A Bayesian analysis of luminescence dating.

Luminescence dating is a widespread dating method used in the fields of archaeology and Quaternary science. As an experimental method it is subject to various uncertainties in the determination of parameters that are used to evaluate age. The need to express these uncertainties fully, combined with the prior archaeological knowledge commonly available, motivates the development of a Bayesian approach to the assessment of age based on luminescence data. The luminescence dating procedure is dissected into its component parts, and each is considered individually before being combined to find the posterior age distribution. We use Bayesian multi-sample calibration to find the palaeodose in the first stage of the model, consider the problem of identifying a plateau in the data, and then use this, along with the annual dose, to estimate age. The true sample age is then modelled, incorporating any prior information available, both for an individual sample and for a collection of samples with related ages

Evaluation of a 12-week weight management group for people with type 2 diabetes and pre-diabetes in a multi-ethnic population

Weight loss offers a positive approach to the treatment of diabetes and has a number of reported benefits, including improved insulin sensitivity, glycaemic control, improved mortality rates, restoration of beta-cell function and reduced dependence on diabetes medications. The aim of this pilot study was to evaluate clinical outcomes of a 12-week weight loss intervention for people with type 2 diabetes mellitus and pre-diabetes from a multi-ethnic population. Thirty-four people were enrolled on the programme and 21 completed the course. This intervention was shown to be clinically effective, with those opting for further support achieving better clinical outcomes. South Asian individuals remain difficult-to-treat in terms of clinical outcomes and intervention adherence. Future research should consider the most appropriate interventions for this patient grou

In vitro effects of single and binary mixtures of regulated mycotoxins and persistent organochloride pesticides on steroid hormone production in MA-10 Leydig cell line

Epidemiological studies have shown strong deterioration in male reproductive health globally due to compromised testosterone production leading to altered spermatogenesis and poor sperm quality. However, the effects and mechanisms through which mycotoxins and persistent organochloride pesticides contribute to poor reproductive health in males remain unclear. The effects of single and binary combinations of ochratoxin A, deoxynivalenol, zearalenone, alpha-zearalenol, beta-zearalenol and 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane on testicular steroidogenesis were evaluated using the MA-10 Leydig cell line after 48 h of exposure. Zearalenone exposure, especially at 16 μM, had a stimulatory effect on progesterone secretion (4.7 ± 0.48 ng/mL compared to 0.60 ± 0.07 ng/mL in control), but inhibited testosterone production after 48 h compared to the solvent control. Ochratoxin A treatment significantly increased both progesterone and testosterone levels. Combination of alpha-zearalenol with beta-zearalenol showed a synergistic stimulation of progesterone hormone level at 1 and 8 μM. The results presented here show that the MA-10 Leydig cell line is a useful model for assessing the effects of xenoestrogens on testicular steroidogenesis. In addition, the inhibitory effects of zearalenone, alpha-zearalenol and beta-zearalenol on testosterone production was enhanced by co-exposure with 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane, further compounding the threat posed by these mycotoxins to male reproductive health

Lack of involvement of known DNA methyltransferases in familial hydatidiform mole implies the involvement of other factors in establishment of imprinting in the human female germline

BACKGROUND: Differential methylation of the two alleles is a hallmark of imprinted genes. Correspondingly, loss of DNA methyltransferase function results in aberrant imprinting and abnormal post-fertilization development. In the mouse, mutations of the oocyte-specific isoform of the DNA methyltransferase Dnmt1 (Dnmt1o) and of the methyltransferase-like Dnmt3L gene result in specific failures of imprint establishment or maintenance, at multiple loci. We have previously shown in humans that an analogous inherited failure to establish imprinting at multiple loci in the female germline underlies a rare phenotype of recurrent hydatidiform mole. RESULTS: We have identified a human homologue of the murine Dnmt1o and assessed its pattern of expression. Human DNMT1o mRNA is detectable in mature oocytes and early fertilized embryos but not in any somatic tissues analysed. The somatic isoform of DNMT1 mRNA, in contrast, is not detectable in human oocytes. In the previously-described family with multi-locus imprinting failure, mutation of DNMT1o and of the other known members of this gene family has been excluded. CONCLUSIONS: Mutation of the known DNMT genes does not underlie familial hydatidiform mole, at least in the family under study. This suggests that trans-acting factors other than the known methyltransferases are required for imprint establishment in humans, a concept that has indirect support from recent biochemical studies of DNMT3L

The effectiveness of mobile app usage in facilitating weight loss: An observational study

Aim: With increasing rates of global obesity and associated health issues, there is an ever‐increasing need for weight management solutions to be more accessible. Mobile applications offer accessible support systems and have the potential to offer a viable and effective weight management solution as an alternative to traditional healthcare models. Objective: To evaluate the effectiveness of the SIMPLE mobile application for time‐restricted eating in achieving weight loss (WL). Methods: User data were analyzed between January 2021 and January 2023. In‐app activity was calculated as the proportion of active days over 12, 26 and 52 weeks. A day is considered active if it contains at least one in‐app action (e.g., logging weight, food, fasting, or physical activity). Users were categorized into four in‐app activity levels: inactive (in‐app activity <33%), medium activity (33%–66%), high activity (66%–99%), and maximal activity (100%). Weight change among in‐app activity groups was assessed at 12, 26, and 52 weeks. Results: Out of 53,482 users, a positive association was found between the use of the SIMPLE app and WL. Active app users lost more weight than their less active counterparts. Active users had a median WL of 4.20%, 5.04%, and 3.86% at 12, 26, and 52 weeks, respectively. A larger percentage of active users—up to 50.26%—achieved clinically significant WL (≥5%) when compared to inactive users. A dose‐response relationship between WL and app usage was found after adjusting for gender, age, and initial Body Mass Index; a 10% increase in app activity correlated with increased WL by 0.43, 0.66 and 0.69 kg at 12, 26, and 52 weeks, respectively. Conclusions: The study demonstrates that the SIMPLE app enables effective WL directly associated with the level of app engagement. Mobile health applications offer an accessible and effective weight management solution and should be considered when supporting adults to lose weight

Mapping the methylation status of the miR-145 promoter in saphenous vein smooth muscle cells from individuals with type 2 diabetes

Type 2 diabetes mellitus prevalence is growing globally, and the leading cause of mortality in these patients is cardiovascular disease. Epigenetic mechanisms such as microRNAs (miRs) and DNA methylation may contribute to complications of type 2 diabetes mellitus. We discovered an aberrant type 2 diabetes mellitus–smooth muscle cell phenotype driven by persistent up-regulation of miR-145. This study aimed to determine whether elevated expression was due to changes in methylation at the miR-145 promoter. Smooth muscle cells were cultured from saphenous veins of 22 non-diabetic and 22 type 2 diabetes mellitus donors. DNA was extracted, bisulphite treated and pyrosequencing used to interrogate methylation at 11 CpG sites within the miR-145 promoter. Inter-patient variation was high irrespective of type 2 diabetes mellitus. Differential methylation trends were apparent between non-diabetic and type 2 diabetes mellitus–smooth muscle cells at most sites but were not statistically significant. Methylation at CpGs −112 and −106 was consistently lower than all other sites explored in non-diabetic and type 2 diabetes mellitus–smooth muscle cells. Finally, miR-145 expression per se was not correlated with methylation levels observed at any site. The persistent up-regulation of miR-145 observed in type 2 diabetes mellitus–smooth muscle cells is not related to methylation at the miR-145 promoter. Crucially, miR-145 methylation is highly variable between patients, serving as a cautionary note for future studies of this region in primary human cell types

Isolation and expression of the human gametocyte-specific factor 1 gene (GTSF1) in fetal ovary, oocytes, and preimplantation embryos

Purpose: Gametocyte-specific factor 1 has been shown in other species to be required for the silencing of retrotransposons via the Piwi-interacting RNA (piRNA) pathway. In this study, we aimed to isolate and assess expression of transcripts of the gametocyte-specific factor 1 (GTSF1) gene in the human female germline and in preimplantation embryos. Methods: Complementary DNA (cDNA) libraries from human fetal ovaries and testes, human oocytes and preimplantation embryos and ovarian follicles isolated from an adult ovarian cortex biopsy were used to as templates for PCR, cloning and sequencing, and real time PCR experiments of GTSF1 expression. Results: GTSF1 cDNA clones that covered the entire coding region were isolated from human oocytes and preimplantation embryos. GTSF1 mRNA expression was detected in archived cDNAs from staged human ovarian follicles, germinal vesicle (GV) stage oocytes, metaphase II oocytes, and morula and blastocyst stage preimplantation embryos. Within the adult female germline, expression was highest in GV oocytes. GTSF1 mRNA expression was also assessed in human fetal ovary and was observed to increase during gestation, from 8 to 21 weeks, during which time oogonia enter meiosis and primordial follicle formation first occurs. In human fetal testis, GTSF1 expression also increased from 8 to 19 weeks. Conclusions: To our knowledge, this report is the first to describe the expression of the human GTSF1 gene in human gametes and preimplantation embryos

Deoxyribonucleic acid methylation profiling of single human blastocysts by methylated CpG-island amplification coupled with CpG-island microarray

Objective To study whether methylated CpG-island (CGI) amplification coupled with microarray (MCAM) can be used to generate DNA (deoxyribonucleic acid) methylation profiles from single human blastocysts. Design A pilot microarray study with methylated CpG-island amplification applied to human blastocyst genomic DNA and hybridized on CpG-island microarrays. Setting University research laboratory. Patient(s) Five cryopreserved sibling 2-pronuclear zygotes that were surplus to requirements for clinical treatment by in vitro fertilization were donated with informed consent from a patient attending Bourn Hall Clinic, Cambridge, United Kingdom. Intervention(s) None. Main Outcome Measure(s) Successful generation of genome-wide DNA methylation profiles at CpG islands from individual human blastocysts, with common genomic regions of DNA methylation identified between embryos. Result(s) Between 472 and 734 CpG islands were methylated in each blastocyst, with 121 CpG islands being commonly methylated in all 5 blastocysts. A further 159 CGIs were commonly methylated in 4 of the 5 tested blastocysts. Methylation was observed at a number of CGIs within imprinted-gene, differentially methylated regions (DMRs), including placental and preimplantation-specific DMRs. Conclusion(s) The MCAM method is capable of providing comprehensive DNA methylation data in individual human blastocysts

Mycotoxin exposure and adverse reproductive health outcomes in Africa: A review

It is well established that mycotoxin exposure can have adverse effects on reproductive health resulting to poor reproductive potential. The most studied mycotoxin in relation to poor reproductive health in humans is aflatoxin, although fumonisins, trichothecenes and zearalenone have also been reported to impair reproductive function and cause abnormal foetal development. These potent fungal toxins contaminate many food products making them a prominent agricultural, food safety and public health challenge, especially in Africa due to little or lack of mycotoxin regulation in agricultural products. Neonates can be exposed to aflatoxins in utero, as the toxins pass from mother to the foetus through the placenta. This exposure may continue during breast feeding, to the introduction of weaning foods, and then foods taken by adults. The consequences of aflatoxin exposure in mothers, foetus and children are many, including anaemia in pregnancy, low birth weight, interference with nutrient absorption, suppression of immune function, child growth retardation and abnormal liver function. In males, reports have indicated a possible relationship between aflatoxin exposure and poor sperm quality culminating in infertility. Maternal exposure to fumonisin during early pregnancy has been associated with increased risk of neural tube defects among newborns in regions where maize is the common dietary staple with the possibility of chronic fumonisin exposure. Furthermore, zearalenone has been linked to precocious puberty and premature thelarche in girls, correlating with extremely high serum oestrogen levels. This review presents an overview of the several reports linking aflatoxins, fumonisins, trichothecenes, and zearalenone exposure to poor reproductive health outcomes in Africa, with emphasis on birth outcomes, foetal health and infertility