Multiplexed siRNA Immunoassay Unveils Spatial and Quantitative Dimensions of siRNA Function, Abundance, and Localization In Vitro and In Vivo.

Small interfering RNAs (siRNAs) have been successfully used as therapeutics to silence disease-causing genes when conjugated to ligands or formulated in lipid nanoparticles to target relevant cell types for efficacy while sparing other cells for safety. To support the development of new methods for delivery of siRNA therapeutics, we developed and characterized a panel of antibodies generated against chemically modified nucleotides used in therapeutic siRNA molecules, identifying a monoclonal antibody that detects a broad range of siRNA representing distinct sequences and modification patterns. By integrating this anti-siRNA antibody with additional reagents, we created a multiplex siRNA immunoassay that simultaneously quantifies siRNA uptake, trafficking, and silencing activity.

Trends and Challenges of the Modern Pathology Laboratory for Biopharmaceutical Research Excellence.

Pathology, a fundamental discipline that bridges basic scientific discovery to the clinic, is integral to successful drug development. Intrinsically multimodal and multidimensional, anatomic pathology continues to be empowered by advancements in molecular and digital technologies enabling the spatial tissue detection of biomolecules such as genes, transcripts, and proteins. Over the past two decades, breakthroughs in spatial molecular biology technologies and advancements in automation and digitization of laboratory processes have enabled the implementation of higher throughput assays and the generation of extensive molecular data sets from tissue sections in biopharmaceutical research and development research units.

Integration of rehabilitation services in primary, secondary, and tertiary levels of health care systems in low- and middle-income countries: a scoping review.

Purpose: Integration is a concept that seeks to strengthen the delivery of services to ensure people receive a continuum of care across the health system. We conducted a scoping review to explore how rehabilitation services have been integrated into health systems in low- and middle- income countries (LMICs).

Materials And Methods: We conducted a scoping review using Valentijn's Rainbow Model of Integrated Care (RMIC) as an organising framework.

The Journey to Early Identification and Intervention for Children with Disabilities in Fiji.

Early identification of developmental delay or disability and access to early intervention improves outcomes for children with disabilities and their families. However, in many low- and middle-income countries, services and systems to enable timely, co-ordinated care and support are lacking. The aim of this research was to explore the experiences of families of children with developmental disabilities in Fiji in accessing services for intervention and support across sectors.

Characterization of Selective M Acetylcholine Muscarinic Receptor Modulators on Dopamine Signaling in the Striatum.

The type-5 muscarinic acetylcholine receptor (mAChR, M) is almost exclusively expressed in dopamine (DA) neurons of the ventral tegmental area and substantia nigra pars compacta; therefore, they are ideally located to modulate DA signaling and underlying behaviors. However, the role of M in shaping DA release is still poorly characterized. In this study, we first quantitatively mapped the expression of M in different neurons of the mouse midbrain, then used voltammetry in mouse striatum to evaluate the effect of M-selective modulators on DA release.