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PLoS Medicine Nov 2016Women are commonly prescribed a variety of medications during pregnancy. As most organ systems are affected by the substantial anatomical and physiological changes that... (Review)
Review
BACKGROUND
Women are commonly prescribed a variety of medications during pregnancy. As most organ systems are affected by the substantial anatomical and physiological changes that occur during pregnancy, it is expected that pharmacokinetics (PK) (absorption, distribution, metabolism, and excretion of drugs) would also be affected in ways that may necessitate changes in dosing schedules. The objective of this study was to systematically identify existing clinically relevant evidence on PK changes during pregnancy.
METHODS AND FINDINGS
Systematic searches were conducted in MEDLINE (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (Ovid), and Web of Science (Thomson Reuters), from database inception to August 31, 2015. An update of the search from September 1, 2015, to May 20, 2016, was performed, and relevant data were added to the present review. No language or date restrictions were applied. All publications of clinical PK studies involving a group of pregnant women with a comparison to nonpregnant participants or nonpregnant population data were eligible to be included in this review. A total of 198 studies involving 121 different medications fulfilled the inclusion criteria. In these studies, commonly investigated drug classes included antiretrovirals (54 studies), antiepileptic drugs (27 studies), antibiotics (23 studies), antimalarial drugs (22 studies), and cardiovascular drugs (17 studies). Overall, pregnancy-associated changes in PK parameters were often observed as consistent findings among many studies, particularly enhanced drug elimination and decreased exposure to total drugs (bound and unbound to plasma proteins) at a given dose. However, associated alterations in clinical responses and outcomes, or lack thereof, remain largely unknown.
CONCLUSION
This systematic review of pregnancy-associated PK changes identifies a significant gap between the accumulating knowledge of PK changes in pregnant women and our understanding of their clinical impact for both mother and fetus. It is essential for clinicians to be aware of these unique pregnancy-related changes in PK, and to critically examine their clinical implications.
Topics: Female; Humans; Pharmaceutical Preparations; Pharmacokinetics; Pregnancy
PubMed: 27802281
DOI: 10.1371/journal.pmed.1002160 -
Signal Transduction and Targeted Therapy Feb 2021The abnormal regulation of alternative splicing is usually accompanied by the occurrence and development of tumors, which would produce multiple different isoforms and...
The abnormal regulation of alternative splicing is usually accompanied by the occurrence and development of tumors, which would produce multiple different isoforms and diversify protein expression. The aim of the present study was to conduct a systematic review in order to describe the regulatory mechanisms of alternative splicing, as well as its functions in tumor cells, from proliferation and apoptosis to invasion and metastasis, and from angiogenesis to metabolism. The abnormal splicing events contributed to tumor progression as oncogenic drivers and/or bystander factors. The alterations in splicing factors detected in tumors and other mis-splicing events (i.e., long non-coding and circular RNAs) in tumorigenesis were also included. The findings of recent therapeutic approaches targeting splicing catalysis and splicing regulatory proteins to modulate pathogenically spliced events (including tumor-specific neo-antigens for cancer immunotherapy) were introduced. The emerging RNA-based strategies for the treatment of cancer with abnormally alternative splicing isoforms were also discussed. However, further studies are still required to address the association between alternative splicing and cancer in more detail.
Topics: Alternative Splicing; Carcinogenesis; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; RNA Splicing; RNA Splicing Factors; RNA, Circular
PubMed: 33623018
DOI: 10.1038/s41392-021-00486-7 -
International Journal of Molecular... Aug 2022Background: Glioblastoma (GBM) is a highly aggressive cancer with poor prognosis that needs better treatment modalities. Moreover, there is a lack of reliable biomarkers... (Meta-Analysis)
Meta-Analysis Review
Background: Glioblastoma (GBM) is a highly aggressive cancer with poor prognosis that needs better treatment modalities. Moreover, there is a lack of reliable biomarkers to predict the response and outcome of current or newly designed therapies. While several molecular markers have been proposed as potential biomarkers for GBM, their uptake into clinical settings is slow and impeded by marker heterogeneity. Detailed assessment of prognostic and predictive value for biomarkers in well-defined clinical trial settings, if available, is scattered throughout the literature. Here we conducted a systematic review and meta-analysis to evaluate the prognostic and predictive significance of clinically relevant molecular biomarkers in GBM patients. Material and methods: A comprehensive literature search was conducted to retrieve publications from 3 databases (Pubmed, Cochrane and Embase) from January 2010 to December 2021, using specific terms. The combined hazard ratios (HR) and confidence intervals (95% CI) were used to evaluate the association of biomarkers with overall survival (OS) in GBM patients. Results: Twenty-six out of 1831 screened articles were included in this review. Nineteen articles were included in the meta-analyses, and 7 articles were quantitatively summarised. Fourteen studies with 1231 GBM patients showed a significant association of MGMT methylation with better OS with the pooled HR of 1.66 (95% CI 1.32−2.09, p < 0.0001, random effect). Five studies including 541 GBM patients analysed for the prognostic significance of IDH1 mutation showed significantly better OS in patients with IDH1 mutation with a pooled HR of 2.37 (95% CI 1.81−3.12; p < 0.00001]. Meta-analysis performed on 5 studies including 575 GBM patients presenting with either amplification or high expression of EGFR gene did not reveal any prognostic significance with a pooled HR of 1.31 (95% CI 0.96−1.79; p = 0.08). Conclusions: MGMT promoter methylation and IDH1 mutation are significantly associated with better OS in GBM patients. No significant associations were found between EGFR amplification or overexpression with OS.
Topics: Biomarkers; Biomarkers, Tumor; Brain Neoplasms; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Glioblastoma; Humans; Tumor Suppressor Proteins
PubMed: 36012105
DOI: 10.3390/ijms23168835 -
Fertility and Sterility Aug 2022To identify the most robust molecular biomarkers in sperm and seminal plasma for the diagnosis of male infertility, and to evaluate their clinical use. (Review)
Review
OBJECTIVE
To identify the most robust molecular biomarkers in sperm and seminal plasma for the diagnosis of male infertility, and to evaluate their clinical use.
DESIGN
Systematic review.
SETTING
Not applicable.
PATIENT(S)
Accessible studies reporting well-defined (in)fertile populations and semen molecular biomarkers were included in this review.
INTERVENTION(S)
A systematic search of the literature published in MEDLINE-PubMed and EMBASE databases was performed, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
MAIN OUTCOME MEASURE(S)
The primary outcome was the content, expression, or activity of molecular biomarkers in human semen samples. Only studies reporting a receiver-operating characteristic (ROC) analysis values were included.
RESULT(S)
Eighty-nine studies were included. Direct evaluation of sperm DNA damage has high potential as a diagnostic biomarker of fertility and assisted reproductive technology outcomes (area under the curve [AUCs] median = 0.67). Regarding strand break-associated chromatin modifications, γH2AX levels show good predictive value for the diagnosis of male infertility (AUCs median = 0.93). Some noncoding ribonucleic acid (RNA) exhibit excellent predictive values; miR-34c-5p in semen is the most well-characterized and robust transcriptomic biomarker (AUCs median = 0.78). While many proteins in semen show fair diagnostic value for sperm quality and fertilizing capacity, the levels of some, such as TEX101, in seminal plasma have an excellent diagnostic potential (AUCs median = 0.69). Although individual metabolites and metabolomic profiles in seminal plasma present good predictive value, the latter seem to be better than the former when inferring sperm quality and fertilizing capacity.
CONCLUSION(S)
The current review supports that some Omics (e.g., DNA structure and integrity, genomics and epigenomics, transcriptomics, metabolomics, and proteomics) could be considered relevant molecular biomarkers that may help identify infertility etiologies and fertilization prognosis with cost-effective, simple, and accurate diagnosis.
Topics: Biomarkers; Fertility; Humans; Infertility, Male; Male; Semen; Semen Analysis; Spermatozoa
PubMed: 35718545
DOI: 10.1016/j.fertnstert.2022.04.028 -
Cell Death & Disease Feb 2023Sepsis is a life-threatening disorder disease defined as infection-induced dysregulated immune responses and multiple organ dysfunction. The imbalance between... (Review)
Review
Sepsis is a life-threatening disorder disease defined as infection-induced dysregulated immune responses and multiple organ dysfunction. The imbalance between hyperinflammation and immunosuppression is a crucial feature of sepsis immunity. Epigenetic modifications, including histone modifications, DNA methylation, chromatin remodeling, and non-coding RNA, play essential roles in regulating sepsis immunity through epi-information independent of the DNA sequence. In recent years, the mechanisms of histone modification in sepsis have received increasing attention, with ongoing discoveries of novel types of histone modifications. Due to the capacity for prolonged effects on immune cells, histone modifications can induce immune cell reprogramming and participate in the long-term immunosuppressed state of sepsis. Herein, we systematically review current mechanisms of histone modifications involved in the regulation of sepsis, summarize their role in sepsis from an immune perspective and provide potential therapeutic opportunities targeting histone modifications in sepsis treatment.
Topics: Humans; Histones; Histone Code; Epigenesis, Genetic; Sepsis; DNA Methylation
PubMed: 36774341
DOI: 10.1038/s41419-023-05656-9 -
Nutrients Sep 2019Whey protein (WP) is a dairy food supplement and, due to its effects on fat-free mass (FFM) gain and fat mass (FM) loss, it has been widely consumed by resistance... (Meta-Analysis)
Meta-Analysis
Whey protein (WP) is a dairy food supplement and, due to its effects on fat-free mass (FFM) gain and fat mass (FM) loss, it has been widely consumed by resistance training practitioners. This review analyzed the impact of WP supplementation in its concentrated (WPC), hydrolyzed (WPH) and isolated (WPI) forms, comparing it exclusively to isocaloric placebos. Random effect meta-analyses were performed from the final and initial body composition values of 246 healthy athletes undergoing 64.5 ± 15.3 days of training in eight randomized clinical trials (RCT) collected systematically from five scientific databases. The weighted mean difference (WMD) was statistically significant for FM loss (WMD = -0.96, 95% CI = -1.37, -0.55, < 0.001) and, in the analysis of subgroups, this effect was maintained for the WPC (WMD = -0.63, 95% CI = -1.19, -0.06, = 0.030), with protein content between 51% and 80% (WMD = -1.53; 95% CI = -2.13, -0.93, < 0.001), and only for regular physical activity practitioners (WMD = -0.95; 95% CI = -1.70, -0.19, = 0.014). There was no significant effect on FFM in any of the scenarios investigated ( > 0.05). Due to several and important limitations, more detailed analyses are required regarding FFM gain.
Topics: Athletes; Body Composition; Dietary Supplements; Humans; Whey Proteins
PubMed: 31480653
DOI: 10.3390/nu11092047 -
International Archives of Allergy and... 2023Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food-induced hypersensitivity disorder that occurs mostly in infants. Long... (Meta-Analysis)
Meta-Analysis
Food protein-induced enterocolitis syndrome (FPIES) is a non-IgE-mediated gastrointestinal food-induced hypersensitivity disorder that occurs mostly in infants. Long considered a rare disease, a recent increase in physician awareness and publication of diagnosis of guidelines has resulted in an increase in recognized FPIES cases. We aimed to conduct a systematic review of FPIES studies in the past 10 years. A search was conducted on PubMed and Embase in March 2022. Our systematic review focused on 2 domains: (1) the most reported FPIES food triggers; and (2) the resolution rate and median age at resolution of patients with FPIES. We found that cow's milk was the most reported trigger globally. Patterns of the most common triggers varied by country, with fish being one of the most common triggers in the Mediterranean region. We also found that the rate and median age of resolution varied by trigger. Patients with FPIES to cow's milk acquired tolerance at a younger age (most by age 3 years), while fish-FPIES was more persistent (mean resolution by age 37 months-7 years). Overall, many studies found a resolution rate of 60% for any food.
Topics: Female; Animals; Cattle; Food Hypersensitivity; Milk; Enterocolitis; Allergens; Syndrome; Dietary Proteins
PubMed: 36882041
DOI: 10.1159/000529138 -
The Journal of Nutrition Jun 2020Increased protein intake has been suggested to improve gains in muscle mass and strength in adults. Furthermore, the timing of protein intake has been discussed as a... (Meta-Analysis)
Meta-Analysis
The Role of Protein Intake and its Timing on Body Composition and Muscle Function in Healthy Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
BACKGROUND
Increased protein intake has been suggested to improve gains in muscle mass and strength in adults. Furthermore, the timing of protein intake has been discussed as a margin of opportunity for improved prevention measures.
OBJECTIVE
This systematic review investigated the effect of protein supplementation on body composition and muscle function (strength and synthesis) in healthy adults, with an emphasis on the timing of protein intake.
METHODS
Randomized controlled trials were identified using PubMed, Web of Science, CINAHL, and Embase, up to March 2019. For meta-analyses, data on lean body mass (LBM), handgrip strength, and leg press strength were pooled by age group (mean age 18-55 or >55 y) and timing of protein intake. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations approach.
RESULTS
Data from 65 studies with 2907 participants (1514 men and 1380 women, 13 unknown sex) were included in the review. Twenty-six, 8, and 24 studies were used for meta-analysis on LBM, handgrip strength, and leg press strength, respectively. The protein supplementation was effective in improving (mean difference; 95% CI) LBM in adults (0.62 kg; 0.36, 0.88) and older adults (0.46 kg; 0.23, 0.70), but not handgrip strength (older adults: 0.26 kg; -0.51, 1.04) and leg press strength (adults: 5.80 kg; -0.33, 11.93; older adults: 1.97 kg; -2.78, 6.72). Sensitivity analyses removing studies without exercise training had no impact on the outcomes. Data regarding muscle synthesis were scarce and inconclusive. Subgroup analyses showed no beneficial effect of a specific timing of protein intake on LBM, handgrip strength, and leg press strength.
CONCLUSION
Overall, the results support the positive impact of protein supplementation on LBM of adults and older adults, independently of intake timing. Effects on muscle strength and synthesis are less clear and need further investigation. This systematic review was registered on PROSPERO as CRD42019126742.
Topics: Adolescent; Adult; Body Composition; Dietary Proteins; Female; Humans; Male; Middle Aged; Muscle, Skeletal; Randomized Controlled Trials as Topic; Resistance Training; Young Adult
PubMed: 32232404
DOI: 10.1093/jn/nxaa049 -
Vaccine Oct 2022Despite literature's evidence about COVID-19 vaccines' safety, concerns have arisen regarding adverse events, including the possible impact on fertility, accentuated by... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Despite literature's evidence about COVID-19 vaccines' safety, concerns have arisen regarding adverse events, including the possible impact on fertility, accentuated by misinformation and anti-vaccine campaigns. The present study aims to answer the question: Is there any impact of COVID-19 vaccines on the fertility of men and women of reproductive age?
METHODS
PubMed, Scopus, Web of Science, Cochrane and Embase databases were searched for eligible studies until June 8th, 2022. The search was restricted to articles regarding humans, published in any languages, without additional restrictions. Studies' quality was assessed by the Newcastle-Ottawa and the Before and After Quality Assessment scales for cohort and pre-post studies, respectively. Random-effect meta-analyses were performed for parameters considered in ≥ 2 studies, calculating means, p-values and 95 % Confidence Intervals (CIs).
RESULTS
Out of 1406 studies screened, 29 were included in the systematic review. These studies, conducted in Israel (34.5 %), USA (24.1 %), Russia (20.7 %) China (10.3 %), Italy (3.5 %), North America (3.5%) and Turkey (3.5 %) were of poor (34.5 %), moderate (58.6 %) and good (6.9 %) quality. Meta-analyses were performed for pre- and post-vaccination sperm progressive motility (44 %, 95 % CI 42 %-62 % vs 43 %, 95 % CI 31 %-59 % p = 0.07) and concentration (50.6 mln/ml, 95 % CI 35.1-72.8 vs 55.4 mln/ml, 95 % CI 37.4-82.2p = 0.12). Biochemical (0.51, 95 % CI 0.40-0.66 vs 0.60, 95 % CI 0.53-0.68p = 0.45) and clinical (0.45, 95 % CI 0.37-0.54 vs 0.47, 95 % CI 0.40-0.55 p = 0.31) pregnancy rate did not differ among vaccinated and not vaccinated groups. Subgroup meta-analyses based on the type of vaccine showed no significant difference: between vaccinated with mRNA vaccines and non-vaccinated regarding biochemical pregnancy rates; pre- and post-vaccination with Gam-COVID-Vac regarding testosterone, FSH and LH levels; pre- and post-vaccination with BNT162b2 vaccines regarding sperm volumes.
CONCLUSION
Based on the studies published so far, there is no scientific proof of any association between COVID-19 vaccines and fertility impairment in men or women.
Topics: BNT162 Vaccine; COVID-19; COVID-19 Vaccines; Female; Fertility; Follicle Stimulating Hormone; Humans; Male; Pregnancy; Semen; Testosterone
PubMed: 36137903
DOI: 10.1016/j.vaccine.2022.09.019 -
Nutrients May 2023Breast milk is tailored for optimal growth in all infants; however, in some infants, it is related to a unique phenomenon referred to as breast milk jaundice (BMJ). BMJ... (Review)
Review
Breast milk is tailored for optimal growth in all infants; however, in some infants, it is related to a unique phenomenon referred to as breast milk jaundice (BMJ). BMJ is a type of prolonged unconjugated hyperbilirubinemia that is often late onset in otherwise healthy-appearing newborns, and its occurrence might be related to breast milk itself. This review aims to systematically evaluate evidence regarding breast milk composition and the development of BMJ in healthy neonates. PubMed, Scopus and Embase were searched up to 13 February 2023 with key search terms, including neonates, hyperbilirubinemia, and breastfeeding. A total of 678 unique studies were identified and 12 were ultimately included in the systematic review with narrative synthesis. These included studies covered both nutritional compositions (e.g., fats and proteins) and bioactive factors (e.g., enzymes and growth factors) of breast milk and formally assessed the difference in the concentration (or presence) of various endogenous components of breast milk collected from mothers of BMJ infants and healthy infants. The results were inconsistent and inconclusive for most of the substances of interest, and there was only a single study available (e.g., total energy and mineral content, bile salts and cytokines); conflicting or even contradictory results arose when there were two or more studies on the subject matter (e.g., fats and free fatty acids contents and epidermal growth factor). The etiology of BMJ is likely multifactorial, and no single constituent of breast milk could explain all the BMJ cases observed. Further well-designed studies are warranted to investigate the complex interaction between maternal physiology, the breast milk system and infant physiology before this field could be progressed to uncover the etiology of BMJ.
Topics: Infant; Female; Humans; Infant, Newborn; Milk, Human; Bilirubin; Jaundice, Neonatal; Breast Feeding; Hyperbilirubinemia; Jaundice
PubMed: 37242142
DOI: 10.3390/nu15102261