Microorganisms are important due to their widespread presence and multifaceted roles across various domains of life, ecology, and industries. In humans, they underlie the proper functioning of ...multiple systems crucial to well-being, including immunological and metabolic functions. Emerging research addressing the presence and roles of microorganisms within human reproduction is increasingly relevant. Studies implementing new methodologies (e.g., to investigate vaginal, uterine, and semen microenvironments) can now provide relevant insights into fertility, reproductive health, or pregnancy outcomes. In that sense, cutting-edge sequencing techniques, as well as others such as meta-metabolomics, culturomics, and meta-proteomics, are becoming more popular and accessible worldwide, allowing the characterization of microbiomes at unprecedented resolution. However, they frequently involve rather complex laboratory protocols and bioinformatics analyses, for which researchers may lack the required expertise. A suitable pipeline would successfully enable both taxonomic classification and functional profiling of the microbiome, providing easy-to-understand biological interpretations. However, the selection of an appropriate methodology would be crucial, as it directly impacts the reproducibility, accuracy, and quality of the results and observations. This review focuses on the different current microbiome-related techniques in the context of human reproduction, encompassing niches like vagina, endometrium, and seminal fluid. The most standard and reliable methods are 16S rRNA gene sequencing, metagenomics, and meta-transcriptomics, together with complementary approaches including meta-proteomics, meta-metabolomics, and culturomics. Finally, we also offer case examples and general recommendations about the most appropriate methods and workflows and discuss strengths and shortcomings for each technique.
Abstract
The mechanistic target of rapamycin complex 1 (mTORC1) integrates cellular nutrient signaling and hormonal cues to control metabolism. We have previously shown that constitutive nutrient ...signaling to mTORC1 by means of genetic activation of
RagA
(expression of GTP-locked RagA, or RagA
GTP
) in mice resulted in a fatal energetic crisis at birth. Herein, we rescue neonatal lethality in
RagA
GTP
mice and find morphometric and metabolic alterations that span glucose, lipid, ketone, bile acid and amino acid homeostasis in adults, and a median lifespan of nine months. Proteomic and metabolomic analyses of livers from
RagA
GTP
mice reveal a failed metabolic adaptation to fasting due to a global impairment in PPARα transcriptional program. These metabolic defects are partially recapitulated by restricting activation of RagA to hepatocytes, and revert by pharmacological inhibition of mTORC1. Constitutive hepatic nutrient signaling does not cause hepatocellular damage and carcinomas, unlike genetic activation of growth factor signaling upstream of mTORC1. In summary, RagA signaling dictates dynamic responses to feeding-fasting cycles to tune metabolism so as to match the nutritional state.
No known cohort study has investigated whether the Mediterranean diet can reduce incident coronary heart disease (CHD) events in a Mediterranean population. This study examined the relation between ...Mediterranean diet adherence and risk of incident CHD events in the 5 Spanish centers of the European Prospective Investigation into Cancer and Nutrition. Analysis included 41,078 participants aged 29–69 years, recruited in 1992–1996 and followed up until December 2004 (mean follow-up:10.4 years). Confirmed incident fatal and nonfatal CHD events were analyzed according to Mediterranean diet adherence, measured by using an 18-unit relative Mediterranean diet score. A total of 609 participants (79% male) had a fatal or nonfatal confirmed acute myocardial infarction (n = 468) or unstable angina requiring revascularization (n = 141). After stratification by center and age and adjustment for recognized CHD risk factors, high compared with low relative Mediterranean diet score was associated with a significant reduction in CHD risk (hazard ratio = 0.60, 95% confidence interval: 0.47, 0.77). A 1-unit increase in relative Mediterranean diet score was associated with a 6% reduced risk of CHD (95% confidence interval: 0.91, 0.97), with similar risk reductions by sex. Mediterranean diet adherence was associated with a significantly reduced CHD risk in this Mediterranean country, supporting its role in primary prevention of CHD in healthy populations.
Some researchers have suggested that zinc (Zn) could reduce the risk of prostate cancer (PC). However, research from observational studies on the relationship between PC risk and biomarkers of Zn ...exposure shows conflicting results.
To evaluate the association between toenail Zn and PC, considering tumour extension and aggressiveness, along with a gene-environment approach, exploring the interaction of individual genetic susceptibility to PC in the relationship between toenail Zn and PC.
In MCC-Spain study we invited all incident PC cases diagnosed in the study period (2008–2013) and recruited randomly selected general population controls. In this report we included 913 cases and 1198 controls with toenail Zn determined by inductively coupled plasma mass spectrometry. To measure individual genetic susceptibility, we constructed a polygenic risk score based on known PC-related single nucleotide polymorphisms. The association between toenail Zn and PC was explored with mixed logistic and multinomial regression models.
Men with higher toenail Zn had higher risk of PC (OR quartile 4 vs.1: 1.41; 95% CI: 1.07–1.85). This association was slightly higher in high-grade PC (ISUP≤2 Relative risk ratio (RRR) quartile 4 vs.1: 1.36; 1.01–1.83) vs. (ISUP3-5 RRR quartile 4 vs.1: 1.64; 1.06–2.54) and in advanced tumours (cT1-cT2a RRR quartile 4 vs.1: 1.40; 95% CI: 1.05–1.89) vs. (cT2b-cT4 RRR quartile 4 vs.1: 1.59; 1.00–2.53). Men with lower genetic susceptibility to PC were those at higher risk of PC associated with high toenail Zn (OR quartile 4 vs.1: 2.18; 95% CI: 1.08–4.40).
High toenail Zn levels were related to a higher risk for PC, especially for more aggressive or advanced tumours. This effect was stronger among men with a lower genetic susceptibility to PC.
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•Although Zn is an essential element for the prostate gland, its role in the development of prostate cancer remains unclear.•The association between Zn exposure and prostate cancer may differ depending on individual genetic risk for prostate cancer.•Men with higher toenail Zn had higher risk of prostate cancer.•The association between toenail Zn and prostate cancer was higher in high-grade prostate cancers and in advance tumours.•Men with lower genetic susceptibility to PC were those at higher risk of prostate cancer associated with high toenail Zn.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Reproductive events are associated with important physiologic changes, yet little is known about how reproductive factors influence long-term health in women. Our objective was to assess the relation ...of reproductive characteristics with all-cause and cause-specific mortality risk.
The analysis was performed within the European Investigation into Cancer and Nutrition prospective cohort study, which enrolled >500,000 women and men from 1992 to 2000, who were residing in a given town/geographic area in 10 European countries. The current analysis included 322,972 eligible women aged 25-70 years with 99 % complete follow-up for vital status. We assessed reproductive characteristics reported at the study baseline including parity, age at the first birth, breastfeeding, infertility, oral contraceptive use, age at menarche and menopause, total ovulatory years, and history of oophorectomy/hysterectomy. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for mortality were determined using Cox proportional hazards regression models adjusted for menopausal status, body mass index, physical activity, education level, and smoking status/intensity and duration.
During a mean follow-up of 12.9 years, 14,383 deaths occurred. The HR (95 % CI) for risk of all-cause mortality was lower in parous versus nulliparous women (0.80; 0.76-0.84), in women who had ever versus never breastfed (0.92; 0.87-0.97), in ever versus never users of oral contraceptives (among non-smokers; 0.90; 0.86-0.95), and in women reporting a later age at menarche (≥15 years versus <12; 0.90; 0.85-0.96; P for trend = 0.038).
Childbirth, breastfeeding, oral contraceptive use, and a later age at menarche were associated with better health outcomes. These findings may contribute to the development of improved strategies to promote better long-term health in women.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
The recently published Clinical Practice Guidelines (CPGs) for the treatment of stages I–IV periodontitis provided evidence‐based recommendations for treating periodontitis patients, ...defined according to the 2018 classification. Peri‐implant diseases were also re‐defined in the 2018 classification. It is well established that both peri‐implant mucositis and peri‐implantitis are highly prevalent. In addition, peri‐implantitis is particularly challenging to manage and is accompanied by significant morbidity.
Aim
To develop an S3 level CPG for the prevention and treatment of peri‐implant diseases, focusing on the implementation of interdisciplinary approaches required to prevent the development of peri‐implant diseases or their recurrence, and to treat/rehabilitate patients with dental implants following the development of peri‐implant diseases.
Materials and Methods
This S3 level CPG was developed by the European Federation of Periodontology, following methodological guidance from the Association of Scientific Medical Societies in Germany and the Grading of Recommendations Assessment, Development and Evaluation process. A rigorous and transparent process included synthesis of relevant research in 13 specifically commissioned systematic reviews, evaluation of the quality and strength of evidence, formulation of specific recommendations, and a structured consensus process involving leading experts and a broad base of stakeholders.
Results
The S3 level CPG for the prevention and treatment of peri‐implant diseases culminated in the recommendation for implementation of various different interventions before, during and after implant placement/loading. Prevention of peri‐implant diseases should commence when dental implants are planned, surgically placed and prosthetically loaded. Once the implants are loaded and in function, a supportive peri‐implant care programme should be structured, including periodical assessment of peri‐implant tissue health. If peri‐implant mucositis or peri‐implantitis are detected, appropriate treatments for their management must be rendered.
Conclusion
The present S3 level CPG informs clinical practice, health systems, policymakers and, indirectly, the public on the available and most effective modalities to maintain healthy peri‐implant tissues, and to manage peri‐implant diseases, according to the available evidence at the time of publication.
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BFBNIB, CMK, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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