Project description:Previous studies have investigated differences in the volumes of subcortical structures (e.g., caudate nucleus, putamen, thalamus, amygdala, and hippocampus) between individuals with and without Tourette syndrome (TS), as well as the relationships between these volumes and tic symptom severity. These volumes may also predict clinical outcome in Provisional Tic Disorder (PTD), but that hypothesis has never been tested. This study aimed to examine whether the volumes of subcortical structures measured shortly after tic onset can predict tic symptom severity at one-year post-tic onset, when TS can first be diagnosed. We obtained T1-weighted structural MRI scans from 41 children with PTD (25 with prospective motion correction (vNavs)) whose tics had begun less than 9 months (mean 4.04 months) prior to the first study visit (baseline). We re-examined them at the 12-month anniversary of their first tic (follow-up), assessing tic severity using the Yale Global Tic Severity Scale. We quantified the volumes of subcortical structures using volBrain software. Baseline hippocampal volume was correlated with tic severity at the 12-month follow-up, with a larger hippocampus at baseline predicting worse tic severity at follow-up. The volumes of other subcortical structures did not significantly predict tic severity at follow-up. Hippocampal volume may be an important marker in predicting prognosis in Provisional Tic Disorder.
Project description:Immunoglobulin heavy chain genes in Raja erinacea (little skate) are organized in clusters consisting of VH, DH, JH segments and CH exons (1). An immunoglobulin heavy chain mu-like isotype that exhibits 61-91% nucleotide sequence identity in coding segments to the Heterodontus francisci (horned shark) mu-type immunoglobulin is described. The overall length of the mu-type clusters is approximately 16 kb; transmembrane exons (TM1 and TM2) are located 3 to CH exon 4 (CH4). In three of four TM-containing genomic clones, a significant deletion is present in TM1. A second isotype of Raja immunoglobulin heavy chain genes has been detected by screening a spleen cDNA library with homologous Raja VH- and CH1-specific probes complementing the respective regions of the mu-like isotype. Weak hybridization with VH-specific probes and no discernable hybridization with C mu-specific probes were considered presumptive evidence for a second immunoglobulin isotype that nominally is designated as X-type. The Vx region of the X-type cDNA is approximately 60% identical at the nucleotide (nt) level to other Raja VH segments and thus represents a second VH family. Putative Dx and Jx sequences also have been identified. The constant region of the X-type immunoglobulin heavy chain gene consists of two characteristic immunoglobulin domains and a cysteine-rich carboxy terminal segment that are only partially homologous with the mu-like isotype. Genomic Southern blotting indicates that the V and C segments of both immunoglobulin heavy chain isotypes are encoded by complex multigene families. Vx- and different Cx-specific probes hybridize to different length transcripts in northern blot analyses of Raja spleen RNA suggesting that the regulation of expression of the X-type genes may involve differential RNA processing.
Project description:BackgroundThe kinetics of the antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) needs to be evaluated since long-term duration of antibody remains largely unknown, particularly in infected healthcare workers (HCW).MethodsProspective study, evaluating the longitudinal profile of anti-SARS-CoV-2 antibody titers in a random sample of 331 seropositive healthcare workers (HCW) of Spanish Hospitals Group. Serial measurements of serum IgG-anti-SARS-CoV-2 were obtained at baseline (April-May,2020), and in 2 follow-up visits. Linear mixed models were used to investigate antibody kinetics and associated factors.ResultsA total of 306 seropositive subjects (median age: 44.7years;69.9% female) were included in the final analysis. After a median follow-up of 274 days between baseline and final measurement, 235(76.8%) maintained seropositivity. Antibody titers decreased in 82.0%, while remained stable in 13.1%. Factors associated with stability of antibodies over time included age≥45 years, higher baseline titers, severe/moderate infection and high-grade exposure to COVID-19 patients. In declining profile, estimated mean antibody half-life was 146.3 days(95%CI:138.6-154.9) from baseline. Multivariate models show independent longer durability of antibodies in HCW with high-risk exposure to COVID-19 patients (+14.1 days;95%CI:0.6-40.2) and with symptomatic COVID-19 (+14.1 days;95%CI:0.9-43.0). The estimated mean time to loss antibodies was 375(95% CI:342-408) days from baseline.ConclusionsWe present the first study measuring the kinetics of antibody response against SARS-CoV-2 in HCW beyond 6 months. Most participants remained seropositive after 9 months but presented a significant decline in antibody-titers. Two distinct antibody dynamic profiles were observed (declining vs. stable). Independent factors associated with longer durability of antibodies were symptomatic infection and higher exposure to COVID-19 patients.
Project description:BackgroundPost-surgical follow-up is a challenge in low- and middle-income countries. Understanding barriers to trachomatous trichiasis (TT) surgical follow-up can inform program improvements. In this study, patient perceived barriers and enabling factors to follow-up after TT surgery are identified.MethodsA longitudinal study was carried out in a community-based cohort of persons who received TT surgery in Bahi district, Tanzania. Questionnaires were administered before TT surgery and again after the scheduled 6-month follow-up. Those who did not return were examined at their homes.ResultsAt baseline, 852 participants were enrolled. Of these, 633 (74%) returned at 6 months and 128 (15%) did not and were interviewed at home. Prior to surgery, attenders were more likely to report familiarity with a community health worker (CHW) (22% vs. 14%; p = 0.01) and less likely to state that time constraints are a potential reason for failure to follow-up (66% vs. 74%; p = .04). At follow-up, non-attenders were more likely to endorse barriers pertaining to knowledge about the need for follow-up, lack of transportation, and satisfaction with surgery. There was no difference in post-operative TT between attenders and non-attenders (23% vs. 18% respectively; p = 0.25).ConclusionsThe outcome of surgery was not a barrier to follow-up. However, better integration of CHWs into their communities and work at coordinating post-surgical care may improve follow-up rates. Moreover, provision of transportation and implementation of effective reminder systems may address patient-perceived barriers to improve follow-up.
Project description:ObjectiveTo examine whether the Unified Protocol (UP) remains equivalent to single-disorder protocols (SDPs) in the treatment of anxiety disorders at 12-month follow-up.MethodWe report results from the 12-month follow-up of a recent randomized equivalence trial [1]. Data are from 179 participants (55.31% female sex, 83.24% White, average age 30.66) who met criteria for a principal anxiety disorder and were randomized to either the UP or SDP conditions. Consistent with the parent trial, the primary outcome was principal diagnosis clinician severity rating (CSR) from the Anxiety Disorder Interview Schedule (ADIS). Secondary outcomes included anxiety, depression, and impairment. Missing data were accommodated using multiple imputation (10,000 imputed data sets) under a missing at random assumption. Equivalence between the UP and SDPs was tested using slope difference scores from latent growth models and 95% confidence interval of between-condition effect sizes.ResultsThe results indicated that the UP and SDP conditions remained equivalent with regard to principal diagnosis clinician severity rating at 12-month follow-up. In addition, there were no significant differences between conditions on secondary outcomes at 12-month follow-up.ConclusionsThe UP continues to yield outcomes comparable to SDPs at 12-month follow-up, and therefore provides a single intervention that can be used to treat the most commonly occurring psychiatric disorders with durable effects.
Project description:BackgroundThe role of tumor-infiltrating B-cells (TIBs) and intratumorally-produced antibodies in cancer-immunity interactions essentially remains terra incognita. In particular, it remains unexplored how driver mutations could be associated with distinct TIBs signatures and their role in tumor microenvironment.MethodsHere we analyzed associations of immunoglobulin isotypes and clonality with survival in TCGA RNA-Seq data for lung adenocarcinoma (LUAD), stratifying patients into 12 driver mutation and phenotypic tumor subgroups.ResultsWe revealed several unexpected associations between TIBs behavior and prognosis. Abundance and high proportion of IgG1 isotype, and low proportion of IgA among all intratumorally produced immunoglobulins were specifically associated with improved overall survival for KRASmut but not KRASwt LUAD, revealing the first link between a driver mutation and B-cell response. We found specific IgG1 signature associated with long survival, which suggests that particular specificities of IgG1+ TIBs could be beneficial in KRASmut LUAD. In contrast to our previous observations for melanoma, highly clonal IgG1 production by plasma cells had no meaningful effect on prognosis, suggesting that IgG1+ TIBs may exert a beneficial effect in KRASmut cases in an alternative way, such as efficient presentation of cognate antigens or direct B cell attack on tumor cells. Notably, a high proportion of the IgG1 isotype is positively correlated with the non-silent mutation burden both in the general LUAD cohort and in most patient subgroups, supporting a role for IgG1+ TIBs in antigen presentation. Complementing the recent finding that the presence of stromal IgG4-producing cells is associated with a favorable prognosis for patients with stage I squamous cell carcinoma, we show that the abundance of IgG4-producing TIBs likewise has a strong positive effect on overall survival in STK11mut and proximal proliferative subgroups of LUAD patients. We hypothesize that the positive role of IgG4 antibodies in some of the lung cancer subtypes could be associated with reported inability of IgG4 isotype to form immune complexes, thus preventing immunosuppression via activation of the myeloid-derived suppressor cell (MDSC) phenotype.ConclusionsWe discover prominent and distinct associations between TIBs antibody isotypes and survival in lung adenocarcinoma carrying specific driver mutations. These findings indicate that particular types of tumor-immunity relations could be beneficial in particular driver mutation context, which should be taken into account in developing strategies of cancer immunotherapy and combination therapies. Specificity of protective B cell populations in specific cancer subgroups could become a clue to efficient targeted immunotherapies for appropriate cohorts of patients.
Project description:Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly around the world, posing a major threat to human health and the economy. Currently, long-term data on viral shedding and the serum antibody responses in COVID-19 patients are still limited. Herein, we report the clinical features, viral RNA loads, and serum antibody levels in a cohort of 112 COVID-19 patients admitted to the Honghu People's Hospital, Hubei Province, China. Overall, 5.36% (6/112) of patients showed persistent viral RNA shedding (> 45 days). The peak viral load was higher in the severe disease group than in the mild group (median cycle threshold value, 36.4 versus 31.5; P = 0.002). For most patients the disappearance of IgM antibodies occurred approximately 4-6 weeks after symptoms onset, while IgG persisted for over 194 days after the onset of symptoms, although patients showed a 46% reduction in antibodies titres against SARS-CoV-2 nucleocapsid protein compared with the acute phase. We also studied 18 asymptomatic individuals with RT-qPCR confirmed SARS-CoV-2 infection together with 17 symptomatic patients, and the asymptomatic individuals were the close contacts of these symptomatic cases. Delayed IgG seroconversion and lower IgM seropositive rates were observed in asymptomatic individuals. These data indicate that higher viral loads and stronger antibody responses are related to more severe disease status in patients with SARS-CoV-2 infection, and the antibodies persisted in the recovered patient for more than 6 months so that the vaccine may provide protection against SARS-CoV-2 infection.