OBJECTIVES: This study aims to explore the lasting effects of stress experienced by pregnant women during World War II (WWII) on body and head measurements of their adult daughters. METHODS: The research sample consists of 336 female university students born in Poland between 1925 and 1951. The data include body measurements and socioeconomic information (parental occupation and number of siblings) acquired from questionnaires collected between the 1950s and 1970s. Student's t-test, Mann-Whitney test and Analysis of Variance were used to analyze differences in body measurements between groups of women born before and during the war, as well as the possible influences of socioeconomic variables. RESULTS: The mean measurements of body height, symphysion height, and waist circumference were lower in women conceived and born during the war compared to those born in the pre-war period. In contrast, the mean measurements of biacromial (shoulder) width, trunk length, and three head dimensions were higher in women conceived and born during the war. Additionally, the number of siblings appeared to be a significant factor that may have influenced the body measurements of women in both groups. For instance, a higher number of living siblings, particularly sisters, was associated with reduced body dimensions, such as body height and waist circumference, while a greater number of deceased siblings was linked to an increase in certain body dimensions. CONCLUSION: The results suggest that war-related prenatal conditions may have influenced the postnatal growth and development of women conceived and born during the war. Notably, the direction of these changes varied, which indicates that the growth response to the war-related conditions was a complex adaptation, reflecting both positive and negative changes in different body parts, rather than a uniform pattern of growth suppression.
- MeSH
- World War II * MeSH
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Stress, Psychological MeSH
- Socioeconomic Factors MeSH
- Pregnancy MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Poland MeSH
PURPOSE: Analyze phenotypic data from knockout mice with late-adult retinal pathologic phenotypes to identify genes associated with development of adult-onset retinal diseases. METHODS: The International Mouse Phenotyping Consortium (IMPC) database was queried for genes associated with abnormal retinal phenotypes in the late-adult knockout mouse pipeline (49-80 weeks postnatal age). We identified human orthologs and performed protein-protein analysis and biological pathways analysis with known inherited retinal disease (IRD) and age-related macular degeneration (AMD) genes using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), PLatform for Analysis of single cell Eye in a Disk (PLAE), Protein Analysis Through Evolutionary Relationships (PANTHER), and Kyoto Encyclopedia of Genes and Genomes (KEGG). RESULTS: Screening of 587 late-adult mouse genes yielded 12 with abnormal retinal phenotypes, which corresponded to 20 human orthologs. Three of the 12 mouse genes and two of the 20 human orthologs were previously implicated in retinal pathology or physiology in a literature review. Although all of the genes demonstrated retinal pathology when deleted from the mouse genome, most do not have established roles in human retinal disease. Furthermore, human protein-protein analysis and biological pathway analysis yielded only a few relationships between the candidate gene list and that of known IRD and AMD genes, suggesting they may represent novel retinal functions. CONCLUSIONS: We identified 12 mouse genes with significant late-adult abnormal retinal pathology, eight of which have not been previously implicated in either mouse or human retinal physiology or pathology. These serve as novel retinal disease gene candidates for late-onset retinal disease.
- MeSH
- Phenotype MeSH
- Humans MeSH
- Macular Degeneration * genetics MeSH
- Disease Models, Animal MeSH
- Mice, Knockout MeSH
- Mice MeSH
- Eye Proteins * genetics MeSH
- Retina * pathology metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: Sacrococcygeal teratoma (SCT) is the most common congenital tumor. The incidence of malignant types is rare but increases with late detection or in case of relapse. Prenatal diagnosis is based on ultrasound examination and magnetic resonance imaging (MRI). Since this is a rare congenital anomaly, we should report all cases to improve prenatal diagnosis and postnatal management. MATERIAL AND METHODS: Retrospective analysis of sixteen cases of sacrococcygeal teratoma delivered and treated at the University Hospital Brno between 2005 and 2020. The following criteria were evaluated: gestational week of the primary diagnosis, exact description of ultrasound findings, pregnancy management, delivery mode, correlation of prenatal ultrasound with postnatal findings in the newborn, as well as the occurrence of early and late complications in newborns and children. RESULTS: Out of sixteen cases, seven cases (43.8%) were indicated for pregnancy termination based on ultrasound findings, the parent's decision, and an estimation of an adverse pregnancy outcome. In nine cases (56.2%), the pregnancy continued and was ended by delivery. In one case, there was an early postnatal death of a newborn after birth in the 25th week of gestation. In eight cases, live fetuses were born in which the tumor was surgically removed between day 1 and 14 months after birth. There was a strong correlation between the tumor description made by prenatal ultrasound diagnosis and related severe complications in newborns. The incidence of severe early and late complications in ongoing pregnancies was very low-only one case of infection in the surgical wound requiring reoperation (12.5%) was described. In two patients (25%), a transient stoma establishment was necessary for secondary ileus. One case of recurrence of the disease at two years of age occurred, requiring the administration of chemotherapy (12.5%), and one patient has mild persistent urinary incontinence. CONCLUSION: Sacrococcygeal teratoma is one of the rarest congenital malformations. A detailed prenatal ultrasound examination is essential to estimate the pregnancy prognosis. The most predictive ultrasound predictor of favorable early and late postnatal outcomes and long-term child development is the presence of cystic sacrococcygeal formation, the most common tumor type, and the absence of signs of cardiac failure due to fetal anemia. In these cases, with early surgical treatment provided, the incidence of severe complications and long-term consequences in children is very low, and parents should be informed during prenatal counseling. It is necessary to register all the SCT cases due to the rarity of this congenital anomaly for further statistical analysis of the importance of ultrasound markers.
- MeSH
- Adult MeSH
- Gestational Age MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Infant, Newborn MeSH
- Prognosis MeSH
- Retrospective Studies MeSH
- Sacrococcygeal Region * diagnostic imaging MeSH
- Pregnancy MeSH
- Teratoma * diagnostic imaging surgery congenital MeSH
- Ultrasonography, Prenatal * MeSH
- Pregnancy Outcome MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
BACKGROUND AND AIMS: Janus kinase (JAK) inhibitors, such as tofacitinib, are potent anti-inflammatory agents used in the treatment of ulcerative colitis (UC). Current guidelines recommend avoiding their use during pregnancy due to safety concerns, as well as during breastfeeding due to the potential excretion into breast milk. METHODS: This case report describes the impact of in utero exposure to tofacitinib during pregnancy and subsequent exposure via breastfeeding on the immune development of the exposed infant. RESULTS: A 37-year-old woman with UC, who was being treated with tofacitinib and vedolizumab, became pregnant and continued both medications, with the tofacitinib dosage reduced from 10 to 5 mg BID at gestational week 28. The infant was born healthy, with normal growth and development, and received all scheduled non-live vaccinations. At 15 months, immune parameters-including response to vaccination-were evaluated. The results showed normal immunoglobulin levels and an adequate serologic response to vaccination, with no signs of immune dysfunction. CONCLUSIONS: This case suggests that prolonged prenatal and postnatal exposure to tofacitinib may not adversely affect infant immune development. However, caution is advised due to the limited number of documented cases. Further research is needed to fully understand the long-term implications of JAK inhibitor exposure during pregnancy and breastfeeding.
- MeSH
- Adult MeSH
- Antibodies, Monoclonal, Humanized therapeutic use MeSH
- Janus Kinase Inhibitors * adverse effects MeSH
- Protein Kinase Inhibitors adverse effects therapeutic use MeSH
- Infant MeSH
- Breast Feeding * MeSH
- Pregnancy Complications drug therapy MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Piperidines * adverse effects therapeutic use MeSH
- Pyrimidines * adverse effects therapeutic use MeSH
- Pyrroles adverse effects therapeutic use MeSH
- Pregnancy MeSH
- Colitis, Ulcerative * drug therapy MeSH
- Prenatal Exposure Delayed Effects * immunology chemically induced MeSH
- Check Tag
- Adult MeSH
- Infant MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
Fibroblasts, the most abundant cell type in the human body, play crucial roles in biological processes such as inflammation and cancer progression. They originate from the mesoderm or neural-crest-derived ectomesenchyme. Ectomesenchyme-derived fibroblasts contribute to facial formation and do not express HOX genes during development. The expression and role of the HOX genes in adult fibroblasts is not known. We investigated whether the developmental pattern persists into adulthood and under pathological conditions, such as cancer. We collected adult fibroblasts of ectomesenchymal and mesodermal origins from distinct body parts. The isolated fibroblasts were characterised by immunocytochemistry, and their transcriptome was analysed by whole genome profiling. Significant differences were observed between normal fibroblasts from the face (ectomesenchyme) and upper limb (mesoderm), particularly in genes associated with limb development, including HOX genes, e.g., HOXA9 and HOXD9. Notably, the pattern of HOX gene expression remained consistent postnatally, even in fibroblasts from pathological tissues, including inflammatory states and cancer-associated fibroblasts from primary and metastatic tumours. Therefore, the distinctive HOX gene expression pattern can serve as an indicator of the topological origin of fibroblasts. The influence of cell position and HOX gene expression in fibroblasts on disease progression warrants further investigation.
- MeSH
- Adult MeSH
- Fibroblasts * metabolism cytology MeSH
- Genes, Homeobox MeSH
- Homeodomain Proteins metabolism genetics MeSH
- Cells, Cultured MeSH
- Humans MeSH
- Mesoderm * metabolism cytology MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND AND AIMS: Despite the last decade's significant development in the scientific study of work addiction/workaholism, this area of research is still facing a fundamental challenge, namely the need for a valid and reliable measurement tool that shows cross-cultural invariance and, as such, allows for worldwide studies on this phenomenon. METHODS: An initial 16-item questionnaire, developed within an addiction framework, was administered alongside job stress, job satisfaction, and self-esteem measures in a total sample of 31,352 employees from six continents and 85 cultures (63.5% females, mean age of 39.24 years). RESULTS: Based on theoretical premises and psychometric testing, the International Work Addiction Scale (IWAS) was developed as a short measure representing essential features of work addiction. The seven-item version (IWAS-7), covering all seven components of work addiction, showed partial scalar invariance across 81 cultures, while the five-item version (IWAS-5) showed it across all 85 cultures. Higher levels of work addiction on both versions were associated with higher job stress, lower job satisfaction, and lower self-esteem across cultures. The optimal cut-offs for the IWAS-7 (24 points) and IWAS-5 (18 points) were established with an overall accuracy of 96% for both versions. DISCUSSION AND CONCLUSIONS: The IWAS is a valid, reliable, and short screening scale that can be used in different cultures and languages, providing comparative and generalizable results. The scale can be used globally in clinical and organizational settings, with the IWAS-5 being recommended for most practical and clinical situations. This is the first study to provide data supporting the hypothesis that work addiction is a universal phenomenon worldwide.
- MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Behavior, Addictive * diagnosis MeSH
- Occupational Stress diagnosis MeSH
- Job Satisfaction * MeSH
- Surveys and Questionnaires standards MeSH
- Psychiatric Status Rating Scales standards MeSH
- Psychometrics * standards instrumentation MeSH
- Reproducibility of Results MeSH
- Self Concept MeSH
- Cross-Cultural Comparison * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Validation Study MeSH
OBJECTIVES: To analyze the prevalence and severity of fetal aortic regurgitation (AR) after undergoing successful fetal aortic valvuloplasty (FAV) and to evaluate its effects on fetal circulation and left ventricular (LV) growth. METHODS: This was a retrospective review of all fetuses with critical aortic stenosis who underwent successful FAV at our center between 2010 and 2024 for whom postnatal echocardiograms were available in digital format. Fetal and postnatal echocardiographic examinations were analyzed for ventricular and valvular dimensions and characteristics, and Z-scores were calculated for middle cerebral artery (MCA) pulsatility index (PI), umbilical artery (UA) PI and cerebroplacental ratio. AR severity was classified into no/mild AR or significant (moderate/severe) AR. The balloon-to-aortic valve ratio (BVR) was calculated as the ratio between the maximum actual balloon diameter and the aortic valve (AV) annulus diameter. The primary endpoints of this study were the prevalence, severity and risk factors for fetal AR following successful FAV. RESULTS: Ninety-nine fetuses who underwent successful FAV were included. Immediate post-FAV echocardiograms showed that 87% of fetuses developed some degree of AR, including 45% of all fetuses with significant AR. BVR was significantly higher in fetuses with significant AR compared to those with no/mild AR (mean, 1.09 (95% CI, 1.06-1.12) vs 1.02 (95% CI, 0.99-1.04); P < 0.001). In a subgroup of 66/99 fetuses with available postnatal echocardiograms, the prevalence of AR decreased significantly from 86% before birth to 58% after birth (P < 0.001), with the proportion of fetuses with significant AR reducing from 47% before birth to 17% after birth (P < 0.001). In the overall cohort of fetuses, AV maximum velocity (Vmax) increased significantly from post-FAV to after birth (mean, 1.93 (95% CI, 1.75-2.11) m/s vs 3.21 (95% CI, 2.89-3.55) m/s; P < 0.001), regardless of AR severity, but Vmax after birth was lower in the significant-AR group compared with the no/mild-AR group (mean, 2.85 m/s vs 3.55 m/s; P = 0.020). Fetuses with significant AR exhibited higher relative LV length increases from immediately post-FAV to after birth than did those with no/mild AR (25% (95% CI, 16-33%) vs 14% (95% CI, 6-21%); P = 0.044), although there was no significant difference in mean LV length Z-score after birth between the two groups. FAV led to significant short-term increases in MCA-PI and UA-PI Z-scores, with greater increases observed in fetuses with significant AR. CONCLUSIONS: FAV is associated with a high prevalence of fetal AR, which lessens in severity over the course of gestation. Significant fetal AR had the largest association with greater BVR and had significant impact on fetal hemodynamics. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
- MeSH
- Aortic Valve diagnostic imaging embryology MeSH
- Aortic Valve Insufficiency * diagnostic imaging epidemiology physiopathology MeSH
- Aortic Valve Stenosis diagnostic imaging embryology epidemiology physiopathology MeSH
- Balloon Valvuloplasty * MeSH
- Adult MeSH
- Echocardiography methods MeSH
- Fetal Heart diagnostic imaging physiopathology MeSH
- Gestational Age MeSH
- Humans MeSH
- Fetal Diseases epidemiology diagnostic imaging MeSH
- Infant, Newborn MeSH
- Prevalence MeSH
- Retrospective Studies MeSH
- Risk Factors MeSH
- Severity of Illness Index MeSH
- Pregnancy MeSH
- Ultrasonography, Prenatal * MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
The temporomandibular joint (TMJ) is one of the most used joints in the body. Defects and wear in the cartilage of the joint, condyle, and fibrocartilage disc lie at the heart of many common TMJ disorders. During postnatal development, the condyle acts as a growth center for the mandible, with cells moving as a conveyor belt away from the top of the condyle as they differentiate. The superficial layers of the condyle have been proposed to contain stem/progenitor populations to allow growth and maintain homeostasis. Here we have focused on the role of fibroblast-specific protein 1 (FSP1; also known as S100a4) as a key fibroblast stem/progenitor marker for the condyle. Lineage tracing with FSP1-Cre;R26RmTmG mice revealed that FSP1-expressing cells were restricted to the superficial fibroblast zone, giving rise to all layers of the condyle over time. The FSP1-expressing cells overlapped with other putative stem cell markers of the condyle, such as Gli1 and scleraxis. BrdU pulse chase experiments highlighted that a subset of FSP1 fibrocartilage was label retaining, suggesting that FSP1 labels a novel stem/progenitor cell population in the condyle. Destruction of FSP1-expressing cells by conditional diphtheria toxin activity in FSP1-Cre;R26RDTA mice resulted in severe TMJ osteoarthritis with loss of the cartilage structure. Lgr5-expressing cells in the superficial layer of the condyle have been shown to create a Wnt inhibitory niche. FSP1 expression postnatally was associated with a reduction in canonical Wnt activity in the condyle. Importantly, constitutive activation of Wnt/β catenin in FSP1-expressing cells led to a downregulation of FSP1 and progressive postnatal loss of TMJ condylar hyaline cartilage due to loss of the superficial stem/progenitor cells. These data demonstrate a novel role for FSP1-expressing cells in the superficial zone in growth and maintenance of the TMJ condylar cartilage and highlight the importance of regulating Wnt activity in this population.
- MeSH
- Fibroblasts metabolism MeSH
- Homeostasis physiology MeSH
- Stem Cells * metabolism physiology MeSH
- Mice, Transgenic MeSH
- Mice MeSH
- Mandibular Condyle growth & development cytology metabolism MeSH
- Receptors, G-Protein-Coupled MeSH
- S100 Calcium-Binding Protein A4 * metabolism physiology MeSH
- Temporomandibular Joint * growth & development cytology MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
The FGF signaling pathway plays an important role in the regulation of limb development, controlling cell migration, proliferation, differentiation, and apoptosis. Sprouty proteins act as antagonists of the FGF pathway and control the extent of FGF signaling as part of a negative feedback loop. Sprouty2/4 deficient mice evince defects in endochondral bone formation and digit patterning in their forelimbs, with pathogenesis recently related to ciliopathies. To understand the mechanisms behind these pathologies, the limb defects in Sprouty2+/-;Sprouty4-/- male and female mice were characterized and correlated to the dynamic expression patterns of Sprouty2 and Sprouty4, and the impact on the main signaling centers of the limb bud was assessed. Sprouty2 and Sprouty4 exhibited dynamic expressions during limb development. Interestingly, despite similar expression patterns in all limbs, the hindlimbs did not evince any obvious alterations in development, while the forelimbs showed consistent phenotypes of variable severity. Prenatally as well as postnatally, the left forelimb was significantly more severely affected than the right one. A broad variety of pathologies was present in the autopodium of the forelimb, including changes in digit number, size, shape, and number of bones, hand clefts, and digit fusions. Ectopic ossification of bones and abnormal bone fusions detected in micro-CT scans were frequently observed in the digital as well as in the carpal and metacarpal areas. Sprouty2+/-;Sprouty4-/- limb buds showed patchy loss of Fgf8 expression in the apical ectodermal ridge, and a loss of tissue underlying these regions. The zone of polarizing activity was also impacted, with lineage analysis highlighting a change in the contribution of Sonic hedgehog expressing cells. These findings support the link between Sproutys and Hedgehog signaling during limb development and highlight the importance of Sprouty2 and Sprouty4 in controlling early signaling centers in the limb.
- Publication type
- Journal Article MeSH
Seizures elicited by corneal 6-Hz stimulation are widely acknowledged as a model of temporal lobe seizures. Despite the intensive research in rodents, no studies hint at this model in developing animals. We focused on seven age groups of both male and female rats. Biphasic pulses with 0.3 ms duration and current intensities from 20 to 80 mA were applied transcorneally for 3 s to calculate threshold intensities for individual age groups. Threshold stimulation intensity necessary for elicitation of clonic seizures was highly age- and sex-dependent. The highest threshold was observed in the youngest (15-day-old) group then it decreased to the age of 25 days and increased again up to adulthood. The threshold current tended to be lower in females of all age groups. The incidence of convulsive seizures increased with stimulation intensity up to postnatal day 25 in either sex. In rats of 31 days old and older convulsions occurred irregularly regardless of the stimulation current and sex. For subsequent analysis, the animals were categorized into two groups: juveniles, aged 15 to 25 days, and adolescents/adults, aged 31 days and older. Our statistical analyses revealed an increased risk of convulsions after the stimulation with higher intensities in juvenile but not adolescent/adult rats. Females tended to be more sensitive to the stimulation with lower currents than males. Seizure severity was higher in females 18- to 25-day old compared to males of the same age and the seizure duration increased with stimulation intensities in juvenile but not adolescent/adult animals. The data extend the use of the rat 6 Hz model to immature animals and may be useful as a model of pediatric temporal lobe seizures.
- MeSH
- Electric Stimulation * MeSH
- Rats MeSH
- Disease Models, Animal MeSH
- Cornea physiopathology pathology MeSH
- Age Factors MeSH
- Seizures * physiopathology etiology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH