Parvovirus B19 infection in pediatric transplant patients

Evidence of recent parvovirus virus infection (as determined by the presence of a positive IgM antibody titer) without other identified causes of anemia was found in 5 of 26 pediatric solid-organ transplant recipients evaluated for moderate-to-severe anemia between June 1990 and July 1991. Anemia tended to be chronic (median duration of anemia at the time of diagnosis was 12 weeks) and was associated with normal red blood cell indices in the absence of reticulocytes. The median age of the children at the time of presentation with anemia due to parvovirus was 1.8 years at a median time of 8 months after transplantation. Four of the 5 children were treated with i.v. immunoglobulin because of persistance of anemia requiring blood transfusions. A response characterized by an increase in reticulocyte count and normalization of hemoglobin was seen in each of these patients 2-4 weeks after treatment. The remaining patient experienced a spontaneous recovery from her anemia. Parvovirus infection should be included in the differential diagnosis of solid-organ transplant recipients presenting with severe anemia associated with low or absent reticulocytes

Theory-Driven Analysis of Natural Language Processing Measures of Thought Disorder Using Generative Language Modeling

BACKGROUND: Natural language processing (NLP) holds promise to transform psychiatric research and practice. A pertinent example is the success of NLP in the automatic detection of speech disorganization in formal thought disorder (FTD). However, we lack an understanding of precisely what common NLP metrics measure and how they relate to theoretical accounts of FTD. We propose tackling these questions by using deep generative language models to simulate FTD-like narratives by perturbing computational parameters instantiating theory-based mechanisms of FTD. METHODS: We simulated FTD-like narratives using Generative-Pretrained-Transformer-2 by either increasing word selection stochasticity or limiting the model's memory span. We then examined the sensitivity of common NLP measures of derailment (semantic distance between consecutive words or sentences) and tangentiality (how quickly meaning drifts away from the topic) in detecting and dissociating the 2 underlying impairments. RESULTS: Both parameters led to narratives characterized by greater semantic distance between consecutive sentences. Conversely, semantic distance between words was increased by increasing stochasticity, but decreased by limiting memory span. An NLP measure of tangentiality was uniquely predicted by limited memory span. The effects of limited memory span were nonmonotonic in that forgetting the global context resulted in sentences that were semantically closer to their local, intermediate context. Finally, different methods for encoding the meaning of sentences varied dramatically in performance. CONCLUSIONS: This work validates a simulation-based approach as a valuable tool for hypothesis generation and mechanistic analysis of NLP markers in psychiatry. To facilitate dissemination of this approach, we accompany the paper with a hands-on Python tutorial

Reproductive Suicide: Similar Mechanisms of Aging in C. elegans and Pacific Salmon

In some species of salmon, reproductive maturity triggers the development of massive pathology resulting from reproductive effort, leading to rapid post-reproductive death. Such reproductive death, which occurs in many semelparous organisms (with a single bout of reproduction), can be prevented by blocking reproductive maturation, and this can increase lifespan dramatically. Reproductive death is often viewed as distinct from senescence in iteroparous organisms (with multiple bouts of reproduction) such as humans. Here we review the evidence that reproductive death occurs in C. elegans and discuss what this means for its use as a model organism to study aging. Inhibiting insulin/IGF-1 signaling and germline removal suppresses reproductive death and greatly extends lifespan in C. elegans, but can also extend lifespan to a small extent in iteroparous organisms. We argue that mechanisms of senescence operative in reproductive death exist in a less catastrophic form in iteroparous organisms, particularly those that involve costly resource reallocation, and exhibit endocrine-regulated plasticity. Thus, mechanisms of senescence in semelparous organisms (including plants) and iteroparous ones form an etiological continuum. Therefore understanding mechanisms of reproductive death in C. elegans can teach us about some mechanisms of senescence that are operative in iteroparous organisms

Photorespiration: metabolic pathways and their role in stress protection

Photorespiration results from the oxygenase reaction catalysed by ribulose-1,5-bisphosphate carboxylase/ oxygenase. In this reaction glycollate-2-phosphate is produced and subsequently metabolized in the photorespiratory pathway to form the Calvin cycle intermediate glycerate-3-phosphate. During this metabolic process, CO2 and NH3 are produced and ATP and reducing equivalents are consumed, thus making photorespiration a wasteful process. However, precisely because of this ine¤ciency, photorespiration could serve as an energy sink preventing the overreduction of the photosynthetic electron transport chain and photoinhibition, especially under stress conditions that lead to reduced rates of photosynthetic CO2 assimilation. Furthermore, photorespiration provides metabolites for other metabolic processes, e.g. glycine for the synthesis of glutathione, which is also involved in stress protection. In this review, we describe the use of photorespiratory mutants to study the control and regulation of photorespiratory pathways. In addition, we discuss the possible role of photorespiration under stress conditions, such as drought, high salt concentrations and high light intensities encountered by alpine plants

Trajectories through semantic spaces in schizophrenia and the relationship to ripple bursts

Human cognition is underpinned by structured internal representations that encode relationships between entities in the world (cognitive maps). Clinical features of schizophrenia-from thought disorder to delusions-are proposed to reflect disorganization in such conceptual representations. Schizophrenia is also linked to abnormalities in neural processes that support cognitive map representations, including hippocampal replay and high-frequency ripple oscillations. Here, we report a computational assay of semantically guided conceptual sampling and exploit this to test a hypothesis that people with schizophrenia (PScz) exhibit abnormalities in semantically guided cognition that relate to hippocampal replay and ripples. Fifty-two participants [26 PScz (13 unmedicated) and 26 age-, gender-, and intelligence quotient (IQ)-matched nonclinical controls] completed a category- and letter-verbal fluency task, followed by a magnetoencephalography (MEG) scan involving a separate sequence-learning task. We used a pretrained word embedding model of semantic similarity, coupled to a computational model of word selection, to quantify the degree to which each participant's verbal behavior was guided by semantic similarity. Using MEG, we indexed neural replay and ripple power in a post-task rest session. Across all participants, word selection was strongly influenced by semantic similarity. The strength of this influence showed sensitivity to task demands (category > letter fluency) and predicted performance. In line with our hypothesis, the influence of semantic similarity on behavior was reduced in schizophrenia relative to controls, predicted negative psychotic symptoms, and correlated with an MEG signature of hippocampal ripple power (but not replay). The findings bridge a gap between phenomenological and neurocomputational accounts of schizophrenia

Reduced coupling between offline neural replay events and default mode network activation in schizophrenia

Schizophrenia is characterized by an abnormal resting state and default mode network brain activity. However, despite intense study, the mechanisms linking default mode network dynamics to neural computation remain elusive. During rest, sequential hippocampal reactivations, known as 'replay', are played out within default mode network activation windows, highlighting a potential role of replay-default mode network coupling in memory consolidation and model-based mental simulation. Here, we test a hypothesis of reduced replay-default mode network coupling in schizophrenia, using magnetoencephalography and a non-spatial sequence learning task designed to elicit off-task (i.e. resting state) neural replay. Participants with a diagnosis of schizophrenia (n = 28, mean age 28.2 years, range 20-40, 6 females, 13 not taking antipsychotic medication) and non-clinical control participants (n = 29, mean age 28.1 years, range 18-45, 6 females, matched at group level for age, intelligence quotient, gender, years in education and working memory) underwent a magnetoencephalography scan both during task completion and during a post-task resting state session. We used neural decoding to infer the time course of default mode network activation (time-delay embedding hidden Markov model) and spontaneous neural replay (temporally delayed linear modelling) in resting state magnetoencephalography data. Using multiple regression, we then quantified the extent to which default mode network activation was uniquely predicted by replay events that recapitulated the learned task sequences (i.e. 'task-relevant' replay-default mode network coupling). In control participants, replay-default mode network coupling was augmented following sequence learning, an augmentation that was specific for replay of task-relevant (i.e. learned) state transitions. This task-relevant replay-default mode network coupling effect was significantly reduced in schizophrenia (t(52) = 3.93, P = 0.018). Task-relevant replay-default mode network coupling predicted memory maintenance of learned sequences (ρ(52) = 0.31, P = 0.02). Importantly, reduced task-relevant replay-default mode network coupling in schizophrenia was not explained by differential replay or altered default mode network dynamics between groups nor by reference to antipsychotic exposure. Finally, task-relevant replay-default mode network coupling during rest correlated with stimulus-evoked default mode network modulation as measured in a separate task session. In the context of a proposed functional role of replay-default mode network coupling, our findings shed light on the functional significance of default mode network abnormalities in schizophrenia and provide for a consilience between task-based and resting state default mode network findings in this disorder