Consultation-Liaison Case Conference: A Case of Factitious Disorder Imposed on Self.

We present the case of a young woman with an extensive medical history that most notably includes over 60 emergency-room visits for unfounded respiratory distress that often prompted intubations. Each presentation displays elements of deceitfulness or inappropriate demands that align with factitious disorder imposed on self. Top experts in the Consultation-Liaison field provide guidance for this commonly encountered clinical case based on their experience and review of available literature. Key teaching topics include a review of risk factors for development of deceptive syndromes, distinguishing factitious disorder from malingering and conversion disorder, and the role of a consulting psychiatrist in such cases. Patients with factitious disorder often show signs of pathologic lying, obstinance, and erratic behavior. Such attributes frequently arouse negative countertransference in providers, causing frustration and dread with continuing care, rendering psychiatric involvement. We address the unique challenges in managing factitious disorder and how to effectively collaborate with an interdisciplinary inpatient team with these cases.

Transient photocurrents in a subthreshold evidence accumulator accelerate perceptual decisions.

Perceptual decisions are complete when a continuously updated score of sensory evidence reaches a threshold. In Drosophila, αß core Kenyon cells (αßc KCs) of the mushroom bodies integrate odor-evoked synaptic inputs to spike threshold at rates that parallel the speed of olfactory choices. Here we perform a causal test of the idea that the biophysical process of synaptic integration underlies the psychophysical process of bounded evidence accumulation in this system. Injections of single brief, EPSP-like depolarizations into the dendrites of αßc KCs during odor discrimination, using closed-loop control of a targeted opsin, accelerate decision times at a marginal cost of accuracy. Model comparisons favor a mechanism of temporal integration over extrema detection and suggest that the optogenetically evoked quanta are added to a growing total of sensory evidence, effectively lowering the decision bound. The subthreshold voltage dynamics of αßc KCs thus form an accumulator memory for sequential samples of information.

Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)-A Systemic Review and Comparison of Clinical Presentation and Symptomatology.

Background and Objectives: Long COVID defines a series of chronic symptoms that patients may experience after resolution of acute COVID-19. Early reports from studies with patients with long COVID suggests a constellation of symptoms with similarities to another chronic medical illness-myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). A review study comparing and contrasting ME/CFS with reported symptoms of long COVID may yield mutualistic insight into the characterization and management of both conditions. Materials and Methods: A systemic literature search was conducted in MEDLINE and PsycInfo through to 31 January 2021 for studies related to long COVID symptomatology. The literature search was conducted in accordance with PRISMA methodology. Results: Twenty-one studies were included in the qualitative analysis. Long COVID symptoms reported by the included studies were compared to a list of ME/CFS symptoms compiled from multiple case definitions. Twenty-five out of 29 known ME/CFS symptoms were reported by at least one selected long COVID study. Conclusions: Early studies into long COVID symptomatology suggest many overlaps with clinical presentation of ME/CFS. The need for monitoring and treatment for patients post-COVID is evident. Advancements and standardization of long COVID research methodologies would improve the quality of future research, and may allow further investigations into the similarities and differences between long COVID and ME/CFS.

In vitro and in vivo hemostatic capabilities of a functionally integrated platelet-mimetic liposomal nanoconstruct.

There is significant clinical interest in synthetic platelet substitutes that can mimic platelet's hemostastic functionalities while allowing scale-up, minimal biological contamination, and long shelf-life. To this end, mimicking active platelet's hemostatically relevant matrix-adhesion properties and aggregation properties independently and then integrating them via heteromultivalent ligand decoration on a single synthetic particle can lead to an efficient platelet substitute design. We have recently reported on the feasibility of this approach in vitro, using liposomes as model particles. Building on these studies, here we demonstrate the capability of optimizing the platelet-mimetic properties of our liposomal constructs in vitro via modulating the ligand-decoration densities and ligand ratios. In addition, we demonstrate the enhanced hemostatic efficacy of the functionally-integrated platelet-mimetic constructs in vivo. Liposomes were surface-decorated with collagen- and VWF-binding peptides (CBP and VBP) to mimic platelet adhesion and a fibrinogen-mimetic peptide (FMP) to promote platelet aggregation. Modulation of VBP- and CBP-densities and relative ratios enabled optimizing construct adhesion under varying shear-flow conditions. Modulation of FMP-density enabled enhancement of construct-promoted platelet aggregation. The VBP-, CBP- and FMP-decorations were integrated on a single liposome, and these functionally-integrated constructs showed significantly higher hemostatic efficacy in vivo in a mouse tail-transection model compared to 'adhesion-only' or 'aggregation-only' constructs.

Mimicking adhesive functionalities of blood platelets using ligand-decorated liposomes.

Platelet transfusion is used for treating a variety of bleeding complications. Natural platelet-based transfusion products have very short storage life (3-7 days) and high risks of biological contamination and side effects. Consequently, there is significant clinical interest in synthetic platelet-mimetic constructs that can promote hemostasis, while allowing convenient large-scale production, easy portability, long storage life, and minimal biological risks. To this end, research efforts are being directed toward particles that can amplify aggregation of activated platelets or can mimic platelet's ability to undergo adhesion to various vascular matrix proteins. Here, we report on a synthetic construct design that combines the mimicry of platelet's shear-dependent adhesion to vWF and shear-independent adhesion to collagen under flow, on a single particle. For this, we have used 150-nm-diameter liposomes as model particles and have decorated their surface simultaneously with vWF-binding and collagen-binding recombinant protein fragments or synthetic peptide motifs. We demonstrate in vitro that these surface-modified liposomes are able to adhere onto vWF surfaces in a shear-dependent fashion and onto collagen surfaces in a shear-independent fashion under flow. Moreover, when the vWF-binding and the collagen-binding were integrated on a single liposomal platform, the resultant heteromultivalent liposomes showed significantly enhanced adhesion to a vWF/collagen mixed surface compared to liposomes bearing vWF-binding or collagen-binding ligands only, as long as the ligand motifs did not spatially interfere with each other. Altogether, our results establish the feasibility of efficiently mimicking platelet's dual adhesion mechanisms on synthetic particles.

Peptide-decorated liposomes promote arrest and aggregation of activated platelets under flow on vascular injury relevant protein surfaces in vitro.

Platelet-mimetic synthetic hemostats are highly attractive in transfusion medicine. To this end, past research reports have described particles that either amplify platelet aggregation or mimic platelet adhesion. However, a construct design that effectively combines both functionalities has not been reported. Here we describe the design of a liposomal construct simultaneously surface-decorated with three peptides (a vWF-binding peptide (VBP), a collagen-binding peptide (CBP), and an active platelet clustering cyclic-RGD (cRGD) peptide), that can integrate platelet-mimetic dual hemostatic activities of adhesion and aggregation. We first demonstrate that surface-immobilized cRGD-liposomes are capable of aggregating activated platelets onto themselves. Subsequently, we demonstrate that hetero-multivalent liposomes bearing VBP, CBP, and cRGD, when introduced in flow with ≈ 20,000 activated platelets per microliter, are capable of adhering to vWF/collagen surfaces and promoting the recruitment/aggregation of platelets onto themselves. We envision that optimizing this construct can lead to a highly refined synthetic hemostat design for potential application in transfusion medicine.

Heteromultivalent liposomal nanoconstructs for enhanced targeting and shear-stable binding to active platelets for site-selective vascular drug delivery.

Activated platelets play multiple roles in vascular diseases. Hence, a delivery vehicle that can specifically target activated platelets and stay retained under a hemodynamic environment can potentially enhance the efficacy of vehicle-encapsulated vascular drug by protecting it from rapid plasma deactivation, reducing its systemic non-specific side-effects, and increasing its therapeutic index at disease sites undergoing platelet hyperactivity. We rationalized that liposomal nanoconstructs surface-modified with two kinds of peptide that simultaneously bind integrin α(IIb)ß(3) and P-selectin on activated platelets can provide synergistic mechanisms for enhanced selectivity to vascular disease sites. We further hypothesized that dual-receptor targeting will enhance binding strength and retention under flow. We tested this using fluorescently-labeled liposomes, surface-modified by an RGD peptide targeted to active α(IIb)ß(3) and an EWVDV peptide targeted to P-selectin. The liposomes were studied for their platelet-specific interactions inside a parallel plate flow chamber at low-to-high shear stresses. The interaction specificity was further confirmed by flow cytometry. Our results indicate that liposomes surface-modified with both RGD and EWVDV simultaneously have higher selectivity as well as retention to activated platelets under flow compared to liposomes bearing any one peptide type. These results establish the potential of our nanoconstructs for enhanced site-selective drug delivery in vascular diseases.