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European Annals of Allergy and Clinical... Dec 2023The prevalence of food allergy (FA) has increased, a possible consequence of intestinal dysbiosis, environmental or genetic factors. Currently, no formal indications... (Review)
Review
The prevalence of food allergy (FA) has increased, a possible consequence of intestinal dysbiosis, environmental or genetic factors. Currently, no formal indications exist for probiotic or prebiotic supplementation in FA. This review aims to analyse the role of probiotics and prebiotics in the prevention and treatment of FA. A PubMed/Medline search was carried out on articles published between 2011 and 2021 with the following query: ("Food Hypersensitivity"[Mesh]) AND (("Probiotics"[Mesh]) OR ("Prebiotics"[Mesh])). Subsequently, the titles and abstracts were analysed and selected according to established criteria. After full reading of these articles, 54 were included and a narrative review was performed. The review was structured in the following sections: i) Cow's Milk Proteins Allergy (CMA), ii) Food Allergy to Peanuts and iii) Prevention of Food Allergy. In CMA, several studies have supported the benefits of extensively hydrolysed casein formula supplemented with in the earlier acquisition of tolerance to cow's milk proteins, resolution of gastrointestinal symptoms and prevention of other allergic manifestations. In peanut oral immunotherapy (OI), supplementation with seems to have a favourable impact in inducing a sustained desensitization response. Regarding the use of probiotics in the prevention of FA, this assumption lacks robust scientific evidence in order to confirm the effectiveness. Current evidence supports the use of oligosaccharides from breast milk in the first months of life for preventing atopic dermatitis, FA and asthma. The potential of probiotics to be used as therapeutic adjuvants in CMA and peanut OI is promising. However, there is inconsistency regarding the type of probiotic, the dose and duration of supplementation. Further studies are needed to clarify the role of probiotics and prebiotics in FA.
PubMed: 38054607
DOI: 10.23822/EurAnnACI.1764-1489.319 -
Frontiers in Immunology 2023Sleep enhances the antibody response to vaccination, but the relationship between sleep and mRNA vaccination against severe acute respiratory syndrome coronavirus 2... (Observational Study)
Observational Study
INTRODUCTION
Sleep enhances the antibody response to vaccination, but the relationship between sleep and mRNA vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not fully understood.
METHODS
In this prospective observational study, we investigated the influence of sleep habits on immune acquisition induced by mRNA vaccines against SARS-CoV-2 in 48 healthy adults (BNT-162b2, n=34; mRNA-1273, n=14; female, n=30, 62.5%; male, n=18, 37.5%; median age, 39.5 years; interquartile range, 33.0-44.0 years) from June 2021 to January 2022. The study measured sleep duration using actigraphy and sleep diaries, which covered the periods of the initial and booster vaccinations.
RESULTS
Multivariable linear regression analysis showed that actigraphy-measured objective sleep duration 3 and 7 days after the booster vaccination was independently and significantly correlated with higher antibody titers (B=0.003; 95% confidence interval, 0.000-0.005; Beta=0.337; p=0.02), even after controlling for covariates, including age, sex, the type of vaccine, and reactogenicity to the vaccination. Associations between acquired antibody titer and average objective sleep duration before vaccination, and any period of subjective sleep duration measured by sleep diary were negligible.
DISCUSSION
Longer objective, but not subjective, sleep duration after booster vaccination enhances antibody response. Hence, encouraging citizens to sleep longer after mRNA vaccination, especially after a booster dose, may increase protection against SARS-CoV-2.
STUDY REGISTRATION
This study is registered at the University Hospital Medical Information Network Center (UMIN: https://www.umin.ac.jp) on July 30, 2021, #UMIN000045009.
Topics: Adult; Female; Humans; Male; COVID-19; COVID-19 Vaccines; Sleep Duration; Vaccination; Antibody Formation; Antibodies, Viral; mRNA Vaccines; Immunization, Secondary
PubMed: 38149250
DOI: 10.3389/fimmu.2023.1242302 -
Annals of Oncology : Official Journal... Oct 2023HER2 mutations are targetable alterations in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC). In the SUMMIT basket study, patients with... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
HER2 mutations are targetable alterations in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC). In the SUMMIT basket study, patients with HER2-mutant MBC received neratinib monotherapy, neratinib + fulvestrant, or neratinib + fulvestrant + trastuzumab (N + F + T). We report results from 71 patients with HR+, HER2-mutant MBC, including 21 (seven in each arm) from a randomized substudy of fulvestrant versus fulvestrant + trastuzumab (F + T) versus N + F + T.
PATIENTS AND METHODS
Patients with HR+ HER2-negative MBC with activating HER2 mutation(s) and prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy received N + F + T (oral neratinib 240 mg/day with loperamide prophylaxis, intramuscular fulvestrant 500 mg on days 1, 15, and 29 of cycle 1 then q4w, intravenous trastuzumab 8 mg/kg then 6 mg/kg q3w) or F + T or fulvestrant alone. Those whose disease progressed on F + T or fulvestrant could cross-over to N + F + T. Efficacy endpoints included investigator-assessed objective response rate (ORR), clinical benefit rate (RECIST v1.1), duration of response, and progression-free survival (PFS). Plasma and/or formalin-fixed paraffin-embedded tissue samples were collected at baseline; plasma was collected during and at end of treatment. Extracted DNA was analyzed by next-generation sequencing.
RESULTS
ORR for 57 N + F + T-treated patients was 39% [95% confidence interval (CI) 26% to 52%); median PFS was 8.3 months (95% CI 6.0-15.1 months). No responses occurred in fulvestrant- or F + T-treated patients; responses in patients crossing over to N + F + T supported the requirement for neratinib in the triplet. Responses were observed in patients with ductal and lobular histology, 1 or ≥1 HER2 mutations, and co-occurring HER3 mutations. Longitudinal circulating tumor DNA sequencing revealed acquisition of additional HER2 alterations, and mutations in genes including PIK3CA, enabling further precision targeting and possible re-response.
CONCLUSIONS
The benefit of N + F + T for HR+ HER2-mutant MBC after progression on CDK4/6is is clinically meaningful and, based on this study, N + F + T has been included in the National Comprehensive Cancer Network treatment guidelines. SUMMIT has improved our understanding of the translational implications of targeting HER2 mutations with neratinib-based therapy.
Topics: Female; Humans; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Fulvestrant; Receptor, ErbB-2; Trastuzumab
PubMed: 37597578
DOI: 10.1016/j.annonc.2023.08.003 -
NPJ Science of Learning Sep 2023We investigated the influence of the time-of-day and sleep on skill acquisition (i.e., skill improvement immediately after a training-session) and consolidation (i.e.,...
We investigated the influence of the time-of-day and sleep on skill acquisition (i.e., skill improvement immediately after a training-session) and consolidation (i.e., skill retention after a time interval including sleep). Three groups were trained at 10 a.m. (G10), 3 p.m. (G3), or 8 p.m. (G8) on a finger-tapping task. We recorded the skill (i.e., the ratio between movement duration and accuracy) before and immediately after the training to evaluate acquisition, and after 24 h to measure consolidation. We did not observe any difference in acquisition according to the time of the day. Interestingly, we found a performance improvement 24 h after the evening training (G8), while the morning (G10) and the afternoon (G3) groups deteriorated and stabilized their performance, respectively. Furthermore, two control experiments (G8 and G8) supported the idea that a night of sleep contributes to the skill consolidation of the evening group. These results show a consolidation when the training is carried out in the evening, close to sleep, and forgetting when the training is carried out in the morning, away from sleep. This finding may have an important impact on the planning of training programs in sports, clinical, or experimental domains.
PubMed: 37658041
DOI: 10.1038/s41539-023-00176-9 -
Biochemical Pharmacology Nov 2023Breast cancer stands as the most prevalent and heterogeneous malignancy affecting women globally, posing a substantial health concern. Enhanced comprehension of tumor... (Review)
Review
Breast cancer stands as the most prevalent and heterogeneous malignancy affecting women globally, posing a substantial health concern. Enhanced comprehension of tumor pathology and the development of novel therapeutics are pivotal for advancing breast cancer treatment. Contemporary breast cancer investigation heavily leans on in vivo models and conventional cell culture techniques. Nonetheless, these approaches often encounter high failure rates in clinical trials due to species disparities and tissue structure variations. To address this, three-dimensional cultivation of organoids, resembling organ-like structures, has emerged as a promising alternative. Organoids represent innovative in vitro models that mirror in vivo tissue microenvironments. They retain the original tumor's diversity and facilitate the expansion of tumor samples from diverse origins, facilitating the representation of varying tumor stages. Optimized breast cancer organoid models, under precise culture conditions, offer benefits including convenient sample acquisition, abbreviated cultivation durations, and genetic stability. These attributes ensure a faithful replication of in vivo traits of breast cancer cells. As intricate cellular entities boasting spatial arrangements, breast cancer organoid models harbor substantial potential in precision medicine, organ transplantation, modeling intricate diseases, gene therapy, and drug innovation. This review delivers an overview of organoid culture techniques and outlines future prospects for organoid modeling.
Topics: Humans; Female; Breast Neoplasms; Drug Evaluation, Preclinical; Early Detection of Cancer; Organoids; Tumor Microenvironment
PubMed: 37709150
DOI: 10.1016/j.bcp.2023.115803 -
Scientific Reports Jun 2023The ability to process sound duration is crucial already at a very early age for laying the foundation for the main functions of auditory perception, such as object...
The ability to process sound duration is crucial already at a very early age for laying the foundation for the main functions of auditory perception, such as object perception and music and language acquisition. With the availability of age-appropriate structural anatomical templates, we can reconstruct EEG source activity with much-improved reliability. The current study capitalized on this possibility by reconstructing the sources of event-related potential (ERP) waveforms sensitive to sound duration in 4- and 9-month-old infants. Infants were presented with short (200 ms) and long (300 ms) sounds equiprobable delivered in random order. Two temporally separate ERP waveforms were found to be modulated by sound duration. Generators of these waveforms were mainly located in the primary and secondary auditory areas and other language-related regions. The results show marked developmental changes between 4 and 9 months, partly reflected by scalp-recorded ERPs, but appearing in the underlying generators in a far more nuanced way. The results also confirm the feasibility of the application of anatomical templates in developmental populations.
Topics: Reproducibility of Results; Brain; Evoked Potentials; Auditory Perception; Auditory Cortex; Electroencephalography; Evoked Potentials, Auditory; Acoustic Stimulation
PubMed: 37355709
DOI: 10.1038/s41598-023-36794-x -
Journal of Speech, Language, and... Aug 2023Nonnative consonant cluster learning has become a useful experimental approach for learning about speech motor learning, and we sought to enhance our understanding of...
PURPOSE
Nonnative consonant cluster learning has become a useful experimental approach for learning about speech motor learning, and we sought to enhance our understanding of this area and to establish best practices for this type of research.
METHOD
One hundred twenty individuals completed a nonnative consonant cluster learning task within a speech motor learning paradigm. Following a brief prepractice, participants then practiced the production of eight word-initial nonnative consonant clusters embedded in bisyllabic nonwords (e.g., GD in /gdivu/). The clusters ranged in difficulty according to linguistic typology and sonority sequencing. Acquisition was operationalized as the change across the practice section and learning was assessed with two retention sessions (R1: 30 min after practice; R2: 2 days after practice). We evaluated changes in accuracy as well as in the acoustic details of the cluster production at each time point.
RESULTS
Overall, participants improved in their production of the consonant clusters. Accuracy increased, and duration measures decreased in specific measures associated with cluster production. The change in coordination measured in the acoustics changed both for clusters that were incorrectly produced and for those that were correctly produced, indicating continued motor learning even in accurate tokens.
CONCLUSIONS
These results aid our understanding of the complexity of nonnative consonant cluster learning. In particular, both factors related to both phonological and speech motor control properties affect the learning of novel speech sequences.
SUPPLEMENTAL MATERIAL
https://doi.org/10.23641/asha.21844185.
Topics: Humans; Phonetics; Speech; Learning; Acoustics
PubMed: 36634242
DOI: 10.1044/2022_JSLHR-22-00322 -
Human Cell Jul 2023Metabolic and inflammatory pathways are highly interdependent, and both systems are dysregulated in Type 2 diabetes (T2D). T2D is associated with pre-activated... (Review)
Review
Metabolic and inflammatory pathways are highly interdependent, and both systems are dysregulated in Type 2 diabetes (T2D). T2D is associated with pre-activated inflammatory signaling networks, aberrant cytokine production and increased acute phase reactants which leads to a pro-inflammatory 'feed forward loop'. Nutrient 'excess' conditions in T2D with hyperglycemia, elevated lipids and branched-chain amino acids significantly alter the functions of immune cells including neutrophils. Neutrophils are metabolically active cells and utilizes energy from glycolysis, stored glycogen and β-oxidation while depending on the pentose phosphate pathway for NADPH for performing effector functions such as chemotaxis, phagocytosis and forming extracellular traps. Metabolic changes in T2D result in constitutive activation and impeded acquisition of effector or regulatory activities of neutrophils and render T2D subjects for recurrent infections. Increased flux through the polyol and hexosamine pathways, elevated production of advanced glycation end products (AGEs), and activation of protein kinase C isoforms lead to (a) an enhancement in superoxide generation; (b) the stimulation of inflammatory pathways and subsequently to (c) abnormal host responses. Neutrophil dysfunction diminishes the effectiveness of wound healing, successful tissue regeneration and immune surveillance against offending pathogens. Hence, Metabolic reprogramming in neutrophils determines frequency, severity and duration of infections in T2D. The present review discusses the influence of the altered immuno-metabolic axis on neutrophil dysfunction along with challenges and therapeutic opportunities for clinical management of T2D-associated infections.
Topics: Humans; Neutrophils; Diabetes Mellitus, Type 2; Glycolysis; Hyperglycemia; Oxidation-Reduction
PubMed: 37115481
DOI: 10.1007/s13577-023-00905-7 -
Heliyon Nov 2023This study examined the differences in the pausing behavior between native and non-native English speakers. Specifically, it examined the location and duration of pauses...
This study examined the differences in the pausing behavior between native and non-native English speakers. Specifically, it examined the location and duration of pauses in relation to the syntactic and lexical complexity of the clauses in which these pauses occur and the nature of the prosodic phrasing of the utterances containing pauses. Speech samples from 10 native (L1) English and 10 Mandarin non-native English speakers from the Archive of L1 and L2 Scripted and Spontaneous Transcripts and Recordings (ALLSSTAR) were included in the analysis. The results showed that lower-level prosodic boundaries and syntactically complex phrases were associated with significantly longer pause duration in the L2 speech. Additionally, phrases with less frequent words tended to induce longer pauses. These findings suggest that insufficient knowledge of the L2 syntax, lexicon, and prosody might determine the location and duration of pauses and ultimately affect the speech fluency of L2 speakers.
PubMed: 37954378
DOI: 10.1016/j.heliyon.2023.e21322