Clinical and immunological outcomes of SARS-CoV-2-infected vaccine responders, vaccine non-responders, and unvaccinated patients evaluated for neutralizing monoclonal antibody treatment at a single German tertiary care center: a retrospective cohort study with prospective follow-up.

PURPOSE: This study assessed the clinical and immunological outcomes of SARS-CoV-2-infected patients with risk factors for severe disease depending on their immunological status. METHODS: In this retrospective study with single follow-up visit, clinical outcome and humoral immunity was monitored in SARS-CoV-2 infected patients at risk. The results were compared based on the patients' initial immunological status: unvaccinated (UV), patients who did not develop neutralizing antibodies after vaccination (vaccine non-responders, VNR), and patients who expressed neutralizing antibodies after vaccination (vaccine responders, VR). Patients who lacked neutralizing antibodies (VNR and UV) were treated with nMABs. RESULTS: In total, 113 patients at risk of severe COVID-19 consented to participate in the study. VR and UV were not admitted to the hospital. During the observation period, UVs had the highest rate of SARS-CoV-2 re-infections. Three of 41 VNRs (7.3%) were hospitalized due to severe COVID-19, with two of them having undergone iatrogenic B-cell depletion. The humoral immune response after infection was significantly lower in the VNR group than in the VR group in terms of anti-N, anti-receptor-binding domain (RBD), anti-S antibody titers, and anti-S antibody avidity. In a sub-analysis of VNR, B cell-deficient non-responders had significantly lower levels of anti-N antibodies and anti-S avidity after infection than other VNRs. CONCLUSION: VNR, particularly B-cell-depleted VNR, remained at risk of hospitalization due to COVID-19. In the VR group, however, no clinical complications or severe disease were observed, despite not receiving nMAbs. Tailoring the administration of nMABs according to patient vaccination and immunological status may be advisable.

Differential content of leaf and fruit pigment in tomatoes culminate in a complex metabolic reprogramming without growth impacts.

Although significant efforts to produce carotenoid-enriched foods either by biotechnology or traditional breeding strategies have been carried out, our understanding of how changes in the carotenoid biosynthesis might affect overall plant performance remains limited. Here, we investigate how the metabolic machinery of well characterized tomato carotenoid mutant plants [namely crimson (old gold-og), Delta carotene (Del) and tangerine (t)] adjusts itself to varying carotenoid biosynthesis and whether these adjustments are supported by a reprogramming of photosynthetic and central metabolism in the source organs (leaves). We observed that mutations og, Del and t did not greatly affect vegetative growth, leaf anatomy and gas exchange parameters. However, an exquisite metabolic reprogramming was recorded on the leaves, with an increase in levels of amino acids and reduction of organic acids. Taken together, our results show that despite minor impacts on growth and gas exchange, carbon flux is extensively affected, leading to adjustments in tomato leaves metabolism to support changes in carotenoid biosynthesis on fruits (sinks). We discuss these data in the context of our current understanding of metabolic adjustments and carotenoid biosynthesis as well as regarding to improving human nutrition.

Screen time is negatively associated with sleep quality and duration only in insufficiently active adolescents: A Brazilian cross-sectional school-based study.

Background: Time spent on screen devices affects sleep quality and duration leading to several health impairments in youth. Although physical activity (PA) benefits sleep patterns and decreases screen time in adolescents, it is unclear whether the relationship between sleep quality/duration and screen time could be influenced by PA levels. Objective: To analyze the association between sleep quality and duration with screen time in Brazilian adolescents according PA levels. Methods: The sample included 1010 adolescents aged 13.2 ± 2.4 years (n = 556 females - 55 % of the sample). Sleep quality and sleep duration, and PA were assessed by Mini Sleep and Baecke questionnaires, respectively. Participants in the highest quartile were classified as physically active. Screen time was analyzed by the self-reported number of hours spent on different screen devices (i.e., television, computer, videogame, and cellphone/tablet). Participants in the highest tertile were classified as having high screen time. Sex, age, and body mass index were considered covariates in binary logistic regression models. Results: Poor sleep quality was observed in 52.3 % of the sample, whereas 46.6 % reported sleeping less than eight hours/day. High screen time was associated with poor sleep quality (OR = 1.45; 95 %CI = 1.01-2.12) and insufficient sleep duration (OR = 1.52; 95 %CI = 1.01-2.03) in adolescents insufficiently active. There were no associations between screen time and sleep parameters in active adolescents. Conclusion: High screen time was associated with poor sleep quality and insufficient sleep duration only in insufficiently active adolescents. These results suggest that high PA levels may contribute to improving sleep patterns in pediatric population.

A Naturalistic Intervention to Promote Executive Functions in Primary School Children: A Pilot Study.

Executive functions are related to the control of cognition, emotion, and behavior. They are essential to lifelong outcomes, including school performance. Naturalistic interventions embedded in children's daily activities and environments have greater effects. Therefore, this pilot study aimed to develop a naturalistic program suitable for schools, based on Goal Management Training (GMT), and to analyze its effects on executive functions and behavior. The participants consisted of 35 students from 2nd to 5th grade with executive dysfunction complaints. They underwent neuropsychological assessments of working memory, inhibition, cognitive flexibility, and intellectual capacity. Teachers and parents answered questionnaires on executive functions and behavior. Students were randomly assigned to an active control group, who participated in sessions on citizenship, and an experimental group (EG), stimulated through the executive function program, both with 16 sessions conducted by psychologists. After the intervention, all participants were reevaluated. The two-way Wald-type statistic (WTS) revealed greater improvement in executive functions for the EG, including working memory and inhibition. Additionally, parents and teachers, blind to the experimental conditions, reported improvements in some measures of executive functions and behavior. The results are encouraging, but further studies should test the intervention when implemented with larger samples and by teachers.

Two-for-one: root microbiota orchestrates both soil pH and plant nutrition.

Aluminum (Al) toxicity is a crucial limiting factor for crop growth in acid soils. Recently, Liu et al. demonstrated that the root microbiota of rice modulates the responses to Al toxicity and phosphorus limitation, offering intriguing insights into microbiome function and opening new research opportunities.

From epidermal cells to functional pores: Understanding stomatal development.

Stomata, small hydromechanical valves in the leaf epidermis, are fundamental in regulating gas exchange and water loss between plants and the environment. Stomatal development involves a series of coordinated events ranging from the initial cell division that determines the meristemoid mother cells to forming specialized structures such as guard cells. These events are orchestrated by the transcription factors SPEECHLESS, FAMA, and MUTE through signaling networks. The role of plant hormones (e.g., abscisic acid, jasmonic acid, and brassinosteroids) in regulating stomatal development has been elucidated through these signaling cascades. In addition, environmental factors, such as light availability and CO2 concentration, also regulate the density and distribution of stomata in leaves, ultimately affecting overall water use efficiency. In this review, we highlight the mechanisms underlying stomatal development, connecting key signaling processes that activate or inhibit cell differentiation responsible for forming guard cells in the leaf epidermis. The factors responsible for integrating transcription factors, hormonal responses, and the influence of climatic factors on the signaling network that leads to stomatal development in plants are further discussed. Understanding the intricate connections between these factors, including the metabolic regulation of plant development, may enable us to maximize plant productivity under specific environmental conditions in changing climate scenarios.

Memories of heat: autophagy and Golgi recovery.

Fluctuations in temperature severely impact crop yield and trigger various plant response mechanisms. In a recent study, Zhou et al. discovered a non-canonical role of autophagy in mediating Golgi apparatus restoration after short-term heat stress (HS). Their results further suggest a critical, yet previously unknown, mechanism of autophagy-related (ATG)-8 in Golgi reassembly after HS.

Societal costs and quality of life analysis in patients undergoing resective epilepsy surgery: A one-year follow-up.

Although effectiveness of Resective Epilepsy Surgery (RES) for patients with drug-resistant epilepsy (DRE) is widely proven, research on the impact of societal costs (SC) is lacking. The aim of this study is to provide both clinical and economic outcomes of RES by offering an overview of treatment effectiveness as well as SC of RES in a cohort of 30 Dutch DRE patients. This project serves as a pilot project to offer an up-to-date model for larger cost-effectiveness studies. Medical consumption, productivity losses, disease-specific and generic health-related quality of life (QoL), and seizure frequency were assessed before and 3-, 6-, and 12-months post-surgery with validated questionnaires. Linear mixed models, ANOVAs, and logistic regressions were performed. SC for the first year after RES entailed €54,376 and decreased over time. Moreover, 50% of patients experienced a clinically important increase in disease-specific QoL and 53% of patients in generic health-related QoL. Lastly, 73% of patients reached seizure freedom 12 months postoperative. Seizure reduction was correlated with increase in disease-specific QoL. Within one year after surgery, RES leads to reduction in SC and improvements in QoL over time. Future research should encompass longer follow-up periods, larger sample size, and a cost-effectiveness analysis with a comparator.

Dynamic shifts in primary metabolism across fruit development stages in Capsicum chinense (cv. Habanero).

The development of fleshy fruits involves changes in size and mass, followed by cell differentiation, which is associated with anatomical and histological changes. Parallel to these changes, metabolic alterations lead to the production of osmolytes and energy that modify cell turgor pressure, thereby promoting cell expansion and fruit growth. Detailed information is known about these processes in climacteric fruits (e.g. tomato); however, the regulation of metabolism and its association with anatomical changes in non-climacteric fruit development are poorly understood. In this study, we used detailed anatomical and histological analyses to define three developmental phases of chili pepper (Capsicum chinense cv. Habanero): cell division, cell expansion, and ripening. We showed that each was marked by distinct metabolic profiles, underpinning the switches in energy metabolism to support cellular processes. Interestingly, mitochondrial activity was high in the early stages of development and declined over time, with a modest increase in O2 consumption by pericarp tissues at the beginning of the ripening stage. This respiratory-like burst was associated with the degradation of starch and malate, which are the sources of energy and carbon required for other processes associated with fruit maturation.

Physiological and metabolic changes in response to Boron levels are mediated by ethylene affecting tomato fruit yield.

Boron (B) is an essential nutrient for the plant, and its stress (both deficiency and toxicity) are major problems that affect crop production. Ethylene metabolism (both signaling and production) is important to plants' differently responding to nutrient availability. To better understand the connections between B and ethylene, here we investigate the function of ethylene in the responses of tomato (Solanum lycopersicum) plants to B stress (deficiency, 0 µM and toxicity, 640 µM), using ethylene related mutants, namely nonripening (nor), ripening-inhibitor (rin), never ripe (Nr), and epinastic (Epi). Our results show that B stress does not necessarily inhibit plant growth, but both B stress and ethylene signaling severely affected physiological parameters, such as photosynthesis, stomatal conductance, and chlorophyll a fluorescence. Under B toxicity, visible symptoms of toxicity appeared in the roots and margins of the older leaves through necrosis, caused by the accumulation of B which stimulated ethylene biosynthesis in the shoots. Both nor and rin (ethylene signaling) mutants presented similar responses, being these genotypes more sensitive and displaying several morphophysiological alterations, including fruit productivity reductions, in response to the B toxicity conditions. Therefore, our results suggest that physiological and metabolic changes in response to B fluctuations are likely mediated by ethylene signaling.

Intimate partner violence is associated with cytomegalovirus among young women in rural South Africa: An HPTN 068 analysis.

ABSTRACTStressful life circumstances (e.g. violence and poverty) have been associated with elevated biomarkers, including C-reactive protein (CRP), cytomegalovirus (CMV), and herpes simplex virus type-1 (HSV-1), among older adults in high-income settings. Yet, it remains unknown whether these relationships exist among younger populations in resource-limited settings. We therefore utilised a cohort of 1,279 adolescent girls and young women (AGYW) from the HIV Prevention Trials Network 068 study in rural South Africa to examine the associations between 6 hypothesized stressors (intimate partner violence (IPV), food insecurity, depression, socioeconomic status (SES), HIV, childhood violence) and 3 biomarkers that were measured using dried blood spots (CRP, CMV, and HSV-1). Ordinal logistic regression estimated the lagged and cross-sectional associations between each stressor and each biomarker. IPV was cross-sectionally associated with elevated CMV (OR = 2.45, 95% CI = 1.05,5.72), while low SES was cross-sectionally associated with reduced CMV (OR = 0.73, 95% CI = 0.58,0.93). AGYW with HIV had elevated biomarkers cross-sectionally (CRP: OR = 1.51, 95% CI = 1.08,2.09; CMV: OR = 1.86, 95% CI = 1.31,2.63; HSV-1: OR = 1.68, 95% CI = 1.17,2.41) and in a lagged analysis. The association between violence and CMV could help explain how violence results in stress and subsequently worse health among AGYW; however, additional research is needed to disentangle the longitudinal nature of IPV and stress.

Acute phase reaction to lipopolysaccharide-induced mastitis in early lactation dairy cows fed nitrogenic, glucogenic, or lipogenic diets.

The availability of certain macronutrients is likely to influence the capacity of the immune system. Therefore, we investigated the acute phase response to intramammary (i.mam.) lipopolysaccharide (LPS) in dairy cows fed a nitrogenic diet (n = 10) high in crude protein, a glucogenic diet (n = 11) high in carbohydrates and glucogenic precursors, or a lipogenic diet (n = 11) high in lipids. Thirty-two dairy cows were fed one of the dietary concentrates directly after calving until the end of trial at 27 ± 3 days in milk (mean ± standard deviation). In wk 3 of lactation, 20 µg of LPS was i.mam. injected in one quarter, and sterile NaCl (0.9%) in the contralateral quarter. Milk samples of the LPS-challenged and control quarter were taken hourly from before (0 h) until 9 h after LPS challenge and analyzed for milk amyloid A (MAA), haptoglobin (HP), and IL-8. In addition, blood samples were taken in the morning, and composite milk samples at morning and evening milkings, from 1 d before until 3 d after LPS challenge, and again on d 9, to determine serum amyloid A (SAA) and HP in blood, and MAA and HP in milk. The mRNA abundance of various immunological and metabolic factors in blood leukocytes was quantified by quantitative reverse-transcription PCR from samples taken at -18, -1, 6, 9, and 23 h relative to LPS application. The dietary concentrates did not affect any of the parameters in blood, milk, and leukocytes. The IL-8 was increased from 2 h, HP from 2 to 3 h, and MAA from 6 h relative to the LPS administration in the milk of the challenged quarter and remained elevated until 9 h. The MAA and HP were also increased at 9 h after LPS challenge in whole-udder composite milk, whereas HP and SAA in blood were increased only after 23 h. All 4 parameters were decreased again on d 9. Similar for all groups, the mRNA abundance of HP and the heat shock protein family A increased after the LPS challenge, whereas the mRNA expression of the tumor necrosis factor α and the leukocyte integrin ß 2 subunit (CD18) were decreased at 6 h after LPS challenge. The glucose transporter (GLUT)1 mRNA abundance decreased after LPS, whereas that of the GLUT3 increased, and that of the GLUT4 was not detectable. The mRNA abundance of GAPDH was increased at 9 h after LPS and remained elevated. The acute phase protein response was detected earlier in milk compared with blood indicating mammary production. However, immunological responses to LPS were not affected by the availability of specific macronutrients provided by the different diets.

The interplay between autophagy and chloroplast vesiculation pathways under dark-induced senescence.

In cellular circumstances where carbohydrates are scarce, plants can use alternative substrates for cellular energetic maintenance. In plants, the main protein reserve is present in the chloroplast, which contains most of the total leaf proteins and represents a rich source of nitrogen and amino acids. Autophagy plays a key role in chloroplast breakdown, a well-recognised symptom of both natural and stress-induced plant senescence. Remarkably, an autophagic-independent route of chloroplast degradation associated with chloroplast vesiculation (CV) gene was previously demonstrated. During extended darkness, CV is highly induced in the absence of autophagy, contributing to the early senescence phenotype of atg mutants. To further investigate the role of CV under dark-induced senescence conditions, mutants with low expression of CV (amircv) and double mutants amircv1xatg5 were characterised. Following darkness treatment, no aberrant phenotypes were observed in amircv single mutants; however, amircv1xatg5 double mutants displayed early senescence and altered dismantling of chloroplast and membrane structures under these conditions. Metabolic characterisation revealed that the functional lack of both CV and autophagy leads to higher impairment of amino acid release and differential organic acid accumulation during starvation conditions. The data obtained are discussed in the context of the role of CV and autophagy, both in terms of cellular metabolism and the regulation of chloroplast degradation.

Skinfold calipers: which instrument to use?

The considerable amount of original and generic types of skinfold calipers available is a source of systematic measurement error. This study is a brief report that critically examines the original and illustrated structural configuration of the three main types of skinfold calipers. For more than half a century, the Harpenden®, Lange® and Slim Guide® skinfolds calipers have been widely used in clinical and research settings. It is well established that the physical, mechanical and functional specificity of each type of skinfold caliper makes its interchangeable use impossible. Our report suggests that commercially available technical specifications are insufficient to judiciously choose a skinfold caliper. The area of the jaws, the coefficient of spring and the static and dynamic downward pressure of each type of skinfold caliper must be determined in the metrological laboratory and added to the technical user manual. Choosing a type of skinfold caliper for regular use, without conflict of commercial interest, requires a critical understanding of the physical, mechanical and functional characteristics that configure it. Therefore, a new downward static calibration test and the first eligibility flowchart for a skinfold caliper have been proposed. Finally, the information gathered in this report may be useful for manufacturers of anthropometric instruments and health professionals who use the skinfold technique as a tool for diagnosis and nutritional control.

Beyond photorespiration: the significance of glycine and serine in leaf metabolism.

The elucidation and removal of photorespiratory metabolic constraints will be necessary to improve crop yield in the next agricultural revolution. Fu et al. studied metabolic fluxes in the photorespiratory pathway and report that serine is the major export, whereas dynamic alterations in glycine pools orchestrate CO2 assimilation during the induction and relaxation of photorespiration.

Does day length matter for nutrient responsiveness?

For over 2500 years, considerable agronomic interest has been paid to soil fertility. Both crop domestication and the Green Revolution shifted photoperiodism and the circadian clock in cultivated species, although this contributed to an increase in the demand for chemical fertilisers. Thus, the uptake of nutrients depends on light signalling, whereas diel growth and circadian rhythms are affected by nutrient levels. Here, we argue that day length and circadian rhythms may be central regulators of the uptake and usage of nutrients, also modulating responses to toxic elements (e.g., aluminium and cadmium). Thus, we suggest that knowledge in this area might assist in developing next-generation crops with improved uptake and use efficiency of nutrients.

On the Significance of the ADNT1 Carrier in Arabidopsis thaliana under Waterlogging Conditions.

Among the adenylate carriers identified in Arabidopsis thaliana, only the AMP/ATP transporter ADNT1 shows increased expression in roots under waterlogging stress conditions. Here, we investigated the impact of a reduced expression of ADNT1 in A. thaliana plants submitted to waterlogging conditions. For this purpose, an adnt1 T-DNA mutant and two ADNT1 antisense lines were evaluated. Following waterlogging, ADNT1 deficiency resulted in a reduced maximum quantum yield of PSII electron transport (significantly for adnt1 and antisense Line 10), indicating a higher impact caused by the stress in the mutants. In addition, ADNT1 deficient lines showed higher levels of AMP in roots under nonstress condition. This result indicates that the downregulation of ADNT1 impacts the levels of adenylates. ADNT1-deficient plants exhibited a differential expression pattern of hypoxia-related genes with an increase in non-fermenting-related-kinase 1 (SnRK1) expression and upregulation of adenylate kinase (ADK) under stress and non-stress conditions. Together, these results indicated that the lower expression of ADNT1 is associated with an early "hypoxic status" due to the perturbation of the adenylate pool caused by reduced AMP import by mitochondria. This perturbation, which is sensed by SnRK1, results in a metabolic reprogramming associated with early induction of the fermentative pathway in ADNT1 deficient plants.

How diverse a genus can be: An integrated multi-layered analysis into Desmonostoc (Nostocaceae, Cyanobacteriota).

Cyanobacteria (Phylum Cyanobacteriota) are Gram-negative bacteria capable of performing oxygenic photosynthesis. Although the taxonomic classification of cyanobacteria was for a long time based primarily on morphological characters, the application of other techniques (e.g. molecular phylogeny), especially in recent decades, has contributed to a better resolution of cyanobacteria systematics, leading to a revision of the phylum. Although Desmonostoc occurs as a new genus/cluster and some species have been described recently, relatively few studies have been carried out to elucidate its diversity, which encompasses strains from different ecological origins, or examine the application of new characterization tools. In this context, the present study investigated the diversity within Desmonostoc, based on morphological, molecular, metabolic, and physiological characteristics. Although the usage of physiological parameters is unusual for a polyphasic approach, they were efficient in the characterization performed here. The phylogenetic analysis based on 16S rRNA gene sequences put all studied strains (25) into the D1 cluster and indicated the emergence of novel sub-clusters. It was also possible to observe that nifD and nifH exhibited different evolutionary histories within the Desmonostoc strains. Collectively, metabolic and physiological data, coupled with the morphometric data, were in general, in good agreement with the separation based on the phylogeny of the 16S rRNA gene. Furthermore, the study provided important information on the diversity of Desmonostoc strains collected from different Brazilian biomes by revealing that they were cosmopolitan strains, acclimatized to low luminous intensities, with a large metabolic diversity and great biotechnological potential.

Urea as a source of nitrogen and carbon leads to increased photosynthesis rates in Chlamydomonas reinhardtii under mixotrophy.

Microalgae is a potential source of bioproducts, including feedstock to biofuels. Urea has been pointed as potential N source for microalgae growth. Considering that urea metabolism releases HCO3- to the medium, we tested the hypothesis that this carbon source could improve photosynthesis and consequently growth rates of Chlamydomonas reinhardtii. In this sense, the metabolic responses of C. reinhardtii grown with ammonium and urea as nitrogen sources under mixotrophic and autotrophic conditions were investigated. Overall, the mixotrophy led to increased cell growth as well as to a higher accumulation of lipids independent of N source, followed by a decrease in photosynthesis over the growth phases. In mixotrophy, urea stimulates growth in terms of cell number and dry weight. Furthermore, higher photosynthesis was verified in late logarithmic phase compared to ammonium. Under autotrophy conditions, although cell number and biomass were reduced, there was higher production of starch independent of N source. Nonetheless, urea-based autotrophic treatments stimulated biomass production compared to ammonium-based treatment. Under mixotrophy higher input of carbon into the cell from acetate and urea optimized photosynthesis and consequently promoted cell growth. Together, these results suggest urea as alternative source of carbon, improving photosynthesis and cell growth in C. reinhardtii.

Harnessing enzyme cofactors and plant metabolism: an essential partnership.

Cofactors are fundamental to the catalytic activity of enzymes. Additionally, because plants are a critical source of several cofactors (i.e., including their vitamin precursors) within the context of human nutrition, there have been several studies aiming to understand the metabolism of coenzymes and vitamins in plants in detail. For example, compelling evidence has been brought forth regarding the role of cofactors in plants; specifically, it is becoming increasingly clear that an adequate supply of cofactors in plants directly affects their development, metabolism, and stress responses. Here, we review the state-of-the-art knowledge on the significance of coenzymes and their precursors with regard to general plant physiology and discuss the emerging functions attributed to them. Furthermore, we discuss how our understanding of the complex relationship between cofactors and plant metabolism can be used for crop improvement.