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Italian Journal of Pediatrics Oct 2021Recurrent respiratory infections (RRIs) are a common clinical condition in children, in fact about 25% of children under 1 year and 6% of children during the first...
Recurrent respiratory infections (RRIs) are a common clinical condition in children, in fact about 25% of children under 1 year and 6% of children during the first 6 years of life have RRIs. In most cases, infections occur with mild clinical manifestations and the frequency of episodes tends to decrease over time with a complete resolution by 12 years of age. However, RRIs significantly reduce child and family quality of life and lead to significant medical and social costs.Despite the importance of this condition, there is currently no agreed definition of the term RRIs in the literature, especially concerning the frequency and type of infectious episodes to be considered. The aim of this consensus document is to propose an updated definition and provide recommendations with the intent of guiding the physician in the complex process of diagnosis, management and prevention of RRIs.
Topics: Adenoidectomy; Adjuvants, Immunologic; Administration, Intranasal; Algorithms; Antibiotic Prophylaxis; Antioxidants; Child; Complementary Therapies; Humans; Hyaluronic Acid; Influenza Vaccines; Pneumococcal Vaccines; Prebiotics; Probiotics; Pyrrolidonecarboxylic Acid; Recurrence; Respiratory Tract Infections; Resveratrol; Thiazolidines; Tonsillectomy; Vitamins
PubMed: 34696778
DOI: 10.1186/s13052-021-01150-0 -
Nutrients Aug 2020Magnesium deficiency may occur for several reasons, such as inadequate intake or increased gastrointestinal or renal loss. A large body of literature suggests a... (Review)
Review
Magnesium deficiency may occur for several reasons, such as inadequate intake or increased gastrointestinal or renal loss. A large body of literature suggests a relationship between magnesium deficiency and mild and moderate tension-type headaches and migraines. A number of double-blind randomized placebo-controlled trials have shown that magnesium is efficacious in relieving headaches and have led to the recommendation of oral magnesium for headache relief in several national and international guidelines. Among several magnesium salts available to treat magnesium deficiency, magnesium pidolate may have high bioavailability and good penetration at the intracellular level. Here, we discuss the cellular and molecular effects of magnesium deficiency in the brain and the clinical evidence supporting the use of magnesium for the treatment of headaches and migraines.
Topics: Administration, Oral; Biological Availability; Dietary Supplements; Headache; Humans; Magnesium; Magnesium Deficiency; Migraine Disorders; Pyrrolidonecarboxylic Acid; Randomized Controlled Trials as Topic
PubMed: 32878232
DOI: 10.3390/nu12092660 -
JAMA Neurology Oct 2022β-amyloid plaques and neurofibrillary tau deposits biologically define Alzheimer disease. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
β-amyloid plaques and neurofibrillary tau deposits biologically define Alzheimer disease.
OBJECTIVE
To perform post hoc analyses of amyloid reduction after donanemab treatment and assess its association with tau pathology and clinical measures.
DESIGN, SETTING, AND PARTICIPANTS
The Study of LY3002813 in Participants With Early Symptomatic Alzheimer's Disease (TRAILBLAZER-ALZ) was a phase 2, placebo-controlled, randomized clinical trial conducted from December 18, 2017, to December 4, 2020, with a double-blind period of up to 76 weeks and a 48-week follow-up period. The study was conducted at 56 centers in the US and Canada. Enrolled were participants from 60 to 85 years of age with gradual and progressive change in memory function for 6 months or more, early symptomatic Alzheimer disease, elevated amyloid, and intermediate tau levels.
INTERVENTIONS
Donanemab (an antibody specific for the N-terminal pyroglutamate β-amyloid epitope) dosing was every 4 weeks: 700 mg for the first 3 doses, then 1400 mg for up to 72 weeks. Blinded dose-reduction evaluations occurred at 24 and 52 weeks based on amyloid clearance.
MAIN OUTCOMES AND MEASURES
Change in amyloid, tau, and clinical decline after donanemab treatment.
RESULTS
The primary study randomized 272 participants (mean [SD] age, 75.2 [5.5] years; 145 female participants [53.3%]). The trial excluded 1683 of 1955 individuals screened. The rate of donanemab-induced amyloid reduction at 24 weeks was moderately correlated with the amount of baseline amyloid (Spearman correlation coefficient r, -0.54; 95% CI, -0.66 to -0.39; P < .001). Modeling provides a hypothesis that amyloid would not reaccumulate to the 24.1-centiloid threshold for 3.9 years (95% prediction interval, 1.9-8.3 years) after discontinuing donanemab treatment. Donanemab slowed tau accumulation in a region-dependent manner as measured using neocortical and regional standardized uptake value ratios with cerebellar gray reference region. A disease-progression model found a significant association between percentage amyloid reduction and change on the integrated Alzheimer Disease Rating Scale only in apolipoprotein E (APOE) ε4 carriers (95% CI, 24%-59%; P < .001).
CONCLUSIONS AND RELEVANCE
Results of post hoc analyses for donanemab-treated participants suggest that baseline amyloid levels were directly associated with the magnitude of amyloid reduction and inversely associated with the probability of achieving complete amyloid clearance. The donanemab-induced slowing of tau was more pronounced in those with complete amyloid clearance and in brain regions identified later in the pathologic sequence. Data from other trials will be important to confirm aforementioned observations, particularly treatment response by APOE ε4 status.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03367403.
Topics: Aged; Alzheimer Disease; Amyloid; Amyloid beta-Peptides; Amyloidosis; Apolipoprotein E4; Epitopes; Female; Humans; Infant; Plaque, Amyloid; Positron-Emission Tomography; Pyrrolidonecarboxylic Acid; tau Proteins
PubMed: 36094645
DOI: 10.1001/jamaneurol.2022.2793 -
Minerva Pediatrica Oct 2020The rising incidence of allergic disease requires more specific, effective and safe therapeutic strategies. In this regard, several kinds of biologically active... (Review)
Review
The rising incidence of allergic disease requires more specific, effective and safe therapeutic strategies. In this regard, several kinds of biologically active substances, commonly known as immunostimulants, have been introduced for the prevention and treatment of allergic diseases in pediatric population. Among the heterogeneous group of biologically active molecules to date available, pidotimod (Axil, Valeas S.p.A, Milan) is proved to be able to ameliorate both innate and adaptive immunity and enhances the immune system properties often impaired in patients with allergic disorders.
Topics: Adaptive Immunity; Adjuvants, Immunologic; Adolescent; Asthma; Child; Child, Preschool; Chronic Urticaria; Dermatitis, Atopic; Desensitization, Immunologic; Food Hypersensitivity; Humans; Hypersensitivity; Immunity, Innate; Immunologic Factors; Pyrrolidonecarboxylic Acid; Rhinitis, Allergic; Thiazolidines
PubMed: 32731733
DOI: 10.23736/S0026-4946.20.05967-8 -
Frontiers in Cellular and Infection... 2022Kidney stones or nephrolithiasis is a chronic metabolic disease characterized by renal colic and hematuria. Currently, a pathogenetic mechanism resulting in kidney stone...
BACKGROUND
Kidney stones or nephrolithiasis is a chronic metabolic disease characterized by renal colic and hematuria. Currently, a pathogenetic mechanism resulting in kidney stone formation remains elusive. We performed a multi-omic study investigating urinary microbial compositions and metabolic alterations during nephrolithiasis.
METHOD
Urine samples from healthy and individuals with nephrolithiasis were collected for 16S rRNA gene sequencing and liquid chromatography-mass spectroscopy. Microbiome and metabolome profiles were analyzed individually and combined to construct interactome networks by bioinformatic analysis.
RESULTS
Distinct urinary microbiome profiles were determined in nephrolithiasis patients compared with controls. Thirty-nine differentially abundant taxa between controls and nephrolithiasis patients were identified, and Streptococcus showed the most significant enrichment in nephrolithiasis patients. We also observed significantly different microbial compositions between female and male nephrolithiasis patients. The metabolomic analysis identified 112 metabolites that were differentially expressed. Two significantly enriched metabolic pathways, including biosynthesis of unsaturated fatty acids and tryptophan metabolism, were also identified in nephrolithiasis patients. Four potentially diagnostic metabolites were also identified, including trans-3-hydroxycotinine, pyroglutamic acid, O-desmethylnaproxen, and FAHFA (16:0/18:2), and could function as biomarkers for the early diagnosis of nephrolithiasis. We also identified three metabolites that contributed to kidney stone size. Finally, our integrative analysis of the urinary tract microbiome and metabolome identified distinctly different network characteristics between the two groups.
CONCLUSIONS
Our study has characterized important profiles and correlations among urinary tract microbiomes and metabolomes in nephrolithiasis patients for the first time. These results shed new light on the pathogenesis of nephrolithiasis and could provide early clinical biomarkers for diagnosing the disease.
Topics: Biomarkers; Female; Humans; Kidney; Kidney Calculi; Male; Pyrrolidonecarboxylic Acid; RNA, Ribosomal, 16S; Tryptophan
PubMed: 36132987
DOI: 10.3389/fcimb.2022.953392 -
Acta Neuropathologica Communications Apr 2022Amyloid plaques contain many proteins in addition to beta amyloid (Aβ). Previous studies examining plaque-associated proteins have shown these additional proteins are...
Amyloid plaques contain many proteins in addition to beta amyloid (Aβ). Previous studies examining plaque-associated proteins have shown these additional proteins are important; they provide insight into the factors that drive amyloid plaque development and are potential biomarkers or therapeutic targets for Alzheimer's disease (AD). The aim of this study was to comprehensively identify proteins that are enriched in amyloid plaques using unbiased proteomics in two subtypes of early onset AD: sporadic early onset AD (EOAD) and Down Syndrome (DS) with AD. We focused our study on early onset AD as the drivers of the more aggressive pathology development in these cases is unknown and it is unclear whether amyloid-plaque enriched proteins differ between subtypes of early onset AD. Amyloid plaques and neighbouring non-plaque tissue were microdissected from human brain sections using laser capture microdissection and label-free LC-MS was used to quantify the proteins present. 48 proteins were consistently enriched in amyloid plaques in EOAD and DS. Many of these proteins were more significantly enriched in amyloid plaques than Aβ. The most enriched proteins in amyloid plaques in both EOAD and DS were: COL25A1, SMOC1, MDK, NTN1, OLFML3 and HTRA1. Endosomal/lysosomal proteins were particularly highly enriched in amyloid plaques. Fluorescent immunohistochemistry was used to validate the enrichment of four proteins in amyloid plaques (moesin, ezrin, ARL8B and SMOC1) and to compare the amount of total Aβ, Aβ40, Aβ42, phosphorylated Aβ, pyroglutamate Aβ species and oligomeric species in EOAD and DS. These studies showed that phosphorylated Aβ, pyroglutamate Aβ species and SMOC1 were significantly higher in DS plaques, while oligomers were significantly higher in EOAD. Overall, we observed that amyloid plaques in EOAD and DS largely contained the same proteins, however the amount of enrichment of some proteins was different in EOAD and DS. Our study highlights the significant enrichment of many proteins in amyloid plaques, many of which may be potential therapeutic targets and/or biomarkers for AD.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Brain; Down Syndrome; Glycoproteins; High-Temperature Requirement A Serine Peptidase 1; Humans; Intercellular Signaling Peptides and Proteins; Plaque, Amyloid; Proteome; Pyrrolidonecarboxylic Acid
PubMed: 35418158
DOI: 10.1186/s40478-022-01356-1 -
BMC Plant Biology Sep 2022Sugar beet is an important crop for sugar production. Sugar beet roots are stored up to several weeks post-harvest waiting for processing in the sugar factories. During...
BACKGROUND
Sugar beet is an important crop for sugar production. Sugar beet roots are stored up to several weeks post-harvest waiting for processing in the sugar factories. During this time, sucrose loss and invert sugar accumulation decreases the final yield and processing quality. To improve storability, more information about post-harvest metabolism is required. We investigated primary and secondary metabolites of six sugar beet varieties during storage. Based on their variety-specific sucrose loss, three storage classes representing well, moderate, and bad storability were compared. Furthermore, metabolic data were visualized together with transcriptome data to identify potential mechanisms involved in the storage process.
RESULTS
We found that sugar beet varieties that performed well during storage have higher pools of 15 free amino acids which were already observable at harvest. This storage class-specific feature is visible at harvest as well as after 13 weeks of storage. The profile of most of the detected organic acids and semi-polar metabolites changed during storage. Only pyroglutamic acid and two semi-polar metabolites, including ferulic acid, show higher levels in well storable varieties before and/or after 13 weeks of storage. The combinatorial OMICs approach revealed that well storable varieties had increased downregulation of genes involved in amino acid degradation before and after 13 weeks of storage. Furthermore, we found that most of the differentially genes involved in protein degradation were downregulated in well storable varieties at both timepoints, before and after 13 weeks of storage.
CONCLUSIONS
Our results indicate that increased levels of 15 free amino acids, pyroglutamic acid and two semi-polar compounds, including ferulic acid, were associated with a better storability of sugar beet taproots. Predictive metabolic patterns were already apparent at harvest. With respect to elongated storage, we highlighted the role of free amino acids in the taproot. Using complementary transcriptomic data, we could identify potential underlying mechanisms of sugar beet storability. These include the downregulation of genes for amino acid degradation and metabolism as well as a suppressed proteolysis in the well storable varieties.
Topics: Beta vulgaris; Plant Roots; Pyrrolidonecarboxylic Acid; Sucrose; Sugars
PubMed: 36076171
DOI: 10.1186/s12870-022-03784-6 -
International Journal of Molecular... May 2021Genomic and phylogenetic analyses of various invertebrate phyla revealed the existence of genes that are evolutionarily related to the vertebrate's decapeptide... (Review)
Review
Genomic and phylogenetic analyses of various invertebrate phyla revealed the existence of genes that are evolutionarily related to the vertebrate's decapeptide gonadotropin-releasing hormone (GnRH) and the GnRH receptor genes. Upon the characterization of these gene products, encoding peptides and putative receptors, GnRH-related peptides and their G-protein coupled receptors have been identified. These include the adipokinetic hormone (AKH) and corazonin (CRZ) in insects and their cognate receptors that pair to form bioactive signaling systems, which network with additional neurotransmitters/hormones (e.g., octopamine and ecdysone). Multiple studies in the past 30 years have identified many aspects of the biology of these peptides that are similar in size to GnRH and function as neurohormones. This review briefly describes the main activities of these two neurohormones and their receptors in the fruit fly . The similarities and differences between AKH/CRZ and mammalian GnRH signaling systems are discussed. Of note, while GnRH has a key role in reproduction, AKH and CRZ show pleiotropic activities in the adult fly, primarily in metabolism and stress responses. From a protein evolution standpoint, the GnRH/AKH/CRZ family nicely demonstrates the developmental process of neuropeptide signaling systems emerging from a putative common ancestor and leading to divergent activities in distal phyla.
Topics: Amino Acid Sequence; Animals; Drosophila melanogaster; Evolution, Molecular; Gonadotropin-Releasing Hormone; Humans; Insect Hormones; Insect Proteins; Neuropeptides; Neurotransmitter Agents; Oligopeptides; Phylogeny; Pyrrolidonecarboxylic Acid; Receptors, G-Protein-Coupled; Signal Transduction
PubMed: 34068603
DOI: 10.3390/ijms22095035 -
Frontiers in Cellular and Infection... 2023Disordered gut microbiota (GM) structure and function may contribute to osteoporosis (OP). This study explores how traditional Chinese medicine (TCM) intervention... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Disordered gut microbiota (GM) structure and function may contribute to osteoporosis (OP). This study explores how traditional Chinese medicine (TCM) intervention affects the structure and function of the GM in patients with OP.
METHOD
In a 3-month clinical study, 43 patients were randomly divided into two groups receiving conventional treatment and combined TCM (Yigu decoction, YGD) treatment. The correlation between the intestinal flora and its metabolites was analyzed using 16S rDNA and untargeted metabolomics and the combination of the two.
RESULTS
After three months of treatment, patients in the treatment group had better bone mineral density (BMD) than those in the control group ( < 0.05). Patients in the treatment group had obvious abundance changes in GM microbes, such as Bacteroides, Escherichia-Shigella, Faecalibacterium, Megamonas, Blautia, Klebsiella, Romboutsia, Akkermansia, and Prevotella_9. The functional changes observed in the GM mainly involved changes in metabolic function, genetic information processing and cellular processes. The metabolites for which major changes were observed were capsazepine, Phe-Tyr, dichlorprop, D-pyroglutamic acid and tamsulosin. These metabolites may act through metabolic pathways, the citrate cycle (TCA cycle) and beta alanine metabolism. Combined analysis showed that the main acting metabolites were dichlorprop, capsazepine, D-pyroglutamic acid and tamsulosin.
CONCLUSION
This study showed that TCM influenced the structure and function of the GM in patients with OP, which may be one mechanism by which TCM promotes the rehabilitation of patients with OP through the GM.
Topics: Humans; Gastrointestinal Microbiome; Pyrrolidonecarboxylic Acid; Tamsulosin; RNA, Ribosomal, 16S
PubMed: 37475958
DOI: 10.3389/fcimb.2023.1091083 -
Journal of Assisted Reproduction and... Dec 2022Polycystic ovary syndrome is a complex heterogeneous endocrine disorder associated with established metabolic abnormalities and is a common cause of infertility in...
PURPOSE
Polycystic ovary syndrome is a complex heterogeneous endocrine disorder associated with established metabolic abnormalities and is a common cause of infertility in females. Glutathione metabolism in the cumulus cells (CCs) of women with PCOS may be correlated to the quality of oocytes for infertility treatment; therefore, we used a metabolomics approach to examine changes in CCs from women with PCOS and oocyte quality.
METHODS
Among 135 women undergoing fertility treatment in the present study, there were 43 women with PCOS and 92 without. CCs were collected from the two groups and levels of pyroglutamic acid were measured using LC-MS/MS followed by qPCR and Western blot analysis to examine genes and proteins involved in pyroglutamic acid metabolism related to glutathione synthesis.
RESULTS
Women with PCOS showed increased levels of L-pyroglutamic acid, L-glutamate, and L-phenylalanine and decreased levels of Cys-Gly and N-acetyl-L-methionine. Gene expression of OPLAH, involved in pyroglutamic synthesis, was significantly increased in women with PCOS compared with those without. Gene expression of GSS was significantly decreased in women with PCOS and synthesis of glutathione synthetase protein was decreased. Expression of nuclear factor erythroid 2-related factor 2, involved in resistance to oxidative stress, was significantly increased in women with PCOS.
CONCLUSIONS
CCs of women with PCOS showed high concentrations of pyroglutamic acid and reduced glutathione synthesis, which causes oxidative stress in CCs, suggesting that decreased glutathione synthesis due to high levels of pyroglutamic acid in CCs may be related to the quality of oocytes in women with PCOS.
Topics: Humans; Female; Polycystic Ovary Syndrome; Cumulus Cells; Pyrrolidonecarboxylic Acid; Chromatography, Liquid; Tandem Mass Spectrometry; Oocytes; Infertility; Glutathione
PubMed: 36322230
DOI: 10.1007/s10815-022-02647-1