette disease (RRD) caused by rose rosette emaravirus (RRV) is a major issue in the U.S. rose industry with no effective method for its management.

Catalyst design in C-H activation: a case study in the use of binding free energies to rationalise intramolecular directing group selectivity in iridium catalysis.

Remote directing groups in a bifunctional molecule do not always behave independently of one another in C-H activation chemistries. A combined DFT and experimental mechanistic study to provide enhanced Ir catalysts for chemoselective C-H deuteration of bifunctional aryl primary sulfonamides is described. This provides a pharmaceutically-relevant and limiting case study in using binding energies to predict intramolecular directing group chemoselectivity.

Feasibility of exercise and weight management for people with hip osteoarthritis and overweight or obesity: A pilot study.

Objective: Determine the feasibility of a 6-month exercise and weight management intervention for people with hip osteoarthritis (OA).

Design: 18 participants with clinical and radiographic hip OA with a body mass index ≥28 ​kg/m and <41 ​kg/m participated. Six consultations with a physiotherapist and six consultations with a dietitian via videoconferencing over six months to deliver, and support, an exercise program and a ketogenic very low-calorie diet with meal replacements.

A Process Evaluation of A UK Classroom-Based Physical Activity Intervention-'Busy Brain Breaks'.

The gap between development of effective physical activity interventions and the wide-scale adoption of these interventions in real-world settings has been reported since the early 2000s. Evaluations have been criticised for failing to report details of context, implementation, adoption and maintenance. 'Busy Brain Breaks' was an intervention designed to improve fundamental movement patterns whilst increasing physical activity within the classroom.

EHealth to empower patients with musculoskeletal pain in rural Australia (EMPoweR) a randomised clinical trial: study protocol.

Background: Low back pain (LBP) and knee osteoarthritis (OA) are major contributors to disability worldwide. These conditions result in a significant burden at both individual and societal levels. Engagement in regular physical activity and exercise programs are known to improve physical function in both chronic LBP and knee OA populations.

Host Suitability for Crapemyrtle Bark Scale () Differed Significantly among Crapemyrtle Species.

Crapemyrtle bark scale (CMBS, ), an invasive polyphagous sap-sucking hemipteran, has spread across 14 states of the United States since 2004. The infestation of CMBS has negatively impacted the flowering of ornamental plants and even the fruiting of some crops. Host identification is critical for determining potential risks in ecosystems and industries and helps develop strategic management.

Computationally-Guided Development of a Chelated NHC-P Iridium(I) Complex for the Directed Hydrogen Isotope Exchange of Aryl Sulfones.

Herein, we report the rational, computationally-guided design of an iridium(I) catalyst system capable of enabling directed hydrogen isotope exchange (HIE) with the challenging sulfone directing group. Substrate binding energy was used as a parameter to guide rational ligand design via an catalyst screen, resulting in a lead series of chelated iridium(I) NHC-phosphine complexes. Subsequent preparative studies show that the optimal catalyst system displays high levels of activity in HIE, and we demonstrate the labeling of a broad scope of substituted aryl sulfones.