“Now he sings”. The My Musical Memories Reminiscence Programme: Personalised Interactive Reminiscence Sessions for People Living With Dementia

This paper explores the impact of the My Musical Memories Reminiscence Programme (MMMRP), an innovative intervention that adopts a music-based reminiscence approach. MMMRP builds on the format of the popular Singing for the Brain sessions with the aim of increasing opportunities for interaction and reminiscence among people living with dementia. Data were collected pre- and post-intervention and three months later using structured observation, interviews and focus groups. Results suggest that that programme had a positive impact on participants by promoting engagement, reminiscence and social interaction. For some individuals the impacts continued beyond their participation in the programme. A range of key facilitators for successful implementation of this approach were identified including the Session Leader role, the involvement of informal carers and the input of volunteers

Control of interjoint coordination during the swing phase of normal gait at different speeds

BACKGROUND: It has been suggested that the control of unconstrained movements is simplified via the imposition of a kinetic constraint that produces dynamic torques at each moving joint such that they are a linear function of a single motor command. The linear relationship between dynamic torques at each joint has been demonstrated for multijoint upper limb movements. The purpose of the current study was to test the applicability of such a control scheme to the unconstrained portion of the gait cycle – the swing phase. METHODS: Twenty-eight neurologically normal individuals walked along a track at three different speeds. Angular displacements and dynamic torques produced at each of the three lower limb joints (hip, knee and ankle) were calculated from segmental position data recorded during each trial. We employed principal component (PC) analysis to determine (1) the similarity of kinematic and kinetic time series at the ankle, knee and hip during the swing phase of gait, and (2) the effect of walking speed on the range of joint displacement and torque. RESULTS: The angular displacements of the three joints were accounted for by two PCs during the swing phase (Variance accounted for – PC1: 75.1 ± 1.4%, PC2: 23.2 ± 1.3%), whereas the dynamic joint torques were described by a single PC (Variance accounted for – PC1: 93.8 ± 0.9%). Increases in walking speed were associated with increases in the range of motion and magnitude of torque at each joint although the ratio describing the relative magnitude of torque at each joint remained constant. CONCLUSION: Our results support the idea that the control of leg swing during gait is simplified in two ways: (1) the pattern of dynamic torque at each lower limb joint is produced by appropriately scaling a single motor command and (2) the magnitude of dynamic torque at all three joints can be specified with knowledge of the magnitude of torque at a single joint. Walking speed could therefore be altered by modifying a single value related to the magnitude of torque at one joint

Rituximab, B-lymphocyte depletion, and preservation of beta-cell function

BACKGROUND: The immunopathogenesis of type 1 diabetes mellitus is associated with T-lymphocyte autoimmunity. However, there is growing evidence that B lymphocytes play a role in many T-lymphocyte-mediated diseases. It is possible to achieve selective depletion of B lymphocytes with rituximab, an anti-CD20 monoclonal antibody. This phase 2 study evaluated the role of B-lymphocyte depletion in patients with type 1 diabetes. METHODS: We conducted a randomized, double-blind study in which 87 patients between 8 and 40 years of age who had newly diagnosed type 1 diabetes were assigned to receive infusions of rituximab or placebo on days 1, 8, 15, and 22 of the study. The primary outcome, assessed 1 year after the first infusion, was the geometric mean area under the curve (AUC) for the serum C-peptide level during the first 2 hours of a mixed-meal tolerance test. Secondary outcomes included safety and changes in the glycated hemoglobin level and insulin dose. RESULTS: At 1 year, the mean AUC for the level of C peptide was significantly higher in the rituximab group than in the placebo group. The rituximab group also had significantly lower levels of glycated hemoglobin and required less insulin. Between 3 months and 12 months, the rate of decline in C-peptide levels in the rituximab group was significantly less than that in the placebo group. CD19+ B lymphocytes were depleted in patients in the rituximab group, but levels increased to 69% of baseline values at 12 months. More patients in the rituximab group than in the placebo group had adverse events, mostly grade 1 or grade 2, after the first infusion. The reactions appeared to be minimal with subsequent infusions. There was no increase in infections or neutropenia with rituximab. CONCLUSIONS: A four-dose course of rituximab partially preserved beta-cell function over a period of 1 year in patients with type 1 diabetes. The finding that B lymphocytes contribute to the pathogenesis of type 1 diabetes may open a new pathway for exploration in the treatment of patients with this condition

Comprehensive Versus Usual Community Care for First-Episode Psychosis: 2-Year Outcomes From the NIMH RAISE Early Treatment Program

The primary aim was to compare the impact of NAVIGATE, a comprehensive, multidisciplinary, team-based treatment approach for first episode psychosis designed for implementation in the U.S. healthcare system, to Community Care on quality of life

Impact of the COVID-19 Pandemic on the Clinical Learning Environment: Addressing Identified Gaps and Seizing Opportunities

The clinical learning environment (CLE) encompasses the learner’s personal characteristics and experiences, social relationships, organizational culture, and the institution’s physical and virtual infrastructure. During the COVID-19 pandemic, all four of these parts of the CLE have undergone a massive and rapid disruption. Personal and social communications have been limited to virtual interactions or shifted to unfamiliar clinical spaces because of redeployment. Rapid changes to the organizational culture required prompt adaptations from learners and educators in their complex organizational systems yet caused increased confusion and anxiety among them. A traditional reliance on a physical infrastructure for classical educational practices in the CLE was challenged when all institutions had to undergo a major transition to a virtual learning environment. However, disruptions spurred exciting innovations in the CLE. An entire cohort of physicians and learners underwent swift adjustments in their personal and professional development and identity as they rose to meet the clinical and educational challenges they faced due to COVID-19. Social networks and collaborations were expanded beyond traditional institutional walls and previously held international boundaries within multiple specialties. Specific aspects of the organizational and educational culture, including epidemiology, public health, and medical ethics, were brought to the forefront in health professions education, while the physical learning environment underwent a rapid transition to a virtual learning space. As health professions education continues in the era of COVID-19 and into a new era, educators must take advantage of these dynamic systems to identify additional gaps and implement meaningful change. In this article, health professions educators and learners from multiple institutions and specialties discuss the gaps and weaknesses exposed, opportunities revealed, and strategies developed for optimizing the CLE in the post–COVID-19 world

The NAVIGATE Program for First-Episode Psychosis: Rationale, Overview, and Description of Psychosocial Components

Comprehensive coordinated specialty care programs for first episode psychosis have been widely implemented in other countries, but not in the U.S. The National Institute of Mental Health’s (NIMH) Recovery After Initial Schizophrenia Episode (RAISE) initiative focused on the development and evaluation of first episode treatment programs designed for the U.S. healthcare system. This paper describes the background, rationale, and nature of the intervention developed by the Early Treatment Program project, the NAVIGATE program, with a particular focus on its psychosocial components. NAVIGATE is a team-based, multi-component treatment program designed to be implemented in routine mental health treatment settings and aimed at guiding people with a first episode of psychosis (and their families) towards psychological and functional health. The core services provided in the NAVIGATE program include the Family Education Program, Individual Resiliency Training, Supported Employment and Education, and Individualized Medication Treatment. NAVIGATE embraces a shared decision-making approach with a focus on strengths and resiliency, and collaboration with clients and family members in treatment planning and reviews. The NAVIGATE program has the potential to fill an important gap in the U.S. healthcare system by providing a comprehensive intervention specially designed to meet the unique treatment needs of persons recovering from a first episode of psychosis. The program is currently being evaluated in cluster randomized controlled trial comparing NAVIGATE to usual community care

p53 Transactivation and the Impact of Mutations, Cofactors and Small Molecules Using a Simplified Yeast-Based Screening System

The p53 tumor suppressor, which is altered in most cancers, is a sequence-specific transcription factor that is able to modulate the expression of many target genes and influence a variety of cellular pathways. Inactivation of the p53 pathway in cancer frequently occurs through the expression of mutant p53 protein. In tumors that retain wild type p53, the pathway can be altered by upstream modulators, particularly the p53 negative regulators MDM2 and MDM4. promoter, ii) single copy, chromosomally located p53-responsive and control luminescence reporters, iii) enhanced chemical uptake using modified ABC-transporters, iv) small-volume formats for treatment and dual-luciferase assays, and v) opportunities to co-express p53 with other cofactor proteins. This robust system can distinguish different levels of expression of WT and mutant p53 as well as interactions with MDM2 or 53BP1.We found that the small molecules Nutlin and RITA could both relieve the MDM2-dependent inhibition of WT p53 transactivation function, while only RITA could impact p53/53BP1 functional interactions. PRIMA-1 was ineffective in modifying the transactivation capacity of WT p53 and missense p53 mutations. This dual-luciferase assay can, therefore, provide a high-throughput assessment tool for investigating a matrix of factors that can influence the p53 network, including the effectiveness of newly developed small molecules, on WT and tumor-associated p53 mutants as well as interacting proteins

A Genome-Wide Association Study of Psoriasis and Psoriatic Arthritis Identifies New Disease Loci

A genome-wide association study was performed to identify genetic factors involved in susceptibility to psoriasis (PS) and psoriatic arthritis (PSA), inflammatory diseases of the skin and joints in humans. 223 PS cases (including 91 with PSA) were genotyped with 311,398 single nucleotide polymorphisms (SNPs), and results were compared with those from 519 Northern European controls. Replications were performed with an independent cohort of 577 PS cases and 737 controls from the U.S., and 576 PSA patients and 480 controls from the U.K.. Strongest associations were with the class I region of the major histocompatibility complex (MHC). The most highly associated SNP was rs10484554, which lies 34.7 kb upstream from HLA-C (P = 7.8×10−11, GWA scan; P = 1.8×10−30, replication; P = 1.8×10−39, combined; U.K. PSA: P = 6.9×10−11). However, rs2395029 encoding the G2V polymorphism within the class I gene HCP5 (combined P = 2.13×10−26 in U.S. cases) yielded the highest ORs with both PS and PSA (4.1 and 3.2 respectively). This variant is associated with low viral set point following HIV infection and its effect is independent of rs10484554. We replicated the previously reported association with interleukin 23 receptor and interleukin 12B (IL12B) polymorphisms in PS and PSA cohorts (IL23R: rs11209026, U.S. PS, P = 1.4×10−4; U.K. PSA: P = 8.0×10−4; IL12B:rs6887695, U.S. PS, P = 5×10−5 and U.K. PSA, P = 1.3×10−3) and detected an independent association in the IL23R region with a SNP 4 kb upstream from IL12RB2 (P = 0.001). Novel associations replicated in the U.S. PS cohort included the region harboring lipoma HMGIC fusion partner (LHFP) and conserved oligomeric golgi complex component 6 (COG6) genes on chromosome 13q13 (combined P = 2×10−6 for rs7993214; OR = 0.71), the late cornified envelope gene cluster (LCE) from the Epidermal Differentiation Complex (PSORS4) (combined P = 6.2×10−5 for rs6701216; OR 1.45) and a region of LD at 15q21 (combined P = 2.9×10−5 for rs3803369; OR = 1.43). This region is of interest because it harbors ubiquitin-specific protease-8 whose processed pseudogene lies upstream from HLA-C. This region of 15q21 also harbors the gene for SPPL2A (signal peptide peptidase like 2a) which activates tumor necrosis factor alpha by cleavage, triggering the expression of IL12 in human dendritic cells. We also identified a novel PSA (and potentially PS) locus on chromosome 4q27. This region harbors the interleukin 2 (IL2) and interleukin 21 (IL21) genes and was recently shown to be associated with four autoimmune diseases (Celiac disease, Type 1 diabetes, Grave's disease and Rheumatoid Arthritis)