Social cognition in youth with a first-degree relative with schizophrenia: A systematic scoping review.

Social-cognitive deficits are present in individuals at familial high-risk (FHR) for schizophrenia and may play a role in the onset of the illness. No literature review has examined the social-cognitive profiles of youth at FHR who are within the peak window of risk for developing schizophrenia, which could provide insight on the endophenotypic role of social cognition. This systematic scoping review (1) summarizes the evidence on social-cognitive deficits in youth at FHR, (2) explores brain correlates, and (3) describes social-cognitive deficits and prodromal symptom associations. We searched PsycInfo and PubMed for studies investigating social cognition in FHR youth aged 35 or younger and included 19 studies (FHR=639; controls=689). Studies report that youth at FHR have difficulty recognizing negative emotions, particularly fear. Youth at FHR also have difficulty performing complex theory of mind tasks. Abnormality in corticolimbic and temporoparietal regions are observed in youth at FHR during social-cognitive tasks, but results are inconsistent. Finally, there is evidence for negative associations between prodromal symptoms and performance on emotion regulation and theory of mind tasks, but the research is scarce. This review highlights the need for studies on youth at FHR using longitudinal designs and extensive social-cognitive, brain imaging and clinical measures.

Feasibility and Efficacy of Virtual Reality Interventions to Improve Psychosocial Functioning in Psychosis: Systematic Review.

BACKGROUND: Functional recovery in psychosis remains a challenge despite current evidence-based treatment approaches. To address this problem, innovative interventions using virtual reality (VR) have recently been developed. VR technologies have enabled the development of realistic environments in which individuals with psychosis can receive psychosocial treatment interventions in more ecological settings than traditional clinics. These interventions may therefore increase the transfer of learned psychosocial skills to real-world environments, thereby promoting long-term functional recovery. However, the overall feasibility and efficacy of such interventions within the psychosis population remain unclear. OBJECTIVE: This systematic review aims to investigate whether VR-based psychosocial interventions are feasible and enjoyable for individuals with psychosis, synthesize current evidence on the efficacy of VR-based psychosocial interventions for psychosis, and identify the limitations in the current literature to guide future research. METHODS: This research followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Literature searches were conducted in PubMed and PsycINFO in May 2021. We searched for peer-reviewed English articles that used a psychosocial intervention with a VR component. Participants in the included studies were diagnosed with schizophrenia, schizoaffective disorder, or another psychotic disorder. The included studies were divided into four categories as follows: cognitive remediation interventions, social skills interventions, vocational skills interventions, and auditory verbal hallucinations and paranoia interventions. The risk of bias assessment was performed for each study. RESULTS: A total of 18 studies were included in this systematic review. Of these 18 studies, 4 (22%) studies used a cognitive remediation intervention, 4 (22%) studies used a social skills intervention, 3 (17%) studies used a vocational skills intervention, and 7 (39%) studies implemented an intervention aimed at improving auditory verbal hallucinations or paranoia. A total of 745 individuals with psychosis were included in the study. All the studies that evaluated feasibility showed that VR-based psychosocial interventions were feasible and enjoyable for individuals with psychosis. The preliminary evidence on efficacy included in this review suggests that VR-based psychosocial interventions can improve cognitive, social, and vocational skills in individuals with psychosis. VR-based interventions may also improve the symptoms of auditory verbal hallucinations and paranoia. The skills that participants learned through these interventions were durable, transferred into real-world environments, and led to improved functional outcomes, such as autonomy, managing housework, and work performance. CONCLUSIONS: VR-based interventions may represent a novel and efficacious approach for improving psychosocial functioning in psychosis. Therefore, VR-based psychosocial interventions represent a promising adjunctive therapy for the treatment of psychosis, which may be used to improve psychosocial skills, community functioning, and quality of life.

The ImageJ ecosystem: Open-source software for image visualization, processing, and analysis.

For decades, biologists have relied on software to visualize and interpret imaging data. As techniques for acquiring images increase in complexity, resulting in larger multidimensional datasets, imaging software must adapt. ImageJ is an open-source image analysis software platform that has aided researchers with a variety of image analysis applications, driven mainly by engaged and collaborative user and developer communities. The close collaboration between programmers and users has resulted in adaptations to accommodate new challenges in image analysis that address the needs of ImageJ's diverse user base. ImageJ consists of many components, some relevant primarily for developers and a vast collection of user-centric plugins. It is available in many forms, including the widely used Fiji distribution. We refer to this entire ImageJ codebase and community as the ImageJ ecosystem. Here we review the core features of this ecosystem and highlight how ImageJ has responded to imaging technology advancements with new plugins and tools in recent years. These plugins and tools have been developed to address user needs in several areas such as visualization, segmentation, and tracking of biological entities in large, complex datasets. Moreover, new capabilities for deep learning are being added to ImageJ, reflecting a shift in the bioimage analysis community towards exploiting artificial intelligence. These new tools have been facilitated by profound architectural changes to the ImageJ core brought about by the ImageJ2 project. Therefore, we also discuss the contributions of ImageJ2 to enhancing multidimensional image processing and interoperability in the ImageJ ecosystem.

Optical imaging of collagen fiber damage to assess thermally injured human skin.

Surgery is the definitive treatment for burn patients who sustain full-thickness burn injuries. Visual assessment of burn depth is made by the clinician early after injury but is accurate only up to 70% of the time among experienced surgeons. Collagen undergoes denaturation as a result of thermal injury; however, the association of collagen denaturation and cellular death in response to thermal injury is unknown. While gene expression assays and histologic staining allow for ex vivo identification of collagen changes, these methods do not provide spatial or integrity information in vivo. Thermal effects on collagen and the role of collagen in wound repair have been understudied in human burn models due to a lack of methods to visualize both intact and denatured collagen. Hence, there is a critical need for a clinically applicable method to discriminate between damaged and intact collagen fibers in tissues. We present two complementary candidate methods for visualization of collagen structure in three dimensions. Second harmonic generation imaging offers a label-free, high-resolution method to identify intact collagen. Simultaneously, a fluorophore-tagged collagen-mimetic peptide can detect damaged collagen. Together, these methods enable the characterization of collagen damage in human skin biopsies from burn patients, as well as ex vivo thermally injured human skin samples. These combined methods could enhance the understanding of the role of collagen in human wound healing after thermal injury and potentially assist in clinical decision-making.

Metabolic mapping of glioblastoma stem cells reveals NADH fluxes associated with glioblastoma phenotype and survival.

SIGNIFICANCE: Glioblastoma multiforme (GBM) is the most frequently diagnosed adult primary brain malignancy with poor patient prognosis. GBM can recur despite aggressive treatment due to therapeutically resistant glioblastoma stem cells (GSCs) that may exhibit metabolic plasticity. AIM: Intrinsic nicotinamide adenine dinucleotide (NADH) fluorescence can be acquired with fluorescence lifetime imaging microscopy (FLIM) to examine its bound and free metabolic states in GSC and GBM tissues. APPROACH: We compared the mean NADH fluorescence lifetime in live human GSCs and normal neural stem cells and validated those results by measuring oxygen consumption rates (OCRs). We also examined the role that invasive versus less-invasive GSCs had on tumor metabolism by measuring the mean NADH lifetimes and the relative amount of the longer-lived component of NADH and correlated these results with survival in an orthotopic mouse xenograft model. RESULTS: Mean NADH lifetime, amount of bound NADH, and OCR were increased in GSCs. Compared with normal mouse brain, mean NADH lifetimes were longer for all GBM tissues. Invasive xenografts had higher relative amounts of the longer-lived NADH component, and this correlated with decreased survival. CONCLUSIONS: FLIM offers cellular resolution quantification of metabolic flux in GBM phenotypes, potentially informing biomedical researchers on improved therapeutic approaches.

Optimization of interstrand interactions enables burn detection with a collagen-mimetic peptide.

Collagen is an abundant component of the extracellular matrix and connective tissues. Some collagen-mimetic peptides (CMPs) that do not form homotrimers can anneal to damaged tissue. Here, through a computational screen, we identify (flpHypGly)7 as an optimal monomeric CMP for heterotrimer formation. We find that (flpHypGly)7 forms stable triple helices with (ProProGly)7 but not with itself. The nonnatural amino acid HflpOH, which is (2S,4S)-4-fluoroproline, is not toxic to human fibroblasts or keratinocytes. Conjugation of (flpHypGly)7 to a fluorescent dye enables the facile detection of burned collagenous tissue with high specificity. The ubiquity of collagen and the prevalence of injuries and diseases that disrupt endogenous collagen suggests widespread utility for this approach.

Beyond the margins: real-time detection of cancer using targeted fluorophores.

Over the past two decades, synergistic innovations in imaging technology have resulted in a revolution in which a range of biomedical applications are now benefiting from fluorescence imaging. Specifically, advances in fluorophore chemistry and imaging hardware, and the identification of targetable biomarkers have now positioned intraoperative fluorescence as a highly specific real-time detection modality for surgeons in oncology. In particular, the deeper tissue penetration and limited autofluorescence of near-infrared (NIR) fluorescence imaging improves the translational potential of this modality over visible-light fluorescence imaging. Rapid developments in fluorophores with improved characteristics, detection instrumentation, and targeting strategies led to the clinical testing in the early 2010s of the first targeted NIR fluorophores for intraoperative cancer detection. The foundations for the advances that underline this technology continue to be nurtured by the multidisciplinary collaboration of chemists, biologists, engineers, and clinicians. In this Review, we highlight the latest developments in NIR fluorophores, cancer-targeting strategies, and detection instrumentation for intraoperative cancer detection, and consider the unique challenges associated with their effective application in clinical settings.

Association of collagen architecture with glioblastoma patient survival.

OBJECTIVE Glioblastoma (GBM) is the most malignant primary brain tumor. Collagen is present in low amounts in normal brain, but in GBMs, collagen gene expression is reportedly upregulated. However, to the authors' knowledge, direct visualization of collagen architecture has not been reported. The authors sought to perform the first direct visualization of GBM collagen architecture, identify clinically relevant collagen signatures, and link them to differential patient survival. METHODS Second-harmonic generation microscopy was used to detect collagen in a GBM patient tissue microarray. Focal and invasive GBM mouse xenografts were stained with Picrosirius red. Quantitation of collagen fibers was performed using custom software. Multivariate survival analysis was done to determine if collagen is a survival marker for patients. RESULTS In focal xenografts, collagen was observed at tumor brain boundaries. For invasive xenografts, collagen was intercalated with tumor cells. Quantitative analysis showed significant differences in collagen fibers for focal and invasive xenografts. The authors also found that GBM patients with more organized collagen had a longer median survival than those with less organized collagen. CONCLUSIONS Collagen architecture can be directly visualized and is different in focal versus invasive GBMs. The authors also demonstrate that collagen signature is associated with patient survival. These findings suggest that there are collagen differences in focal versus invasive GBMs and that collagen is a survival marker for GBM.

Successful treatment of cerebellar ataxia and tremor in multiple sclerosis with topiramate: a case report.

We describe the clinical efficacy of topiramate for treatment of cerebellar dysfunction in a 33-year-old female patient with relapsing remitting multiple sclerosis. The patient presented severe ataxia and tremor precluding many activities of daily life. Topiramate was administered as a monotherapy and slowly tapered in to 150 mg daily without negative side effects. Treatment was well tolerated and led to a marked and lasting improvement of tremor as well as ataxia during an observation period of 2 years. Upon transient withdrawal of topiramate, ataxia and tremor worsened but were again improved after re-dosing of the drug. Multiple sclerosis immunotherapy was not changed in this period. In conclusion, topiramate may be a new therapeutic option to treat cerebellar tremor and ataxia in patients with multiple sclerosis.