Regulation of human oocyte maturation in vivo during the final maturation of follicles.

STUDY QUESTION: Which substances and signal transduction pathways are potentially active downstream to the effect of FSH and LH in the regulation of human oocyte maturation in vivo? SUMMARY ANSWER: The regulation of human oocyte maturation appears to be a multifactorial process in which several different signal transduction pathways are active. WHAT IS KNOWN ALREADY: Many studies in animal species have provided insight into the mechanisms that govern the final maturation of oocytes. Currently, these studies have identified several different mechanisms downstream to the effects of FSH and LH. Some of the identified mechanisms include the regulation of cAMP/cGMP levels in oocytes involving C-type natriuretic peptide (CNP), effects of epidermal growth factor (EGF)-related peptides such as amphiregulin (AREG) and/or epiregulin (EREG), effect of TGF-ß family members including growth differentiation factor 9 (GDF9) and morphogenetic protein 15 (BMP15), activins/inhibins, follicular fluid meiosis activating sterol (FF-MAS), the growth factor midkine (MDK), and several others. However, to what extent these pathways and mechanisms are active in humans in vivo is unknown. STUDY DESIGN, SIZE, DURATION: This prospective cohort study included 50 women undergoing fertility treatment in a standard antagonist protocol at a university hospital affiliated fertility clinic in 2016-2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: We evaluated the substances and signalling pathways potentially affecting human oocyte maturation in follicular fluid (FF) and granulosa cells (GCs) collected at five time points during the final maturation of follicles. Using ELISA measurement and proteomic profiling of FF and whole genome gene expression in GC, the following substances and their signal transduction pathways were collectively evaluated: CNP, the EGF family, inhibin-A, inhibin-B, activins, FF-MAS, MDK, GDF9, and BMP15. MAIN RESULTS AND THE ROLE OF CHANCE: All the evaluated substances and signal transduction pathways are potentially active in the regulation of human oocyte maturation in vivo except for GDF9/BMP15 signalling. In particular, AREG, inhibins, and MDK were significantly upregulated during the first 12-17 h after initiating the final maturation of follicles and were measured at significantly higher concentrations than previously reported. Additionally, the genes regulating FF-MAS synthesis and metabolism were significantly controlled in favour of accumulation during the first 12-17 h. In contrast, concentrations of CNP were low and did not change during the process of final maturation of follicles, and concentrations of GDF9 and BMP15 were much lower than reported in small antral follicles, suggesting a less pronounced influence from these substances. LARGE SCALE DATA: None. LIMITATIONS, REASONS FOR CAUTION: Although GC and cumulus cells have many similar features, it is a limitation of the current study that information for the corresponding cumulus cells is not available. However, we seldom recovered a cumulus-oocyte complex during the follicle aspiration from 0 to 32 h. WIDER IMPLICATIONS OF THE FINDINGS: Delineating the mechanisms governing the regulation of human oocyte maturation in vivo advances the possibility of developing a platform for IVM that, as for most other mammalian species, results in healthy offspring with good efficacy. Mimicking the intrafollicular conditions during oocyte maturation in vivo in small culture droplets during IVM may enhance oocyte nuclear and cytoplasmic maturation. The primary outlook for such a method is, in the context of fertility preservation, to augment the chances of achieving biological children after a cancer treatment by subjecting oocytes from small antral follicles to IVM. Provided that aspiration of oocytes from small antral follicles in vivo can be developed with good efficacy, IVM may be applied to infertile patients on a larger scale and can provide a cheap alternative to conventional IVF treatment with ovarian stimulation. Successful IVM has the potential to change current established techniques for infertility treatment. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the University Hospital of Copenhagen, Rigshospitalet, the Independent Research Fund Denmark (grant number 0134-00448), and the Interregional EU-sponsored ReproUnion network. There are no conflicts of interest to be declared.

Prevalence of Heterotrophic Methylmercury Detoxifying Bacteria across Oceanic Regions.

Microbial reduction of inorganic divalent mercury (Hg2+) and methylmercury (MeHg) demethylation is performed by the mer operon, specifically by merA and merB genes, respectively, but little is known about the mercury tolerance capacity of marine microorganisms and its prevalence in the ocean. Here, combining culture-dependent analyses with metagenomic and metatranscriptomic data, we show that marine bacteria that encode mer genes are widespread and active in the global ocean. We explored the distribution of these genes in 290 marine heterotrophic bacteria (Alteromonas and Marinobacter spp.) isolated from different oceanographic regions and depths, and assessed their tolerance to diverse concentrations of Hg2+ and MeHg. In particular, the Alteromonas sp. ISS312 strain presented the highest tolerance capacity and a degradation efficiency for MeHg of 98.2% in 24 h. Fragment recruitment analyses of Alteromonas sp. genomes (ISS312 strain and its associated reconstructed metagenome assembled genome MAG-0289) against microbial bathypelagic metagenomes confirm their prevalence in the deep ocean. Moreover, we retrieved 54 merA and 6 merB genes variants related to the Alteromonas sp. ISS312 strain from global metagenomes and metatranscriptomes from Tara Oceans. Our findings highlight the biological reductive MeHg degradation as a relevant pathway of the ocean Hg biogeochemical cycle.

Model validity of randomised placebo-controlled trials of non-individualised homeopathic treatment.

BACKGROUND: The comprehensive systematic review of randomised placebo-controlled trials (RCTs) in homeopathy requires examination of a study's model validity of homeopathic treatment (MVHT) as well as its risk of bias (extent of reliable evidence). OBJECTIVE: To appraise MVHT in those RCTs of non-individualised homeopathy that an associated investigation had judged as 'not at high risk of bias'. DESIGN: Systematic review. METHODS: An assessment of MVHT was ascribed to each of 26 eligible RCTs. Another 49 RCTs were ineligible due to their high risk of bias. MAIN OUTCOME MEASURES: MVHT and the prior risk of bias rating per trial were merged to obtain a single overall quality designation ('high', 'moderate', 'low'), based on the GRADE principle of downgrading. RESULTS: The trials were rated as 'acceptable MVHT' (N = 9), 'uncertain MVHT' (N = 10) and 'inadequate MVHT' (N = 7); and, previously, as 'reliable evidence' (N = 3) and 'non-reliable evidence' (N = 23). The 26 trials were designated overall as: 'high quality' (N = 1); 'moderate quality' (N = 18); 'low quality' (N = 7). CONCLUSION: Of the 26 RCTs of non-individualised homeopathy that were judged 'not at high risk of bias', nine have been rated 'acceptable MVHT'. One of those nine studies was designated 'high quality' overall ('acceptable MVHT' and 'reliable evidence'), and is thus currently the only reported RCT that represents best therapeutic practice as well as unbiased evidence in non-individualised homeopathy. As well as minimising risk of bias, new RCTs in this area must aim to maximise MVHT and clarity of reporting.

Estimating SIT-driven population reduction in the Mediterranean fruit fly, Ceratitis capitata, from sterile mating.

Area-wide sterile insect technique (SIT) programs assume that offspring reduction of the target population correlates with the mating success of the sterile males released. However, there is a lack of monitoring tools to prove the success of these programs in real-time. Field-cage tests were conducted under the environmental conditions of the Mediterranean coast of Spain to estimate: (a) the mating success of sterile Vienna-8 (V8) Ceratitis capitata males using molecular markers and (b) their efficacy to reduce C. capitata populations under six release ratios of wild females to wild males to V8 males (1:0:0, 1:1:0, 1:1:1, 1:1:5, 1:1:10, and 1:1:20). Statistical models were developed to predict: (a) the number of females captured in traps, (b) sperm ID (sterile or not) in spermathecae of the trapped females, and (c) the viable offspring produced, using release ratio and temperature as predictors. The number of females captured was affected by relative humidity. However, its influence in the model was low. Female captures were significantly higher in ratios 1:0:0 compared to ratios where V8 males were released. The proportion of V8 sperm in spermathecae increased with temperature and with the number of V8 males released, but leveled off between ratios 1:1:10 and 1:1:20. In all seasons, except winter (no offspring), viable offspring increased with temperature and was lowest for ratio 1:1:20. For the first time, a strong negative relationship between proportion of V8 sperm detected by molecular tools and C. capitata offspring was established. The models obtained should contribute to enhance the efficacy of SIT programs against this pest.

"Spanish Palliative Care Nurses' Degree of Acceptance of a Proposal for Nursing Competencies in Palliative Care".

Background: In Spain, palliative care (PC) nursing is not a recognized specialization and PC nurses do not receive systematic specialized academic training in PC. To ensure the quality of PC in Spain, the Spanish Association of Palliative Care Nursing has been working since 2011 to design a model of competencies for PC nurses. Objective: Verify whether a sample of Spanish PC nurses accepts the proposed model of PC nursing competencies describing their work. Methods: Descriptive cross-sectional observational study based on an ad-hoc questionnaire about 98 proposed competencies, which participants rated for whether they belong to the purview of PC nurses and for their degree of concordance with their own practice and their degree of importance in PC nursing. Competencies receiving approval by more than 75% of participants for the three dimensions were considered to have been accepted by consensus. Mixed logistical models were developed to study the association between demographic variables and the responses. Results: Sixty-two out of 98 proposed competencies were accepted by more than 75% of participants. We therefore considered these competencies to have been accepted by consensus. Thirty-six proposed competencies failed to meet the threshold of 75% acceptance. For competencies that were accepted overall, participants with more than 10 years of experience in PC and participants with specialized training in PC were more likely to report that these competencies were part of the purview of PC nursing. Participants age >50 were less likely to report that competencies related to research concorded with their practice. Participants accepted the importance of all 98 proposed competencies. Conclusion: The variables of experience, training and age had a statistically significant relationship with the acceptance or rejection of the proposed competencies on the basis of purview and concordance. Further research is necessary to understand more fully these relationships to eventually arrive at a consensus model for the competencies of PC nurses.