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Scientific Reports May 2024Repair and reconstruction of the myopectineal orifice area using meshes is the mainstay of surgical treatment of inguinal hernias. However, the limitations of existing...
Repair and reconstruction of the myopectineal orifice area using meshes is the mainstay of surgical treatment of inguinal hernias. However, the limitations of existing meshes are becoming increasingly evident in clinical applications; thus, the idea of using three-dimensionally (3D)-printed biological meshes was put forward. According to the current level of the 3D printing technology and the inherent characteristics of biological materials, the direct use of the 3D printing technology for making biological materials into finished products suitable for clinical applications is not yet supported, but synthetic materials can be first printed into 3D form carriers, compounded with biological materials, and finally made into finished products. The purpose of this study was to develop a technical protocol for making 3D-printed biomesh carriers using polyurethane as a raw material. In our study: raw material, polyurethane; weight, 20-30 g/m; weaving method, hexagonal mesh; elastic tension aspect ratio, 2:1; diameters of pores, 0.1-1 mm; surface area, 8 × 12 cm; the optimal printing layer height, temperature and velocity were 0.1 mm, 210-220 °C and 60 mm/s. Its clinical significance lies in: (1) applied to preoperative planning and design a detailed surgical plan; (2) applied to special types of surgery including patients in puberty, recurrent and compound inguinal hernias; (3) significantly improve the efficiency of doctor-patient communication; (4) it can shorten the operation and recovery period by about 1/3 and can save about 1/4 of the cost for patients; (5) the learning curve is significantly shortened, which is conducive to the cultivation of reserve talents.
Topics: Printing, Three-Dimensional; Polyurethanes; Surgical Mesh; Humans; Hernia, Inguinal; Biocompatible Materials; Herniorrhaphy; Materials Testing
PubMed: 38806559
DOI: 10.1038/s41598-024-63000-3 -
Genome Medicine May 2024The role of metabolism in the variation of age at menarche (AAM) and age at natural menopause (ANM) in the female population is not entirely known. We aimed to...
BACKGROUND
The role of metabolism in the variation of age at menarche (AAM) and age at natural menopause (ANM) in the female population is not entirely known. We aimed to investigate the causal role of circulating metabolites in AAM and ANM using Mendelian randomization (MR).
METHODS
We combined MR with genetic colocalization to investigate potential causal associations between 658 metabolites and AAM and between 684 metabolites and ANM. We extracted genetic instruments for our exposures from four genome-wide association studies (GWAS) on circulating metabolites and queried the effects of these variants on the outcomes in two large GWAS from the ReproGen consortium. Additionally, we assessed the mediating role of the body mass index (BMI) in these associations, identified metabolic pathways implicated in AAM and ANM, and sought validation for selected metabolites in the Avon Longitudinal Study of Parents and Children (ALSPAC).
RESULTS
Our analysis identified 10 candidate metabolites for AAM, but none of them colocalized with AAM. For ANM, 76 metabolites were prioritized (FDR-adjusted MR P-value ≤ 0.05), with 17 colocalizing, primarily in the glycerophosphocholines class, including the omega-3 fatty acid and phosphatidylcholine (PC) categories. Pathway analyses and validation in ALSPAC mothers also highlighted the role of omega and polyunsaturated fatty acids levels in delaying age at menopause.
CONCLUSIONS
Our study suggests that metabolites from the glycerophosphocholine and fatty acid families play a causal role in the timing of both menarche and menopause. This underscores the significance of specific metabolic pathways in the biology of female reproductive longevity.
Topics: Humans; Menarche; Mendelian Randomization Analysis; Female; Menopause; Metabolome; Genome-Wide Association Study; Age Factors; Metabolomics; Body Mass Index
PubMed: 38802955
DOI: 10.1186/s13073-024-01322-7 -
A causal examination of the correlation between hormonal and reproductive factors and low back pain.Frontiers in Endocrinology 2024The relationship between hormonal fluctuations in the reproductive system and the occurrence of low back pain (LBP) has been widely observed. However, the causal impact...
BACKGROUND
The relationship between hormonal fluctuations in the reproductive system and the occurrence of low back pain (LBP) has been widely observed. However, the causal impact of specific variables that may be indicative of hormonal and reproductive factors, such as age at menopause (ANM), age at menarche (AAM), length of menstrual cycle (LMC), age at first birth (AFB), age at last live birth (ALB) and age first had sexual intercourse (AFS) on low back pain remains unclear.
METHODS
This study employed Bidirectional Mendelian randomization (MR) using publicly available summary statistics from Genome Wide Association Studies (GWAS) and FinnGen Consortium to investigate the causal links between hormonal and reproductive factors on LBP. Various MR methodologies, including inverse-variance weighted (IVW), MR-Egger regression, and weighted median, were utilized. Sensitivity analysis was conducted to ensure the robustness and validity of the findings. Subsequently, Multivariate Mendelian randomization (MVMR) was employed to assess the direct causal impact of reproductive and hormone factors on the risk of LBP.
RESULTS
After implementing the Bonferroni correction and conducting rigorous quality control, the results from MR indicated a noteworthy association between a decreased risk of LBP and AAM (OR=0.784, 95% CI: 0.689-0.891; p=3.53E-04), AFB (OR=0.558, 95% CI: 0.436-0.715; p=8.97E-06), ALB (OR=0.396, 95% CI: 0.226-0.692; p=0.002), and AFS (OR=0.602, 95% CI: 0.518-0.700; p=3.47E-10). Moreover, in the reverse MR analysis, we observed no significant causal effects of LBP on ANM, AAM, LMC and AFS. MVMR analysis demonstrated the continued significance of the causal effect of AFB on LBP after adjusting for BMI.
CONCLUSION
Our study explored the causal relationship between ANM, AAM, LMC, AFB, AFS, ALB and the prevalence of LBP. We found that early menarche, early age at first birth, early age at last live birth and early age first had sexual intercourse may decrease the risk of LBP. These insights enhance our understanding of LBP risk factors, offering valuable guidance for screening, prevention, and treatment strategies for at-risk women.
Topics: Humans; Low Back Pain; Female; Mendelian Randomization Analysis; Genome-Wide Association Study; Menarche; Menopause; Risk Factors; Adult; Menstrual Cycle; Age Factors; Middle Aged
PubMed: 38800490
DOI: 10.3389/fendo.2024.1326761 -
BioRxiv : the Preprint Server For... May 2024The human genome contains 24 -like capsid genes derived from deactivated retrotransposons conserved among eutherians. Although some of their encoded proteins retain the...
The human genome contains 24 -like capsid genes derived from deactivated retrotransposons conserved among eutherians. Although some of their encoded proteins retain the ability to form capsids and even transfer cargo, their fitness benefit has remained elusive. Here we show that the -like genes and support reproductive capacity. Six-week-old mice lacking either or are indistinguishable from wild-type littermates, but by six months the mutant mice become prematurely subfertile, with precipitous drops in sex hormone levels, gonadal atrophy, and abdominal obesity; overall they produce markedly fewer offspring than controls. Analysis of donated human ovaries shows that expression of both genes declines normally with aging, while several and variants identified in genome-wide association studies are causally associated with low testosterone, altered puberty onset, or obesity. These findings expand our understanding of factors that maintain human reproductive health and lend insight into the domestication of retrotransposon-derived genes.
PubMed: 38798495
DOI: 10.1101/2024.05.11.592987 -
Aging Cell May 2024Recent studies have demonstrated the remarkable potential of early life intervention strategies at influencing the course of postnatal development, thereby offering...
Recent studies have demonstrated the remarkable potential of early life intervention strategies at influencing the course of postnatal development, thereby offering exciting possibilities for enhancing longevity and improving overall health. Metformin (MF), an FDA-approved medication for type II diabetes mellitus, has recently gained attention for its promising anti-aging properties, acting as a calorie restriction mimetic, and delaying precocious puberty. Additionally, trodusquemine (MSI-1436), an investigational drug, has been shown to combat obesity and metabolic disorders by inhibiting the enzyme protein tyrosine phosphatase 1b (Ptp1b), consequently reducing hepatic lipogenesis and counteracting insulin and leptin resistance. In this study, we aimed to further explore the effects of these compounds on young, developing mice to uncover biomolecular signatures that are central to liver metabolic processes. We found that MSI-1436 more potently alters mRNA and miRNA expression in the liver compared with MF, with bioinformatic analysis suggesting that cohorts of differentially expressed miRNAs inhibit the action of phosphoinositide 3-kinase (Pi3k), protein kinase B (Akt), and mammalian target of rapamycin (Mtor) to regulate the downstream processes of de novo lipogenesis, fatty acid oxidation, very-low-density lipoprotein transport, and cholesterol biosynthesis and efflux. In summary, our study demonstrates that administering these compounds during the postnatal window metabolically reprograms the liver through induction of potent epigenetic changes in the transcriptome, potentially forestalling the onset of age-related diseases and enhancing longevity. Future studies are necessary to determine the impacts on lifespan and overall quality of life.
PubMed: 38798180
DOI: 10.1111/acel.14227 -
Archives of Pathology & Laboratory... May 2024Interpretation of alkaline phosphatase (ALP) activity is essential for the diagnosis of certain diseases. ALP changes during life and may vary between different...
CONTEXT.—
Interpretation of alkaline phosphatase (ALP) activity is essential for the diagnosis of certain diseases. ALP changes during life and may vary between different populations.
OBJECTIVE.—
To establish reference intervals (RIs) and percentile charts for ALP activity in the Spanish population through a multicentric observational study and to compare the RIs to those defined in other countries.
DESIGN.—
A total of 662 350 ALP measurements from individuals ages 0 to 99 years from 9 Spanish tertiary care centers collected between 2020 and 2022 were analyzed. This study is the largest published in the literature to date.
RESULTS.—
Continuous percentile charts for ALP according to sex and age were established which can be used as RIs. Higher levels are reached during the first weeks of life. In puberty, a differential evolution is observed in both sexes, reaching a peak at 10 to 13 years of age in boys and remaining stable in girls at this age. Significant differences were also observed in adults, higher in men between ages 20 and 49 years and between ages 50 and 79 years in women, as reported in some countries.
CONCLUSIONS.—
ALP activity follows an age- and sex-dependent fluctuation with geographic differences. It is important to have appropriate reference values for each population in order to allow for a correct diagnostic interpretation and early diagnosis of diseases related to ALP abnormalities.
PubMed: 38797525
DOI: 10.5858/arpa.2023-0335-OA -
Nutrients May 2024Eating disorders (EDs) are mental health illnesses with a multifactorial origin. At present, no review of indexed publications studying their prevalence in Spain is... (Review)
Review
INTRODUCTION
Eating disorders (EDs) are mental health illnesses with a multifactorial origin. At present, no review of indexed publications studying their prevalence in Spain is available.
MATERIAL AND METHODS
A scoping review (PROSPERO -CRD42019140884-) was carried out through systematic searches (MEDLINE, EMBASE and PsycINFO) until January 2022. Papers published in Spanish/English analysing the prevalence of EDs in Spain (population < 65 years) were selected.
RESULTS
A total of 766 articles were identified (186 eliminated as duplicates). A total of 580 articles were analysed on the basis of title and abstract, and 67 articles were selected for full-text analysis. A total of 37 studies analysed the prevalence of EDs in Spain.
CONCLUSIONS
This is the first scoping review to analyse the prevalence of EDs in Spain. Puberty and adolescence are the most extensively studied stages. There is a high heterogeneity in the use of ED screening tools and a paucity of information on diagnostic tools.
Topics: Humans; Spain; Feeding and Eating Disorders; Prevalence; Adolescent; Female; Male; Adult; Child; Young Adult; Middle Aged
PubMed: 38794750
DOI: 10.3390/nu16101513 -
Journal of Clinical Medicine May 2024Recognizing insulin resistance (IR) in children remains challenging due to uncertain IRI-HOMA cut-offs and unclear recommendations for evaluating IR based on OGTT. In...
Comparison of the Clinical Utility of Two Insulin Resistance Indices: IRI-HOMA and IRI-Belfiore in Diagnosing Insulin Resistance and Metabolic Complications in Children Based on the Results Obtained for the Polish Population.
Recognizing insulin resistance (IR) in children remains challenging due to uncertain IRI-HOMA cut-offs and unclear recommendations for evaluating IR based on OGTT. In our study, we compare the effectiveness of IRI-HOMA and IRI-Belfiore (OGTT-based) in detecting IR and its metabolic complications in children. The analysis included 553 children who were hospitalized at the Department of Endocrinology and Metabolic Diseases of the Polish Mother's Memorial Hospital Research Institute (PMMH-RI) in Lodz, Poland, between 2002 and 2018 due to various reasons-of these, 67.5% were girls. All underwent OGTT for glucose and insulin assessment. IR diagnosis relied on IRI-HOMA and IRI-Belfiore. IR based on IRI-HOMA was evaluated using three criteria: (A) >2.5; (B) >2.67 in boys and >2.22 in girls before puberty and >5.22 and >3.82 during puberty, respectively; (C) >95th percentile according to charts for IRI-HOMA in children. Prepubertal children exhibited significantly lower IRI-HOMA and IRI-Belfiore than their pubertal counterparts ( < 0.00005). IRI-HOMA and IRI-Belfiore values positively correlated with age and BMI SDS value ( < 0.000001 for all calculations). As many as 26% to 46.9% of children with normal IRI-HOMA showed elevated IRI-Belfiore, with notably higher levels of triglycerides, a lower HDL cholesterol fraction, and a lower HDL/total cholesterol ratio in this subgroup. A notable proportion of children exhibited elevated IRI-Belfiore levels despite having normal IRI-HOMA values. This suggests the possibility of peripheral IR preceding hepatic IR in children-omitting an OGTT may therefore lead to overlooking cases of IR. Children diagnosed with IR via OGTT displayed significantly poorer lipid profiles compared to those without IR (characterized by normal values in both IRI-HOMA and IRI-Belfiore). This underscores the ability of OGTT-derived IR indices to identify individuals at risk of developing complications associated with obesity and IR before the onset of metabolic syndrome (MS) symptoms. If IR is already detected in children based on fasting glucose and insulin levels (IRI-HOMA), further evaluation may not be warranted, as OGTT results often simply confirm the diagnosis.
PubMed: 38792408
DOI: 10.3390/jcm13102865 -
Genes May 2024Insulin receptor signaling promotes cell differentiation, proliferation, and growth which are essential for oocyte maturation, embryo implantation, endometrial...
Insulin receptor signaling promotes cell differentiation, proliferation, and growth which are essential for oocyte maturation, embryo implantation, endometrial decidualization, and placentation. The dysregulation of insulin signaling in women with metabolic syndromes including diabetes exhibits poor pregnancy outcomes that are poorly understood. We utilized the Cre/LoxP system to target the tissue-specific conditional ablation of insulin receptor () and insulin-like growth factor-1 receptor () using an anti-Mullerian hormone receptor 2 () Cre-driver which is active in ovarian granulosa and uterine stromal cells. Our long-term goal is to examine insulin-dependent molecular mechanisms that underlie diabetic pregnancy complications, and our conditional knockout models allow for such investigation without confounding effects of ligand identity, source and cross-reactivity, or global metabolic status within dams. Puberty occurred with normal timing in all conditional knockout models. Estrous cycles progressed normally in females but were briefly stalled in diestrus in and double receptor (DKO) mice. The expression of vital ovulatory genes (, , ) was not significantly different in 12 h post-hCG superovulated ovaries in knockout mice. Antral follicles exhibited an elevated apoptosis of granulosa cells in and DKO mice. However, the distribution of ovarian follicle subtypes and subsequent ovulations was normal in all insulin receptor mutants compared to littermate controls. While ovulation was normal, all knockout lines were subfertile suggesting that the loss of insulin receptor signaling in the uterine stroma elicits implantation and decidualization defects responsible for subfertility in -Cre-derived insulin receptor mutants.
Topics: Animals; Female; Mice; Pregnancy; Granulosa Cells; Infertility, Female; Mice, Knockout; Ovary; Ovulation; Receptor, IGF Type 1; Receptor, Insulin; Signal Transduction
PubMed: 38790245
DOI: 10.3390/genes15050616