Temporal dynamics of normalization reweighting.

For decades, neural suppression in early visual cortex has been thought to be fixed. But recent work has challenged this assumption by showing that suppression can be reweighted based on recent history; when pairs of stimuli are repeatedly presented together, suppression between them strengthens. Here we investigate the temporal dynamics of this process using a steady-state visual evoked potential (SSVEP) paradigm that provides a time-resolved, direct index of suppression between pairs of stimuli flickering at different frequencies (5 and 7 Hz). Our initial analysis of an existing electroencephalography (EEG) dataset (N = 100) indicated that suppression increases substantially during the first 2-5 seconds of stimulus presentation (with some variation across stimulation frequency). We then collected new EEG data (N = 100) replicating this finding for both monocular and dichoptic mask arrangements in a preregistered study designed to measure reweighting. A third experiment (N = 20) used source-localized magnetoencephalography and found that these effects are apparent in primary visual cortex (V1), consistent with results from neurophysiological work. Because long-standing theories propose inhibition/excitation differences in autism, we also compared reweighting between individuals with high versus low autistic traits, and with and without an autism diagnosis, across our three datasets (total N = 220). We find no compelling differences in reweighting that are associated with autism. Our results support the normalization reweighting model and indicate that for prolonged stimulation, increases in suppression occur on the order of 2-5 seconds after stimulus onset.

Virus-specific humoral immune response in Bulgarian COVID-19 patients with varying disease severity.

INTRODUCTION: Our study aimed to analyze virus-specific humoral immune responses in COVID-19 patients with varying disease severity. METHODOLOGY: A total of 109 serum samples from 87 patients, symptomatic for COVID-19 were studied using anti-SARS-CoV-2 immunoassays detecting different classes of immunoglobulins. RESULTS: Clinical samples were divided into 2 groups - collected up to and more than 2 weeks post-onset of symptoms (PoS). In the first group, the highest percentage of positive samples was found for IgA class virus-specific antibodies (78.1%), followed by IgM (71.9%/59.4%) and IgG (56.3%/53.1%). In the second group, samples positive for virus-specific IgA class antibodies were also the most (97.7%) along with those positive for IgG. A total of 72 IgA and/or IgM and/or IgG positive samples were further tested for SARS-CoV-2 neutralizing antibodies (NAbs) - 89.1% and 100% of samples obtained up to and after 2 weeks PoS, respectively were positive. Serological test results were also analyzed depending on the severity of the disease - SARS-CoV-2 positive samples in mild forms of COVID-19 were fewer than in moderate and severe forms but this difference was not statistically significant. CONCLUSIONS: SARS-CoV-2 specific antibodies and a high virus neutralization capacity of these antibodies appear early PoS; Immunoglobulins of IgA class are of most significant diagnostic value for detection of SARS-CoV-2 infection; Timing of testing is the most important factor for positivity rate.

Organ transplantation in Bulgaria.

The transplantation program in Bulgaria started in 1968 with renal transplantations to a child and adult woman. In 1986 the first heart transplantation was performed. To date a total of 10 heart transplants have been performed, including one combined heart/lung. A liver transplantation program was launched in 2005 with a total number of 16 transplantations-7 from living donors and 9 from deceased donors. The highest transplantation activity is registered in the field of renal transplantation. During the period 1980-2006, 462 Bulgarian recipients of kidney were transplanted in Bulgaria. The ratio between transplantations from deceased and living related donors is approximately 1:0.9. Annual transplantation activity varies among the years from 1 to 12 renal transplantations p.m.p./per year. The 1- (80.7% vs. 63.1%), 5- (57.86% vs. 39.0%) and 10-year (42.65% vs. 23.62%) graft survival rates are higher for recipients of living donor kidneys compared to those of deceased donor. In 1983 a National kidney waiting list was established. Currently the number of the registered patients eligible for renal transplantation is 885. The proportion of sensitized patients in the waiting list is 20.45% and 4.34% of them are hyperimmunized. Recently HLAMatchmaker program has been implemented not only for sensitized patients but also for those with rare alleles and haplotypes. Post-transplant immunological monitoring showed a strong association between alloantibody presence and delayed graft function (Chi-square=10.73, P<0.001), acute rejection (Chi-square=14.504, P<0.001), chronic rejection (Chi-square=12.84, P<0.001) and graft loss (Chi-square=20.283, P<0.001). Based on the experience in our transplant center a strategy for improvement of long-term renal graft survival was developed and implemented.

Association of cytokine gene polymorphisms with malignant melanoma in Caucasian population.

It has been hypothesized that polymorphisms expected to result in functional changes in cytokine genes may influence susceptibility to cancer, including malignant melanoma (MM). Here, we have screened 24 potentially functional polymorphisms in five cytokine genes by PCR-SBT and PCR-SSP methods in 122 MM cell lines derived from Caucasian patients. The polymorphic positions studied were: TNFA -1031, -863, -857, -851, -574, -376, -308, -238, +488; TGFB1 -988, -800, -509, +869, +915, +652, +673, +713, +788; IL10 -1082, -819, -592; IL6 -174; IFNG -333, +874. The frequencies of cytokine genotypes of melanoma tumours were compared with those published for healthy Caucasians. It was found that TNFA -238 GA, TGFB1 -509 CT, -800 GG, IFNG +874 AT, IL6 -174 GG, IL10 -1082 GA genotypes were significantly decreased, while TNFA -238 AA, -857 CC, TGFB1 -509 TT, IFNG +874 AA, IL6 -174 CC, IL10 -1082 AA, -819 TT, -592 AA genotypes were significantly increased, in MM. This suggests that genotypes provisionally associated with low expression of pro-inflammatory and immunomodulatory TNF-alpha, IFN-gamma and IL-6 and anti-inflammatory IL-10 and TGF-beta1 could be involved in the mechanisms of cancer progression and escape from immunosurveillance.

Clinical relevance of anti-HLA antibodies detected by flow-cytometry bead-based assays--single-center experience.

The purpose of this study was to define the incidence, dynamics, and profiles of anti-human leukocyte antigen antibodies (HLA-Abs) produced after kidney transplantation and their impact on graft outcome. A total of 72 first cadaver donor kidney recipients were prospectively monitored for the development of HLA-Abs using bead-based flow-cytometry assays (One Lambda FlowPRA tests). Sixteen recipients (22.2%) developed HLA-Abs after transplantation (class I, n = 7; class I+II, n = 6; class II, n = 3), in most cases (81.25%) within the first 2 weeks posttransplantation. A strong association between alloantibody presence and delayed graft function (Chi-square = 7.659, p < 0.01), acute rejection (Chi-square = 14.504, p < 0.001), chronic rejection (Chi-square = 12.84, p < 0.001), and graft loss (Chi-square = 20.283, p < 0.001) was found. Patients with higher alloantibody titers experienced acute rejections and even early graft loss, compared with those with lower titers for whom chronic rejections were more common. Immunologic complications occurred in recipients with both donor-specific and cross-reacting groups or non-donor-specific antibodies alone. A positive correlation (Pearson correlation, 0.245; p < 0.05) between HLA class I amino acid triplet incompatibility and alloantibody production was observed, mainly resulting from immunogenic triplotypes. Given the results obtained in this study, an alloantibody testing algorithm has been designed and implemented for routine monitoring and to define optimally the alloantibody reactivity in kidney transplant recipients.