Identifying and Targeting Cancer Stem Cells in Colorectal Cancer

The cancer stem cell hypothesis posits that cancer stem cells (CSCs) are the driving force behind tumour progression and metastasis, making them ideal therapeutic targets. Previous research identified Leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) as a marker of CSCs in colorectal cancer (CRC). However, it is not known whether more than one CSC population exists in CRC. Identifying and targeting CSCs in CRC is important for effective treatment of cancer patients. Here, I show that Keratin-19 (K19) labels intestinal CSCs in mouse tumours that recapitulate the early stages of CRC. Moreover, selective ablation of Lgr5 has no effect on tumour initiation or growth. These results demonstrate additional CSC populations exist besides those labeled by Lgr5, which are important for tumour initiation and growth. Consequently, these findings have important clinical implications for the development of new therapies targeting CSCs

INCOG 2.0 Guidelines for Cognitive Rehabilitation Following Traumatic Brain Injury, Part III: Executive Functions

Introduction: Moderate-to-severe traumatic brain injury (MS-TBI) causes debilitating and enduring impairments of executive functioning and self-awareness, which clinicians often find challenging to address. Here, we provide an update to the INCOG 2014 guidelines for the clinical management of these impairments. Methods: An expert panel of clinicians/researchers (known as INCOG) reviewed evidence published from 2014 and developed updated recommendations for the management of executive functioning and self-awareness post-MS-TBI, as well as a decision-making algorithm, and an audit tool for review of clinical practice. Results: A total of 8 recommendations are provided regarding executive functioning and self-awareness. Since INCOG 2014, 4 new recommendations were made and 4 were modified and updated from previous recommendations. Six recommendations are based on level A evidence, and 2 are based on level C. Recommendations retained from the previous guidelines and updated, where new evidence was available, focus on enhancement of self-awareness (eg, feedback to increase self-monitoring; training with video-feedback), meta-cognitive strategy instruction (eg, goal management training), enhancement of reasoning skills, and group-based treatments. New recommendations addressing music therapy, virtual therapy, telerehabilitation-delivered metacognitive strategies, and caution regarding other group-based telerehabilitation (due to a lack of evidence) have been made. Conclusions: Effective management of impairments in executive functioning can increase the success and well-being of individuals with MS-TBI in their day-to-day lives. These guidelines provide management recommendations based on the latest evidence, with support for their implementation, and encourage researchers to explore and validate additional factors such as predictors of treatment response

INCOG 2.0 Guidelines for Cognitive Rehabilitation Following Traumatic Brain Injury: What’s Changed From 2014 to Now?

IT IS CRITICAL TO KEEP clinical practice guidelines (CPGs) up to date through integration of the latest evidence. Therefore, it is with great excitement that the INCOG team presents the INCOG 2.0 Guidelines for Cognitive Rehabilitation Following Traumatic Brain Injury (TBI). In this brief introduction, we provide an overview of changes in the evidence from 2014; share insights into the current state and challenges implementing cognitive rehabilitation; and provide an overview of INCOG 2022

INCOG 2.0 Guidelines for Cognitive Rehabilitation Following Traumatic Brain Injury, Part V: Memory

Introduction: Memory impairments affecting encoding, acquisition, and retrieval of information after moderate-to-severe traumatic brain injury (TBI) have debilitating and enduring functional consequences. The interventional research reviewed primarily focused on mild to severe memory impairments in episodic and prospective memory. As memory is a common focus of cognitive rehabilitation, clinicians should understand and use the latest evidence. Therefore, the INCOG (“International Cognitive”) 2014 clinical practice guidelines were updated. Methods: An expert panel of clinicians/researchers reviewed evidence published since 2014 and developed updated recommendations for intervention for memory impairments post-TBI, a decision-making algorithm, and an audit tool for review of clinical practice. Results: The interventional research approaches for episodic and prospective memory from 2014 are synthesized into 8 recommendations (6 updated and 2 new). Six recommendations are based on level A evidence and 2 on level B. In summary, they include the efficacy of choosing individual or multiple internal compensatory strategies, which can be delivered in a structured or individualized program. Of the external compensatory strategies, which should be the primary strategy for severe memory impairment, electronic reminder systems such as smartphone technology are preferred, with technological advances increasing their viability over traditional systems. Furthermore, microprompting personal digital assistant technology is recommended to cue completion of complex tasks. Memory strategies should be taught using instruction that considers the individual\u27s functional and contextual needs while constraining errors. Memory rehabilitation programs can be delivered in an individualized or mixed format using group instruction. Computer cognitive training should be conducted with therapist guidance. Limited evidence exists to suggest that acetylcholinesterase inhibitors improve memory, so trials should include measures to assess impact. The use of transcranial direct current stimulation (tDCS) is not recommended for memory rehabilitation. Conclusion: These recommendations for memory rehabilitation post-TBI reflect the current evidence and highlight the limitations of group instruction with heterogeneous populations of TBI. Further research is needed on the role of medications and tDCS to enhance memory

The Future of INCOG (Is Now)

IT HAS BEEN 8 years since the first iteration of the INCOG clinical practice guidelines (CPGs) were published. Much has happened since 2014, and a considerable body of evidence has been published in the various domains of cognitive rehabilitation research represented in this special issue. Over this time, significant developments in the science of identifying, appraising, and distilling research evidence into practically applicable CPGs have emerged, as well as implementation efforts to ensure meaningful change in care delivery

INCOG 2.0 Guidelines for Cognitive Rehabilitation Following Traumatic Brain Injury, Part IV: Cognitive-Communication and Social Cognition Disorders

Introduction: Moderate to severe traumatic brain injury causes significant cognitive impairments, including impairments in social cognition, the ability to recognize others\u27 emotions, and infer others\u27 thoughts. These cognitive impairments can have profound negative effects on communication functions, resulting in a cognitive-communication disorder. Cognitive-communication disorders can significantly limit a person\u27s ability to socialize, work, and study, and thus are critical targets for intervention. This article presents the updated INCOG 2.0 recommendations for management of cognitive-communication disorders. As social cognition is central to cognitive-communication disorders, this update includes interventions for social cognition. Methods: An expert panel of clinicians/researchers reviewed evidence published since 2014 and developed updated recommendations for interventions for cognitive-communication and social cognition disorders, a decision-making algorithm tool, and an audit tool for review of clinical practice. Results: Since INCOG 2014, there has been significant growth in cognitive-communication interventions and emergence of social cognition rehabilitation research. INCOG 2.0 has 9 recommendations, including 5 updated INCOG 2014 recommendations, and 4 new recommendations addressing cultural competence training, group interventions, telerehabilitation, and management of social cognition disorders. Cognitive-communication disorders should be individualized, goal- and outcome-oriented, and appropriate to the context in which the person lives and incorporate social communication and communication partner training. Group therapy and telerehabilitation are recommended to improve social communication. Augmentative and alternative communication (AAC) should be offered to the person with severe communication disability and their communication partners should also be trained to interact using AAC. Social cognition should be assessed and treated, with a focus on personally relevant contexts and outcomes. Conclusions: The INCOG 2.0 recommendations reflect new evidence for treatment of cognitive-communication disorders, particularly social interactions, communication partner training, group treatments to improve social communication, and telehealth delivery. Evidence is emerging for the rehabilitation of social cognition; however, the impact on participation outcomes needs further research

Evaluating Changes in Omega-3 Fatty Acid Intake after Receiving Personal FADS1 Genetic Information: A Randomized Nutrigenetic Intervention

Nutrigenetics research is anticipated to lay the foundation for personalized dietary recommendations; however, it remains unclear if providing individuals with their personal genetic information changes dietary behaviors. Our objective was to evaluate if providing information for a common variant in the fatty acid desaturase 1 (FADS1) gene changed omega-3 fatty acid (FA) intake and blood levels in young female adults (18–25 years). Participants were randomized into Genetic (intervention) and Non-Genetic (control) groups, with measurements taken at Baseline and Final (12 weeks). Dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was assessed using an omega-3 food frequency questionnaire. Red blood cell (RBC) FA content was quantified by gas chromatography. Implications of participation in a nutrigenetics study and awareness of omega-3 FAs were assessed with online questionnaires. Upon completion of the study, EPA and DHA intake increased significantly (p = 1.0 × 10−4) in all participants. This change was reflected by small increases in RBC %EPA. Participants in the Genetic group showed increased awareness of omega-3 terminology by the end of the study, reported that the dietary recommendations were more useful, and rated cost as a barrier to omega-3 consumption less often than those in the Non-Genetic group. Providing participants FADS1 genetic information did not appear to influence omega-3 intake during the 12 weeks, but did change perceptions and behaviors related to omega-3 FAs in this timeframe