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Genes Feb 2023Defect of , the human mitochondrial tRNA-modifying enzyme, can lead to Combined Oxidative Phosphorylation Deficiency 23 (COXPD23). Up to now, about 20 different variants...
Defect of , the human mitochondrial tRNA-modifying enzyme, can lead to Combined Oxidative Phosphorylation Deficiency 23 (COXPD23). Up to now, about 20 different variants of the gene have been reported; however, genotype-phenotype analysis has rarely been described. Here, we reported a 9-year-old boy with COXPD23 who presented with hyperlactatemia, hypertrophic cardiomyopathy, seizures, feeding difficulties, intellectual disability and motor developmental delay, and abnormal visual development. Biallelic pathogenic variants of the gene were identified in this boy, one novel variant c.1102dupC (p. Arg368Profs*22) inherited from the mother and the other known variant c.689A>C (p. Gln230Pro) inherited from father. We curated 18 COXPD23 patients with variants to investigate the genotype-phenotype correlation. We found that hyperlactatemia and cardiomyopathy were critical clinical features in COXPD23 and the average onset age was 1.7 years (3 months of age for the homozygote). Clinical classification of COXPD23 for the two types, severe and mild, was well described in this study. We observed arrhythmia and congestive heart failure frequently in the severe type with early childhood mortality, while developmental delay was mainly observed in the mild type. The proportion of homozygous variants (71.4%) significantly differed from that of compound heterozygous variants (18.1%) in the severe type. Compared with the variants in gnomAD, the proportion of LOFVs in was higher in COXPD23 patients (48.6% versus 8.9%, < 0.0001 ****), and 31% of them were frameshift variants, showing the LOF mechanism of . Additionally, the variants in patients were significantly enriched in the TrmE-type G domain, indicating that the G domain was crucial for protein function. The TrmE-type G domain contained several significant motifs involved in the binding of guanine nucleotides and Mg, the hydrolysis of GTP, and the regulation of the functional status of GTPases. In conclusion, we reported a mild COXPD23 case with typical -related symptoms, including seizures and abnormal visual development seldom observed previously. Our study provides novel insight into understanding the clinical diagnosis and genetic counseling of patients with COXPD23 by exploring the genetic pathogenesis and genotype-phenotype correlation of COXPD23.
Topics: Child; Child, Preschool; Humans; Infant; Male; GTP-Binding Proteins; Hyperlactatemia; Mitochondrial Diseases; Seizures
PubMed: 36980825
DOI: 10.3390/genes14030552 -
Children (Basel, Switzerland) Mar 2023Vitamin B6-dependent epilepsies include treatable diseases responding to pyridoxine or pyridoxal-5Iphosphate (ALDH7A1 deficiency, PNPO deficiency, PLP binding protein... (Review)
Review
BACKGROUND
Vitamin B6-dependent epilepsies include treatable diseases responding to pyridoxine or pyridoxal-5Iphosphate (ALDH7A1 deficiency, PNPO deficiency, PLP binding protein deficiency, hyperprolinemia type II and hypophosphatasia and glycosylphosphatidylinositol anchor synthesis defects).
PATIENTS AND METHODS
We conducted a systematic review of published pediatric cases with a confirmed molecular genetic diagnosis of vitamin B6-dependent epilepsy according to PRISMA guidelines. Data on demographic features, seizure semiology, EEG patterns, neuroimaging, treatment, and developmental outcomes were collected.
RESULTS
497 published patients fulfilled the inclusion criteria. Seizure onset manifested at 59.8 ± 291.6 days (67.8% of cases in the first month of life). Clonic, tonic-clonic, and myoclonic seizures accounted for two-thirds of the cases, while epileptic spasms were observed in 7.6%. Burst-suppression/suppression-burst represented the most frequently reported specific EEG pattern (14.4%), mainly in PLPB, ALDH7A1, and PNPO deficiency. Pyridoxine was administered to 312 patients (18.5% intravenously, 76.9% orally, 4.6% not specified), and 180 also received antiseizure medications. Pyridoxine dosage ranged between 1 and 55 mg/kg/die. Complete seizure freedom was achieved in 160 patients, while a significant seizure reduction occurred in 38. PLP, lysine-restricted diet, and arginine supplementation were used in a small proportion of patients with variable efficacy. Global developmental delay was established in 30.5% of a few patients in whom neurocognitive tests were performed.
CONCLUSIONS
Despite the wide variability, the most frequent hallmarks of the epilepsy phenotype in patients with vitamin B6-dependent seizures include generalized or focal motor seizure semiology and a burst suppression/suppression burst pattern in EEG.
PubMed: 36980111
DOI: 10.3390/children10030553 -
Biomolecules Feb 2023Albumin is a highly abundant plasma protein with multiple functions, including the balance of fluid between body compartments and fatty acid trafficking. Humans with... (Review)
Review
Albumin is a highly abundant plasma protein with multiple functions, including the balance of fluid between body compartments and fatty acid trafficking. Humans with congenital analbuminemia (CAA) do not express albumin due to homozygosity for albumin gene mutation. Lessons about physiological control could be learned from CAA. Remarkably, these patients exhibit an apparently normal lifespan, without substantial impairments in physical functionality. There was speculation that tolerance to albumin deficiency would be characterized by significant upregulation of other plasma proteins to compensate for analbuminemia. It is unknown but possible that changes in plasma protein expression observed in CAA are required for the well-documented survival and general wellness. A systematic review of published case reports was performed to assess plasma protein pattern remodeling in CAA patients who were free of other illnesses that would confound interpretation. From a literature search in Pubmed, Scopus, and Purdue Libraries (updated October 2022), concentration of individual plasma proteins and protein classes were assessed. Total plasma protein concentration was below the reference range in the vast majority of CAA patients in the analysis, as upregulation of other proteins was not sufficient to prevent the decline of total plasma protein when albumin was absent. Nonetheless, an impressive level of evidence in the literature indicated upregulated plasma levels of multiple globulin classes and various specific proteins which may have metabolic functions in common with albumin. The potential role of this altered plasma protein expression pattern in CAA is discussed, and the findings may have implications for other populations with hypoalbuminemia.
Topics: Humans; Hypoalbuminemia; Blood Proteins; Albumins; Mutation; Plasma
PubMed: 36979342
DOI: 10.3390/biom13030407 -
Frontiers in Cardiovascular Medicine 2022Myocardial infarction is the leading cause of death and disability worldwide, and the development of new treatments can help reduce the size of myocardial infarction and...
Myocardial infarction is the leading cause of death and disability worldwide, and the development of new treatments can help reduce the size of myocardial infarction and prevent adverse cardiovascular events. Cardiac repair after myocardial infarction can effectively remove necrotic tissue, induce neovascularization, and ultimately replace granulation tissue. Cardiac inflammation is the primary determinant of whether beneficial cardiac repair occurs after myocardial infarction. Immune cells mediate inflammatory responses and play a dual role in injury and protection during cardiac repair. After myocardial infarction, genetic ablation or blocking of anti-inflammatory pathways is often harmful. However, enhancing endogenous anti-inflammatory pathways or blocking endogenous pro-inflammatory pathways may improve cardiac repair after myocardial infarction. A deficiency of neutrophils or monocytes does not improve overall cardiac function after myocardial infarction but worsens it and aggravates cardiac fibrosis. Several factors are critical in regulating inflammatory genes and immune cells' phenotypes, including DNA methylation, histone modifications, and non-coding RNAs. Therefore, strict control and timely suppression of the inflammatory response, finding a balance between inflammatory cells, preventing excessive tissue degradation, and avoiding infarct expansion can effectively reduce the occurrence of adverse cardiovascular events after myocardial infarction. This article reviews the involvement of neutrophils, monocytes, macrophages, and regulatory T cells in cardiac repair after myocardial infarction. After myocardial infarction, neutrophils are the first to be recruited to the damaged site to engulf necrotic cell debris and secrete chemokines that enhance monocyte recruitment. Monocytes then infiltrate the infarct site and differentiate into macrophages and they release proteases and cytokines that are harmful to surviving myocardial cells in the pre-infarct period. As time progresses, apoptotic neutrophils are cleared, the recruitment of anti-inflammatory monocyte subsets, the polarization of macrophages toward the repair phenotype, and infiltration of regulatory T cells, which secrete anti-inflammatory factors that stimulate angiogenesis and granulation tissue formation for cardiac repair. We also explored how epigenetic modifications regulate the phenotype of inflammatory genes and immune cells to promote cardiac repair after myocardial infarction. This paper also elucidates the roles of alarmin S100A8/A9, secreted frizzled-related protein 1, and podoplanin in the inflammatory response and cardiac repair after myocardial infarction.
PubMed: 36698953
DOI: 10.3389/fcvm.2022.1077290 -
Italian Journal of Pediatrics Jan 2023Nutrition practices for preterm infants include phases of parenteral nutrition, gradually interrupted parenteral nutrition (transition phase), and full enteral... (Review)
Review
Nutrition practices for preterm infants include phases of parenteral nutrition, gradually interrupted parenteral nutrition (transition phase), and full enteral nutrition. However, nutrition management during the transition phase is frequently overlooked. This review examined the relationship between nutrient intake during the transition phase and preterm infant growth. PubMed, Embase, Web of Science, Cochrane, Chinese National Knowledge Infrastructure Database, Wanfang Database, and Chinese Science and Technique Journals Database were searched for studies examining the relationship between nutrient intake during the transition phase and postnatal growth of preterm infants from each database's earliest inception through February 28, 2022. The quality of the studies was assessed using the Newcastle-Ottawa scale. A total of three studies conducted in the USA, Italy and China met the inclusion criteria. The growth indicators were extrauterine growth restriction (weight < 10th percentile for post-menstrual age) or inadequate weight growth velocity (growth velocity < 15 g/kg/d) at discharge or the end of the transition phase. The transition phase was divided into two periods in two studies: the early period (parenteral energy intake > 50% of total energy intake) and the late period (enteral energy intake > 50% of the total energy intake). The cumulative protein intake in the transition phase was generally lower in preterm infants with extrauterine growth restriction or inadequate weight growth velocity, especially in the early transition phase. The deficiency of energy and protein intake during the transition phase cannot be explicitly determined due to differences in growth indicators and definitions of the transition phase. However, enteral protein intake should be closely monitored in the early transition phase to ensure a better growth rate for preterm infants. To elucidate potential associations, further well-designed research will be required.
Topics: Infant; Infant, Newborn; Humans; Infant, Premature; Nutritional Status; Enteral Nutrition; Energy Intake; Eating; Infant, Very Low Birth Weight
PubMed: 36670430
DOI: 10.1186/s13052-022-01406-3 -
International Journal of Health Policy... 2023This review was conducted to identify the impact of economic sanctions on household food and nutrition security and policies to cope with them in countries exposed to...
BACKGROUND
This review was conducted to identify the impact of economic sanctions on household food and nutrition security and policies to cope with them in countries exposed to sanctions.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines 2020 were used to identify, select, appraise, and synthesize studies. Electronic databases in addition to Persian ones have been systematically searched for all related documents published until March 2022. Exclusion criteria were: lack of data related to food insecurity in countries subject to sanction and very low quality of the article. The quality of included studies was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal checklists. The results were presented as qualitative and quantitative syntheses.
RESULTS
Of 1428 identified studies, 36 publications remained in the review, which belong to Iran (n=8), Cuba (n=8), Russia (n=7), Iraq (n=7), and Haiti (n=6), respectively. Declining gross domestic product (GDP), devaluation of the national currency, and the quality of food, increase in inflation, unemployment, and consumer prices, infant and under 5 years mortality, energy, and protein deficiency, and the poverty rate were reported as sanction consequences. The most important strategies to improve food security were the humanitarian assistance provided by the international community (Haiti), equity and priority for vulnerable groups mainly by expanding the healthcare system (Cuba), adopting a food ration system in the oil-for-food program, and fixing the price of food baskets (Iraq), import substitution and self-sufficiency (Russia), support domestic production, direct and indirect support and compensation packages for vulnerable households (the approach of resistance economy in Iran).
CONCLUSION
Due to the heterogeneity of studies, meta-analysis was not possible. Since inadequate physical and economic food access caused by sanctions affects especially disadvantaged and vulnerable groups, planning to improve food security and providing support packages for these groups seems necessary.
Topics: Infant; Humans; Gross Domestic Product; Policy; Academies and Institutes; Checklist; Cuba
PubMed: 38618825
DOI: 10.34172/ijhpm.2023.7362 -
The Cochrane Database of Systematic... Nov 2022Chronic arthropathy is a potentially debilitating complication for people with haemophilia - a genetic, X-linked, recessive bleeding disorder, characterised by the... (Review)
Review
BACKGROUND
Chronic arthropathy is a potentially debilitating complication for people with haemophilia - a genetic, X-linked, recessive bleeding disorder, characterised by the absence or deficiency of a clotting factor protein. Staging classifications, such as the Arnold-Hilgartner classification for haemophilic arthropathy of the knee, radiologically reflect the extent of knee joint destruction with underlying chronic synovitis. Management of this highly morbid disease process involves intensive prophylactic measures, and chemical or radioisotope synovectomy in its early stages. However, failure of non-surgical therapy in people with progression of chronic arthropathy often prompts surgical management, including synovectomy, joint debridement, arthrodesis, and arthroplasty, depending on the type of joint and extent of the damage. To date, management of people with mild to moderate chronic arthropathy from haemophilia remains controversial; there is no agreed standard treatment. Thus, the benefits and disadvantages of non-surgical and surgical management of mild to moderate chronic arthropathy in people with haemophilia needs to be systematically reviewed. OBJECTIVES: To assess the efficacy and safety of surgery for mild to moderate chronic arthropathy in people with haemophilia A or B.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register, CENTRAL, MEDLINE, Embase, CINAHL, and two trial registers to August 2022. We also handsearched relevant journals and conference abstract books.
SELECTION CRITERIA
Randomized controlled trials (RCTs) and quasi-RCTs comparing surgery and non-surgical interventions, for any joint with chronic arthropathy, in people with haemophilia, who were at least 12 years old.
DATA COLLECTION AND ANALYSIS
The review authors did not identify any trials to include in this review.
MAIN RESULTS
The review authors did not identify any trials to include in this review.
AUTHORS' CONCLUSIONS
The review authors did not identify any trials to include in this review. Due to a lack of research in this particular area, we plan to update the literature search every two years, and will update review if any new evidence is reported. There is a need for a well-designed RCT that assesses the safety and efficacy of surgical versus non-surgical interventions for chronic arthropathy in people with haemophilia.
Topics: Child; Humans; Hemophilia A; Joint Diseases; Knee Joint; MEDLINE; Randomized Controlled Trials as Topic
PubMed: 36448638
DOI: 10.1002/14651858.CD013634.pub2 -
World Journal of Surgical Oncology Nov 2022Many studies have reported the relationship between prognosis and Slug protein expression in breast cancer patients, but the results are discrepant. Therefore, there is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Many studies have reported the relationship between prognosis and Slug protein expression in breast cancer patients, but the results are discrepant. Therefore, there is a need for meta-analyses with high statistical power to investigate and further explore their relationship.
METHODS
We used PubMed, Embase, the Cochrane Library, Scopus, MEDLINE, and the Web of Science to find studies on breast cancer and Slug. Overall survival (OS) and disease-free survival (DFS) were the study's primary endpoints. We pooled hazard ratios (HRs) and odds ratios (ORs) to assess the association between Slug protein expression and prognostic and clinicopathological parameters. This study was performed using STATA version 14.0 for data analysis. (Stata Corporation, TX, USA).
RESULTS
We conducted a literature search by searching six online databases. Ultimately, we obtained eight studies including 1458 patients through strict exclusion criteria. The results showed that increased Slug protein expression resulted in poorer OS (HR = 2.21; 95% CI = 1.47-3.33; P < 0.001) and DFS (HR = 2.03; 95% CI = 1.26-3.28; P = 0.004) in breast cancer patients. In addition, the results suggested that breast cancer patients with increased Slug protein expression had a higher TNM stage (I-II vs III-IV; OR = 0.42; 95% CI = 0.25-0.70; P = 0.001), a greater tendency to have axillary lymph node metastases (N+ vs N0; OR = 2.16; 95% CI = 1.31-3.56; P = 0.003) and were more prone to estrogen receptor deficiency (positive vs negative; OR = 0.67; 95% CI = 0.45-0.99; P = 0.042). However, Slug protein expression was not associated with age, histological grade, tumor size, progesterone receptor status, or human epidermal growth factor receptor 2 status in breast cancer patients.
CONCLUSION
This meta-analysis showed that elevated Slug protein expression may be related to poor outcomes in patients with breast cancer. Therefore, Slug is not only an indicator of patient survival but may also become a new target for breast cancer therapy.
Topics: Humans; Female; Prognosis; Breast Neoplasms; Disease-Free Survival; Lymphatic Metastasis; Receptors, Estrogen
PubMed: 36372891
DOI: 10.1186/s12957-022-02825-6 -
BMC Pregnancy and Childbirth Nov 2022Vitamin D deficiency, a common problem among pregnant women, is linked with maternal inflammation, oxidative stress and consequent adverse pregnancy outcomes. The aim of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vitamin D deficiency, a common problem among pregnant women, is linked with maternal inflammation, oxidative stress and consequent adverse pregnancy outcomes. The aim of this systematic review was to evaluate the effect of vitamin D supplementation on oxidative stress and inflammatory biomarkers in pregnant women according to the PRISMA guidance.
METHODS
Four databases including PubMed/MEDLINE, Scopus, Web of Science and Cochrane were used for searching papers published until 25 July 2022. Clinical trials that assessed 25-Hydroxyvitamin D (25(OH)D), inflammatory markers (including high sensitivity C-reactive protein (hs-CRP) and certain cytokines) and oxidative stress markers (including malondialdehyde (MDA), total antioxidant capacity (TAC) and glutathione (GSH)) in pregnant women, were included in this review. The primary search of three databases displayed 21571 records. After removing duplicates and irrelevant articles, 17 eligible RCTs included for more evaluation. Random effect model and Der Simonian-Laird method were used to pool the data of studies. Risk of bias assessed according to version 2 of the Cochrane risk-of-bias tool for randomized trials.
RESULTS
According to the meta-analysis result, vitamin D supplementation caused a significant increase in the maternal circulating concentrations of 25(OH)D (SMD 2.07; 95%, CI 1.51, 2.63; p < 0.001), TAC (SMD 2.13, 95% CI 1.04 to 3.23, p < 0.001) and GSH (SMD 4.37, 95% CI 2.9 to 5.74, p < 0.001) as well as a significant decrease in the levels of MDA (SMD -0.46, 95% CI -0.87 to -0.05, p = 0.02). However, it had no significant impact on hs-CRP concentrations (SMD 0.24; 95% CI, -0.55, 1.03; p = 0.50).
CONCLUSION
In the present study, vitamin D supplementation led to increased levels of 25(OH)D, TAC and GSH and also decreased concentration of MDA. Nevertheless, because of low certainty of evidence, these findings have to be declared conservatively.
TRIAL REGISTRATION
Registration code in PROSPERO website: CRD42020202600.
Topics: Female; Pregnancy; Humans; C-Reactive Protein; Dietary Supplements; Pregnant Women; Oxidative Stress; Biomarkers; Vitamin D; Antioxidants
PubMed: 36335311
DOI: 10.1186/s12884-022-05132-w -
Nutricion Hospitalaria Dec 2022Previous studies have pointed to a possible relationship between vitamin D deficiency and the severity of the disease promoted by SARS-CoV-2, reducing respiratory and...
Previous studies have pointed to a possible relationship between vitamin D deficiency and the severity of the disease promoted by SARS-CoV-2, reducing respiratory and cardiovascular complications caused by a hyperreaction of the immune system known as "cytokine storm". This vitamin exerts multiple functions that depend on the presence and levels of different proteins, such as the vitamin D receptor (VDR) and the vitamin D binding protein (DBP), and the existence of single nucleotide polymorphisms (SNPs) of the genes that encode these proteins. The objective of this review is to assess whether some VDR and GC SNPs are risk factors for the most severe forms of COVID-19 disease and whether they condition the response to vitamin D supplementation. A search was performed in PubMed, Google Scholar and Scielo, finding that genotypes in patients affected by COVID-19, were rarely performed, although some studies find a relationship between different alleles and the severity of the disease. The ApaI polymorphism of the VDR gene stands out, as the minor allele "a" increases the risk of mortality from COVID-19 (OR = 11.828, CI: 2,493-56,104, p = 0.002). Results divergency in the efficacy of vitamin D supplementation suggest the need for a larger number of studies. In conclusion, the study of VDR and GC polymorphisms seems essential to effectively treat vitamin D deficiency and particularly to protect against COVID-19. Well-designed studies are needed to elucidate whether plasma vitamin D levels play a role of casuality or causality.
Topics: Humans; COVID-19; Genotype; Polymorphism, Single Nucleotide; Receptors, Calcitriol; SARS-CoV-2; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein
PubMed: 36327123
DOI: 10.20960/nh.04299