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Nature Communications Sep 2023Tumor recognition by T cells is essential for antitumor immunity. A comprehensive characterization of T cell diversity may be key to understanding the success of...
Tumor recognition by T cells is essential for antitumor immunity. A comprehensive characterization of T cell diversity may be key to understanding the success of immunomodulatory drugs and failure of PD-1 blockade in tumors such as multiple myeloma (MM). Here, we use single-cell RNA and T cell receptor sequencing to characterize bone marrow T cells from healthy adults (n = 4) and patients with precursor (n = 8) and full-blown MM (n = 10). Large T cell clones from patients with MM expressed multiple immune checkpoints, suggesting a potentially dysfunctional phenotype. Dual targeting of PD-1 + LAG3 or PD-1 + TIGIT partially restored their function in mice with MM. We identify phenotypic hallmarks of large intratumoral T cell clones, and demonstrate that the CD27 and CD27 T cell ratio, measured by flow cytometry, may serve as a surrogate of clonal T cell expansions and an independent prognostic factor in 543 patients with MM treated with lenalidomide-based treatment combinations.
Topics: Adult; Humans; Animals; Mice; Multiple Myeloma; T-Lymphocytes; Programmed Cell Death 1 Receptor; Lenalidomide; Clone Cells
PubMed: 37730678
DOI: 10.1038/s41467-023-41562-6 -
Ugeskrift For Laeger Mar 2024Gestational surrogacy, in which an infertile couple contracts with a woman to carry a foetus that the intended parents will raise, increases worldwide, and offers a... (Review)
Review
Gestational surrogacy, in which an infertile couple contracts with a woman to carry a foetus that the intended parents will raise, increases worldwide, and offers a route to parenthood for individuals and couples who otherwise have limited options. However, the situation in Denmark at present is that surrogacy with the help of healthcare professionals is illegal, and international adoption is no longer available. This review gives an overview of the legal situation of surrogacy in Denmark, the impact of the legislation, and medical issues to be aware of as healthcare professionals in the future.
Topics: Pregnancy; Female; Humans; Surrogate Mothers; Contracts; Infertility; Denmark
PubMed: 38533857
DOI: 10.61409/V10230662 -
Clinical Chemistry Jul 2023Large β-globin gene cluster deletions (hereditary persistence of fetal hemoglobin [Hb] or β-, δβ-, γδβ-, and ϵγδβ-thalassemia), are associated with widely...
BACKGROUND
Large β-globin gene cluster deletions (hereditary persistence of fetal hemoglobin [Hb] or β-, δβ-, γδβ-, and ϵγδβ-thalassemia), are associated with widely disparate phenotypes, including variable degrees of microcytic anemia and Hb F levels. When present, increased Hb A2 is used as a surrogate marker for β-thalassemia. Notably, ϵγδβ-thalassemias lack the essential regulatory locus control region (LCR) and cause severe transient perinatal anemia but normal newborn screen (NBS) results and Hb A2 levels. Herein, we report a novel deletion of the ϵ, Aγ, Gγ, and ψβ loci with intact LCR, δ-, and β-regions in 2 women and newborn twins.
METHODS
Capillary electrophoresis (CE), high-performance liquid chromatography (HPLC), DNA sequencing, multiplex ligation-dependent probe amplification (MLPA), gap-polymerase chain reaction (gap-PCR), and long-read sequencing (LRS) were performed.
RESULTS
NBS showed an Hb A > Hb F pattern for both twins. At 20 months, Hb A2 was increased similarly to that in the mother and an unrelated woman. Unexplained microcytosis was absent and the twins lacked severe neonatal anemia. MLPA, LRS, and gap-PCR confirmed a 32 599 base pair deletion of ϵ (HBE1) through ψβ (HBBP1) loci.
CONCLUSIONS
This deletion represents a hemoglobinopathy category with a distinct phenotype that has not been previously described, an ϵγ-thalassemia. Both the NBS Hb A > F pattern and the subsequent increased Hb A2 without microcytosis are unusual. A similar deletion should be considered when this pattern is encountered and appropriate test methods selected for detection. Knowledge of the clinical impact of this new category will improve genetic counselling, with distinction from the severe transient anemia associated with ϵγδβ-thalassemia.
Topics: Humans; Female; Thalassemia; Hemoglobinopathies; beta-Thalassemia; Fetal Hemoglobin; Multiplex Polymerase Chain Reaction
PubMed: 37086467
DOI: 10.1093/clinchem/hvad038 -
Bioethics Jul 2023Assisted reproduction often involves biological contributions by third parties such as egg/sperm donors, mitochondrial DNA donors, and surrogate mothers. However, these...
Assisted reproduction often involves biological contributions by third parties such as egg/sperm donors, mitochondrial DNA donors, and surrogate mothers. However, these arrangements are also characterised by a biological relationship between the child and at least one intending parent. For example, one or both intending parents might use their own eggs/sperm in surrogacy, or an intending mother might conceive using donor sperm or gestate a donor embryo. What happens when this relationship is absent, as in the case of 'double-donor surrogacy' arrangements (DDS)? Here, a child is conceived using both donor eggs and sperm, carried by a surrogate, and raised by the commissioning parents. In this paper, I critically examine proposals to allow DDS in the United Kingdom, and the intentionalist justification for treating this practice distinctly (morally and legally speaking) from private adoption. I argue that the intentionalist approach cannot plausibly justify such a distinction and that other approaches to moral parenthood are also unlikely to succeed.
PubMed: 37467043
DOI: 10.1111/bioe.13204 -
Bioscience Trends Sep 2023China's birth rates hit a record low in 2021. The high demand for having children has spawned a massive market for surrogacy, which, however, is a dilemma in China...
China's birth rates hit a record low in 2021. The high demand for having children has spawned a massive market for surrogacy, which, however, is a dilemma in China involving a series of moral and legal issues under the current circumstances. First, special populations, including infertile patients, families who have lost their sole child, and homosexuals, wanted to have children, giving rise to surrogacy. Then, the development of and innovation in assisted reproductive technology allowed surrogacy to mature. A high return offsets a high risk, and consequently, an underground surrogacy market has emerged, causing various social issues for the Chinese Government, such as civil disputes, gender disproportion, crime, and the spread of disease. At the same time, surrogacy violates moral ethics, traditional Chinese culture, and the rights and interests of vulnerable groups.
Topics: Female; Child; Pregnancy; Humans; Surrogate Mothers; Reproductive Techniques, Assisted; China
PubMed: 37081669
DOI: 10.5582/bst.2022.01263 -
European Journal of Health Law Oct 2023In the sphere of new modalities of creating offspring, one of the most controversial issues is related to surrogacy because it opens the space to unforeseeable ethical,...
In the sphere of new modalities of creating offspring, one of the most controversial issues is related to surrogacy because it opens the space to unforeseeable ethical, legal, sociological and psychological world of dilemmas. Surrogacy is the process whereby a woman carries and gives birth to a baby for a couple who cannot conceive naturally and it has become increasingly popular worldwide. This reproductive method relativized the biological fact of birth and denied the central moment in identifying motherhood, expressed in the ancient Roman proverb that the mother of a child is the woman who gave birth to it. Surrogate motherhood changes the notion of motherhood as it separates the natural functions of a woman as a mother, or it separates the genetic from the gestational motherhood. In such a situation, the biological riddle is: Who is the real mother of the child: the one who gives the genetic material or the one who gives birth to it? The answer to this question opens many moral and ethical dilemmas in complex relationships: the surrogate mother, the couple-clients and the child. As the successful medical practice of giving birth to another undeniably exists in different countries of the world, the further fate of this method of reproduction will significantly depend on ethical justifications.
Topics: Child; Female; Humans; Pregnancy; Surrogate Mothers; Morals
PubMed: 38382555
DOI: 10.1163/15718093-bja10115 -
Journal of Assisted Reproduction and... Nov 2023In the last four decades, the assisted reproductive technology (ART) field has witnessed advances, resulting in improving pregnancy rates and diminishing complications,... (Review)
Review
In the last four decades, the assisted reproductive technology (ART) field has witnessed advances, resulting in improving pregnancy rates and diminishing complications, in particular reduced incidence of multiple births. These improvements are secondary to advanced knowledge on embryonic physiology and metabolism, resulting in the ability to design new and improved culture conditions. Indeed, the incubator represents only a surrogate of the oviduct and uterus, and the culture conditions are only imitating the physiological environment of the female reproductive tract. In vivo, the embryo travels through a dynamic and changing environment from the oviduct to the uterus, while in vitro, the embryo is cultured in a static fashion. Importantly, while culture media play a critical role in optimising embryo development, a large host of additional factors are equally important. Additional potential variables, including but not limited to pH, temperature, osmolality, gas concentrations and light exposure need to be carefully controlled to prevent stress and permit optimal implantation potential. This manuscript will provide an overview of how different current culture conditions may affect oocyte and embryo viability with particular focus on human literature.
Topics: Pregnancy; Humans; Female; Reproductive Techniques, Assisted; Embryo Implantation; Embryonic Development; Embryo, Mammalian; Culture Media; Embryo Culture Techniques; Fertilization in Vitro
PubMed: 37725178
DOI: 10.1007/s10815-023-02934-5 -
Gynecologie, Obstetrique, Fertilite &... Jun 2024
Topics: Humans; France; Surrogate Mothers; Female; Pregnancy; Altruism
PubMed: 38340981
DOI: 10.1016/j.gofs.2024.02.001 -
Clinical and Molecular Hepatology Oct 2023The current requirement for biomarkers to detect hepatitis B virus (HBV) infection is polarized. One is a fully-automated and highly sensitive measurement system; the... (Review)
Review
The current requirement for biomarkers to detect hepatitis B virus (HBV) infection is polarized. One is a fully-automated and highly sensitive measurement system; the other is a simple system for point-of-care testing (POCT) in resource-limited areas. Hepatitis B core-related antigen (HBcrAg) reflects intrahepatic covalently closed circular DNA and serum HBV DNA. Even in patients with undetectable serum HBV DNA or HBsAg loss, HBcrAg may remain detectable. Decreased HBcrAg levels are associated with reduction of the occurrence of hepatocellular carcinoma (HCC) in chronic hepatitis B. Recently, a fully-automated, novel high-sensitivity HBcrAg assay (iTACT-HBcrAg, cut-off value: 2.1 logIU/mL) has been developed. This attractive assay has been released in Japan very recently. iTACT-HBcrAg can be useful for monitoring HBV reactivation and prediction of HCC occurrence, as an alternative to HBV DNA. Moreover, monitoring HBcrAg may be suitable for determining the therapeutic effectiveness of approved drugs and novel drugs under development. Presently, international guidelines recommend anti-HBV prophylaxis for pregnant women with high viral loads to prevent mother-to-child transmission of HBV. However, >95% of HBV-infected individuals live in countries where HBV DNA quantification is not available. Worldwide elimination of HBV needs the scaling-up of examination and medication services in resource-limited areas. Based on this situation, a rapid and easy HBcrAg assay as a POCT is valuable. This review provides the latest information regarding the clinical use of a new surrogate marker, HBcrAg, in HBV management, based on iTACT-HBcrAg or POCT, and introduces novel agents targeting HBV RNA/protein.
Topics: Pregnancy; Female; Humans; Hepatitis B virus; Hepatitis B Core Antigens; Carcinoma, Hepatocellular; DNA, Viral; Liver Neoplasms; Infectious Disease Transmission, Vertical; Hepatitis B, Chronic; Hepatitis B; Biomarkers; Hepatitis B Surface Antigens
PubMed: 36891607
DOI: 10.3350/cmh.2022.0434 -
Philosophy, Ethics, and Humanities in... Jul 2023Comprehensive commercial surrogacy became legal in India in 2002, and many foreigners, including individuals and same-sex couples, sought Indian surrogacy services due...
BACKGROUND
Comprehensive commercial surrogacy became legal in India in 2002, and many foreigners, including individuals and same-sex couples, sought Indian surrogacy services due to their affordability. Numerous scandals resulted, with increasing calls for the government to eliminate the exploitation of women in lower social strata. In 2015, the Indian government decided to exclude foreign clients and commercial surrogacy remained legal for local Indian couples only. Furthermore, to eliminate exploitation, the concept of altruistic surrogacy was introduced in 2016. In 2020, some restrictions within altruistic surrogacy practice were removed. Controversy remains, however, in various sectors, not least because surrogacy is a relatively new concept in India. In this paper, the advantages and disadvantages of both altruistic and commercial surrogacy in the Indian context are considered, and more appropriate policy concerning surrogacy practices is suggested.
METHODS
This paper is based on fieldwork conducted in India from 2010 to 2018. Interview surveys were conducted among doctors, policy makers, activists, former surrogates, and brokers. Government documents and media reports were also important sources.
RESULTS
Surrogacy for commercial purposes began in India in 2002, and stakeholders within the commercial surrogacy industry became well established. It was found that such stakeholders were strongly opposed to altruistic surrogacy as introduced in 2016. It was also found that women in lower social strata still sought some form of financial compensation from their reproductive labor. Controversies surrounding altruistic surrogacy continue within Indian society.
CONCLUSION
Policies and practices aimed at eliminating exploitive need to consider the Indian context carefully. Any surrogacy practice might potentially be exploitive, and the distinction between commercial and altruistic surrogacy is too simplistic to be useful, with more nuanced understanding required. It is of critical importance that investigation continues on how to eliminate the exploitation of Indian surrogate mothers throughout the process, regardless of monetary compensation. The entire surrogacy process should be managed with sensitivity, particularly in relation to the well-being of the mother and child.
Topics: Female; Humans; Pregnancy; Altruism; India; Policy; Reproduction; Surrogate Mothers
PubMed: 37420245
DOI: 10.1186/s13010-023-00130-y