Citations

AbstractBackgroundARIA is a common side effect of aducanumab, the first anti‐amyloid pharmacotherapy approved by the US Food and Drug Administration (FDA) to treat Alzheimer’s disease. Regular MRI is required by FDA to detect and monitor different forms of ARIA during initiation of therapy. MRI protocols must be a) high resolution to detect abnormalities with high sensitivity, b) fast to accommodate workflow and ensure patient compliance and c) standardized to maximize data acquisition consistency across sites. Based on a vendor agnostic protocol recommendation by Benzinger et al (CTAD 2021), we propose specific parameters for 3T Philips systems, for an accelerated and enhanced protocol.MethodThe protocol was developed on a 3T Philips Elition X scanner, using 32‐channel head coil, and included 3D T1, 3D FLAIR, 2D DWI, 2D T2* and multi echo 3D Susceptibility Weighted Imaging (SWI) sequences.ResultAcquisition voxel resolution of 3D T1, 3D FLAIR, T2* and DWI matches current recommendations. 3D SWI resolution is 0.7x0.7x2mm. Compressed‐SENSE (C‐SENSE) acceleration is applied on 3D T1, 3D FLAIR, T2* and 3D SWI. SENSE is applied on DWI (Figure 1). Total acquisition time including the additional 3D SWI scan is 11 minutes, 6 minutes faster than the original recommendation. Qualitative assessment of images showed high signal‐to‐noise and contrast‐to‐noise. Images were free of acceleration related artifacts. Automated slice prescription localizer ensures better reproducibility for longitudinal assessment.ConclusionImaging protocol standardization is necessary to ensure consistent accuracy for diagnosing ARIA. Broad recommendations leave room for variability, therefore specific parameters are needed to achieve cross‐platform standardization. Our protocol is applicable for 3T Philips systems with compressed‐SENSE capability and 32‐channel head coil. The recommended C‐SENSE values maintain image quality with shorter exam time. This is more comfortable for patients and easier to fit into the workflow. The higher sensitivity of SWI can improve thresholds for therapy monitoring and provide additional quantitative measurements.

AbstractBackgroundARIA is a common side effect of aducanumab, the first anti‐amyloid pharmacotherapy approved by the US Food and Drug Administration (FDA) to treat Alzheimer’s disease. Regular MRI is required by FDA to detect and monitor different forms of ARIA during initiation of therapy. MRI protocols must be a) high resolution to detect abnormalities with high sensitivity, b) fast to accommodate workflow and ensure patient compliance and c) standardized to maximize data acquisition consistency across sites. Based on a vendor agnostic protocol recommendation by Benzinger et al (CTAD 2021), we propose specific parameters for 3T Philips systems, for an accelerated and enhanced protocol.MethodThe protocol was developed on a 3T Philips Elition X scanner, using 32‐channel head coil, and included 3D T1, 3D FLAIR, 2D DWI, 2D T2* and multi echo 3D Susceptibility Weighted Imaging (SWI) sequences.ResultAcquisition voxel resolution of 3D T1, 3D FLAIR, T2* and DWI matches current recommendations. 3D SWI resolution is 0.7x0.7x2mm. Compressed‐SENSE (C‐SENSE) acceleration is applied on 3D T1, 3D FLAIR, T2* and 3D SWI. SENSE is applied on DWI (Figure 1). Total acquisition time including the additional 3D SWI scan is 11 minutes, 6 minutes faster than the original recommendation. Qualitative assessment of images showed high signal‐to‐noise and contrast‐to‐noise. Images were free of acceleration related artifacts. Automated slice prescription localizer ensures better reproducibility for longitudinal assessment.ConclusionImaging protocol standardization is necessary to ensure consistent accuracy for diagnosing ARIA. Broad recommendations leave room for variability, therefore specific parameters are needed to achieve cross‐platform standardization. Our protocol is applicable for 3T Philips systems with compressed‐SENSE capability and 32‐channel head coil. The recommended C‐SENSE values maintain image quality with shorter exam time. This is more comfortable for patients and easier to fit into the workflow. The higher sensitivity of SWI can improve thresholds for therapy monitoring and provide additional quantitative measurements.

AbstractThis manuscript presents a conceptual model—the Sexual Health and Integrative Pleasure (SHIP) Model—for the clinical assessment and intervention of sexual health concerns. The model was developed by a group of couple/marital family therapy and psychologists who specialize in the treatment of sexual problems. The model consists of five philosophical foundations (systems framework, intersectionality, biopsychosocial model, lifespan approach, and empiricism) and five core therapeutic components (sexual literacy, sexual adaptation and resilience, relational intimacy, pleasure‐oriented positive sexuality, and multidisciplinary care). We define each foundation and component, and compare and contrast the SHIP model with other existing sexual health models. Finally, we demonstrate how the SHIP model was used to provide individual and couple therapy with a cis/heterosexual couple in a university‐based sexual health clinic and make recommendations for additional clinical applications of the model.

Abstract BACKGROUND The topologically associated domain (TAD) on 8q24 surrounding MYC is important for many types of cancer. The region is also important in the formation of IDH-mutant glioma; the risk allele rs55705857 being associated with the development of these tumors. The rs55705857 risk allele significantly increased the formation of tumors in an IDH-mutant mouse model. Cerebral organoids have been found to recapitulate the early development of the brain. We hypothesized that the rs55705857 risk allele may alter the phenotype of cerebral organoids. METHODS Isogenic induced pluripotent stem cells (iPSCs) were developed with (n=3) and without (n=2) the rs55705857 risk allele from the parental cell line PGP-1 (GM23338). These cells were cultured and differentiated into unpatterned cerebral organoids and observed throughout differentiation. Organoids were fixed, sectioned, and stained by H&E and immunofluorescence. RESULTS Organoids containing the risk allele were smaller throughout development, starting at the embryoid body stage and continuing up to over 75 days in culture, compared to two isogenic non-risk lines. At 4 weeks the risk allele containing organoids also contained a larger number of small rosette-like neuroepithelia, instead of the more continuous neuroepithelia observed in the non-risk allele organoids. At 75 days, the organoids with the risk allele maintained a larger proportion of Sox2 positive cells, which are enriched in the tight clusters of small cells with round nuclei. CONCLUSIONS The risk allele rs55705857 in the MYC TAD at 8q24 is altering the development of unpatterned cerebral organoids. This difference is visible as early as embryoid body development and persists through neuroepithelial development. Further studies of these differences may help our understanding of how rs55705857 accelerates IDH-mutant glioma development.

Abstract Prolonged infections in immunocompromised individuals may be a source for novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants, particularly when both the immune system and antiviral therapy fail to clear the infection and enable within-host evolution. Here we describe a 486-day case of SARS-CoV-2 infection in an immunocompromised individual. Following monotherapy with the monoclonal antibody Bamlanivimab, the individual’s virus acquired resistance, likely via the earliest known occurrence of Spike amino acid variant E484T. Recently, E484T has arisen again as a derivative of E484A in the Omicron Variant of Concern, supporting the hypothesis that prolonged infections can give rise to novel variants long before they become prevalent in the human population.