Engineering Low Volume Resuscitants for the Prehospital Care of Severe Hemorrhagic Shock.

Globally, traumatic injury is a leading cause of suffering and death. The ability to curtail damage and ensure survival after major injury requires a time-sensitive response balancing organ perfusion, blood loss, and portability, underscoring the need for novel therapies for the prehospital environment. Currently, there are few options available for damage control resuscitation (DCR) of trauma victims. We hypothesize that synthetic polymers, which are tunable, portable, and stable under austere conditions, can be developed as effective injectable therapies for trauma medicine. In this work, we design injectable polymers for use as low volume resuscitants (LVRs). Using RAFT polymerization, we evaluate the effect of polymer size, architecture, and chemical composition upon both blood coagulation and resuscitation in a rat hemorrhagic shock model. Our therapy is evaluated against a clinically used colloid resuscitant, Hextend. We demonstrate that a radiant star poly(glycerol monomethacrylate) polymer did not interfere with coagulation while successfully correcting metabolic deficit and resuscitating animals from hemorrhagic shock to the desired mean arterial pressure range for DCR - correcting a 60 % total blood volume (TBV) loss when given at only 10 % TBV. This highly portable and non-coagulopathic resuscitant has profound potential for application in trauma medicine.

Aptamer-Based Chromatographic Methods for Efficient and Economical Separation of Leukocyte Populations.

The manufacturing process of chimeric antigen receptor T cell therapies includes isolation systems that provide pure T cells. Current magnetic-activated cell sorting and immunoaffinity chromatography methods produce desired cells with high purity and yield but require expensive equipment and reagents and involve time-consuming incubation steps. Here, we demonstrate that aptamers can be employed in a continuous-flow resin platform for both depletion of monocytes and selection of CD8+ T cells from peripheral blood mononuclear cells at low cost with high purity and throughput. Aptamer-mediated cell selection could potentially enable fully synthetic, traceless isolations of leukocyte subsets from a single isolation system.

Aptamers 101: aptamer discovery and in vitro applications in biosensors and separations.

Aptamers are single-stranded nucleic acids that bind and recognize targets much like antibodies. Recently, aptamers have garnered increased interest due to their unique properties, including inexpensive production, simple chemical modification, and long-term stability. At the same time, aptamers possess similar binding affinity and specificity as their protein counterpart. In this review, we discuss the aptamer discovery process as well as aptamer applications to biosensors and separations. In the discovery section, we describe the major steps of the library selection process for aptamers, called systematic evolution of ligands by exponential enrichment (SELEX). We highlight common approaches and emerging strategies in SELEX, from starting library selection to aptamer-target binding characterization. In the applications section, we first evaluate recently developed aptamer biosensors for SARS-CoV-2 virus detection, including electrochemical aptamer-based sensors and lateral flow assays. Then we discuss aptamer-based separations for partitioning different molecules or cell types, especially for purifying T cell subsets for therapeutic applications. Overall, aptamers are promising biomolecular tools and the aptamer field is primed for expansion in biosensing and cell separation.

High-molecular weight impurity screening by size-exclusion chromatography on a reversed-phase column.

Monitoring polymerization events leading to the discovery of new high-molecular weight (MW) impurities is challenging during chemical syntheses of active pharmaceutical ingredients. Employing reversed-phase chromatography (RPC) stationary phases (SPs) in size-exclusion chromatography (SEC) mode could be a potential solution given their high efficiency, sensitivity, and extensive solvent compatibility. However, there is a lack of generalized means for trace polymeric impurities across a wide range of physicochemical properties. Herein, we developed a SEC-based approach with a C18 SP for screening such high-MW impurities. Seven polymer standards presenting a variety of functional groups, consisting of hydrophobic, heterocyclic, ionic, and neutral hydrophilic moieties, were utilized as model impurities to establish the screening conditions. Nine mobile phases (tetrahydrofuran-based, buffered methanol, and buffered acetonitrile) were proposed to cover all model polymers and a majority of potential high-MW impurities in small molecule chemical syntheses. The established screening system demonstrated a linearity of 0.05-1.0 % w/w (R2>0.99) for the selected model impurities with proper elution conditions. Two real high-MW impurities, BMT-041910 (polymeric degradation) and poly(phenyl thiirane) (by-product polymerization), were identified from the proposed high-MW impurity screening. The successful conditions yielded a quantitative limit better than 0.1 % w/w in both cases. We believe the developed screening platform is applicable to the analysis of a wide variety of unknown high-MW impurities of low abundance potentially generated during drug substance development.

Trigeminal neuralgia associated with a variant of persistent trigeminal artery.

A persistent trigeminal artery variant (PTAV) is an anomalous vessel that originates from the internal carotid artery and directly supplies the cerebellum without interposition of the basilar artery. This anatomic variant is usually found incidentally on imaging but can rarely have clinical implications. We describe a case of a 74-year-old woman presenting with multiple years of lower jaw pain attributed to trigeminal neuralgia, unresolved with medication. A persistent trigeminal artery variant compressing the trigeminal nerve was identified on magnetic resonance imaging and magnetic resonance angiography. The characteristic imaging findings of PTAV are essential for identifying an etiology of medically refractory trigeminal neuralgia and may assist with preoperative planning.

Anaplastic meningioma seeding of the abdominal wall following calvarial bone flap preservation.

Meningiomas are common intracranial tumors that rarely metastasize. We present a highly unusual case of a 42-year-old man with direct seeding of meningioma to the abdominal wall. The patient had a history of multiple operations for a recurrent intracranial meningioma with decompressive craniectomy and preservation of the calvarial bone flap by implantation into the subcutaneous layer of the anterior abdominal wall. Following removal of the bone flap, a new abdominal wall mass was identified, consistent with iatrogenic implantation of anaplastic meningioma.

The Clinical Utility of the TYM and RBANS in a One-Stop Memory Clinic in Singapore: A Pilot Study.

BACKGROUND: We aimed to examine the discriminant validity of a brief self-administered cognitive screening test, the Test Your Memory (TYM) and a brief neuropsychological test, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), supplemented with executive and language tests (Color Trail Test [CTT] and modified Boston Naming Test [mBNT], respectively), in detecting cognitive impairment (CI) in a one-stop memory clinic in Singapore. METHODS: Ninety patients ≥50 years old with a diagnosis of no cognitive impairment, mild cognitive impairment, and mild Alzheimer disease were recruited from memory clinic. They received the TYM, Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), RBANS, CTT, mBNT, and a gold-standard formal neuropsychological test battery. RESULTS: The TYM had a significantly larger area under the curve (AUC) than MMSE (0.96 vs 0.88, P = .03) and was equivalent to MoCA in detecting CI (0.96 vs 0.95, P = .80). At the optimal cutoff points, the TYM (<38) was significantly more sensitive than the MMSE (<24) and MoCA (<20; P < .001). The RBANS had an AUC equivalent to the RBANS supplemented with CTT and mBNT (0.92 vs 0.86, P = .22) in detecting CI. The RBANS supplemented with CTT and mBNT was more sensitive than RBANS alone in detecting CI (sensitivity: 0.98 vs 0.93, P = .016) among patients screened negative using TYM. CONCLUSION: The self-administered TYM is superior to MMSE and equivalent to MoCA in detecting CI and could be implemented routinely. The RBANS supplemented with CTT and mBNT is more sensitive in detecting CI than RBANS alone therefore could be used for diagnostic purposes.