A role for human leucocyte antigens in the susceptibility to SARS‐Cov‐2 infection observed in transplant patients

We analysed data from 80 patients who tested positive for SARS‐CoV‐2 RNA who had previously been HLA typed to support transplantation. Data were combined from two adjacent centres in Manchester and Leeds to achieve a sufficient number for early analysis. HLA frequencies observed were compared against two control populations: first, against published frequencies in a UK deceased donor population (n = 10,000) representing the target population of the virus, and second, using a cohort of individuals from the combined transplant waiting lists of both centres (n = 308), representing a comparator group of unaffected individuals of the same demographic. We report a significant HLA association with HLA‐ DQB1*06 (53% vs. 36%; p < .012; OR 1.96; 95% CI 1.94–3.22) and infection. A bias towards an increased representation of HLA‐A*26, HLA‐DRB1*15, HLA‐DRB1*10 and DRB1*11 was also noted but these were either only significant using the UK donor controls, or did not remain significant after correction for multiple tests. Likewise, HLA‐A*02, HLA‐B*44 and HLA‐C*05 may exert a protective effect, but these associations did not remain significant after correction for multiple tests. This is relevant information for the clinical management of patients in the setting of the current SARS‐CoV‐2 pandemic and potentially in risk‐assessing staff interactions with infected patients

The Jacob2 Lectin of the Entamoeba histolytica Cyst Wall Binds Chitin and Is Polymorphic

For many years, we and others have used cysts of Entamoeba invadens (Ei), a reptilian parasite, to model the infectious and diagnostic cysts of the human pathogen Entamoeba histolytica (Eh). The Ei cyst wall is composed of chitin fibrils, as well as Jacob and Jessie lectins that have unique chitin-binding domains. Our recent results suggest a “wattle and daub” model of the Ei cyst wall, where the wattle or sticks (chitin fibrils bound by multivalent Jacob lectins) is constructed prior to the addition of the mortar or daub (self-aggregating Jessie3 lectins). Here we “humanize” the Ei model of the cyst wall with four findings. First, a recombinant Eh Jacob2 lectin, which has three predicted chitin-binding domains surrounding a large spacer domain, binds chitin beads. Second, polymorphisms in the spacer domain of EhJacob2 discriminate clinical isolates of Entamoeba. Third, chitinase, Jacob2 lectin, and Jessie3 lectin are present in cyst walls of clinical isolates of Entamoeba. Finally, numerous sera from patients infected with Entamoeba recognize recombinant Eh Jacob1 and Jessie3 lectins

Motion processing with wide-field neurons in the retino-tecto-rotundal pathway

The retino-tecto-rotundal pathway is the main visual pathway in non-mammalian vertebrates and has been found to be highly involved in visual processing. Despite the extensive receptive fields of tectal and rotundal wide-field neurons, pattern discrimination tasks suggest a system with high spatial resolution. In this paper, we address the problem of how global processing performed by motion-sensitive wide-field neurons can be brought into agreement with the concept of a local analysis of visual stimuli. As a solution to this problem, we propose a firing-rate model of the retino-tecto-rotundal pathway which describes how spatiotemporal information can be organized and retained by tectal and rotundal wide-field neurons while processing Fourier-based motion in absence of periodic receptive-field structures. The model incorporates anatomical and electrophysiological experimental data on tectal and rotundal neurons, and the basic response characteristics of tectal and rotundal neurons to moving stimuli are captured by the model cells. We show that local velocity estimates may be derived from rotundal-cell responses via superposition in a subsequent processing step. Experimentally testable predictions which are both specific and characteristic to the model are provided. Thus, a conclusive explanation can be given of how the retino-tecto-rotundal pathway enables the animal to detect and localize moving objects or to estimate its self-motion parameters

Evidence for a “Wattle and Daub” Model of the Cyst Wall of Entamoeba

The cyst wall of Entamoeba invadens (Ei), a model for the human pathogen Entamoeba histolytica, is composed of fibrils of chitin and three chitin-binding lectins called Jacob, Jessie3, and chitinase. Here we show chitin, which was detected with wheat germ agglutinin, is made in secretory vesicles prior to its deposition on the surface of encysting Ei. Jacob lectins, which have tandemly arrayed chitin-binding domains (CBDs), and chitinase, which has an N-terminal CBD, were each made early during encystation. These results are consistent with their hypothesized roles in cross-linking chitin fibrils (Jacob lectins) and remodeling the cyst wall (chitinase). Jessie3 lectins likely form the mortar or daub of the cyst wall, because 1) Jessie lectins were made late during encystation; 2) the addition to Jessie lectins to the cyst wall correlated with a marked decrease in the permeability of cysts to nucleic acid stains (DAPI) and actin-binding heptapeptide (phalloidin); and 3) recombinant Jessie lectins, expressed as a maltose-binding proteins in the periplasm of Escherichia coli, caused transformed bacteria to agglutinate in suspension and form a hard pellet that did not dissociate after centrifugation. Jessie3 appeared as linear forms and rosettes by negative staining of secreted recombinant proteins. These findings provide evidence for a “wattle and daub” model of the Entamoeba cyst wall, where the wattle or sticks (chitin fibrils likely cross-linked by Jacob lectins) is constructed prior to the addition of the mortar or daub (Jessie3 lectins)

Epilepsy is related to theta band brain connectivity and network topology in brain tumor patients

<p>Abstract</p> <p>Background</p> <p>Both epilepsy patients and brain tumor patients show altered functional connectivity and less optimal brain network topology when compared to healthy controls, particularly in the theta band. Furthermore, the duration and characteristics of epilepsy may also influence functional interactions in brain networks. However, the specific features of connectivity and networks in tumor-related epilepsy have not been investigated yet. We hypothesize that epilepsy characteristics are related to (theta band) connectivity and network architecture in operated glioma patients suffering from epileptic seizures. Included patients participated in a clinical study investigating the effect of levetiracetam monotherapy on seizure frequency in glioma patients, and were assessed at two time points: directly after neurosurgery (t1), and six months later (t2). At these time points, magnetoencephalography (MEG) was recorded and information regarding clinical status and epilepsy history was collected. Functional connectivity was calculated in six frequency bands, as were a number of network measures such as normalized clustering coefficient and path length.</p> <p>Results</p> <p>At the two time points, MEG registrations were performed in respectively 17 and 12 patients. No changes in connectivity or network topology occurred over time. Increased theta band connectivity at t1 and t2 was related to a higher total number of seizures. Furthermore, higher number of seizures was related to a less optimal, more random brain network topology. Other factors were not significantly related to functional connectivity or network topology.</p> <p>Conclusions</p> <p>These results indicate that (pathologically) increased theta band connectivity is related to a higher number of epileptic seizures in brain tumor patients, suggesting that theta band connectivity changes are a hallmark of tumor-related epilepsy. Furthermore, a more random brain network topology is related to greater vulnerability to seizures. Thus, functional connectivity and brain network architecture may prove to be important parameters of tumor-related epilepsy.</p

Kidney Transplantation From Deceased Donors With Vaccine-induced Immune Thrombocytopenia and Thrombosis: An Updated Analysis of the UK Experience

Background: The emergence and attendant mortality of vaccine-induced immune thrombocytopenia and thrombosis (VITT) as a consequence of vaccination against severe acute respiratory syndrome coronavirus 2 have resulted in some patients with VITT being considered as deceased organ donors. Outcomes after kidney transplantation in this context are poorly described. Because the disease seems to be mediated by antiplatelet factor 4 antibodies, there is a theoretical risk of transmission via passenger leukocytes within the allograft. Methods: We analyzed the experience of kidney transplantation from donors with VITT in the United Kingdom between January and June 2021. We followed-up all recipients of kidney-only transplants from donors with VITT to detect major postoperative complications or features of disease transmission and assess graft survival and function. Results: There were 16 kidney donors and 30 single kidney transplant recipients in our study period. Of 11 preimplantation biopsies, 4 showed widespread glomerular microthrombi. After a median of 5 mo, patient and graft survival were 97% and 90%, respectively. The median 3-mo estimated glomerular filtration rate was 51 mL/min/1.73 m2. Two recipients had detectable antiplatelet factor 4 antibodies but no evidence of clinical disease after transplantation. Major hemorrhagic complications occurred in 3 recipients, all of whom had independent risk factors for bleeding, resulting in the loss of 2 grafts. The involvement of VITT could not be completely excluded in one of these cases. Conclusions: The UK experience to date shows that favorable outcomes are possible after kidney transplantation from donors with VITT but highlights the need for ongoing vigilance for donor-related complications in these patients

‘Functional Connectivity’ Is a Sensitive Predictor of Epilepsy Diagnosis after the First Seizure

Background: Although epilepsy affects almost 1 % of the world population, diagnosis of this debilitating disease is still difficult. The EEG is an important tool for epilepsy diagnosis and classification, but the sensitivity of interictal epileptiform discharges (IEDs) on the first EEG is only 30–50%. Here we investigate whether using ‘functional connectivity ’ can improve the diagnostic sensitivity of the first interictal EEG in the diagnosis of epilepsy. Methodology/Principal Findings: Patients were selected from a database with 390 standard EEGs of patients after a first suspected seizure. Patients who were later diagnosed with epilepsy (i.e. $two seizures) were compared to matched nonepilepsy patients (with a minimum follow-up of one year). The synchronization likelihood (SL) was used as an index of functional connectivity of the EEG, and average SL per patient was calculated in seven frequency bands. In total, 114 patients were selected. Fifty-seven patients were diagnosed with epilepsy (20 had IEDs on their EEG) and 57 matched patients had other diagnoses. Epilepsy patients had significantly higher SL in the theta band than non-epilepsy patients. Furthermore, theta band SL proved to be a significant predictor of a diagnosis of epilepsy. When only those epilepsy patients without IEDs were considered (n = 74), theta band SL could predict diagnosis with specificity of 76 % and sensitivity of 62%. Conclusion/Significance: Theta band functional connectivity may be a useful diagnostic tool in diagnosing epilepsy

Motor coordination problems in children and adolescents with ADHD rated by parents and teachers: effects of age and gender

Summary. Objective. ADHD is frequently accompanied by motor coordination problems. However, the co-occurrence of poor motor performance has received less attention in research than other coexisting problems in ADHD. The underlying mechanisms of this association remain unclear. Therefore, we investigated the prevalence of motor coordination problems in a large sample of children with ADHD, and the relationship between motor coordination problems and inattentive and hyperactive/impulsive symptoms. Furthermore, we assessed whether the association between ADHD and motor coordination problems was comparable across ages and was similar for both genders. Method. We investigated 486 children with ADHD and 269 normal controls. Motor coordination problems were rated by parents (Developmental Coordination Disorder Questionnaire) and teachers (Groningen Motor Observation Scale). Results. Parents and teachers reported motor coordination problems in about one third of children with ADHD. Problems of fine and gross motor skills, coordination skills and motor control were all related to inattentive rather than hyperactive/impulsive symptoms. Relative to controls, motor coordination problems in ADHD were still present in teenagers according to parents; the prevalence diminished somewhat according to teachers. Boys and girls with ADHD were comparably affected, but motor performance in controls was better in girls than in boys. Conclusions. Motor coordination problems were reported in one third of children with ADHD and affected both boys and girls. These problems were also apparent in adolescents with ADHD. Clinicians treating children with ADHD should pay attention to co-occurring motor coordination problems because of the high prevalence and the negative impact of motor coordination problems on daily life