Father Research Articles

Machine learning algorithms for prediction of measles one vaccination dropout among 12–23 months children in Ethiopia

IntroductionDespite the availability of a safe and effective measles vaccine in Ethiopia, the country has experienced recurrent and significant measles outbreaks, with a nearly fivefold increase in confirmed cases from...

Robert Rosen’s Relational Biology Theory and His Emphasis on Non-Algorithmic Approaches to Living Systems

This paper examines the use of algorithms and non-algorithmic models in mathematics and science, especially in biology, during the past century by summarizing the gradual development of a conceptual rationale for non-algorithmic models in biology. First, beginning a century ago, mathematicians found it impossible to constrain mathematics in an algorithmic straitjacket via öö’s Incompleteness Theorems, so how would it be possible in biology? By the 1930s, biology was resolutely imitating classical physics, with biologists enforcing a reductionist agenda to expunge function, purpose, teleology, and vitalism from biology. Interestingly, physicists and mathematicians often understood better than biologists that mathematical representations of living systems required different approaches than those of dead matter. Nicolas Rashevsky, the Father of Mathematical Biology, and Robert Rosen, his student, pointed out that the complex systems of life cannot be reduced to machines or mechanisms as per the Newtonian paradigm. Robert Rosen concluded that living systems are not amenable to algorithmic models that are primarily syntactical. Life requires semantics for its description. Rashevsky and Rosen pioneered Relational Biology, initially using Graph Theory to model living systems. Later, Rosen created a metabolic–repair model (M, R)-system using Category Theory to encode the basic entailments of life itself. Although reductionism still dominates in current biology, several subsequent authors have built upon the Rashevsky–Rosen intellectual foundation and have explained, extended, and explored its ramifications. Algorithmic formulations have become increasingly inadequate for investigating and modeling living systems. Biology is shifting from a science of simple systems to complex ones. This transition will only be successful once mathematics fully depicts what it means to be alive. This paper is a call to mathematicians from biologists asking for help in doing this.

Mutational signature analyses in multi-child families reveal sources of age-related increases in human germline mutations.

Whole-genome sequencing studies of parent-offspring trios have provided valuable insights into the potential impact of de novo mutations (DNMs) on human health and disease. However, the molecular mechanisms that drive DNMs are unclear. Studies with multi-child families can provide important insight into the causes of inter-family variability in DNM rates but they are highly limited. We characterized 2479 de novo single nucleotide variants (SNVs) in 13 multi-child families of Mexican-American ethnicity. We observed a strong paternal age effect on validated de novo SNVs with extensive inter-family variability in the yearly rate of increase. Children of older fathers showed more C > T transitions at CpG sites than children from younger fathers. Validated SNVs were examined against one cancer (COSMIC) and two non-cancer (human germline and CRISPR-Cas 9 knockout of human DNA repair genes) mutational signature databases. These analyses suggest that inaccurate DNA mismatch repair during repair initiation and excision processes, along with DNA damage and replication errors, are major sources of human germline de novo SNVs. Our findings provide important information for understanding the potential sources of human germline de novo SNVs and the critical role of DNA mismatch repair in their genesis.

Perinatal Risk Factors in Single-suture Craniosynostosis: A Systematic Review and Meta-analysis.

To our knowledge, there has not been a review article summarizing the current evidence with regard to perinatal risk factors, and our aim is to perform a systematic review and meta-analysis of the evidence of perinatal risk factors in single suture craniosynostosis to inform our practice and identify any need for further research in this area. Our target population was pediatric single-suture craniosynostosis patients, and the intervention was perinatal risk factors. The comparison group was an age and sex-matched control group without craniosynostosis and the outcome we investigated was presence of single suture craniosynostosis. The literature search was done using OVID MEDLINE, Pubmed, and Embase databases from 1946 to 2023. A PRISMA flowchart was created, and statistical analysis was performed using RevMan pooled odds ratios, and 95% CIs were used to combine results from individual studies. Our initial search identified 625 abstracts and these were narrowed down to 16 articles, which were included in the final selection for the review. Out of these, 13 were used for the quantitative meta-analysis. Our meta-analysis showed a possible association between craniosynostosis and the following perinatal risk factors; presence of maternal thyroid disease, maternal age greater than 29, paternal age greater than 29, maternal smoking, gestational age above 37 weeks, and maternal underweight (BMI<18.5). Further prospective studies are warranted to investigate definite associations. The next step is to set up a multicenter prospective study among a craniofacial unit network.

Concepts of reproductive behaviour and motherhood in Soviet cinema of the 1920–1930s

The article examines representations of motherhood and reproductive behaviour in Soviet cinema from Revolution 1917 to the mid-1930s (films “Children are the Flowers of Life”, “The Road to Happiness”, “Katka's Reinette Apples”, “Bed and Sofa”, etc.) through the study of the reproductive choice mechanism, demonstration of pregnancy, childbirth and child care. Conclusions are drawn about the presence of several main conceptual frameworks, such as happy Soviet motherhood as opposed to pre-revolutionary motherhood; the unreliability of the parental function of the biological father, but the support of the collective and the acquisition of a new partner, which means the creation of a two-parents family; transition from the demonstration of medical instruments and the process of childbirth to the withdrawal of this segment; etc.

Reflections on timing of motherhood - a qualitative online study with women of reproductive age

BackgroundThe age of Danish women giving birth to their first child has risen throughout the last 50 years, and the number of women and men who are having their first child when they are at advanced maternal or paternal age is increasing worldwide. Postponing parenthood is not unique to Denmark, as the same pattern is seen especially in other European and Western countries. The aim of this study was in a social media setting to explore reflections on the timing of motherhood among Danish women of reproductive age who not yet had children.MethodThis study was a qualitative study based on three online focus groups on Facebook. Twenty-six women of reproductive age discussed the timing of motherhood for three days in January 2020. Data were analyzed using Systematic Text Condensation.ResultsThree main themes were identified: ‘Life before parenthood’, ‘To plan for a child’ and ‘A life without children’. Several external and internal conditions influence whether and if so when women consider becoming mothers. Regarding the biological capacity for having children, women compare themselves with their female relatives and friends and colleagues regarding the social norms surrounding motherhood. Women with no children often experience either positive or negative pressure from family, friends, and colleagues regarding when to have children.ConclusionSeveral internal and external considerations influence when and if women become mothers. Social surroundings such as family, friends, and colleagues have an impact on women’s reproductive considerations in terms of pressure to have children in the future. Danish women tend to compare their reproductive capacity to their female relatives and compare the social norms surrounding motherhood to their female friends. Women in this study were positive towards discussing the timing of motherhood with other women of reproductive age on social media.

Depression is associated with unintended pregnancy among fathers during the first 3 years after childbirth

BackgroundThe aim of the present study is to estimate the prevalence of unintended pregnancy in fathers with children aged less than or equal to 36 months and evaluate whether unintended pregnancy is associated with depression after controlling for covariates. MethodsWe used data from the Brazilian National Health Survey (PNS) of 2019, a cross-sectional study that comprised a representative sample of residents in private households in Brazil. For the analysis of this study, we selected 30,579 men (> 14 years old) who answered to the Selected Resident questionnaire of the PNS and reported having a biological child (son). Among these 4806 had a child with less than 4 years of age and were used in our analysis. ResultsThe prevalence of unintended pregnancy in this group of fathers with a child ≤ 3 years was 35.0 % (95 % CI 32.6–37.5). In the final adjusted model, the variables associated with depression were: PHQ-9 total score (OR: 1.07, 95 % CI 1.03–1.11, p ≤0.001), a higher father's age (OR 1.01, 95 % CI 1.01–1.02), a higher father's age at birth (OR: 0.92, 95 % CI 0.90–0.94), self-reported black (OR: 3.00, 95 % CI 1.94–4.66), brown (OR: 1.63, 95 % CI 1.25–2.13) or indigenous (OR: 0.22, 95 % CI 0.07–0.69) skin color, lower per capita family income >1 to 2 MW (OR: 1.54, 95 % CI 1.01–2.35), ½ to 1 MW (OR: 2.22, 95 % CI 1.46–3.38) and up to 1 MW (OR: 1.76, 95 % CI 1.19–2.59) and not participating in the partner's prenatal appointments (OR: 2.04, 95 % CI 1.55–2.68). DiscussionIn our study, the prevalence of unplanned pregnancy among fathers of child less than 4 years of age is high, and it is associated with depression. Black and brown self-reported skin color, lower family income and higher father's age are associated with increased risk of unintended pregnancy.

A random forest approach to analyzing socioeconomic influences on U.S. infant mortality

Abstract. One important measure of a society's overall health and well-being is infant mortality. However, the infant mortality in US has long been the highest for years among all the high-income nations. While technical and medical factors are often considered, this study posits that socioeconomic determinants also play a critical role. The random forest model, known as its great ability of ranking importance of factors, is an ideal instrument for evaluating how various socioeconomic factors affect infant mortality in the United States. Using data Wonder database, this study applies a random forest approach to evaluate and rank the significance of different socioeconomic factors. The results indicate that the fathers age, mothers education level, parental birthplace, and fathers race are the four most influential factors affecting infant mortality rates in the U.S. Based on these findings, this study advocates for increased attention from policymakers and the public to address these critical socioeconomic factors in efforts to reduce infant mortality.

Paternal behaviour is associated with high levels of OT in plasma and the presence OTR in the mPOA/BNST in the Mongolian gerbil (Meriones unguiculatus)

The exhibition of paternal behaviour has been associated with high peripheral concentrations of oxytocin (OT) and levels of oxytocin receptors (OTRs) in the paraventricular and supraoptic nuclei of the hypothalamus. The presence of OTRs in the medial preoptic area (mPOA), bed nucleus of the stria terminalis (BNST), medial amygdala (MeA), and olfactory bulb (OB) has not been studied extensively in the paternal context, although these nuclei are essential in the regulation of paternal behaviour. The aim of this study was to determine whether there is an association between paternal response of sexually inexperienced males of the Mongolian gerbils (Meriones unguiculatus) and OT concentrations in plasma, as well as the presence of OTRs in the mPOA, BNST, MeA, and OB. We used sexually inexperienced gerbils: ten paternal (PAT) males and 10 males aggressive with pups (AGG). PAT males and AGG males were subjected to paternal behaviour tests. Then, blood samples were taken to quantify OT concentrations. The brains were dissected for OTR immunohistochemistry analyses. PAT males had significantly higher plasma levels of OT and numbers of cells with OTR immunoreactivity (ir) in the mPOA/BNST. These results indicated an association between paternal behaviour and peripheral concentrations of OT, as well as the presence of OTRs in the mPOA and BNST. This suggests that OT and OTRs could participate in the regulation of paternal behaviour in the Mongolian gerbil.

Associations between family factors and physical activity clustering in preschool children: a cross-sectional study.

This study aimed to examine the association between family factors and physical activity (PA) clustering in preschool children. Preschoolers' PA and sedentary behavior (SB) were assessed consecutively for 7 days using ActiGraph accelerometers based on the cutoff counts developed by Pate et al. Information about children, their parents, and their families was collected using questionnaires. We developed a two-step approach to clustering PA both inside and outside of kindergarten. The Euclidean distance metric was utilized to distinguish between groups, while the Schwarz-Bayesian criterion was applied to identify the most optimal sub-group model. A one-way ANOVA was used to assess the clustering effect, and logistic regression was used to analyze the influencing factors of different clustering. We collected data from 291 preschool children aged 3 to 6 years and divided them into three clusters-Inactive (50.2%), Active in kindergarten (26.8%), and Active outside kindergarten (23.0%)-with significant differences in PA and SB, revealing distinct temporal and spatial clustering patterns (silhouette coefficient = 0.3, p < 0.05). Furthermore, preschooler activity levels correlated significantly with factors including gender (OR = 0.35, 95% CI: 0.19-0.66), age (OR = 1.05, 95% CI: 1.00-1.10), birth weight (OR = 1.79, 95% CI: 1.16-2.76), paternal age (OR = 1.01, 95% CI: 1.00-1.02), and maternal income (OR = 0.68, 95% CI: 0.48-0.96). This study shows that the family environment or parents significantly influence the PA of preschool children. Older fathers may promote preschool children's PA through greater educational focus and financial stability, while higher maternal income can provide more opportunities and resources for preschool children to engage in active lifestyles. Thus, it is suggested that families providing more attention and exercise opportunities for preschool children's education can help improve their PA levels in the future.

Parental age at birth, telomere length, and autism spectrum disorders in the UK Biobank cohort.

Older parental age at birth is associated with increased risk of autism spectrum disorders (ASD) in offspring. Independently, shorter telomere length (TL) has also been shown to be associated with ASD in children. However, older paternal age at birth, with or without controlling for maternal age, has been associated with longer TL, a seemingly contradictory finding. Here, we conducted a retrospective cohort study among participants in the UK Biobank to disentangle associations between leukocyte TL and ASD status in adults, and the potential moderation by parental age on adult offspring's TL. Participants with ASD diagnosis (N = 87) with a mean age of 46.0 (SD 4.4) years were matched to participants without ASD diagnosis (N = 870) based on age, sex, ethnicity, education, household income, and assessment center. No statistically significant differences were seen in TL between participants with and without ASD when parental age at birth was not considered. However, there was a significant interaction between ASD diagnostic status and parental age on participants' TL, such that older paternal or maternal age at birth was more strongly associated with longer TL in participants with ASD. This study suggests that the shortened TL observed in children with ASD in previous research may partially depend on parental age at birth. Future studies tracking TL attrition before ASD diagnosis are warranted to depict temporal associations and the interacting effects of parental age at birth and ASD status on TL across the lifespan.

&lt;b&gt;Estilos de crianza y personalidad: un estudio en adultos costarricenses&lt;/b&gt;

The reason for this research was the growing concern to find a connection between the parting style given by biological mothers and fathers and the personality of adults in Costa Rica. The goal of the research was to determine how parenting styles and a 110 personalities of Costa Rican adults influence and related; the average age of the participants was (M=33.25, SD=13.93), with an ages ranging from 18 to 76 years old, from multiple parts of the country and who were raised in Costa Rica in their childhood and adolescence. A non-experimental quantitative methodology with a cross-sectional design was used and the data recollection was carried out by convenience, virtually in October 2022. To answer the pending question the Big Five Inventory Scale (BFI) and the Perceiver Parenting Styles and Parental Inconsistency Scale (EPIPP, in Spanish) were applied. The data analysis was done with the statistical program IBM SPSS, v. 26.0 and results showed outstanding aspects in personality traits of openness to experience; in parenting there was an overprotective parenting style for the mother and an authoritative style for the father. In addition, differences were found between the ages in the mother’s answers and the generations with respect to the personalities of the participants.

Divergent interpretations of child abuse in legal judgments: perspectives from clinicians and forensic experts

BackgroundChild abuse in Taiwan is a major societal concern that severely affects the well-being of children. Despite the complexity in detecting abuse, reports of child abuse are increasing, evidenced by a rise in cases and heightened awareness. This study utilizes judicial judgments as a lens to understand the varied interpretations of child abuse by clinical and forensic experts and explores the broader epidemiological trends of such abuse within the declining youth population of Taiwan.MethodsWe conducted a retrospective study by analyzing official court judgments on child abuse allegations judged from 2008 to 2022 from the online database of Judicial Yuan. Furthermore, the study analyzed demographic factors, injury patterns, and opinions from various experts.ResultsThe results reveal that severe criminal cases of child abuse predominantly involve biological fathers as the primary offenders and physical abuse as the most common form of maltreatment. Victims are typically aged less than 5 years, which frequently leads to an unfavorable prognosis. Analysis also highlights the TEN-4-FACESp acronym as a highly predictive indicator of child abuse and underscores the prevalence of abusive head trauma (AHT). Moreover, the findings emphasize ongoing disparities in opinions between forensic medical examiners and clinical physicians, especially in AHT cases, which potentially influences judicial decisions.ConclusionsIn summary, the study reveals ongoing disagreements between forensic medical examiners and clinical physicians, especially in cases of AHT, which may impact judicial decisions. Promoting consensus through interdisciplinary collaboration and improved communication can aid in revealing the truth in child abuse cases.

How do fathers' educational level contribute to children's school problems? Overparenting and children's gender and surgency in a moderated mediation model.

This study aims to investigate (a) the mediating role of overparenting between father's educational level and children's school problems, and (b) the joint moderating role of children's gender and surgency in the indirect relationship between father's educational level and school problems. Participants were 203 school children, 96 boys (47.3%) and 107 girls (52.7%), aged 7-8 years (M = 92.42 months, SD = 3.52). Fathers reported their educational level, age and employment status and their children's gender and number of siblings, as well as their overparenting behaviors by Anticipatory Problem Solving (APS) scale. Teachers informed children's school problems by the Behavior Assessment System for Children (BASC T-2). Parents together informed their children's surgency levels by a subscale of Children's Behavior Questionnaire (CBQ). Results showed that, in girls, the father's educational level was negatively related to the child's school problems via overparenting behaviors, controlling the number of siblings and father's age and employment status. However, among boys, fathers' overparenting protect their shy sons from the risk of a low educational level for school problems. These findings highlight the relevance of considering the gender and surgency to a better understanding of the effects of contextual factors on children's outcomes.

Parental Age and Severity of Non-Syndromic Orofacial Clefts: Relationship with De Novo Mutations

Background: This study investigates the relationship between paternal and maternal age, and the severity of orofacial clefts and the presence of de novo mutations in children. Methods: This was a retrospective study of individuals who were diagnosed with non-syndromic cleft lip and/or palate (CL/P) and their unaffected parents, from 2012 to 2019. We obtained data from the AfriCRAN project database for Nigerians with non-syndromic orofacial clefts. These individuals were recruited at the Oral and Maxillofacial Surgery Clinic, Lagos University Teaching Hospital, Lagos. Results: There was no statistically significant association between type of CL ± P and parental age in young fathers (p = 0.93). When older fathers were considered, the percentage of complete (more severe) CL ± P cases increased, especially when they were married to older mothers, and this was statistically significant (p = 0.036). In older fathers, the risk of CL ± P in their offspring was increased (OR: 2.66, CI: 1.04-6.80), and there was also an increased risk of developing right-sided CL ± P (OR: 1.61, CI: 1.0-2.59). There was a reduced risk of isolated clefts of the soft palate in younger fathers (OR: 0.36, CI: 0.07–1.71), but the risk increased when considering complete types (more severe) of isolated clefts of the hard and soft palates (OR: 1.63, CI: 0.7–1.7). There was an increase in de novo mutation in children as the difference between paternal and maternal age increased. Conclusion: The study showed that a higher risk of CL ± P and de novo mutations in children is associated with increased parental age.

CLINICAL AND MOLECULAR CHARACTERIZATION OF A PATIENT WITH SYNDROMIC CRANIOSYNOSTOSIS, A CASE REPORT

Introduction: Craniosynostosis is a craniofacial disorder characterized by premature fusion of one or more cranial sutures, inhibiting bone growth perpendicular to the affected suture. In syndromic craniosynostosis, anomalies of the limbs, heart and central nervous system may be present, in addition to genetic mutations affecting the cranial vault. Its etiology is associated with paternal age, teratogenic factors and external pressure on the skull; the main genes causing syndromic craniosynostosis are the growth factor receptors (FGFR1, FGFR2, and FGFR3, TWIST1 and EFNB1), for these reasons it is of utmost importance to recognize the existing types of syndromic craniosynostosis, and its clinical and molecular characteristics to reach an optimal and accurate diagnosis. Objective: to present the clinical and molecular characterization of an individual with syndromic craniosynostosis in a case. Methodology:an objective description of the clinical case and a review with analysis of a total of 24 articles, including review and original articles, as well as clinical cases, of which 18 bibliographies were used because the other articles were not relevant to this study. The sources of information were indexed journals as well as search engines such as PubMed, Google Scholar and Cochrane; the terms used to search for information were: syndrome, craniosynostosis, gene, mutation, FGFR. Results: the present report shows a clinical case of syndromic craniosynostosis. The diagnosis was made during an evaluation by means of radiographic analysis in a 15-year-old female patient, and corroborated by genetic blood tests with the following results: heterozygous variant at position 755 of the c.DNA, where a variant in Cytosine is visualized by a Guanine. This determines a change at the level of the FGFR2 protein. Conclusions: the case report describes the clinical and molecular diagnosis of a 15-year-old female patient, revealing a heterozygous genetic variant in the FGFR2 gene (c.755&gt;G), associated with changes in the FGFR2 protein. This finding is relevant, as similar variants have not been reported in Ecuador or South America, underscoring the need for further research on syndromic craniosynostosis and Apert syndrome. A multidisciplinary approach to treatment is recommended, involving various medical specialties to ensure proper brain development and improved esthetics. In addition, the existence of similar cases in Indonesia and Congo is mentioned, suggesting a possible founder effect related to the migration of people with character. KEY WORDS: syndrome, craniosynostosis, gene, mutation, FGFR

Secular variation and risk factors of preterm birth in Hainan, the Free Trade Port in China from 2010 to 2021

ObjectivesPreterm delivery rates have increased obviously worldwide over the past decade, yet reliable epidemiological studies on the incidence of preterm birth and temporal trends are not available in Hainan, The Free Trade Port in China. We aimed to describe the rate of preterm birth and trends between 2010 and 2021 and to primarily explore risk factors associated with preterm birth in Hainan, China.MethodsThis was an observational study was based on data from the Hainan Provincial Birth Certificate System (HPBCS) for live births between 1 January 2010 and 31 December 2021. We included pregnancies resulting in at least one live birth, with newborns born at a gestational age of 28 weeks or greater, or with a birth weight of 1000 g or more. The outcome were preterm birth rates and their trends over time. Potential risk factors were collected, including infant gender, maternal age, paternal age, maternal ethnicity, paternal ethnicity, home address, and single or multiple pregnancies. The logistic regression model was used to assess the relationship between preterm birth and potential risk factors.ResultsA total of 1,537,239 live births and 86,328 preterm births were investigated, giving a total preterm birth rate of 5.62%. The overall preterm birth rate increased from 4.47% in 2010 to 7.12% in 2021 (compound annual growth rate [CAGR] 4.32). The CAGR of late preterm birth is consistent with the overall preterm birth rate (4.32%). The fastest growth is observed in the rate of very preterm births (5.53%), while the rate of moderate preterm births exhibits the slowest growth (3.87%). Infant gender, multiple pregnancy, home address, parental age, and ethnicity had significant effects on preterm birth.ConclusionThe preterm birth rate was increasing year by year from 2010 to 2021 in Hainan, The Free Trade Port in China. Incidence of preterm births in Hainan Province in relation to multiple pregnancies, infant sex, parental age, parental race and residential address.

Cancer mortality risk in the Urals Cohort of Exposed Population Offspring

The objective of the study is to analyze solid cancer mortality and estimate the risk value of solid cancer mortality in the offspring of parents irradiated in the Southern Urals, depending on the dose to the parents' gonads as well as to conduct a preliminary assessment of the mortality risk from cancer of individual locations depending on the gonadal dose. The issue of the transgenerational effects of the human gonad exposure is still very important. There exists conclusive evidence of the presence of such effects in experimental animals. However, there is no proof of the existence of these effects in humans despite a great number of research on this subject. International scientific community and international organizations, UNSCEAR and ICRP being among them, regard this issue as the one that has not been solved yet and requires further studies. Urals Cohort of offspring of the population exposed on the Techa River and on the territory of the East Ural radioactive trace was established in the Urals research Center for Radiation medicine in 2022. The key feature of the cohort is the exclusion of the offspring with postnatal exposure. The size of the cohort as of September 2023 is 31,154 persons. The number of person-years over the whole follow-up period from 1950 through 2020 is 1 226 380. Mean dose to the gonads of mothers of all the cohort members is 41 mGy, to those of the fathers' — 35 mGy, mean combined gonad dose is 76 mGy. Over the whole follow-up period 3,774 deaths from all causes including 284 deaths from solid cancers were registered in the cohort. The mean age of the cohort members at the end of the follow-up period was 42 years. The risk of death was analyzed using Poisson regression by the programs of the EPICURE statistical software package. Three models of dose dependence were tested: linear, quadratic, and linear-quadratic models of paternal gonadal dose, maternal gonadal dose, and total gonadal dose. Mortality risk analysis of all solid cancers in the offspring cohort showed no statistically significant effect with parental gonadal dose (we have obtained positive although statistically insignificant values of solid cancers mortality risk) which is consistent with the results of other studies in human populations. At the same time, the analysis for the first time obtained a statistically significant linear dependence of the solid cancer mortality risk in offspring with father's age over 45 years depending on the dose to the father's gonads. The excess relative risk of death was 8.09/Gy, (0.51-22.93), p &lt; 0.05. Also, for the first time, evidence of dose dependence of the mortality risk of lung cancer in male offspring on maternal gonadal dose, paternal gonadal dose, and combined gonadal dose was obtained. The values of excess relative risk of lung cancer and 95% confidence intervals according to the linear model were 5.39/Gy (0.46; 15.56) from paternal gonad dose, 4.36/Gy (0.15; 13.48) from maternal gonad dose, and - 3.95/Gy (0.55; 12.14) from combined gonad dose. Point risk estimates of lung cancer at this stage are characterized by wide confidence intervals and require additional studies to assess the influence of possible effect modifiers, but with a high degree of probability indicate the presence of dose dependence of this effect. Increasing the follow-up period and attained age, will increase the number of cancers in the future and will reduce dose response uncertainties and provide more accurate estimates of the risk of death in the offspring cohort.

Advanced paternal age exacerbates neuroinflammation in offspring via m6A modification-mediated intergenerational inheritance

BackgroundThe trend of postponing childbearing age is prevalent worldwide. Advanced paternal age (APA) is associated with adverse pregnancy outcomes and offspring health. However, the underlying mechanism by which paternal aging affects the risk of offspring neuropsychiatric disorders is unclear. Our study aims to explore the behavioral phenotypes and the pathologic epigenetic alterations of APA offspring inherited from aging sperm.MethodsBehavioral tests, ELISA assay, immunofluorescence and western blotting were performed on offspring mice. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA immunoprecipitation sequencing (RIP-seq) were used to investigate the modified N6-methyladenosine (m6A) profiles of paternal sperm and offspring hippocampus. Intervention of gene expression by lentivirus and adeno-associated virus in both vivo and vitro examined the potential therapeutic targets of intergenerational inherited neuroinflammation.ResultsIn our study, APA offspring exhibit cognitive impairment and autism-like behavior. An increase in neuroinflammation in APA offspring is associated with microglial overactivation, which manifests as abnormal morphology and augmented engulfment. MeRIP-seq of F0 sperm and F1 hippocampus reveal that Nr4a2 is hypermethylated with decreased expression in APA offspring involving in synaptic plasticity and microglial function. In addition, Ythdc1, an m6A reader protein, is markedly elevated in aging sperm and remains elevated in adult hippocampus of APA group. Enhanced Ythdc1 recognizes and suppresses the hypermethylated Nr4a2, thereby contributing to the abnormal phenotype in offspring. The overexpression of Ythdc1 triggers microglial activation in vitro and its suppression in the hippocampus of APA progeny alleviates behavioral aberrations and attenuates neuroinflammation.ConclusionOur study provides additional evidence of the abnormal behavioral phenotypes of APA offspring and reveals potential epigenetic inheritance signatures and targeted genes for future research.

Paternal age, de novo mutations, and offspring health? New directions for an ageing problem.

This Directions article examines the mechanisms by which a father's age impacts the health and wellbeing of his children. Such impacts are significant and include adverse birth outcomes, dominant genetic conditions, neuropsychiatric disorders, and a variety of congenital developmental defects. As well as age, a wide variety of environmental and lifestyle factors are also known to impact offspring health via changes mediated by the male germ line. This picture of a dynamic germ line responsive to a wide range of intrinsic and extrinsic factors contrasts with the results of trio studies indicating that the incidence of mutations in the male germ line is low and exhibits a linear, monotonic increase with paternal age (∼two new mutations per year). While the traditional explanation for this pattern of mutation has been the metronomic plod of replication errors, an alternative model pivots around the 'faulty male' hypothesis. According to this concept, the genetic integrity of the male germ line can be dynamically impacted by age and a variety of other factors, and it is the aberrant repair of such damage that drives mutagenesis. Fortunately, DNA proofreading during spermatogenesis is extremely effective and these mutant cells are either repaired or deleted by apoptosis/ferroptosis. There appear to be only two mechanisms by which mutant germ cells can escape this apoptotic fate: (i) if the germ cells acquire a mutation that by enhancing proliferation or suppressing apoptosis, permits their clonal expansion (selfish selection hypothesis) or (ii) if a genetically damaged spermatozoon manages to fertilize an oocyte, which then fixes the damage as a mutation (or epimutation) as a result of defective DNA repair (oocyte collusion hypothesis). Exploration of these proposed mechanisms should not only help us better understand the aetiology of paternal age effects but also inform potential avenues of remediation.