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Persistence of malaria parasites in asymptomatic hosts is crucial in areas of seasonally-interrupted transmission, where P. falciparum bridges wet seasons months apart. During the dry season, infected erythrocytes exhibit extended circulation with reduced cytoadherence, increasing the risk of splenic clearance of infected cells and hindering parasitaemia increase. However, what determines parasite persistence for long periods of time remains unknown. Here, we investigated whether seasonality affects plasma composition so that P. falciparum can detect and adjust to changing serological cues; or if alternatively, parasite infection length dictates clinical presentation and persistency. Data from Malian children exposed to alternating ~6-month wet and dry seasons show that plasma composition is unrelated to time of year in non-infected children, and that carrying P. falciparum only minimally affects plasma constitution in asymptomatic hosts. Parasites persisting in the blood of asymptomatic children from the dry into the ensuing wet season rarely if ever appeared to cause malaria in their hosts as seasons changed. In vitro culture in the presence of plasma collected in the dry or the wet seasons did not affect parasite development, replication or host-cell remodelling. The absence of a parasite-encoded sensing mechanism was further supported by the observation of similar features in P. falciparum persisting asymptomatically in the dry season and parasites in age- and sex-matched asymptomatic children in the wet season. Conversely, we show that P. falciparum clones transmitted early in the wet season had lower chance of surviving until the end of the following dry season, contrasting with a higher likelihood of survival of clones transmitted towards the end of the wet season, allowing for the re-initiation of transmission. We propose that the decreased virulence observed in persisting parasites during the dry season is not due to the parasites sensing ability, nor is it linked to a decreased capacity for parasite replication but rather a consequence decreased cytoadhesion associated with infection length., (© 2024. The Author(s).)

Introduction: Psychiatric comorbidities have proven a consistent challenge. Recent approaches emphasize the need to move away from categorical descriptions of symptom clusters towards a dimensional view of mental disorders. From the perspective of phenomenological psychopathology, this shift is not enough, as a more detailed understanding of patients' lived experience is necessary as well. One phenomenology-informed approach suggests that we can better understand the nature of psychiatric disorders through personalized network models, a comprehensive description of a person's lifeworld in the form of salient nodes and the relationships between them. We present a detailed case study of a patient with multiple comorbidities, maladaptive coping mechanisms, and adverse childhood experiences., Methods: The case was followed for a period of two years, during which we collected multiple streams of data, ranging from phenomenological interviews, neuropsychological assessments, language analysis, and semi-structured interviews (Examination of Anomalous Self Experience and Examination of Anomalous World Experience). We analytically constructed a personalized network model of his lifeworld., Results: We identified an experiential category "the crisis of objectivity" as the core psychopathological theme of his lifeworld. It refers to his persistent mistrust towards any information that he obtains that he appraises as originating in his subjectivity. We can developmentally trace the crisis of objectivity to his adverse childhood experience, as well as him experiencing a psychotic episode in earnest. He developed various maladaptive coping mechanisms in order to compensate for his psychotic symptoms. Interestingly, we found correspondence between his subjective reports and other sources of data., Discussion: Hernan exhibits difficulties in multiple Research Domain Criteria constructs. While we can say that social sensorimotor, positive valence, and negative valence systems dysfunctions are likely associated with primary deficit (originating in his adverse childhood experience), his cognitive symptoms may be tied to his maladaptive coping mechanisms (although, they might be related to his primary disorder as well)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Oblak, Kuclar, Horvat Golob, Holnthaner, Battelino, Skodlar and Bon.)

This research aimed to study the dynamic changes in phenolic antioxidants between the germ and the rest of the germinated seed of wheat and spelt and to evaluate the whole grain flour from germinated seeds as a functional supplement. Longer germination resulted in higher TPC, DPPH, and ABTS values when considering the entire germinated seed, while the optimal germination time was not consistent when considering the germ and the remaining germinated seed separately. While in the germinated seed (without germ) the majority of TPC was determined to be bound phenolics (up to 92%), the extractable form dominated in the germ (up to 69%). The most abundant phenolic antioxidants in germinated wheat and spelt seeds, trans -ferulic acid, cis -ferulic acid, and p -coumaric acid, increased significantly with germination. Only breads with 5% germinated spelt or wheat flour were suitable for the production of a food product, showing higher extractable TPC, antioxidant activity, individual phenolic acids, and improved specific volume, and were preferred because of their appearance, aroma, and color. The PCA biplot showed that the addition of 15% and 30% germinated flours had the greatest positive impact on phenolic properties, while breads with the addition of 5% germinated flour had the greatest positive impact on specific volume and color.

Purpose: Early diagnosis of primary immunodeficiency disorders (PIDDs) is critical for maximizing patient survival and clinical outcomes. Consequently, there is significant interest in developing broad-based, high-throughput, screening approaches capable of utilizing small blood volumes to identify patients with PIDD., Experimental Design: We developed a novel proteomic screening approach using tandem mass spectrometry to simultaneously identify specific signature peptides derived from the transmembrane protein cluster of differentiation 3 (CD3)ɛ and the intracellular proteins Wiskott-Aldrich syndrome protein (WASP) and Bruton's tyrosine kinase (BTK) as markers of three life-threatening PIDDs; severe combined immunodeficiency, Wiskott-Aldrich syndrome, and X-linked Agammaglobulinemia. Signature peptides were analyzed by LC/MS-MS in proteolytically digested lysates from cell lines and white blood cells (WBCs). The amount of each peptide was determined by the ratio of the signature peptide peak area to that of a known amount of labeled standard peptide. Peptide concentrations were normalized to actin., Results: We show that signature peptides from CD3ɛ, WASP, and BTK were readily detected in proteolytically digested cell lysate and their absence could correctly identify PIDD patients., Conclusions and Clinical Relevance: This proof of concept study demonstrates the applicability of this approach to screen for PIDD and raises the possibility that it could be further multiplexed to identify additional PIDDs and potentially other disorders., (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)