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Biomedicines Apr 2024In the biomedical field, the differentiation between sex and gender is crucial for enhancing the understanding of human health and personalizing medical treatments,... (Review)
Review
Investigating and Practicing Orthopedics at the Intersection of Sex and Gender: Understanding the Physiological Basis, Pathology, and Treatment Response of Orthopedic Conditions by Adopting a Gender Lens: A Narrative Overview.
In the biomedical field, the differentiation between sex and gender is crucial for enhancing the understanding of human health and personalizing medical treatments, particularly within the domain of orthopedics. This distinction, often overlooked or misunderstood, is vital for dissecting and treating musculoskeletal conditions effectively. This review delves into the sex- and gender-specific physiology of bones, cartilage, ligaments, and tendons, highlighting how hormonal differences impact the musculoskeletal system's structure and function, and exploring the physiopathology of orthopedic conditions from an epidemiological, molecular, and clinical perspective, shedding light on the discrepancies in disease manifestation across sexes. Examples such as the higher rates of deformities (adolescent idiopathic and adult degenerative scoliosis and hallux valgus) in females and osteoporosis in postmenopausal women illustrate the critical role of sex and gender in orthopedic health. Additionally, the review addresses the morbidity-mortality paradox, where women, despite appearing less healthy on frailty indexes, show lower mortality rates, highlighting the complex interplay between biological and social determinants of health. Injuries and chronic orthopedic conditions such osteoarthritis exhibit gender- and sex-specific prevalence and progression patterns, necessitating a nuanced approach to treatment that considers these differences to optimize outcomes. Moreover, the review underscores the importance of recognizing the unique needs of sexual minority and gender-diverse individuals in orthopedic care, emphasizing the impact of gender-affirming hormone therapy on aspects like bone health and perioperative risks. To foster advancements in sex- and gender-specific orthopedics, we advocate for the strategic disaggregation of data by sex and gender and the inclusion of "Sexual Orientation and Gender Identity" (SOGI) data in research and clinical practice. Such measures can enrich clinical insights, ensure tailored patient care, and promote inclusivity within orthopedic treatments, ultimately enhancing the precision and effectiveness of care for diverse patient populations. Integrating sex and gender considerations into orthopedic research and practice is paramount for addressing the complex and varied needs of patients. By embracing this comprehensive approach, orthopedic medicine can move towards more personalized, effective, and inclusive treatment strategies, thereby improving patient outcomes and advancing the field.
PubMed: 38790936
DOI: 10.3390/biomedicines12050974 -
Genes May 2024The estrogen receptor signaling pathway plays an important role in vertebrate embryonic development and sexual differentiation. There are four major estrogen receptors...
The estrogen receptor signaling pathway plays an important role in vertebrate embryonic development and sexual differentiation. There are four major estrogen receptors in zebrafish: , , and . However, the specific role of different estrogen receptors in zebrafish is not clear. To investigate the role of in zebrafish development and reproduction, this study utilized TALENs technology to generate an knockout homozygous zebrafish line. The number of eggs laid by knockout female zebrafish did not differ significantly from that of wild zebrafish. The embryonic development process of wild-type and knockout zebrafish was observed, revealing a significant developmental delay in the knockout zebrafish. Additionally, mortality rates were significantly higher in knockout zebrafish than in their wild-type counterparts at 24 hpf. The reciprocal cross experiment between knockout zebrafish and wild-type zebrafish revealed that the absence of resulted in a decline in the quality of zebrafish oocytes, while having no impact on sperm cells. The knockout of also led to an abnormal sex ratio in the adult zebrafish population, with a female-to-male ratio of approximately 1:7. The quantitative PCR (qPCR) and in situ hybridization results demonstrated a significant downregulation of expression in knockout embryos compared to wild-type embryos throughout development (at 2 dpf, 3 dpf and 4 dpf). Additionally, the estrogen-mediated induction expression of was attenuated, while the estradiol-induced upregulated expression of was disrupted. These results suggest that is involved in regulating zebrafish oocyte development and sex differentiation.
Topics: Animals; Zebrafish; Female; Male; Zebrafish Proteins; Sex Ratio; Aromatase; Embryonic Development; Gene Expression Regulation, Developmental; Gene Knockout Techniques; Estrogen Receptor beta; Sex Differentiation; Oocytes
PubMed: 38790265
DOI: 10.3390/genes15050636 -
Genes May 2024It is widely known that all-female fish production holds economic value for aquaculture. , a preeminent economic species, exhibits a sex dimorphism, with females...
It is widely known that all-female fish production holds economic value for aquaculture. , a preeminent economic species, exhibits a sex dimorphism, with females surpassing males in growth. In this regard, achieving all-female black rockfish production could significantly enhance breeding profitability. In this study, we utilized the widely used male sex-regulating hormone, 17α-methyltestosterone (MT) at three different concentrations (20, 40, and 60 ppm), to produce pseudomales of for subsequent all-female offspring breeding. Long-term MT administration severely inhibits the growth of , while short term had no significant impact. Histological analysis confirmed sex reversal at all MT concentrations; however, both medium and higher MT concentrations impaired testis development. MT also influenced sex steroid hormone levels in pseudomales, suppressing E2 while increasing T and 11-KT levels. In addition, a transcriptome analysis revealed that MT down-regulated ovarian-related genes ( and ) while up-regulating male-related genes () in pseudomales. Furthermore, MT modulated the TGF-β signaling and steroid hormone biosynthesis pathways, indicating its crucial role in sex differentiation. Therefore, the current study provides a method for achieving sexual reversal using MT in and offers an initial insight into the underlying mechanism of sexual reversal in this species.
Topics: Animals; Methyltestosterone; Male; Female; Sex Differentiation; Perciformes; Testis; Fishes; Fish Proteins
PubMed: 38790234
DOI: 10.3390/genes15050605 -
European Journal of Investigation in... May 2024The past decade has seen a global increase in population age, especially in developed countries, where aging involves visual diseases such as age-related macular...
The past decade has seen a global increase in population age, especially in developed countries, where aging involves visual diseases such as age-related macular degeneration (AMD), which severely affect quality of life (QoL) and mental health, as well as increase isolation and care costs. This study investigated how persons with AMD perceive the impact of technology use on their QoL, focusing on potential disparities between urban and rural contexts in Spain. Using a cross-sectional observational design, data from the 2020 National Statistics Institute's Disability, Personal Autonomy, and Dependency Situations Survey were analyzed, focusing on QoL aspects based on the WHO items of the WHOQOL-100 scale. The results revealed a generally positive perception of technology among participants, with urban residents perceiving technology's positive impact more favorably. Sex discrepancies in technology perception were also observed, as women exhibited a more positive outlook on technology's influence on QoL. The analysis of QoL aspects, such as 'Visibility', 'Learning', 'Mobility', and 'Domestic life', highlighted distinct challenges faced by rural and urban populations, underscoring the importance of context-specific approaches in technology interventions. However, these perceptions were intertwined with comorbidities, which can exacerbate AMD-related issues. Furthermore, this study explored the role of technology in enhancing QoL among older adults with AMD, examining how it influences daily activities and independence, particularly in the context of AMD management. This study concluded that developing more-inclusive policies tailored to the specific needs of persons with AMD, with special attention to environmental and sex differences, is imperative to enhance the positive impact of technology on their QoL.
PubMed: 38785595
DOI: 10.3390/ejihpe14050097 -
Frontiers in Neuroscience 2024White matter hyperintensities (WMHs), presented on T2-weighted or fluid-attenuated inversion recovery magnetic resonance imaging (MRI) sequences, are lesions in the...
BACKGROUND AND AIM
White matter hyperintensities (WMHs), presented on T2-weighted or fluid-attenuated inversion recovery magnetic resonance imaging (MRI) sequences, are lesions in the human brain that can be observed in both migraine and multiple sclerosis (MS).
METHODS
Seventeen migraine patients and 15 patients with relapsing-remitting multiple sclerosis with WMHs, and 17 healthy subjects age-and sex-matched to the migraine group were prospectively enrolled and underwent conventional and advanced MRI studies with diffusion-and perfusion-weighted imaging and single voxel proton magnetic resonance spectroscopy.
RESULTS
In both disease groups, elevated T2 relaxation time, apparent diffusion coefficient (ADC) values, and decreased -acetyl-aspartate levels were found in the intralesional white matter compared to the contralateral normal-appearing white matter (NAWM), while there was no difference between the hemispheres of the control subjects. Migraine patients had the lowest intralesional creatine + phosphocreatine and myo-inositol (mI) values among the three groups, while patients with MS showed the highest intralesional T1 and T2 relaxation times, ADC, and mI values. In the contralateral NAWM, the same trend with mI changes was observed in migraineurs and MS patients. No differences in perfusion variables were observed in any groups.
CONCLUSION
Our multimodal study showed that tissue damage is detectable in both diseases. Despite the differences in various advanced MRI measures, with more severe injury detected in MS lesions, we could not clearly differentiate the two white matter lesion types.
PubMed: 38784095
DOI: 10.3389/fnins.2024.1384073 -
Boletin Medico Del Hospital Infantil de... 2024Pilomatrixoma, also known as calcifying epithelioma of Malherbe, is a benign cutaneous neoplasm that demonstrates differentiation towards the matrix portion of hair... (Observational Study)
Observational Study
BACKGROUND
Pilomatrixoma, also known as calcifying epithelioma of Malherbe, is a benign cutaneous neoplasm that demonstrates differentiation towards the matrix portion of hair follicles. It is the most common benign cutaneous neoplasm in childhood and youth, although it can occur at any age. With a general incidence ranging from 0.001% to 0.0031% of all cutaneous tumors. There is a slight predilection for females, with a female-to-male ratio of 1.15:1.
METHODS
Observational, descriptive, retrospective, and cross-sectional study conducted using the electronic database of the dermatopathology department of Dr. Manuel Gea González General Hospital, from January 1992 to July 2023. Only cases with a histopathological diagnosis of pilomatrixoma, pilomatricoma, and Malherbe's calcifying epithelioma were included.
RESULTS
A total of 200 pilomatrixomas were recorded in 177 patients. The tumor predominantly affected females in the pediatric age group, with an average age of 22.98 years in the studied population. The most common location was the head (periorbital region), followed by the upper extremities and trunk. Upon separating the population into pediatric and adult groups, 111 and 89 cases were identified, respectively.
CONCLUSIONS
We present a detailed study on pilomatrixomas with a comprehensive overview of the demographic, clinical, and epidemiological characteristics of this benign cutaneous neoplasm. The results revealed robust statistical data highlighting the distribution by age, gender, topography, morphology, accompanying symptoms, and frequency of clinical differential diagnoses. This study significantly contributes to the existing knowledge of pilomatrixomas and serves as a valuable reference for future research and clinical practice.
Topics: Humans; Pilomatrixoma; Female; Male; Skin Neoplasms; Retrospective Studies; Child; Cross-Sectional Studies; Adolescent; Hair Diseases; Child, Preschool; Young Adult; Adult; Infant; Middle Aged; Sex Distribution; Incidence; Age Distribution
PubMed: 38768510
DOI: 10.24875/BMHIM.23000156 -
Biomedical Reports Jun 2024Colorectal cancer (CRC), one of the most prevalent types of cancer, is accompanied by a notably high incidence of thrombotic complications. The present study aimed to...
Combining gene status with preoperative D‑dimer levels as a predictive marker of venous thromboembolism risk in patients with resectable colorectal cancer: A prospective cohort study.
Colorectal cancer (CRC), one of the most prevalent types of cancer, is accompanied by a notably high incidence of thrombotic complications. The present study aimed to elucidate the association between mutations and hypercoagulability in operable CRC. The prognostic value of preoperative D-dimer levels was also investigated, thus providing novel insights into the development of therapeutic strategies to enhance patient survival and diminish morbidity. Therefore, a prospective analysis of 333 CRC cases post-surgery at Yan'an Hospital Affiliated to Kunming Medical University, between May 2019 and October 2022 was performed. Data on demographics, tumor characteristics and D-dimer levels were compiled from the electronic health records. Venous thromboembolism (VTE) was diagnosed by doppler or computed tomography angiography, with D-dimer thresholds set at 550 and 1,650 µg/l. mutations at codons 12 and 13 were assessed in a subset of 56 cases. Subsequently, the factors affecting the hypercoagulable state in these patients were prospectively analyzed, focusing on the pivotal role of . The results showed that mutations were associated with elevated preoperative D-dimer levels, with 1,076 µg/l compared with 485 µg/l in the wild-type cohort, indicative of a hypercoagulable state. Increased D-dimer levels were also associated with vascular invasion, distant metastases and a heightened risk of postoperative VTE. Furthermore, multivariate analyses identified mutations, distant metastases and vascular invasion as independent predictors of elevated D-dimer levels, with relative risk values of 2.912, 1.884 and 1.525, respectively. Conversely, sex, age, tumor location, differentiation grade, Ki67 index and tumor stage could not significantly affect D-dimer levels, thus indicating a complex interplay between tumor genetics and coagulation dysfunction in CRC. The current study suggested that the mutation status, distant metastasis and vascular invasion could be considered as independent risk factors of blood hypercoagulability in patients with CRC, potentially serving as prognostic factors for VTE risk.
PubMed: 38765860
DOI: 10.3892/br.2024.1784 -
Heliyon May 2024The incidence of pulmonary nodules is increasing because of the promotion and popularisation of low-dose computed tomography (LDCT) screening for populations with...
BACKGROUND
The incidence of pulmonary nodules is increasing because of the promotion and popularisation of low-dose computed tomography (LDCT) screening for populations with suspected lung cancer. However, a high rate of false positives and concerns regarding the radiation-related cancer risk of repeated CT scanning remain major obstacles to its wide application. This study aimed to investigate the clinical value of seven tumour-associated autoantibodies (7-TAAbs) in the differentiation of malignant pulmonary tumours from benign ones and the early detection of lung cancer in routine clinical practice.
METHODS
We included 377 patients who underwent both the 7-TAAbs panel test and LDCT screening, and were diagnosed with pulmonary nodules using LDCT. An enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels antibodies for P53, PGP9.5, SOX2, GAGE7, GBU4-5, CAGE, and MAGE-A1. The relationships between the positive rates of the 7-TAAbs and the patient sex, and age, and the number, size, and composition of pulmonary nodules were analysed. We then statistically evaluated the clinical application value.
RESULTS
The positive rates of the 7-TAAbs did not correlate with sex, age, number, size, or composition of pulmonary nodules. The serum antibody level of GBU4-5 in patients with pulmonary nodules tended to increase with age; the serum antibody level of SOX2 tended to increase with nodule size and was the highest among patients with mixed ground-glass opacity (mGGO) nodules. The antibody positive rate for CAGE in female patients with pulmonary nodules was significantly higher than that in male patients ( < 0.05). The positive rate of GBU4-5 antibody in patients aged 60 years and above was higher than that in younger patients ( < 0.05). The positive rate of GAGE7 antibody in patients with pulmonary nodules sized 8-20 mm was also significantly higher than that in patients with pulmonary nodules sized less than 8 mm ( < 0.01). Significant differences were observed in the GAGE7 antibody levels of patients with pulmonary nodules of different compositions ( < 0.01). The positive rate of the 7-TAAbs panel test in patients with lung cancer was significantly higher than in patients with pulmonary nodules ( < 0.01). Serum levels of P53, SOX2, GBU4-5, and MAGE-A1 antibodies were significantly higher in patients with lung cancer than in those with pulmonary nodules ( < 0.05).
CONCLUSION
The low positive rates of serum 7-TAAbs in patients with lung cancer and pulmonary nodules may be related to different case selection, population differences, geographical differences, different degrees of progression, and detection methods. The combined detection of 7-TAAbs has some clinical value for screening and early detection of lung cancer.
PubMed: 38765082
DOI: 10.1016/j.heliyon.2024.e30576 -
Frontiers in Cell and Developmental... 2024Sex differences in the developing human brain are primarily attributed to hormonal influence. Recently however, genetic differences and their impact on the developing...
Sex differences in the developing human brain are primarily attributed to hormonal influence. Recently however, genetic differences and their impact on the developing nervous system have attracted increased attention. To understand genetically driven sexual dimorphisms in neurodevelopment, we investigated genome-wide gene expression in an differentiation model of male and female human embryonic stem cell lines (hESC), independent of the effects of human sex hormones. Four male and four female-derived hESC lines were differentiated into a population of mixed neurons over 37 days. Differential gene expression and gene set enrichment analyses were conducted on bulk RNA sequencing data. While similar differentiation tendencies in all cell lines demonstrated the robustness and reproducibility of our differentiation protocol, we found sex-biased gene expression already in undifferentiated ESCs at day 0, but most profoundly after 37 days of differentiation. Male and female cell lines exhibited sex-biased expression of genes involved in neurodevelopment, suggesting that sex influences the differentiation trajectory. Interestingly, the highest contribution to sex differences was found to arise from the male transcriptome, involving both Y chromosome and autosomal genes. We propose 13 sex-biased candidate genes (10 upregulated in male cell lines and 3 in female lines) that are likely to affect neuronal development. Additionally, we confirmed gene dosage compensation of X/Y homologs escaping X chromosome inactivation through their Y homologs and identified a significant overexpression of the Y-linked demethylase and in male hESC during neuron development, confirming previous results in neural stem cells. Our results suggest that genetic sex differences affect neuronal differentiation trajectories, which could ultimately contribute to sex biases during human brain development.
PubMed: 38764741
DOI: 10.3389/fcell.2024.1341373 -
Journal of Translational Medicine May 2024The study of the functional genome in mice and humans has been instrumental for describing the conserved molecular mechanisms regulating human reproductive biology, and... (Review)
Review
The study of the functional genome in mice and humans has been instrumental for describing the conserved molecular mechanisms regulating human reproductive biology, and for defining the etiologies of monogenic fertility disorders. Infertility is a reproductive disorder that includes various conditions affecting a couple's ability to achieve a healthy pregnancy. Recent advances in next-generation sequencing and CRISPR/Cas-mediated genome editing technologies have facilitated the identification and characterization of genes and mechanisms that, if affected, lead to infertility. We report established genes that regulate conserved functions in fundamental reproductive processes (e.g., sex determination, gametogenesis, and fertilization). We only cover genes the deletion of which yields comparable fertility phenotypes in both rodents and humans. In the case of newly-discovered genes, we report the studies demonstrating shared cellular and fertility phenotypes resulting from loss-of-function mutations in both species. Finally, we introduce new model systems for the study of human reproductive biology and highlight the importance of studying human consanguineous populations to discover novel monogenic causes of infertility. The rapid and continuous screening and identification of putative genetic defects coupled with an efficient functional characterization in animal models can reveal novel mechanisms of gene function in human reproductive tissues.
Topics: Humans; Gametogenesis; Animals; Fertilization; Sex Differentiation; Conserved Sequence; Female; Male
PubMed: 38764035
DOI: 10.1186/s12967-024-05162-2