The Role of One-Carbon Metabolism and Methyl Donors in Medically Assisted Reproduction: A Narrative Review of the Literature.

One-carbon (1-C) metabolic deficiency impairs homeostasis, driving disease development, including infertility. It is of importance to summarize the current evidence regarding the clinical utility of 1-C metabolism-related biomolecules and methyl donors, namely, folate, betaine, choline, vitamin B12, homocysteine (Hcy), and zinc, as potential biomarkers, dietary supplements, and culture media supplements in the context of medically assisted reproduction (MAR). A narrative review of the literature was conducted in the PubMed/Medline database. Diet, ageing, and the endocrine milieu of individuals affect both 1-C metabolism and fertility status. In vitro fertilization (IVF) techniques, and culture conditions in particular, have a direct impact on 1-C metabolic activity in gametes and embryos. Critical analysis indicated that zinc supplementation in cryopreservation media may be a promising approach to reducing oxidative damage, while female serum homocysteine levels may be employed as a possible biomarker for predicting IVF outcomes. Nonetheless, the level of evidence is low, and future studies are needed to verify these data. One-carbon metabolism-related processes, including redox defense and epigenetic regulation, may be compromised in IVF-derived embryos. The study of 1-C metabolism may lead the way towards improving MAR efficiency and safety and ensuring the lifelong health of MAR infants.

Cancer Associated PRDM9: Implications for Linking Genomic Instability and Meiotic Recombination.

The PR domain-containing 9 or PRDM9 is a gene recognized for its fundamental role in meiosis, a process essential for forming reproductive cells. Recent findings have implicated alterations in the PRDM9, particularly its zinc finger motifs, in the onset and progression of cancer. This association is manifested through genomic instability and the misregulation of genes critical to cell growth, proliferation, and differentiation. In our comprehensive study, we harnessed advanced bioinformatic mining tools to delve deep into the intricate relationship between PRDM9F and cancer. We analyzed 136,752 breakpoints and found an undeniable association between specific PRDM9 motifs and the occurrence of double-strand breaks, a phenomenon evidenced in every cancer profile examined. Utilizing R statistical querying and the Regioner package, 55 unique sequence variations of PRDM9 were statistically correlated with cancer, from a pool of 1024 variations. A robust analysis using the Enrichr tool revealed prominent associations with various cancer types. Moreover, connections were noted with specific phenotypic conditions and molecular functions, underlining the pervasive influence of PRDM9 variations in the biological spectrum. The Reactome tool identified 25 significant pathways associated with cancer, offering insights into the mechanistic underpinnings linking PRDM9 to cancer progression. This detailed analysis not only confirms the pivotal role of PRDM9 in cancer development, but also unveils a complex network of biological processes influenced by its variations. The insights gained lay a solid foundation for future research aimed at deciphering the mechanistic pathways of PRDM9, offering prospects for targeted interventions and innovative therapeutic approaches in cancer management.

The economics of sediment quality on barrier shoreline restoration.

This paper depicts a simulation-based assessment of sediment quality on the performance of dedicated dredging projects for barrier island restoration in coastal Louisiana, USA. The research involved the development and integration of two sub-models. In the first, geomorphic modeling was used to simulate sediment transport dynamics within a proxy barrier island template over a 50-year trajectory. The template was assumed to be nourished with one of two sources of dredged material: nearshore (NS) sediments of lower quality (smaller grain diameter, higher organic fines); or higher quality sediments from distal sources located on the Outer Continental Shelf (OCS). In the second model, agency project records and commercial bids were used to estimate project construction costs as a function of dredge material quantity, transport distance, and project target elevation. These sub-models were coupled within a net present value framework from which average annual break-even values for ecosystem services (EBEV) were derived as an efficiency metric for comparing the economic performance of NS- and OCS-sourced projects. Results indicate that in some cases, the physical resiliency afforded by even small increases in sand diameter (+4 µm d50) can translate to greater long-term economic viability (lower EBEV) for OCS-sourced sediment transported over longer distances. Moreover, projects constructed with much higher diameter OCS sediment (+44 µm d50) with low fines and transported over relatively long distances (200 µm, 5% fines, 15-20 miles) were found to be more cost-effective than all comparably-sized projects constructed with lower quality NS sediments obtained from proximal sources (156 µm, 20% fines, 3-5 miles). For some comparisons, this quality advantage yielded a lower EBEV for OCS-sourced projects with transport distances exceeding 30 miles. Under storm-punctuated simulations, these quality advantages were more pronounced, with greater physical and economic implications for earlier (Y5) versus later (Y20) occurring storms. Budgeting for dedicated dredging projects has traditionally centered on the value of sediment as a commodity, with a focus on material placement cost. The findings of this study, however, indicate that a more comprehensive accounting of sediment quality and performance is required to maximize the economic efficiency of coastal restoration spending.

Effects of Different Drug Therapies and COVID-19 mRNA Vaccination on Semen Quality in a Man with Ankylosing Spondylitis: A Case Report.

Background and Objectives: Ankylosing spondylitis (AS) is a condition that affects 0.1% to 0.5% of the adult population. The aim of this case report was to investigate the possible effects of the drugs taken for treatment of AS as well as mRNA vaccination for COVID-19 on semen quality by performing a highly detailed analysis. Materials and Methods: Sperm characteristics were examined by light microscopy, DNA fragmentation (DFI) was analysed by flow cytometry and morphology was evaluated by transmission electron microscopy (TEM). Results: Semen analysis under therapy with (1) celecoxib and sulphasalazine showed: concentration 47 million/mL, 53% progressive motility, 7% normal morphology and 9.6% DFI, (2) Golimumab and before mRNA Vaccination showed: concentration 108 million/mL, 82% progressive motility, 1% normal morphology and 7.6% DFI, and (3) Golimumab and after 3 doses of mRNA Vaccination showed: concentration 142 million/mL, 85% progressive motility, 1% normal morphology and 6.8% DFI. TEM revealed head, neck and tail abnormalities, as well as the presence of cells with incomplete spermiogenesis white cells and phagocytes in the sample under therapy with celecoxib and sulphasalazine. Golimumab treatment lead to an increased incidence of elongated heads but in general reduced inflammation as no white cells were evident in TEM. Conclusion: The anti-inflamatory drugs celecoxib and sulphasalazine had no adverse effect on sperm quality as all parameters were within normal limits and the patient achieved under that treatment 2 pregnancies following natural conception that lead to the birth of a healthy boy and girl respectively. Anti-TNFa treatment with Golimumab exerted a negative effect on morphology but not on concentration, motility and DFI. After 3 doses of mRNA Vaccination, sperm concentration increased while motility, morphology and DFI remained similar to the values before vaccination suggesting no negative effect of the mRNA vaccine for COVID-19 on sperm quality.

Personal protective equipment and infection prevention and control: a national survey of UK medical students and interim foundation doctors during the COVID-19 pandemic.

BACKGROUND: The adequacy of personal protective equipment (PPE) and infection prevention and control (IPC) training in UK medical students and interim Foundation Year 1 (FiY1) doctors during the COVID-19 pandemic is unknown, as is its impact on COVID-19-related anxiety. METHODS: Cross-sectional, multi-centre study analysing self-reported adequacy of PPE and IPC training and correlation to a modified pandemic anxiety scale. Participants were current medical students and FiY1 doctors in the UK. Data were collected by an online survey. RESULTS: Participants reported that they received insufficient PPE information (43%) and IPC training (56%). Significantly, fewer participants identifying as women or BAME/mixed ethnicity reported receiving sufficient PPE information, compared with those identifying as men and White British/White Other, respectively. COVID-19-related anxiety was significantly higher in those without sufficient reported PPE or IPC training, in women compared with men, and in FiY1 doctors compared with medical students. CONCLUSIONS: With medical students currently volunteering in and imminently returning to hospitals in an educational capacity, levels of self-reported PPE and IPC training are sub-optimal. Better training is paramount to avoid harm to patients and healthcare professionals and to reduce COVID-19-related anxiety among medical students and FiY1 doctors.

A Novel εγδß-Thalassemia Deletion Associated with Severe Anemia at Birth and a ß-Thalassemia Intermedia Phenotype Later in Life in Three Generations of a Greek Family.

We describe a novel deletion causing heterozygous εγδß-thalassemia (εγδß-thal) across three generations of a Greek family. The Greek deletion is about 72 kb in length, spanning from the hypersensitive site 4 (HS4) in the locus control region (LCR) to the 3' end of the ß-globin gene, thus encompassing the entire ß-globin gene cluster. The deletion caused severe but transient neonatal anemia and a non transfusion-dependent chronic hemolytic anemia state later in life, resembling mild ß-thalassemia intermedia (ß-TI) rather than ß-thalassemia (ß-thal) trait, as had been previously reported. Apart from the presentation of clinical and laboratory characteristics, the challenges involving clinical management are also discussed.

An open study of valproate in subfertile men with epilepsy.

OBJECTIVES: The aim of the study was to assess whether, male patients with epilepsy, switching from valproic acid (VPA) to levetiracetam (LEV) or lamotrigine (LMG) critically improves sperm counts and parameters, increasing chance of patients' female partners to spontaneously conceive. MATERIALS AND METHODS: This is an observational prospective study recruiting all consecutive infertile male patients with epilepsy followed up at the outpatient Epilepsy Clinic of University Hospital of Ioannina, Northwest Greece. Infertile couples were referred to the Laboratory of Assisted Reproduction and Treatment of the University Hospital of Ioannina to conduct semen analysis. The first sample was collected while the patients were receiving VPA, and the second semen sample was collected after the patients were switched to LEV or LMG. RESULTS: Seventeen infertile male patients were recruited in the study. Nine patients were switched to LEV, and eight patients were switched to LMG. The mean sperm count increased after VPA withdraw P = .06. Motility was improved with an increase of total motility and non-progressive motility (P = .02 and P = .03, accordingly), whether sperm defects were decreased, mainly head defects (P = .03). Differences between patients switched to LEV or LMG were minimal and showed no significant findings. Spontaneous pregnancies were reported in three of the patients' partners, without any other clinical intervention offered to the couple. CONCLUSION: Switching from valproic acid to levetiracetam or lamotrigine improved sperm counts and other sperm parameters in subfertile male patients and increased the chance of spontaneously conceiving in subfertile couples.

Follicle inhibition at the primordial stage without increasing apoptosis, with a combination of everolimus, verapamil.

The aim of the present study was to test whether inhibition of ovarian primordial follicles and subsequent activation can be achieved by transient mTOR inhibition. In this preclinical investigation, forty-five female immature Wistar rats were randomized in 5 groups. The control group received subcutaneous saline injections. The other groups received Everolimus, Everolimus plus Verapamil, Everolimus plus Fisetin, and Fisetin alone. Primary and secondary outcomes were measured in the left ovary after a treatment period of 8 weeks. Ten days later, animals received 35 IU FSH for 4 days and 35 IU of hCG on the 5th day. The same parameters were examined in the right ovary. AMH, estradiol, and progesterone levels were assessed at the end of both interventions. Significantly, more primordial and less atretic follicles were observed in the Everolimus plus Verapamil group. AMH and progesterone levels were substantially lower in the Everolimus group. Interestingly, after ovarian stimulation higher levels of AMH and progesterone were observed in the Everolimus plus Verapamil group. Immunoblot analysis of ovarian extracts revealed that the administration of Everolimus led to a significant reduction in the mTORC1-mediated phosphorylation of the 70-kDa ribosomal protein S6 kinase 1. This decrease was reversed in the presence of FSH after stopping drug administration. The expression of the anti-apoptotic molecule Bcl2 as well as of LC3-II and ATG12 was increased after removal of the Everolimus plus Verapamil combination, indicating reduced apoptosis and increased autophagy, whereas the levels of the proliferation marker PCNA in the granulosa cells were elevated, consistent with initiation of follicular growth.Thus, the combination of Everolimus plus Verapamil is capable of increasing the number of competent primordial follicles while reducing atresia.

Reproductive health in patients with epilepsy.

The aim of the present study was to review existing knowledge on the impact of epilepsy in reproductive health of both sexes. Extensive searches of relevant documentation published until February 2020 were retrieved from PubMed and Google Scholar literature in English or in other languages with an English abstract. In females, epilepsy may lead to estrogen and androgen level abnormalities. Women with epilepsy may develop Polycystic Ovaries Syndrome (PCOS), anovulatory cycles, and menstrual disorders. In men, epilepsy may cause sex hormone dysregulation and influence spermatogenesis. Males with epilepsy may also suffer from sexual dysfunction. Antiepileptic drugs (AEDs) have adverse effects on peripheral endocrine glands, influence hormones' biosynthesis and protein binding, diminish the bioactivity of serum sex hormones, and lead to secondary endocrine disorders related to changes concerning body weight and insulin sensitivity. Valproic acid (VPA) was the first recognized AED to cause disturbances potentially due to metabolic changes and increasing weight. Women taking VPA may develop PCOS, while men may have sperm abnormalities and/or sexual dysfunction. Liver enzyme inducing AEDs may also cause menstrual and sexual disorders in women and sexual dysfunction in men. Newer AEDs are much safer but studies still suggest reduced sexuality and erectile dysfunction.

Rare Association of Hb D-Los Angeles (HBB: c.364G>C) with Hb H Disease: Diagnosis and Clinical Implications.

Hb D-Los Angeles (or Hb D-Punjab) (HBB: c.364G > C) is found worldwide and is derived from a point mutation in the ß-globin gene prevalent in the Punjab region of Northwestern India. Heterozygous or homozygous inheritance does not cause significant medical problems, whereas association with other hemoglobinopathies, especially ß-thalassemia (ß-thal) and sickle cell disease, changes the phenotype. Coinheritance of Hb D-Los Angeles with Hb H disease (α-/- -) has never been reported before. The presence of this rare combination in a family of Greek origin is herein described, and the challenges involving clinical management are discussed.

ROBO2 gene variants in children with primary nonsyndromic vesicoureteral reflux with or without renal hypoplasia/dysplasia.

BACKGROUND: Primary nonsyndromic vesicoureteral reflux (VUR) and VUR with renal hypoplasia/dysplasia (VUR-RHD) are common congenital anomalies of the kidney and urinary tract (CAKUT). Sequence variations of the ROBO2 gene were investigated in children with nonsyndromic VUR or VUR-RHD. METHODS: Single-strand conformation polymorphism (SSCP) electrophoresis or multiple restriction fragment SSCP (MRF-SSCP), followed occasionally by direct sequencing, was used to screen 103 patients and 200 controls for nucleotide changes. Gene polymorphisms and transposable elements were investigated using bioinformatics. RESULTS: Two single-nucleotide polymorphisms were detected: IVS1-53 and IVS5-31. The frequency of A allele of IVS1-53G>A did not differ significantly between patients and controls. IVS1-53 does not affect mRNA splicing according to in silico analysis. IVS5-31A>G substitution was found in one patient, reported here for the first time in VUR. In silico results demonstrated alteration in two serine/arginine-rich (SR) protein-binding sites and two additional acceptor sites. The ROBO2 gene sequence was found to contain 25.9% transposable elements. CONCLUSION: ROBO2 variants were not found to be associated with nonsyndromic VUR or VUR-RHD, providing further evidence for genetic heterogeneity. The role of transposable elements in ROBO2 gene expression in CAKUT needs further investigation since they are generally considered to be mutagens.

The ovarian response to standard gonadotropin stimulation is influenced by AMHRII genotypes.

The aim of the current study was to explore whether anti-Müllerian hormone receptor II (AMHRII) genetic variants influence the hormonal profile and the ovarian response to standard gonadotropin stimulation of women undergoing medically assisted reproduction. Three hundred in vitro fertilization or intracytoplasmic sperm injection patients constituted the study population, while 300 women with at least one spontaneous pregnancy participated as controls. The follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and AMH levels were determined at the third day of the menstrual cycle. AMHRII 10A > G (rs11170555), 1749C > T (rs2071558) and -482A > G (rs2002555) polymorphisms were genotyped. The follicle and oocyte numbers, the follicle size and the clinical pregnancies were recorded. Regarding the AMHRII 1749C > T polymorphism, 1749CT women presented with higher total follicle and small follicle numbers compared to 1749CC women (p = 0.04 and p = 0.01, respectively). Whereas, as concerns the -482A > G polymorphism, -482AG women were characterized by higher total follicle and small follicle numbers comparing with -482AA women (p = 0.07 and p = 0.004, respectively). Finally, -482AG women presented with increased FSH levels compared to -482AA women (p < 0.05). However, no associations of AMHRII gene polymorphisms with serum AMH levels or clinical pregnancy rates were observed. AMHRII 1749C > T and -482A > G genetic variants were associated with the ovarian response to standard gonadotropin stimulation, affecting mainly the follicular growth.

The combination of Everolimus with Verapamil reduces ovarian weight and vascular permeability on ovarian hyperstimulation syndrome: a preclinical experimental randomized controlled study.

The efficacy of pathways inhibition and the combined effect of Everolimus (mTOR inhibitor) and Verapamil (CYP3A inhibitor) in ovarian hyperstimulation syndrome (OHSS) need to be tested. Therefore, the impact of a leucotriene receptor antagonist, an anticoagulant, a GnRH antagonist as well as Everolimus plus Verapamil (at various doses and days of administration) on an OHSS rat model was tested. Sixty three female Wistar rats were randomly divided into seven groups. The control group received saline, while the OHSS group received rec-FSH for four consecutive days. The other five groups received rec-FSH for four days and Montelukast daily, Heparin daily, GnRH antagonist daily, Everolimus plus Verapamil in the last two days (half days group) and Everolimus plus Verapamil (half dose group) daily, respectively. All groups received also hCG at the fifth day. Significantly reduced ovarian weight was observed in the Everolimus plus Verapamil groups (half days and half-dose groups) and the Montelukast group compared to the OHSS group (p = 0.001 and p = 0.001, respectively). The vascular permeability was significantly reduced in the Everolimus plus Verapamil group (half dose group) and the GnRH antagonist group compared to the OHSS group (p < 0.001 and p = 0.011, respectively). However, estradiol and progesterone levels did not differ significantly between the groups. Studying the inhibition of different pathways, we concluded that the co-administration of Everolimus and Verapamil (at half dose) is beneficial for reducing ovarian weight and vascular permeability in an OHSS animal model.

Everolimus, an mTOR pathway inhibitor, is highly successful on ovarian hyperstimulation syndrome by reducing ovarian weight and progesterone levels: a preclinical experimental randomized controlled study.

The usefulness of various pathways inhibitors, Everolimus, an inhibitor of mammalian target of rapamycin (mTOR), Infliximab, a monoclonal antibody which blocks the tumor necrosis factor-a (TNF-a), Erlotinib, a tyrosine protein kinase inhibitor of the epidermal growth factor receptor (EGFR), Metformin, an activator of AMP-activated protein kinase enzyme (AMPK) and vascular permeability reducers were explored in an ovarian hyperstimulation syndrome (OHSS) rat model. Sixty-three female Wistar rats were randomly divided in seven groups. The control group received saline, while the OHSS group received recombinant -- follicle-stimulating hormone (rec-FSH) for four consecutive days. The other five groups received rec-FSH for 4 d and Everolimus daily, Infliximab once, Erlotinib daily, Metformin daily and Vitamin C daily, respectively. All groups received human chorionic gonadotropin (hCG) at the fifth day. The efficacy of Everolimus administration for various intervals was also explored. Significantly reduced ovarian weight was observed in the Everolimus group (rec-FSH + hCG + mTOR inhibitor) compared to the OHSS group (p < 0.001). The Everolimus group also showed the lowest progesterone (PRG) concentration (p = 0.007). The Erlotinib group (rec-FSH + hCG + EGFR inhibitor) presented with the lowest graafian follicle number, while the Everolimus group was characterized by the lowest corpus luteum number. The vascular permeability and the estradiol levels did not differ between groups. Finally, the Everolimus intra-comparison showed no difference in all measured outcomes. Studying the different pathways linked to vascular endothelial growth factor (VEGF) pathway, we conclude that targeting mTOR pathways is beneficial for reducing ovarian weight and PRG levels in an OHSS animal model.

Association of the (TTTA)n repeat polymorphism of CYP19 gene with bone mineral density in Greek peri- and postmenopausal women.

UNLABELLED: Aromatase is encoded by the CYP19 gene and catalyses the conversion of androgens to oestrogens, which in turn regulate skeletal homeostasis. CYP19 gene polymorphisms have been studied for their association with bone mineral density (BMD) in the general population with mixed results. OBJECTIVE: To explore the influence of the CYP19 (TTTA)n repeat polymorphism on BMD and serum levels of osteoprotegerin (OPG), receptor activator of nuclear factor-κΒ ligand (RANKL), and bone metabolic markers in a Greek female population. DESIGN: Cross-sectional study. PARTICIPANTS AND MEASUREMENTS: Two hundred and seventeen peri- and postmenopausal women aged 42-63 years were enrolled. All participants underwent spinal BMD evaluation by dual-energy X-ray absorptiometry (DXA). Genotyping of the (TTTA)n repeat polymorphism was performed by polymerase chain reaction. Levels of OPG, soluble RANKL (sRANKL) and bone metabolic markers were measured. RESULTS: Genotype analysis revealed alleles having 7-12 TTTA repeats. Women carrying the (TTTA)11 and/or (TTTA)12 alleles had significantly higher spinal BMD than women not carrying these alleles in the total study population as well as in the subgroup of women with osteoporosis (P = 0·042 and P = 0·006, respectively). The aforementioned associations remained significant after adjustment for age, years since menopause, smoking and body mass index (P = 0·048 and P = 0·023, respectively, by multivariate analysis). Moreover, the urinary calcium to creatinine ratio was associated with the (TTTA)n polymorphism. No association of the (TTTA)n polymorphism with circulating levels of OPG, sRANKL was observed. CONCLUSIONS: The (TTTA)n polymorphism of the CYP19 gene is associated with spinal BMD in peri- and postmenopausal Greek women.

Role of 9p21 and 2q36 variants and arterial stiffness in the prediction of coronary artery disease.

BACKGROUND: Genetic polymorphisms and arterial stiffness indices have been associated with cardiovascular prognosis and the presence and extent of angiographic coronary artery disease (CAD). We aimed to investigate whether arterial stiffness indices and 9p21 and 2q36 variants may improve prediction of CAD presence and extent when added to classical cardiovascular risk factors in patients at high risk for CAD. MATERIALS AND METHODS: In this cross-sectional study, we enrolled 183 consecutive patients with suspected stable CAD (age 61 ± 9 years, 134 males) referred for diagnostic coronary angiography. Framingham risk score (FRS) was calculated. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (PWV) and central augmentation index (AIx) using applanation tonometry. Genetic polymorphisms of 9p21 (rs1333049) and 2q36 (rs2943634) loci were also analysed. RESULTS: Higher FRS and PWV and the presence of rs2943634 risk allele were independent predictors of CAD (Nagelkerke R(2) 0·252, P < 0·001), while higher FRS and the presence of rs1333049 risk allele were independent predictors of multivessel CAD (Nagelkerke R(2) 0·190, P < 0·001). Genetic polymorphisms and vascular indices did not improve the predictive accuracy of FRS-based models (P > 0·1 for all) for CAD presence or extent. CONCLUSIONS: In these high-risk patients, 9p21 and 2q36 variants and PWV were independently associated with CAD presence and extent, but the addition of both genetic data and arterial stiffness indices to FRS did not improve the prediction of CAD compared with FRS alone. Further studies are needed to clarify the prognostic role of genetic and vascular indices in the prediction of angiographic CAD.

Ovarian hyperstimulation syndrome inhibition by targeting VEGF, COX-2 and calcium pathways: a preclinical randomized study.

OBJECTIVE: The efficacy of vascular endothelial growth factor (VEGF), COX-2, calcium and aromatase inhibitors in an ovarian hyperstimulation syndrome (OHSS) rat model was tested. METHODS: One hundred and eight female Wistar rats were randomly divided in nine groups. The control group received saline, while the OHSS group received rec-FSH for 4 consecutive days. The other seven groups received rec-FSH (4d) and Bevacizumab twice, Parecoxib daily, Verapamil daily, Parecoxib daily and Bevacizumab twice, Verapamil daily and Bevacizumab twice, Parecoxib and Verapamil daily, Letrozole and Meloxicam daily, respectively. All groups received also hCG at the 5th day. RESULTS: All intervention groups were characterized by reduced vascular permeability compared to the OHSS group, which in the groups of Verapamil (Calcium inhibition) and Parecoxib + Verapamil (COX-2 + Calcium inhibition) presented significant statistical difference. The Verapamil group showed the lowest corpus luteum formation, while the Parecoxib (COX-2 inhibition), the Parecoxib + Verapamil (COX-2 + Calcium inhibition), the Bevacizumab + Parecoxib (VEGF + COX-2 inhibition) and the Bevacizumab + Verapamil (VEGF + Calcium inhibition) groups were also characterized by lower corpus luteum numbers compared to the OHSS group. Furthermore, lower graafian follicle formation was observed in the above groups, while the ovarian weight and the hormonal profile were not significantly affected. CONCLUSIONS: Studying the different check points of the VEGF pathway, we conclude that targeting calcium pathways could be beneficial for the vascular permeability control in an OHSS animal model.

Storm and tidal interactions control sediment exchange in mixed-energy coastal systems.

Storms can have devasting effects on shorelines, causing flooding and the destruction of property and infrastructure. As global warming and the frequency and magnitude of tropical storms increase, barrier islands comprising 10% of the world's coast may undergo significant change caused by beach erosion, loss of dunes, and formation of washovers and tidal inlets. Understanding how storms affect sediment transport at tidal inlets is an understudied subject that directly influences barrier island erosional-depositional processes and long-term sediment budgets. This study models hydrodynamics and sediment transport at a conceptualized mixed-energy, mesotidal inlet system using 10 synthetic storm tracks. We investigate the provenance and the role of various storm characteristics and timing between the peak storm surge and high tide on sediment fluxes for different grain sizes. We find that most storms (38 of 40) cause a net import of sediment into the basin that is sourced primarily from the updrift and downdrift nearshore and secondly from the ebb-delta. Very little sediment comes from inlet channel scour. Cumulative (net) transport correlates well with peak significant wave height because wave height influences bottom shear stresses and sediment suspension on the ebb-tidal delta and in the nearshore. The duration of the storm surge also correlates with net transport because it controls the period of flood-directed currents. Our findings help explain the formation of flood deltas inside tidal inlets and the formation of sand shoals in backbarrier regions. Storm-induced enlargement of these deposits represents a permanent long-term loss of sand from barrier islands that will lead to erosion.

Evolution of Minimally Invasive and Non-Invasive Preimplantation Genetic Testing: An Overview.

Preimplantation genetic testing (PGT) has become a common supplementary diagnοstic/testing tοol for in vitro fertilization (ΙVF) cycles due to a significant increase in cases of PGT fοr mοnogenic cοnditions (ΡGT-M) and de novο aneuplοidies (ΡGT-A) over the last ten years. This tendency is mostly attributable to the advancement and application of novel cytogenetic and molecular techniques in clinical practice that are capable of providing an efficient evaluation of the embryonic chromosomal complement and leading to better IVF/ICSI results. Although PGT is widely used, it requires invasive biopsy of the blastocyst, which may harm the embryo. Non-invasive approaches, like cell-free DNA (cfDNA) testing, have lower risks but have drawbacks in consistency and sensitivity. This review discusses new developments and opportunities in the field of preimplantation genetic testing, enhancing the overall effectiveness and accessibility of preimplantation testing in the framework of developments in genomic sequencing, bioinformatics, and the integration of artificial intelligence in the interpretation of genetic data.

Retrotransposons and Diabetes Mellitus.

Retrotransposons are invasive genetic elements, which replicate by copying and pasting themselves throughout the genome in a process called retrotransposition. The most abundant retrotransposons by number in the human genome are Alu and LINE-1 elements, which comprise approximately 40% of the human genome. The ability of retrotransposons to expand and colonize eukaryotic genomes has rendered them evolutionarily successful and is responsible for creating genetic alterations leading to significant impacts on their hosts. Previous research suggested that hypomethylation of Alu and LINE-1 elements is associated with global hypomethylation and genomic instability in several types of cancer and diseases, such as neurodegenerative diseases, obesity, osteoporosis, and diabetes mellitus (DM). With the advancement of sequencing technologies and computational tools, the study of the retrotransposon's association with physiology and diseases is becoming a hot topic among researchers. Quantifying Alu and LINE-1 methylation is thought to serve as a surrogate measurement of global DNA methylation level. Although Alu and LINE-1 hypomethylation appears to serve as a cellular senescence biomarker promoting genomic instability, there is sparse information available regarding their potential functional and biological significance in DM. This review article summarizes the current knowledge on the involvement of the main epigenetic alterations in the methylation status of Alu and LINE-1 retrotransposons and their potential role as epigenetic markers of global DNA methylation in the pathogenesis of DM.