bluuebunny/crossref_metadata_2025 huggingface dataset:
Memory B Cell Activation Induced by Pertussis Booster Vaccination in Four Age Groups of Three Countries
Authors: Versteegen Pauline , Barkoff Alex-Mikael , Valente Pinto Marta , van de Kasteele Jan , Knuutila Aapo , Bibi Sagida , de Rond Lia , Teräsjärvi Johanna , Sanders Katherine , de Zeeuw-Brouwer Mary-lène , Luoto Raakel , ten Hulscher Hinke , Clutterbuck Elizabeth A. , Sanders Elisabeth A. M. , Mertsola Jussi , Berbers Guy A. M. , He Qiushui , Kelly Dominic F. , Buisman Anne-Marie ,   PERISCOPE Consortium
Published: May 2022

Background

Immunogenicity of acellular pertussis (aP) vaccines is conventionally assessed by measuring antibody responses but antibody concentrations wane quickly after vaccination. Memory B cells, however, are critical in sustaining long-term protection and therefore may be an important factor when assessing pertussis immunity after vaccination.

Aim

We studied pertussis specific memory B cell (re)activation induced by an aP booster vaccination in four different age groups within three countries.

Materials and methods

From a phase IV longitudinal interventional study, 268 participants across Finland, the Netherlands and the United Kingdom were included and received a 3-component pertussis booster vaccine: children (7-10y, n=53), adolescents (11-15y, n=66), young adults (20-34y, n=74), and older adults (60-70y, n=75). Memory B cells at baseline, day 28, and 1 year post-vaccination were measured by a pertussis toxin (Ptx), filamentous haemagglutinin (FHA), and pertactin (Prn) specific ELISpot assay. Antibody results measured previously were available for comparison. Furthermore, study participants were distributed into groups based on their baseline memory B cell frequencies, vaccine responses were monitored between these groups.

Results

Geometric mean (GM) memory B cell frequencies for pertussis antigens at baseline were low. At 28 days post-vaccination, these frequencies increased within each age group and were still elevated one year post-booster compared to baseline. Highest frequencies at day 28 were found within adolescents (GM: 5, 21, and 13, for Ptx, FHA and Prn, respectively) and lowest within older adults (GM: 2, 9, and 3, respectively). Moderate to strong correlations between memory B cell frequencies at day 28 and antibody concentrations at day 28 and 1 year were observed for Prn. Memory B cell frequencies > 1 per 100,000 PBMCs at baseline were associated with significantly higher memory responses after 28 days and 1 year.

Conclusions

An aP booster vaccine (re)activated memory B cells in all age groups. Still elevated memory B cell frequencies after one year indicates enhanced immunological memory. However, antigen specific memory B cell activation seems weaker in older adults, which might reflect immunosenescence. Furthermore, the presence of circulating memory B cells at baseline positively affects memory B cell responses. This study was registered at www.clinicaltrialsregister.eu: No. 2016-003678-42.
Immunopsychiatry – Innovative Technology to Characterize Disease Activity in Autoantibody-Associated Psychiatric Diseases
Authors: Hansen Niels
Published: May 2022

Background

Anti-neural autoantibody-associated psychiatric disease is a novel field in immunopsychiatry that has been attracting attention thanks to its potentially positive therapeutic outcome and distinct prognosis compared with non-organic psychiatric disease. This review aims to describe recent novel technological developments for improving diagnostics in the field of autoantibody-related psychiatric disease.

Methods

We screened for relevant articles in PubMed for this narrative article. We focused on research methods such as neuroimaging, immune cells and inflammation markers, and molecular biomarkers in human biofluids like serum and cerebrospinal fluid and plasma proteomics.

Results

We introduce several novel methods for investigating autoinflammation with the aim of optimizing therapies for autoantibody-associated psychiatric disease. We describe measuring the translocator protein 18kDa in activated microglia via positron emission tomography imaging, brain volumetric assessment, flow cell cytometry of cerebrospinal fluid and blood, and blood biological probes as well as psychopathological cues to help us gain insights into diagnosing inflammation and brain damage better in psychiatric patients presenting a suspected autoimmune etiology.

Conclusion

Our short methodological review provides an overview of recent developments in the field of autoantibody-related immunopsychiatry. More research is needed to prove their usefulness in diagnosing and treating autoantibody-associated psychiatric disease and its subtypes.
Standardized Whole Blood Assay and Bead-Based Cytokine Profiling Reveal Commonalities and Diversity of the Response to Bacteria and TLR Ligands in Cattle
Authors: Lesueur Jérémy , Walachowski Sarah , Barbey Sarah , Cebron Nathan , Lefebvre Rachel , Launay Frédéric , Boichard Didier , Germon Pierre , Corbiere Fabien , Foucras Gilles
Published: May 2022

Recent developments in multiplex technologies enable the determination of a large nu\mber of soluble proteins such as cytokines in various biological samples. More than a one-by-one determination of the concentration of immune mediators, they permit the establishment of secretion profiles for a more accurate description of conditions related to infectious diseases or vaccination. Cytokine profiling has recently been made available for bovine species with the development of a Luminex® technology-based 15-plex assay. Independently from the manufacturer, we evaluated the bovine cytokine/chemokine multiplex assay for limits of detection, recovery rate, and reproducibility. Furthermore, we assessed cytokine secretion in blood samples from 107 cows upon stimulation with heat-killed bacteria and TLR2/4 ligands compared to a null condition. Secretion patterns were analyzed either using the absolute concentration of cytokines or using their relative concentration with respect to the overall secretion level induced by each stimulus. Using Partial Least Square-Discriminant Analysis, we show that the 15-cytokine profile is different under Escherichia coli, Staphylococcus aureus, and Streptococcus uberis conditions, and that IFN-γ, IL-1β, and TNF-α contribute the most to differentiate these conditions. LPS and E. coli induced largely overlapping biological responses, but S. aureus and S. uberis were associated with distinct cytokine profiles than their respective TLR ligands. Finally, results based on adjusted or absolute cytokine levels yielded similar discriminative power, but led to different stimuli-related signatures.
Lactobacillus: Friend or Foe for Systemic Lupus Erythematosus?
Authors: Wang Weijie , Fan Yongsheng , Wang Xinchang
Published: May 2022

The cause of Systemic Lupus Erythematosus (SLE) remains largely unknown, despite the fact that it is well understood that a complex interaction between genes and environment is required for disease development. Microbiota serve as activators and are essential to immune homeostasis. Lactobacillus is thought to be an environmental agent affecting the development of SLE. However, beneficial therapeutic and anti-inflammatory effects of Lactobacillus on SLE were also explored. The discovery of Lactobacillus involvement in SLE will shed light on how SLE develops, as well as finding microbiota-targeted biomarkers and novel therapies. In this review, we attempt to describe the two sides of Lactobacillus in the occurrence, development, treatment and prognosis of SLE. We also discuss the effect of different strains Lactobacillus on immune cells, murine lupus, and patients. Finally, we try to illustrate the potential immunological mechanisms of Lactobacillus on SLE and provide evidence for further microbiota-targeted therapies.
A Holistic View of the Goto-Kakizaki Rat Immune System: Decreased Circulating Immune Markers in Non- Obese Type 2 Diabetes
Authors: Seal Snehaa V. , Henry Mathilde , Pajot Clémentine , Holuka Cyrielle , Bailbé Danielle , Movassat Jamileh , Darnaudéry Muriel , Turner Jonathan D.
Published: May 2022

Type-2 diabetes is a complex disorder that is now considered to have an immune component, with functional impairments in many immune cell types. Type-2 diabetes is often accompanied by comorbid obesity, which is associated with low grade inflammation. However,the immune status in Type-2 diabetes independent of obesity remains unclear. Goto-Kakizaki rats are a non-obese Type-2 diabetes model. The limited evidence available suggests that Goto-Kakizaki rats have a pro-inflammatory immune profile in pancreatic islets. Here we present a detailed overview of the adult Goto-Kakizaki rat immune system. Three converging lines of evidence: fewer pro-inflammatory cells, lower levels of circulating pro-inflammatory cytokines, and a clear downregulation of pro-inflammatory signalling in liver, muscle and adipose tissues indicate a limited pro-inflammatory baseline immune profile outside the pancreas. As Type-2 diabetes is frequently associated with obesity and adipocyte-released inflammatory mediators, the pro-inflammatory milieu seems not due to Type-2 diabetesper se; although this overall reduction of immune markers suggests marked immune dysfunction in Goto-Kakizaki rats.
The Small-Scale Flow Field Around Dipsastraea favus Corals
Authors: Shavit Uri , Mass Tali , Genin Amatzia
Published: May 2022

Key biological processes that are related to feeding, growth, and mortality in corals and other benthic organisms, depend on the flow field around them. For example, in the absence of flow, oxygen is accumulated inside and around photoautotrophic organisms such as algae and corals, and the rate of photosynthesis is therefore reduced. When mixing by turbulence and by streamline separation is suppressed, nutrient supply is reduced and prey capture becomes insufficient. Despite the overwhelming ecological impacts of flow on corals, almost no in-situ studies focused on the hydrodynamics at the scale of the coral polyps and their tentacles. Here we report on in-situ measurements obtained by an underwater Particle Image Velocimetry (PIV) above the tentacles of the massive coral Dipsastraea favus. The tentacles in this species, approximately 5-10 mm long, extend during the night and contract during the day. A comparison was made between the flow field around the coral when the tentacles were contracted and extended. As in large-scale canopy flows such as forests or urban areas, we found that when the tentacles were extended, a mixing layer rather than a boundary layer was formed above the coral. Velocities in between the tentacles were reduced, resident time increased, and velocity instabilities developed around the tentacle tips. Our in-situ measurements under the conditions of contracted tentacles agreed well with laboratory measurements obtained above dead skeletons of D. favus. When the tentacles were extended, a velocity profile typical for canopy flows developed, having a clear inflection point near the interface between the tentacles and the layer of free flow. The relative velocity fluctuations increased up to 3.5-fold compared with the state of contracted tentacles. The highest mixing was around the distal ends of the tentacles, where knob-like spheres named acrospheres contain extremely high concentrations of nematocytes. The intense mixing, the ensuing slowing down of prey movement, and its longer residence time within that zone may augment prey capture by the coral. These findings can explain the ubiquitous occurrence of acrospheres in benthic cnidarians.
Spatiotemporal Variability of Microplastics in the Eastern Baltic Sea
Authors: Mishra Arun , Buhhalko Natalja , Lind Kati , Lips Inga , Liblik Taavi , Väli Germo , Lips Urmas
Published: May 2022

Microplastic (MP) pollution is present in all aquatic environments and is gaining critical concern. We have conducted sea surface MP monitoring with a Manta trawl at 16 sampling stations in the eastern Baltic Sea in 2016–2020. The concentrations varied from 0.01 to 2.45 counts/m3 (0.002–0.43 counts/m2), and the mean was 0.49 counts/m3 (0.08 counts/m2). The fibers and fragments had, on average, an approximately equal share in the samples. Correlation between the concentration of fibers and fragments was higher near the land and weaker further offshore. The following spatial patterns were revealed: higher mean values were detected in the Baltic Proper (0.65 counts/m3) (0.11 counts/m2) and the Gulf of Finland (0.46–0.65) (0.08–0.11) and lower values were detected in the Gulf of Riga (0.33) (0.06) and Väinameri Archipelago Sea (0.11) (0.02). The difference between the latter three sub-basins and the meridional gradient in the Gulf of Riga can likely be explained by the degree of human pressure in the catchment areas. The MP concentration was higher in autumn than in summer in all regions and stations, probably due to the seasonality of the biofouling and consequent sinking rate of particles. A weak negative correlation between the wind speed and the MP concentration was detected only in the central Gulf of Finland, and positive correlation in the shallow area near river mouth. We observed a 60-fold difference in MP concentrations during coastal downwelling/upwelling. Divergence/convergence driven by the (sub)mesoscale processes should be one of the subjects in future studies to enhance the knowledge on the MP pathways in the Baltic Sea.
Bleeding During Veno-Venous ECMO: Prevention and Treatment
Authors: Kalbhenn Johannes , Zieger Barbara
Published: May 2022

Veno-venous extracorporeal membrane oxygenation (vvECMO) has become a routine treatment for severe lung failure in specialized centers. Spontaneous bleeding complications, however, are observed in 30–60% of patients during vvECMO treatment. Bleeding increases mortality by factors 2–3. Anticoagulation in combination with several acquired bleeding disorders caused by the mechanical pump and the foreign layer of the extracorporeal system contribute to the risk of bleeding. In this review, the mechanisms of the underlying pathologies and the route from diagnosis to treatment are described.
Species-Dependent Metabolic Response to Lipid Mixtures in Wine Yeasts
Authors: Mbuyane Lethiwe L. , Bauer Florian F. , Bloem Audrey , Camarasa Carole , Ortiz-Julien Anne , Divol Benoit
Published: May 2022

Lipids are essential energy storage compounds and are the core structural elements of all biological membranes. During wine alcoholic fermentation, the ability of yeasts to adjust the lipid composition of the plasma membrane partly determines their ability to cope with various fermentation-related stresses, including elevated levels of ethanol and the presence of weak acids. In addition, the lipid composition of grape juice also impacts the production of many wine-relevant aromatic compounds. Several studies have evaluated the impact of lipids and of their metabolism on fermentation performance and aroma production in the dominant wine yeastSaccharomyces cerevisiae, but limited information is available on other yeast species. Thus, the aim of this study was to evaluate the influence of specific fatty acid and sterol mixtures on various non-Saccharomycesyeast fermentation rates and the production of primary fermentation metabolites. The data show that the response to different lipid mixtures is species-dependent. ForMetschnikowia pulcherrima, a slight increase in carbon dioxide production was observed in media enriched with unsaturated fatty acids whereasKluyveromyces marxianusfermented significantly better in synthetic media containing a higher concentration of polyunsaturated fatty acids than monounsaturated fatty acids.Torulaspora delbrueckiifermentation rate increased in media supplemented with lipids present at an equimolar concentration. The data indicate that these different responses may be linked to variations in the lipid profile of these yeasts and divergent metabolic activities, in particular the regulation of acetyl-CoA metabolism. Finally, the results suggest that the yeast metabolic footprint and ultimately the wine organoleptic properties could be optimizedviaspecies-specific lipid adjustments.
Rational Design of P450 aMOx for Improving Anti-Markovnikov Selectivity Based on the “Butterfly” Model
Authors: Pan Yue , Bao Jinxiao , Zhang Xingyi , Ni Hui , Zhao Yue , Zhi Fengdong , Fang Bohuan , He Xiao , Zhang John Z. H. , Zhang Lujia
Published: May 2022

Aromatic aldehydes are important industrial raw materials mainly synthesized by anti-Markovnikov (AM) oxidation of corresponding aromatic olefins. The AM product selectivity remains a big challenge. P450 aMOx is the first reported enzyme that could catalyze AM oxidation of aromatic olefins. Here, we reported a rational design strategy based on the “butterfly” model of the active site of P450 aMOx. Constrained molecular dynamic simulations and a binding energy analysis of key residuals combined with an experimental alanine scan were applied. As a result, the mutant A275G showed high AM selectivity of >99%. The results also proved that the “butterfly” model is an effective design strategy for enzymes.
CD38-Induced Apoptosis and Mitochondrial Damage is Restored by Nicotinamide in Prostate Cancer
Authors: Kanayama Mayuko , Luo Jun
Published: May 2022

Nicotinamide adenine dinucleotide (NAD+) is an essential molecule for living organisms. CD38 is a key NAD+-dependent enzyme which breaks down NAD+ to cyclic ADP-ribose (ADPR) and nicotinamide (NAM, vitamin B3), and NAM can be recycled to synthesize NAD+. CD38 expression is consistently silenced by methylation in prostate cancer and progressively downregulated in advanced castration-resistant prostate cancer, suggesting a connection between NAD+ and prostate carcinogenesis as well as prostate cancer progression. However, the functional interplay between NAD+, CD38, and NAM remains largely uncharacterized in prostate cancer cells. In this study, we generated stable LNCaP95 cell clones expressing varying levels of CD38 upon induction by doxycycline. We demonstrate that CD38 overexpression resulted in growth suppression and apoptosis accompanied by cleavage of poly (ADP-ribose) polymerase 1 (PARP1). CD38 overexpression also dramatically reduced intracellular NAD+ levels and decreased mitochondrial respiration as measured by oxygen consumption rate. We further show that some but not all of these CD38-induced phenotypes could be rescued by exogenous NAM. Treatment of cells with NAM rescued CD38-induced apoptosis and mitochondrial stress but did not restore intracellular NAD+ levels. We also found that NAM demonstrated biphasic effect on mitochondria function, a finding that can be explained by the dual role of NAM as both a precursor of NAD+ and also as a suppressor of a number of NAD+-dependent enzymes. Collectively, these findings provide additional insight supporting the functional relevance of CD38 loss in prostate cancer by linking cell-autonomous regulation of mitochondrial function and prostate cancer.
GW5074 Increases Microglial Phagocytic Activities: Potential Therapeutic Direction for Alzheimer’s Disease
Authors: Connor Sarah M. , Rashid Mamunur , Ryan Katie J. , Patel Kruti , Boyd Justin D. , Smith Jennifer , Elyaman Wassim , Bennett David A. , Bradshaw Elizabeth M.
Published: May 2022

Microglia, the resident immune cells of the central nervous system (CNS), are responsible for maintaining homeostasis in the brain by clearing debris and are suggested to be inefficient in Alzheimer’s Disease (AD), a progressive neurodegenerative disorder for which there is no disease-modifying drug. Besides pathological approaches, unbiased evidence from genome-wide association studies (GWAS) and gene network analysis implicate genes expressed in microglia that reduce phagocytic ability as susceptibility genes for AD. Thus, a central feature toward AD therapy is to increase the microglial phagocytic activities while maintaining synaptic integrity. Here, we developed a robust unbiased high content screening assay to identify potential therapeutics which can reduce the amyloid-beta (Aβ1–42) load by increasing microglial uptake ability. Our screen identified the small-molecule GW5074, an inhibitor of c-RAF, a serine/threonine kinase, which significantly increased the Aβ1–42 clearance activities in human monocyte-derived microglia-like (MDMi) cells, a microglia culture model that recapitulates many genetic and phenotypic aspects of human microglia. Notably, GW5074 was previously reported to be neuroprotective for cerebellar granule cells and cortical neurons. We found that GW5074 significantly increased the expression of key AD-associated microglial molecules known to modulate phagocytosis: TYROBP, SIRPβ1, and TREM2. Our results demonstrated that GW5074 is a potential therapeutic for AD, by targeting microglia.
Opioid-Use, COVID-19 Infection, and Their Neurological Implications
Authors: Jalodia Richa , Antoine Danielle , Braniff Regina Gonzalez , Dutta Rajib Kumar , Ramakrishnan Sundaram , Roy Sabita
Published: May 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an imminent threat to human health and public safety. ACE2 and transmembrane serine protease 2 proteins on host cells provide the viral entry point to SARS-CoV-2. Although SARS-CoV-2 mainly infects the respiratory system, there have been reports of viral neurotropism and central nervous system injury as indicated by plasma biomarkers, including neurofilament light chain protein and glial fibrillary acidic protein. Even with a small proportion of infections leading to neurological manifestation, the overall number remains high. Common neurological manifestations of SARS-CoV-2 infection include anosmia, ageusia, encephalopathy, and stroke, which are not restricted to only the most severe infection cases. Opioids and opioid antagonists bind to the ACE2 receptor and thereby have been hypothesized to have therapeutic potential in treating COVID-19. However, in the case of other neurotropic viral infections such as human immunodeficiency virus (HIV), opioid use has been established to exacerbate HIV-mediated central nervous system pathogenesis. An analysis of electronic health record data from more than 73 million patients shows that people with Substance Use Disorders are at higher risk of contracting COVID-19 and suffer worse consequences then non-users. Our in-vivo and in-vitro unpublished studies show that morphine treatment causes increased expression of ACE2 in murine lung and brain tissue as early as 24 h post treatment. At the same time, we also observed morphine and lipopolysaccharides treatment lead to a synergistic increase in ACE2 expression in the microglial cell line, SIM-A9. This data suggests that opioid treatment may potentially increase neurotropism of SARS-CoV-2 infection. We have previously shown that opioids induce gut microbial dysbiosis. Similarly, gut microbiome alterations have been reported with SARS-CoV-2 infection and may play a role in predicting COVID-19 disease severity. However, there are no studies thus far linking opioid-mediated dysbiosis with the severity of neuron-specific COVID-19 infection.
Analysis of Age-Dependent Transcriptomic Changes in Response to Intracerebral Hemorrhage in Mice
Authors: Li Xinhui , Yang Wensong , Shen Yiqing , Liu Fangyu , Xiong Xin , Wu Qingyuan , Xiao Zhongsong , Yang Xun , Dang Ruozhi , Manaenko Anatol , Xie Peng , Li Qi
Published: May 2022

Age is a well-known risk factor that is independently associated with poor outcomes after intracerebral hemorrhage (ICH). However, the interrelationship between age and poor outcomes after ICH is not well defined. In this study, we aimed to investigate this relationship based on collagenase-induced ICH mice models. After being assessed neurological deficit 24 h after ICH, mice were euthanized and brain perihematomal tissues were used for RNA-sequencing (RNA-seq). And then the functions of differentially expressed genes (DEGs) identified by RNA-seq were analyzed using Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, Ingenuity Pathway Analysis (IPA) and protein-protein interaction (PPI) analysis. In addition, we performed real-time quantitative polymerase chain reaction (RT-qPCR) for validation of candidate DEGs. In the behavioral tests, aged mice presented significantly worse neurological function than young mice and greater weight loss than aged sham controls 24 h after ICH. In DEGs analysis, ICH affected the expression of more genes in young mice (2,337 DEGs) compared with aged mice (2,005 DEGs). We found aged mice exhibited increased brain inflammatory responses compared with young animals and ICH induced significant activation of the interferon-β (IFN-β) and IFN signaling pathways exclusively in aged mice. Moreover, further analysis demonstrated that ICH resulted in the activation of cytosolic DNA-sensing pathway with the production of downstream molecule type I IFN, and the response to type I IFN was more significant in aged mice than in young mice. In agreement with the results of RNA-seq, RT-qPCR indicated that the expression of candidate genes of cyclic GMP-AMP synthase (cGAS), Z-DNA-binding protein 1 (ZBP1), and IFN-β was significantly altered in aged mice after ICH. Taken together, our study indicated that compared to young animals, aged mice exhibit increased vulnerability to ICH and that the differences in transcriptional response patterns to ICH between young and aged mice. We believe that these findings will facilitate our understanding of ICH pathology and help to translate the results of preclinical studies into a clinical setting.
Dietary Intake and Pneumococcal Vaccine Response Among Children (5–7 Years) in Msambweni Division, Kwale County, Kenya
Authors: Migliore Eleonora , Amaitsa Vivian K. , Mutuku Francis M. , Malhotra Indu J. , Mukoko Dunstan , Sharma Anika , Kalva Prathik , Kang Amrik S. , King Charles H. , LaBeaud A. Desiree
Published: May 2022

Background

Vaccine and sufficient food availability are key factors for reducing pneumonia outbreaks in sub-Saharan Africa.

Methods

In this study, the 10-valent pneumococcal conjugate vaccine (Synflorix® or PCV10) was administered to a child cohort (5–7 years old, n = 237) in Msambweni, Kenya, to determine relationships between dietary intake, nutritional/socioeconomic status of mothers/caregivers, and vaccine response. 7-day food frequency questionnaire (FFQ), dietary diversity score (DDS) and single 24-h dietary recall were used to address participants' dietary assessment and nutritional status. Individual food varieties were recorded and divided into 9 food groups as recommended by Food and Agriculture Organization. Anthropometric measurements, nasopharyngeal swabs and vaccine administration were performed at the initial visit. Participants were followed 4–8 weeks with a blood draw for pneumococcal IgG titers assessed by Luminex assay.

Findings

Chronic malnutrition was prevalent in the cohort (15% stunting, 16% underweight). Unbalanced dietary intake was observed, with mean energy intake 14% below Recommended Dietary Allowances (1,822 Kcal) for 5–7 years age range. 72% of the daily energy was derived from carbohydrates, 18% from fats and only 10% from proteins. Poor anthropometric status (stunting/underweight) was associated with low socioeconomic/educational status and younger mother/caregiver age (p < 0.002). Limited intake of essential micronutrients (vitamins A, E, K) and minerals (calcium, potassium) associated with low consumption of fresh fruits, vegetables, and animal source foods (dairy, meat) was observed and correlated with poor vaccine response (p < 0.001). In contrast, children who consumed higher amounts of dietary fiber, vitamin B1, zinc, iron, and magnesium had adequate vaccine response (p < 0.05). Correlation between higher dietary diversity score (DDS), higher Vitamin E, K, Zinc intake and adequate vaccine response was also observed (p < 0.03).

Interpretation

Overall, this study highlights ongoing food scarcity and malnutrition in Kenya and demonstrates the links between adequate socioeconomic conditions, adequate nutrient intake, and vaccine efficacy.
Sugar-Sweetened Beverages and Depressive and Social Anxiety Symptoms Among Children and Adolescents Aged 7–17 Years, Stratified by Body Composition
Authors: Liu Jieyu , Chen Ting , Chen Manman , Ma Ying , Ma Tao , Gao Di , Li Yanhui , Ma Qi , Chen Li , Wang Xinxin , Zhang Yi , Ma Jun , Dong Yanhui
Published: May 2022

Background

Rare studies investigated the associations between sugar-sweetened beverage (SSB) consumption with depressive and social anxiety symptoms among children and adolescents, particularly in different stratification of body composition, which was our purpose.

Methods

A cross-sectional survey of children and adolescents aged 7–17 years was conducted in Beijing, China, in 2020, with an average age of 12.07 (SD: 3.09) years. Children's Depression Inventory (CDI) questionnaires and social anxiety scale for children (SASC) were completed in the baseline questionnaires. SSB consumption and body composition were assessed using child-reported questionnaires and a GE Healthcare Lunar iDXA dual-energy X-ray bone densitometer. Multivariate logistic regression was used to assess the associations between SSB consumption with depressive and social anxiety symptoms. Confounders were evaluated by child-reported and parental questionnaires, including age, sex, parental educational attainment, maternal smoking status, single-child status, BMI, incomes, fruit consumption, physical activity, screen time, and the frequency of fried food consumption. Stratified analyses were performed to explore whether the associations were influenced by body composition.

Results

A total of 1,311 children and adolescents, including 658 boys and 653 girls, were included in the final analysis. There were 13.96 and 29.75% of the study population with depressive and social anxiety symptoms, respectively. Overall, about 63.77% of the children and adolescents consumed SSB, and the average SSB intake was 0.35 servings per day. In the fully adjusted model, compared to participants who did not consume SSB each day, SSB consumption of ≥1 servings/day was positively associated with depressive symptoms [odds ratio (OR) = 2.28, 95% CI = 1.30–4.01] and social anxiety (OR = 1.10, 95% CI = 0.69–1.77), though the latter did not reach statistical significance. When individuals had higher body fat or lower fat-free mass (FFM) or muscle, the ORs of depressive symptoms were more evident among children and adolescents who drank SSB for ≥1 servings/day (P < 0.05).

Conclusion

Higher consumption of SSB could be associated with increased OR of depressive symptoms in children and adolescents. The association remained robust, especially in groups with higher body fat or lower fat-free mass or muscle.
Global Regulatory Frameworks for Fermented Foods: A Review
Authors: Mukherjee Arghya , Gómez-Sala Beatriz , O'Connor Eibhlís M. , Kenny John G. , Cotter Paul D.
Published: May 2022

In recent years, there has been a global resurgence of public interest in fermented foods. In parallel, there have been several new studies that associate the consumption of fermented foods with a variety of beneficial impacts. These combined developments have led to a renewed focus in research and innovation vis-à-vis fermented foods, particularly traditional fermented foods, with an aim to harness this information to develop novel fermented foodstuffs and ingredients and make them available in the market. Consequently, an ever greater and more diverse array of fermented foods, including functional fermented foods with health benefits, are becoming available for public consumption in global markets, with the number expected to grow substantially in the coming decade. This rapidly expanding portfolio of commercially available fermented foods has in turn required an evolution in the corresponding global regulatory frameworks. Due to the innovative and emerging nature of these foods, combined with historical differences in regulator approaches, significant disharmony exists across these frameworks, with individual nations and organizations often adopting unique approaches relating to the establishment of standards and specifications. In this review, we provide an overview of the current regulatory frameworks for a diversity of fermented foods across multiple jurisdictions, with special emphasis on differences in legislative structures and approaches, regulatory harmonization, and current legislative limitations. Overall, the review provides important perspective and context in relation to current global fermented food regulatory practices with possible directions and recommendations for future legislative efforts.
Clinical Relevance of Estrogen Reactivity in the Breast Cancer Microenvironment
Authors: Takeshita Takashi , Tokumaru Yoshihisa , Oshi Masanori , Wu Rongrong , Patel Ankit , Tian Wanqing , Hatanaka Yutaka , Hatanaka Kanako C. , Yan Li , Takabe Kazuaki
Published: May 2022

Purpose

Estrogen signals play an important role in the phenotype of estrogen receptor-positive breast cancer. However, comprehensive analyses of the effect of responsiveness to estrogen signals on the tumor microenvironment and survival in large cohorts of primary breast cancer patients have been lacking. We aimed to test the hypothesis that estrogen reactivity affects gene expression and immune cell infiltration profiles in the tumor microenvironment and survival.

Methods

A total of 3,098 breast cancer cases were analyzed: 1,904 from the Molecular Taxonomy of Breast Cancer (METABRIC) cohort, 1,082 from The Cancer Genome Atlas (TCGA) cohort, and 112 from the Hokkaido University Hospital cohort. We divided the group into estrogen reactivity-high and estrogen reactivity-low groups utilizing the scores of ESTROGEN_RESPONSE_EARLY and ESTROGEN_RESPONSE_LATE in Gene Set Variation Analysis.

Results

Breast cancer with high estrogen reactivity was related to Myc targets, metabolism-related signaling, cell stress response, TGF-beta signaling, androgen response, and MTORC1 signaling gene sets in the tumor microenvironment. Low estrogen reactivity was related to immune-related proteins, IL2-STAT5 signaling, IL6-JAK-STAT3 signaling, KRAS signaling, cell cycle-related gene sets, and EMT. In addition, breast cancer with high levels of estrogen reactivity had low immune cytolytic activity and low levels of immunostimulatory cells. It also had low levels of stimulatory and inhibitory factors of the cancer immunity cycle. Patients with high estrogen reactivity were also associated with a better prognosis.

Conclusion

We demonstrated the relationship between estrogen reactivity and the profiles of immune cells and gene expression, as well as survival.
Sensitization of Non-Small Cell Lung Cancer Cells to Gefitinib and Reversal of Epithelial–Mesenchymal Transition by Aloe-Emodin Via PI3K/Akt/TWIS1 Signal Blockage
Authors: Peng Minghui , Zheng Zhuifeng , Chen Shaoyang , Fang Le , Feng Rongxiu , Zhang Lijun , Tang Qingnan , Liu Xuewen
Published: May 2022

Objective

To explore the impacts of AE (aloe-emodin) in gefitinib-resistant NSCLC (non-small cell lung cancer) cells and the corresponding mechanism.

Methods

PC9 and PC9-GR cells were cultured and treated by gefitinib, AE, or the combination of the two drugs. Then, viability, apoptosis, migration and invasion of cells were investigated using CCK-8, TUNEL, wound healing assay, and transwell assay, respectively. Female BALB/c nude mice were employed for the establishment of xenograft tumor models to examine the role of AE in tumor growth.

Results

PC9-GR cells showed reduced apoptosis and enhanced cell viability, migration and invasion upon treatment by gefitinib, compared with PC9 cells. E-cahherin in PC9-GR cells was down-regulated, while Vimentin, Snail2 (or Slug) and Twist1 in PC9-GR cells were up-regulated, compared with PC9 cells. Meanwhile, treatment by a combination of gefitinib and AE significantly strengthened apoptosis of PC9-GR cells, while attenuated their migration and invasion, compared with the control group or treatment by gefitinib or AE alone. WB results showed that AE could reverse EMT and activation of PI3K/AKT signalling pathway in PC9-GR cells. In vivo experiments showed that tumor growth and EMT of PC9-GR cells were dramatically repressed after treatment by a combination of AE and gefitinib. Additionally, the use of SC97 (a PI3K/Akt pathway activator) could counteract the effects of AE in gefitinib-resistant PC9 cells.

Conclusions

AE could enhance the gefitinib sensitivity of PC9-GR cells and reverse EMT by blocking PI3K/Akt/TWIS1 signal pathway.
Family-Assisted Severity of Illness Monitoring for Hospitalized Children in Low-Resource Settings—A Two-Arm Interventional Feasibility Study
Authors: von Saint Andre-von Arnim Amelie O. , Kumar Rashmi K. , Clark Jonna D. , Wilfond Benjamin S. , Nguyen Quynh-Uyen P. , Mutonga Daniel M. , Zimmerman Jerry J. , Oron Assaf P. , Walson Judd L.
Published: May 2022

Introduction

Pediatric mortality remains unacceptably high in many low-resource settings, with inpatient deaths often associated with delayed recognition of clinical deterioration. The Family-Assisted Severe Febrile Illness ThERapy (FASTER) tool has been developed for caregivers to assist in monitoring their hospitalized children and alert clinicians. This study evaluates feasibility of implementation by caregivers and clinicians.

Methods

Randomized controlled feasibility study at Kenyatta National Hospital, Kenya. Children hospitalized with acute febrile illness with caregivers at the bedside for 24 h were enrolled. Caregivers were trained using the FASTER tool. The primary outcome was the frequency of clinician reassessments between intervention (FASTER) and standard care arms. Poisson regression with random intercept for grouping by patient was used, adjusting for admission pediatric early warning score, age, gender. Secondary outcomes included survey assessments of clinician and caregiver experiences with FASTER.

Results

One hundred and fifty patient/caregiver pairs were enrolled, 139 included in the analysis, 74 in the intervention, 65 in the control arm. Patients' median age was 0.9 (range 0.2–10) and 1.1 years (range 0.2–12) in intervention vs. control arms. The most common diagnoses were pneumonia (80[58%]), meningitis (58[38%]) and malaria (34 [24%]). 134 (96%) caregivers were patients' mothers. Clinician visits/hour increased with patients' illness severity in both arms, but without difference in frequency between arms (point estimate for difference −0.9%, p = 0.97). Of the 16 deaths, 8 (four/arm) occurred within 2 days of enrollment. Forty clinicians were surveyed, 33 (82%) reporting that FASTER could improve outcomes of very sick children in low-resource settings; 26 (65%) rating caregivers as able to adequately capture patients' severity of illness. Of 70 caregivers surveyed, 63 (90%) reported that FASTER training was easy to understand; all (100%) agreed that the intervention would improve care of hospitalized children and help identify sick children in their community.

Discussion

We observed no difference in recorded frequency of clinician visits with FASTER monitoring. However, the tool was rated positively by caregivers and clinicians., Implementation appears feasible but requires optimization. These feasibility data may inform a larger trial powered to measure morbidity and mortality outcomes to determine the utility of FASTER in detecting and responding to clinical deterioration in low-resource settings.

Clinical Trial Registration

ClinicalTrials.gov, identifier: NCT03513861.
Treated Pierre Robin Sequence Using Placed Allogenic Acellular Bone Matrix and Mandibular Distraction Osteogenesis in the Neonate
Authors: Han Tao , Ji Yi , Cui Jie , Kong Liangliang , Shi Lijun , Chen Jianbin , Shen Weimin
Published: May 2022

Objective

The aim of the study was to report our experience with placed allogenic acellular bone matrix and mandibular distraction osteogenesis in Pierre Robin sequence (PRS), and explore the role of distraction in the osteogenesis of acellular bone.

Materials and Methods

A total of 428 neonates with severe PRS managed with placing allogenic acellular bone and bilateral mandibular distraction osteogenesis were included in the study. The procedure included using oblique-shaped osteotomy, fixing bilateral mandibular distractor, instantly extending a 4–6 mm gap, and placing allogenic acellular bone into the gap. The length of allogenic acellular bone was 4–5 mm. Although the surgical techniques, distraction, and consolidation periods were similar, the allogenic acellular bone matrix we placed was quite different from the traditional distraction. With the technology we used, tracheal intubation could be immediately removed, thus quickly improving breathing conditions compared to traditional methods after the surgery. The jaw extending and oral feeding could begin on the 5th day. The jaw was extended 0.6 mm twice a day until the mandible was overcorrected by 20%.

Results

All 428 cases included in this study were successfully extubated after the operation, and the difficulty in breathing was instantly relieved. Total mandibular distraction was 15–20 mm. Oral feeding was started at 6 h to 6 days postoperatively, while hospital stay ranged from 18 to 20 days postoperatively. No major complications were reported. Medium to long-term results was good. Mandibular distractors were removed after 3 months.

Conclusions

Bilateral mandibular distraction osteogenesis combined with placing allogenic acellular bone in the neonate are safe and accurate procedures, which are the primary treatment options for cases of severe PRS. It can be considered that the tension of distraction can promote osteogenesis in acellular bone and thus improve distractive effect of the mandible.
Conversations About End-of-Life Decisions in Neonatology: Do Doctors and Parents Implement Shared Decision-Making?
Authors: Schouten Esther S. , Beyer Maria F. , Flemmer Andreas W. , de Vos Mirjam A. , Kuehlmeyer Katja
Published: May 2022

Introduction:

Advances in perinatal medicine have contributed to significantly improved survival of newborns. While some infants die despite extensive medical treatment, a larger proportion dies following medical decision-making (MDM). International guidelines about end-of-life (EOL) MDM for neonates unify in their recommendation for shared decision-making (SDM) between doctors and parents. Yet, we do not know to what extent SDM is realized in neonatal practice.

Objective

We aim at examining to which extent SDM is implemented in the NICU setting.

Methods

By means of Qualitative Content Analysis, audio-recorded conversations between neonatologists and parents were analyzed. We used a framework by de Vos that was used to analyze similar conversations on the PICU.

Results

In total we analyzed 17 conversations with 23 parents of 12 NICU patients. SDM was adopted only to a small extent in neonatal EOL-MDM conversations. The extent of sharing decreased considerably over the stages of SDM. The neonatologists suggested finding a decision together with parents, while at the same time seeking parents' agreement for the intended decision to forgo life-sustaining treatment.

Conclusions

Since SDM was only realized to a small extent in the NICU under study, we propose evaluating how parents in this unit experience the EOL-MDM process and whether they feel their involvement in the process acceptable and beneficial. If parents evaluate their involvement in the current approach beneficial, the need for implementation of SDM to the full extent, as suggested in the guidelines, may need to be critically re-assessed.
Further Evidence that Inhibition of Neuronal Voltage-Gated Calcium Channels Contributes to the Hypnotic Effect of Neurosteroid Analogue, 3β-OH
Authors: Timic Stamenic Tamara , Manzella Francesca M. , Maksimovic Stefan , Krishnan Kathiresan , Covey Douglas F. , Jevtovic-Todorovic Vesna , Todorovic Slobodan M.
Published: May 2022

We recently reported that a neurosteroid analogue with T-channel-blocking properties (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile (3β-OH), induced hypnosis in rat pups without triggering neuronal apoptosis. Furthermore, we found that the inhibition of the CaV3.1 isoform of T-channels contributes to the hypnotic properties of 3β-OH in adult mice. However, the specific mechanisms underlying the role of other subtypes of voltage-gated calcium channels in thalamocortical excitability and oscillations in vivo during 3β-OH-induced hypnosis are largely unknown. Here, we used patch-clamp recordings from acute brain slices, in vivo electroencephalogram (EEG) recordings, and mouse genetics with wild-type (WT) and CaV2.3 knock-out (KO) mice to further investigate the molecular mechanisms of neurosteroid-induced hypnosis. Our voltage-clamp recordings showed that 3β-OH inhibited recombinant CaV2.3 currents. In subsequent current-clamp recordings in thalamic slices ex vivo, we found that selective CaV2.3 channel blocker (SNX-482) inhibited stimulated tonic firing and increased the threshold for rebound burst firing in WT animals. Additionally, in thalamic slices we found that 3β-OH inhibited spike-firing more profoundly in WT than in mutant mice. Furthermore, 3β-OH reduced bursting frequencies in WT but not mutant animals. In ensuing in vivo experiments, we found that intra-peritoneal injections of 3β-OH were less effective in inducing LORR in the mutant mice than in the WT mice, with expected sex differences. Furthermore, the reduction in total α, β, and low γ EEG power was more profound in WT than in CaV2.3 KO females over time, while at 60 min after injections of 3β-OH, the increase in relative β power was higher in mutant females. In addition, 3β-OH depressed EEG power more strongly in the male WT than in the mutant mice and significantly increased the relative δ power oscillations in WT male mice in comparison to the mutant male animals. Our results demonstrate for the first time the importance of the CaV2.3 subtype of voltage-gated calcium channels in thalamocortical excitability and the oscillations that underlie neurosteroid-induced hypnosis.
Application of Traditional Japanese Drug Jidabokuippo in a Modern Society
Authors: Nakae Hajime , Irie Yasuhito , Kitamura Toshiharu , Okuyama Manabu
Published: May 2022

Background:Jidabokuippo (JDI) (治打撲一方) has been used in Japan to alleviate contusion-induced swelling and pain since medieval times.

Method:This review investigated the effects of JDI on various symptoms in patients with trauma or static blood[TM1]. The PubMed and Igaku Chuo Zasshi databases were searched until 24 December 2021. We summarize the benefits of applying JDI to inflammatory conditions, including bruises.

Results:JDI has been used to resolve blood[TM1]stasis, regulate qi in trauma patients, and treat inflammatory swelling and pain caused by rheumatoid arthritis and cellulitis. As the adverse event rate associated with JDI is low (1.3%), JDI is considered a safe drug.

Conclusion:JDI can be used to resolve blood[TM1]stasis in trauma patients without adverse events associated with nonsteroidal anti-inflammatory drugs.