Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Psychological effects of “Gossip girl”, “Game of thrones” and “Breaking bad” on the lebanese audience

This research investigates the psychological effects of American television series on the Lebanese audience. The research was split into two studies: the first study was a quantitative analysis of the theories of identification and social learning, applied on a Lebanese female audience who watched the series Gossip Girl and Game of Thrones. The second study was a qualitative analysis of the theory of desensitization applied on two Lebanese participants, each watching respectively the series Breaking Bad and Game of Thrones. In the first study, a total of 115 Lebanese female participants were split into two groups: 75 participants who had watched only Gossip Girl and had an average age of 18 years old, and 40 participants who had watched both Gossip Girl and Game of Thrones and had an average age of 25 years old. The participants completed a survey based on the Wishful Identification Scale, the Parasocial Interaction Scale, the Attitude Similarity Scale, the Character’s Attributes Scale, the Connectedness Scale, and the Social Group Setting Scale. A T-Test and a Chi-Square analysis revealed that the Lebanese female audience of Group 1, with the average age of 18 years old, found similarities with the characters of the series Gossip Girl, which affected their identification with the characters, and their imitation of the characters’ attitudes. Further, the analysis revealed that the Lebanese female audience of Group 2, with the average age of 25 years old, watched and discussed the series Game of Thrones in a social group setting, which allowed the participants to build parasocial interactions with the characters and identify with them. In the second study, two participants were chosen based on the fact that one had never watched Breaking Bad and the second had never watched Game of Thrones. The participants were interviewed pre-series, and then interviewed throughout the exposure to several episodes. The qualitative in-depth analysis of the interview answers led to the results that after repeated exposure to Game of Thrones and Breaking Bad, the Lebanese viewer, even if already tolerant to on-screen violence, experienced desensitization signs to the violence, drugs, incest and rape portrayed on-screen in these two series

Psychological effects of "Gossip girl", "Game of thrones" and "Breaking bad" on the lebanese audience

This research investigates the psychological effects of American television series on the Lebanese audience. The research was split into two studies: the first study was a quantitative analysis of the theories of identification and social learning, applied on a Lebanese female audience who watched the series Gossip Girl and Game of Thrones. The second study was a qualitative analysis of the theory of desensitization applied on two Lebanese participants, each watching respectively the series Breaking Bad and Game of Thrones. In the first study, a total of 115 Lebanese female participants were split into two groups: 75 participants who had watched only Gossip Girl and had an average age of 18 years old, and 40 participants who had watched both Gossip Girl and Game of Thrones and had an average age of 25 years old. The participants completed a survey based on the Wishful Identification Scale, the Parasocial Interaction Scale, the Attitude Similarity Scale, the Character's Attributes Scale, the Connectedness Scale, and the Social Group Setting Scale. A T-Test and a Chi-Square analysis revealed that the Lebanese female audience of Group 1, with the average age of 18 years old, found similarities with the characters of the series Gossip Girl, which affected their identification with the characters, and their imitation of the characters' attitudes. Further, the analysis revealed that the Lebanese female audience of Group 2, with the average age of 25 years old, watched and discussed the series Game of Thrones in a social group setting, which allowed the participants to build parasocial interactions with the characters and identify with them. In the second study, two participants were chosen based on the fact that one had never watched Breaking Bad and the second had never watched Game of Thrones. The participants were interviewed pre-series, and then interviewed throughout the exposure to several episodes. The qualitative in-depth analysis of the interview answers led to the results that after repeated exposure to Game of Thrones and Breaking Bad, the Lebanese viewer, even if already tolerant to on-screen violence, experienced desensitization signs to the violence, drugs, incest and rape portrayed on-screen in these two series

Use of scanning electron microscopy and energy dispersive X‐ray for urine analysis: A preliminary investigation

International audienc

Immune modulation in transplant medicine: a comprehensive review of cell therapy applications and future directions.

Balancing the immune response after solid organ transplantation (SOT) and vascularized composite allotransplantation (VCA) remains an ongoing clinical challenge. While immunosuppressants can effectively reduce acute rejection rates following transplant surgery, some patients still experience recurrent acute rejection episodes, which in turn may progress to chronic rejection. Furthermore, these immunosuppressive regimens are associated with an increased risk of malignancies and metabolic disorders. Despite significant advancements in the field, these IS related side effects persist as clinical hurdles, emphasizing the need for innovative therapeutic strategies to improve transplant survival and longevity. Cellular therapy, a novel therapeutic approach, has emerged as a potential pathway to promote immune tolerance while minimizing systemic side-effects of standard IS regiments. Various cell types, including chimeric antigen receptor T cells (CAR-T), mesenchymal stromal cells (MSCs), regulatory myeloid cells (RMCs) and regulatory T cells (Tregs), offer unique immunomodulatory properties that may help achieve improved outcomes in transplant patients. This review aims to elucidate the role of cellular therapies, particularly MSCs, T cells, Tregs, RMCs, macrophages, and dendritic cells in SOT and VCA. We explore the immunological features of each cell type, their capacity for immune regulation, and the prospective advantages and obstacles linked to their application in transplant patients. An in-depth outline of the current state of the technology may help SOT and VCA providers refine their perioperative treatment strategies while laying the foundation for further trials that investigate cellular therapeutics in transplantation surgery

Comparison of acarological risk metrics derived from active and passive surveillance and their concordance with tick-borne disease incidence

Tick-borne diseases continue to threaten human health across the United States. Both active and passive tick surveillance can complement human case surveillance, providing spatio-temporal information on when and where humans are at risk for encounters with ticks and tick-borne pathogens. However, little work has been done to assess the concordance of the acarological risk metrics from each surveillance method. We used data on Ixodes scapularis and its associated human pathogens from Connecticut (2019–2021) collected through active collections (drag sampling) or passive submissions from the public to compare county estimates of tick and pathogen presence, infection prevalence, and tick abundance by life stage. Between the surveillance strategies, we found complete agreement in estimates of tick and pathogen presence, high concordance in infection prevalence estimates for Anaplasma phagocytophilum, Borrelia burgdorferi sensu stricto, and Babesia microti, but no consistent relationships between actively and passively derived estimates of tick abundance or abundance of infected ticks by life stage. We also compared nymphal metrics (i.e., pathogen prevalence in nymphs, nymphal abundance, and abundance of infected nymphs) with reported incidence of Lyme disease, anaplasmosis, and babesiosis, but did not find any consistent relationships with any of these metrics. The small spatial and temporal scale for which we had consistently collected active and passive data limited our ability to find significant relationships. Findings are likely to differ if examined across a broader spatial or temporal coverage with greater variation in acarological and epidemiological outcomes. Our results indicate similar outcomes between some actively and passively derived tick surveillance metrics (tick and pathogen presence, pathogen prevalence), but comparisons were variable for abundance estimates

Immune modulation in transplant medicine: a comprehensive review of cell therapy applications and future directions

Balancing the immune response after solid organ transplantation (SOT) and vascularized composite allotransplantation (VCA) remains an ongoing clinical challenge. While immunosuppressants can effectively reduce acute rejection rates following transplant surgery, some patients still experience recurrent acute rejection episodes, which in turn may progress to chronic rejection. Furthermore, these immunosuppressive regimens are associated with an increased risk of malignancies and metabolic disorders. Despite significant advancements in the field, these IS related side effects persist as clinical hurdles, emphasizing the need for innovative therapeutic strategies to improve transplant survival and longevity. Cellular therapy, a novel therapeutic approach, has emerged as a potential pathway to promote immune tolerance while minimizing systemic side-effects of standard IS regiments. Various cell types, including chimeric antigen receptor T cells (CAR-T), mesenchymal stromal cells (MSCs), regulatory myeloid cells (RMCs) and regulatory T cells (Tregs), offer unique immunomodulatory properties that may help achieve improved outcomes in transplant patients. This review aims to elucidate the role of cellular therapies, particularly MSCs, T cells, Tregs, RMCs, macrophages, and dendritic cells in SOT and VCA. We explore the immunological features of each cell type, their capacity for immune regulation, and the prospective advantages and obstacles linked to their application in transplant patients. An in-depth outline of the current state of the technology may help SOT and VCA providers refine their perioperative treatment strategies while laying the foundation for further trials that investigate cellular therapeutics in transplantation surgery

Mast cell progenitors : Origin, development and migration to tissues

Mast cells in tissues are developed from mast cell progenitors emerging from the bone marrow in a process highly regulated by transcription factors. Through the advancement of the multicolor flow cytometry technique, the mast cell progenitor population in the mouse has been characterized in terms of surface markers. However, only cell populations with enriched mast cell capability have been described in human. In naïve mice, the peripheral tissues have a constitutive pool of mast cell progenitors. Upon infections in the gut and in allergic inflammation in the lung, the local mast cell progenitor numbers increase tremendously. This review focuses on the origin and development of mast cell progenitors. Furthermore, the evidences for cells and molecules that govern the migration of these cells in mice in vivo are described