CoDesign of a digital intervention for parents with bipolar disorder informed by integrated knowledge translation principles.

OBJECTIVES: To provide detailed information on the codesign of a digital intervention to support parents with bipolar disorder (BD) who have young children. Each step of this process is reported, as well as a detailed description of the final version of the intervention in line with the TIDieR framework. METHODS: Clinical experience and lived experience experts participated in online workshops, meetings, and remote feedback requests, informed by Integrated Knowledge Translation (IKT) principles. The IKT research group responded to each phase of recommendations from the knowledge users. RESULTS: Five clinical experience experts and six lived experience experts engaged with the codesign process. Their recommendations for principles, content, look, and feel, and functionality of the digital intervention were structured over five iterative phases. This led to a final implemented design that was identified by the clinical and lived experience experts (referred to together as the knowledge users group) as genuinely reflecting their input. CONCLUSIONS: The IKT principles offer an accessible structure for engaging with clinical and lived experience experts throughout a codesign process, in this case for a digital intervention for parents with BD. The resulting intervention is described in detail for transparency to aid further evaluation and development and to help other teams planning codesign approaches to intervention development.

Development, validation and application of an LC-MS/MS method quantifying free forms of the micronutrients queuine and queuosine in human plasma using a surrogate matrix approach.

Queuosine (Q) is a hypermodified 7-deaza-guanosine nucleoside exclusively synthesized by bacteria. This micronutrient and its respective nucleobase form queuine (q) are salvaged by humans either from gut microflora or digested food. Depletion of Q-tRNA in human or mouse cells causes protein misfolding that triggers endoplasmic reticular stress and the activation of the unfolded protein responses. In vivo, this reduces the neuronal architecture of the mouse brain affecting learning and memory. Herein, a sensitive method for quantifying free q and Q in human blood was developed, optimised and validated. After evaluating q/Q extraction efficiency in several different solid-phase sorbents, Bond Elut PBA (phenylboronic acid) cartridges were found to have the highest extraction recovery for q (82%) and Q (71%) from pooled human plasma. PBS with 4% BSA was used as surrogate matrix for method development and validation. An LC-MS/MS method was validated across the concentration range of 0.0003-1 µM for both q and Q, showing excellent linearity (r2 = 0.997 (q) and r2 = 0.998 (Q)), limit of quantification (0.0003 µM), accuracy (100.39-125.71%) and precision (CV% < 15.68%). In a sampling of healthy volunteers (n = 44), there was no significant difference in q levels between male (n = 14; mean = 0.0068 µM) and female (n = 30; mean = 0.0080 µM) participants (p = 0.50). Q was not detected in human plasma. This validated method can now be used to further substantiate the role of q/Q in nutrition, physiology and pathology.

Platform Design for Optical Screening and Conditioning for Injury Resilience.

INTRODUCTION: Musculoskeletal injuries (MSKIs) among active duty soldiers result in more than 10 million limited duty days each year and account for more than 70% of the medically nondeployable population. Overuse injuries in lower limbs from running, foot marching long distances with heavy loads, and lifting heavy objects are the most common types of injuries in the military. Physical training and rehabilitation exercises for greater resiliency through aerobic, muscle strength, endurance, and agility conditioning programs can prevent or reduce the effects of MSKIs if Soldiers adhere to proper biomechanics and training techniques. We are introducing a three-dimensional (3D) camera-based platform for Optical Screening and Conditioning for Injury Resilience (OSCIR) that is designed to identify and correct high-risk movement patterns based on quantifiable biomechanical measurements in clinical or field settings. Our goal is to improve resilience to MSKI by offering greater access to quality of movement skills in warfighters through an autonomous device that can be used in Sports Medicine and Reconditioning Team (SMART) clinics and High-Intensity Tactical Training (HITT) sites. MATERIALS AND METHODS: OSCIR fuses four pairs of Kinect Azure cameras into a concise footprint to achieve suitable sampling rates and an unobstructed field of view for accurate dynamic movement tracking using a custom point cloud solution. We designed a unique multistage 3D joint tracking algorithm architecture to methodically isolate the human body point cloud from the background, identify individual limb segments, and perform iterative joint optimization at the global and local joint levels. We evaluated the feasibility of our prototype system among N = 12 control participants (6 M/6 F; 21-37 years) in compliance with the Western Institutional Review Board (Tracking #20225920, approved on November 4, 2022). Five task-specific MSKI outcome metrics identified by end-user physical therapists and athletic trainers as indicators for movement quality were assessed across 7 lower-extremity exercises derived from standardized MSK assessment/conditioning batteries used in the military. Data were recorded concurrently by OSCIR and a reference standard Vicon motion capture system for validating system accuracy. RESULTS: Task-specific MSKI indicators for knee flexion and hip flexion range of motion achieved an average error of 4.05 ± 2.34°, while 3D position-based postural outcomes of left-right foot distance, left-right hand distance, and step length obtained mean absolute errors of 2.58 ± 2.30 cm. Results support the feasibility of our system in achieving outcomes that are comparable to currently accepted laboratory standards. CONCLUSIONS: Our study describes the integration process for a 3D camera-based clinical system for MSKI conditioning and rehabilitation. The impact of our system will enable key stakeholders in the military to manage MSKIs in warfighters by automating key assessment and rehabilitation test batteries; making tests more readily accessible, and interpretations more accurate by providing objective biomechanical measures. OSCIR is undergoing turn-key design features to serve as a screening tool for warfighters to readily assess susceptibility to MSKI or as a training platform to help guide exercise techniques to achieve resiliency against future injuries.

Plasma metabolites distinguish dementia with Lewy bodies from Alzheimer's disease: a cross-sectional metabolomic analysis.

Background: In multifactorial diseases, alterations in the concentration of metabolites can identify novel pathological mechanisms at the intersection between genetic and environmental influences. This study aimed to profile the plasma metabolome of patients with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD), two neurodegenerative disorders for which our understanding of the pathophysiology is incomplete. In the clinical setting, DLB is often mistaken for AD, highlighting a need for accurate diagnostic biomarkers. We therefore also aimed to determine the overlapping and differentiating metabolite patterns associated with each and establish whether identification of these patterns could be leveraged as biomarkers to support clinical diagnosis. Methods: A panel of 630 metabolites (Biocrates MxP Quant 500) and a further 232 metabolism indicators (biologically informative sums and ratios calculated from measured metabolites, each indicative for a specific pathway or synthesis; MetaboINDICATOR) were analyzed in plasma from patients with probable DLB (n = 15; age 77.6 ± 8.2 years), probable AD (n = 15; 76.1 ± 6.4 years), and age-matched cognitively healthy controls (HC; n = 15; 75.2 ± 6.9 years). Metabolites were quantified using a reversed-phase ultra-performance liquid chromatography column and triple-quadrupole mass spectrometer in multiple reaction monitoring (MRM) mode, or by using flow injection analysis in MRM mode. Data underwent multivariate (PCA analysis), univariate and receiving operator characteristic (ROC) analysis. Metabolite data were also correlated (Spearman r) with the collected clinical neuroimaging and protein biomarker data. Results: The PCA plot separated DLB, AD and HC groups (R2 = 0.518, Q2 = 0.348). Significant alterations in 17 detected metabolite parameters were identified (q ≤ 0.05), including neurotransmitters, amino acids and glycerophospholipids. Glutamine (Glu; q = 0.045) concentrations and indicators of sphingomyelin hydroxylation (q = 0.039) distinguished AD and DLB, and these significantly correlated with semi-quantitative measurement of cardiac sympathetic denervation. The most promising biomarker differentiating AD from DLB was Glu:lysophosphatidylcholine (lysoPC a 24:0) ratio (AUC = 0.92; 95%CI 0.809-0.996; sensitivity = 0.90; specificity = 0.90). Discussion: Several plasma metabolomic aberrations are shared by both DLB and AD, but a rise in plasma glutamine was specific to DLB. When measured against plasma lysoPC a C24:0, glutamine could differentiate DLB from AD, and the reproducibility of this biomarker should be investigated in larger cohorts.

Pharmacological evaluation of Rhazya stricta root extract / Evaluación farmacológica del extracto de raíz de Rhazya stricta

The present study aimed to screen the Rhazya stricta Decne root for its antihyperglycemic and antioxidants potential through invitro assays along with phytochemical and elemental analyses. The crude extract was prepared through maceration and fractionated using solvent-solvent extraction technique. The spectroscopic studies indicated the presence of various phytochemical classes in the extract and its fractions. The antioxidant assays showed notable results along with a good concentration of phenolic and flavonoid contents. Enzyme inhibition assays demonstrated glucose-lowering effects by inhibiting the enzyme activity which could reduce post-prandial blood glucose level. The Dipeptidyl peptidase-IV (DPP-IV) inhibition assay results showed the novel DPP-IV inhibition activity of the plant extract and all fractions showed noteworthy enzyme inhibition and antihyperglycemic activity. Conclusively, the Rhazya stricta root extract displayed its antioxidant and antihyperglycemic potential due to the presence of various classes of phytochemicals and micro-nutrients.

El presente estudio tuvo como objetivo examinar la raíz de Rhazya stricta Decne por su potencial antihiperglicémico y antioxidante a través de ensayos in vitro junto con análisis fitoquímicos y elementales. El extracto crudo se preparó por maceración y se fraccionó usando una técnica de extracción solvente-solvente. Los estudios espectroscópicos indicaron la presencia de varias clases fitoquímicas en el extracto y sus fracciones. Los ensayos antioxidantes mostraron resultados notables junto con una importante concentración de contenido fenólico y flavonoide. Los ensayos de inhibición enzimática demostraron efectos reductores de la glucosa al inhibir la actividad enzimática que podría reducir el nivel de glucosa posprandial en sangre. Los resultados del ensayo de inhibición de Dipeptidyl peptidase-IV (DPP-IV) mostraron la nueva actividad de inhibición de DPP-IV del extracto de la planta y todas las fracciones mostraron una notable inhibición enzimática y actividad antihiperglicémica. En conclusión, el extracto de raíz de Rhazya stricta Decne mostró su potencial antioxidante y antihiperglicémico debido a la presencia de varias clases de fitoquímicos y micronutrientes.

Effects of Undaria pinnatifida, Himanthalia elongata and Porphyra umbilicalis extracts on in vitro alpha-glucosidase activity and glucose diffusion / Efectos de extractos de undaria pinnatifida, himantalia elongata y porfira umbilicalis sobre la actividad alpha-glucosidasa y la difusion de la glucosa in vitro

Background: Seaweeds are good sources of dietary fibre, which can influence glucose uptake and glycemic control. Objective: To investigate and compare the in vitro inhibitory activity of different extracts from Undaria pinnatifida (Wakame), Himanthalia elongata (Sea spaghetti) and Porphyra umbilicalis (Nori) on α-glucosidase activity and glucose diffusion. Methods: The in vitro effects chloroform-, ethanol- and water-soluble extracts of the three algae were assayed on α- glucosidase activity and glucose diffusion through membrane. Principal Components Analysis (PCA) was applied to identify patterns in the data and to discriminate which extract will show the most proper effect. Results: Only water extracts of Sea spaghetti possessed significant in vitro inhibitory effects on α-glucosidase activity (26.2% less mmol/L glucose production than control, p < 0.05) at 75 min. PCA distinguished Sea spaghetti effects, supporting that soluble fibre and polyphenols were involved. After 6 h, Ethanol-Sea spaghetti and water-Wakame extracts exerted the highest inhibitory effects on glucose diffusion (65.0% and 60.2% vs control, respectively). This extracts displayed the lowest slopes for glucose diffusion-time lineal adjustments (68.2% and 62.8% vs control, respectively). Conclusions: The seaweed hypoglycemic effects appear multi-faceted and not necessarily concatenated. According to present results, ethanol and water extracts of Sea spaghetti, and water extracts of Wakame could be useful for the development of functional foods with specific hypoglycemic properties (AU)

Antecedentes: Las algas son importante fuente alimentaria de fibra dietética y puede influir sobre la absorción de glucosa y el control glucémico. Objetivo: Evaluar y comparar in vitro los efectos de diferentes extractos de las algas Undaria pinnatifida (Wakame), Himanthalia elongata (Espagueti de mar) y Porphyra umbilicalis (Nori) sobre la actividad enzimática α-glucosidasa y la difusión de glucosa. Métodos: Se estudiaron los efectos de los extractos clorofórmicos, etánólicos y acuosos de las tres algas sobre la actividad α-glucosidasa y la difusión de glucosa a través de una membrana de diálisis. Se aplicó a los resultados un análisis de los componentes principales (PCA) para identificar posibles patrones de composición y seleccionar el extracto que mejores propiedades posea. Resultados: El extracto acuoso de Espagueti de mar inhibió de forma significativa la actividad α-glucosidasa (26,2% menos liberación de glucosa, p < 0,05). El PCA sugiere que la fibra soluble y los polifenoles son los responsables de tal efecto. Respecto a la difusión de glucosa, el extracto etanólico de Espagueti de mar y el acuoso de Wakame mostraron un mayor efecto inhibidor después de 6 horas (65% y 60,2% vs control, respectivamente) y las menores pendientes en los ajustes lineales difusión de glucosa-tiempo (68,2% y 62,8% vs control respectivamente). Conclusiones: Los resultados de los diferentes extractos sugieren que los efectos hipogluceminates de las algas son variados y no están necesariamente concatenados. Los extractos acuosos y etanólicos de Espagueti de mar y los acuosos de Wakame parecen los más adecuados para el desarrollo de alimentos funcionales con propiedades hipoglucemiantes (AU)