-
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 -
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 -
International Journal of Molecular... Oct 2023Children undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are prone to developing acute kidney injury (AKI). Markers of kidney damage: kidney injury...
Children undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are prone to developing acute kidney injury (AKI). Markers of kidney damage: kidney injury molecule (KIM)-1, interleukin (IL)-18, and neutrophil gelatinase-associated lipocalin (NGAL) may ease early diagnosis of AKI. The aim of this study was to assess serum concentrations of KIM-1, IL-18, and NGAL in children undergoing HSCT in relation to classical markers of kidney function (creatinine, cystatin C, estimated glomerular filtration rate (eGFR)) and to analyze their usefulness as predictors of kidney damage with the use of artificial intelligence tools. Serum concentrations of KIM-1, IL-18, NGAL, and cystatin C were assessed by ELISA in 27 children undergoing HSCT before transplantation and up to 4 weeks after the procedure. The data was used to build a Random Forest Classifier (RFC) model of renal injury prediction. The RFC model established on the basis of 3 input variables, KIM-1, IL-18, and NGAL concentrations in the serum of children before HSCT, was able to effectively assess the rate of patients with hyperfiltration, a surrogate marker of kidney injury 4 weeks after the procedure. With the use of the RFC model, serum KIM-1, IL-18, and NGAL may serve as markers of incipient renal dysfunction in children after HSCT.
Topics: Child; Humans; Acute Kidney Injury; Artificial Intelligence; Biomarkers; Cystatin C; Hematopoietic Stem Cell Transplantation; Interleukin-18; Kidney; Lipocalin-2; Machine Learning; Pilot Projects
PubMed: 37958774
DOI: 10.3390/ijms242115791 -
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 -
Health and Human Rights Dec 2023Surrogacy operates in a regulatory void in Argentina. Despite attempts to legislate this practice, Argentine law contains no univocal rules governing the legality and... (Review)
Review
Surrogacy operates in a regulatory void in Argentina. Despite attempts to legislate this practice, Argentine law contains no univocal rules governing the legality and enforceability of surrogacy agreements. Unsurprisingly, this has not stopped intended parents from pursuing surrogacy; quite the contrary, it has steered them into the courts, thrusting the issue into the realm of judicial policy. Through a comprehensive review and qualitative study of 32 court rulings, I address the judicial scenario regarding surrogacy in Argentina. I describe the profile of litigants who are bringing altruistic gestational surrogacy claims, the legal arguments used by courts, and the types of orders issued. I explain how the judiciary, through judicial review of the current legal framework and the application of international human rights law, including the principle of the best interests of the child, is playing a key role in ensuring access to this form of third-party assisted reproductive technology. Finally, I make the case for regulation by critically assessing these rulings to highlight the intricacies, challenges, and complexities that come with the judicial regulation of surrogacy.
Topics: Female; Pregnancy; Child; Humans; Human Rights; Surrogate Mothers; Argentina; Reproductive Techniques, Assisted; Law Enforcement
PubMed: 38145139
DOI: No ID Found -
Human Reproduction (Oxford, England) Oct 2023What are the experiences of single men using egg donation and surrogacy as a route to parenthood?
STUDY QUESTION
What are the experiences of single men using egg donation and surrogacy as a route to parenthood?
SUMMARY ANSWER
The fathers mainly had a positive relationship with the surrogate and simultaneously exercised agency, and experienced challenges, during the process of surrogacy.
WHAT IS KNOWN ALREADY
Little is known about single men's experiences of egg donation and surrogacy arrangements. Studies have focused on single men's decision-making processes about the use of surrogacy and family functioning once these families are formed. Questions remain about how fathers experience and navigate the process of surrogacy as a single man.
STUDY DESIGN, SIZE, DURATION
The study is an international, in-depth qualitative study of fathers who chose to begin a family and parent alone. Data were collected between 2018 and 2021 as part of a larger study of solo fathers with different routes to parenthood. The present study reports on 21 fathers who used surrogacy and egg donation to begin their family. The average age of the fathers was 44 years, the fathers had young children aged 6 years or younger, and lived in countries across Australia, Europe, and North America.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Purposive sampling was used to recruit participants. In-depth semi-structured interviews were conducted. Interview topics included fathers' experiences of the process of using egg donation and surrogacy, and navigating the relationship with the surrogate. The audio-recorded interviews lasted around 2 hours and were subsequently transcribed verbatim.
MAIN RESULTS AND THE ROLE OF CHANCE
Data were analysed using reflexive thematic analysis and qualitative content analysis. Most of the fathers chose an identifiable egg donor. Regarding the relationship with the surrogate, many fathers had remained in contact with her, but to differing degrees, and they generally reported positive relationships. Thematic analysis led to the identification of three themes relating to the fathers' experiences of choosing surrogacy as a single man: the ability to make choices; challenges and constraints; and special relationship.
LIMITATIONS, REASONS FOR CAUTION
Due to the variation between different countries regarding laws on surrogacy, contextual factors may have impacted on the experiences of single fathers, and the sample size was small. However, the research provides new insights into an area with little academic literature.
WIDER IMPLICATIONS OF THE FINDINGS
Given the growing trend of single men having children through surrogacy, the findings suggest that this new path to parenthood can be both rewarding and challenging. Single men may benefit from tailored support and counselling to help them navigate the surrogacy journey.
STUDY FUNDING/COMPETING INTEREST(S)
This study was funded by the Wellcome Trust (grant number 208013/Z/17/Z). The authors have no conflicts of interest to declare.
TRIAL REGISTRATION NUMBER
n/a.
Topics: Humans; Male; Child; Pregnancy; Female; Child, Preschool; Adult; Surrogate Mothers; Men; Counseling; Europe; Fathers
PubMed: 37528054
DOI: 10.1093/humrep/dead152 -
World Journal of Experimental Medicine Mar 2024Gestational diabetes is typically diagnosed in the late second or third trimester of pregnancy. It is one of the most common metabolic disorders among expectant mothers,... (Review)
Review
Gestational diabetes is typically diagnosed in the late second or third trimester of pregnancy. It is one of the most common metabolic disorders among expectant mothers, with potential serious short- and long-term complications for both maternal and offspring health. C-peptide is secreted from pancreatic beta-cells into circulation in equimolar amounts with insulin. It is a useful biomarker to estimate the beta-cell function because it undergoes negligible hepatic clearance and consequently it has a longer half-life compared to insulin. Pregnancy induces increased insulin resistance due to physiological changes in hormonal and metabolic homeostasis. Inadequate compensation by islet beta-cells results in hyperglycemia. The standard oral glucose tolerance test at 24-28 wk of gestation sets the diagnosis. Accumulated evidence from prospective studies indicates a link between early pregnancy C-peptide levels and the risk of subsequent gestational diabetes. Elevated C-peptide levels and surrogate glycemic indices at the beginning of pregnancy could prompt appropriate strategies for secondary prevention.
PubMed: 38590302
DOI: 10.5493/wjem.v14.i1.89320 -
Reproductive Biomedicine Online Oct 2023How did Danish permanently infertile couples experience surrogacy when going abroad and what impact did the war in Ukraine and the COVID-19 pandemic have on this?
RESEARCH QUESTION
How did Danish permanently infertile couples experience surrogacy when going abroad and what impact did the war in Ukraine and the COVID-19 pandemic have on this?
DESIGN
A qualitative study was performed between May and September 2022. The in-depth semi-structured interviews were conducted with 14 permanently infertile couples across Denmark who were in different stages of using surrogacy. The interviews were transcribed and analysed using systematic text condensation.
RESULTS
All except one couple went abroad, mainly to Ukraine, to have an enforceable transparent contract, professionals to advise them and the possibility of using the eggs of the intended mother. They did not feel that this was a 'choice' but rather the only option they had to have the longed-for child. According to current Danish legislation, the intended mother could not obtain legal motherhood over the child, not even through stepchild adoption, and this increased the feeling of not being a 'worthy mother'. This study expanded on the term 'reproductive exile' by identifying four different forms of exile: the exiled Danish couple, the gestational carrier in exile, exile at home and, finally, the reproductive body in exile.
CONCLUSIONS
Understanding infertile couples' experiences when crossing borders is important for several reasons. It may, among others, assist politicians and authorities in developing a sound Danish legal policy on surrogacy to address the current issues of legal parenthood and avoid missing reproductive opportunities for permanently infertile couples.
Topics: Female; Humans; Pregnancy; COVID-19; Denmark; Infertility; Mothers; Pandemics; Surrogate Mothers; Ukraine; Male
PubMed: 37517186
DOI: 10.1016/j.rbmo.2023.06.013