Search Results (1,376)

Objective: This retrospective observational study evaluated the efficacy and safety of an ovarian stimulation protocol for embryo banking that involves continuous administration of clomiphene citrate (CC) in combination with gonadotropins, without the use of GnRH antagonists. Methods: Conducted at the Serum IVF Clinic in Athens, Greece, the study included 250 women aged 25–45 who underwent IVF for embryo banking. The protocol involved administering 150 mg of CC daily from day 2 of the menstrual cycle until the day before hCG trigger, alongside 150 IU/day of Meriofert. Outcomes assessed included oocyte yield, fertilization rates, incidence of ovarian hyperstimulation syndrome (OHSS), and hormonal correlations. Comparative and regression analyses explored differences between age groups and predictors of success. Results: The protocol demonstrated a favorable safety profile with no cases of OHSS and yielded a mean of 10.25 oocytes per patient. Group analysis showed significantly more oocytes retrieved in women under 40 (mean: 12.5) versus those over 40 (mean: 8.43), while fertilization rates were paradoxically higher in the older cohort (59.16% vs. 30.68%, p < 0.0001). Regression models revealed basal FSH to be a significant inverse predictor of oocyte yield, but it was positively associated with fertilization rate. Continuous CC use effectively suppressed premature LH surges without compromising oocyte or embryo quality, allowing flexible and cost-effective stimulation with minimal monitoring. Conclusions: Continuous administration of clomiphene citrate in combination with gonadotropins presents a promising, antagonist-free ovarian stimulation protocol for embryo banking. The approach is economically efficient, reduces monitoring requirements, and maintains safety and effectiveness and is particularly notable in women over 40. Further studies are warranted to validate these findings and refine protocol mechanisms. Full article

Background: Uterine fibroids (UFs) and endometriosis are gynecological conditions that significantly increase morbidity among women of reproductive age. Relugolix, a novel gonadotropin-releasing hormone receptor antagonist, is approved in combined therapy for the management of symptoms related to these disorders. However, its potential impact on bone mineral density (BMD) and osteoporosis risk should be considered when using a gonadotropin-releasing hormone (GnRH) antagonist. This systematic review aims to evaluate the effects of daily relugolix intake in monotherapy and combination therapy on BMD, ensuring safe long-term management. Methods: A systematic literature review was conducted following PRISMA 2020 guidelines. Searches were performed in PubMed, Medline, and the Cochrane Library. Relevant clinical guidelines from international societies were also reviewed. Studies assessing the impact of relugolix on BMD were selected, and data on treatment efficacy, adverse effects, and bone health outcomes were synthesized. Results: Relugolix monotherapy has been associated with significant BMD loss due to its potent estrogen-suppressing effect. To mitigate this, combination therapy with estradiol and norethisterone acetate has been developed. Although initial monotherapy before transitioning to combination therapy results in transient BMD reduction, clinical trials have demonstrated that relugolix combination therapy maintains BMD over two years while effectively reducing endometriosis- and UF-related symptoms. Conclusions: Relugolix combination therapy is an effective and well-tolerated treatment for UFs and endometriosis, minimizing the risk of hypoestrogenism-related bone loss while maintaining clinical benefits. Although monotherapy may lead to transient BMD reduction, combination therapy appears to stabilize bone health. Full article

Chemotherapeutic agents and radiotherapy are highly effective in treating malignancies. However, they carry a significant risk of harming the gonads and may lead to endocrine dysfunction and reproductive issues. This review outlines the molecular mechanisms of gonadotoxic therapies, focusing on radiation, alkylating agents, and platinum compounds. It discusses the loss of PMFs due to gonadotoxic exposure, including DNA double-strand breaks, oxidative stress, and dysregulated signaling pathways like PI3K/PTEN/Akt/mTOR and TAp63-mediated apoptosis. Furthermore, it explores strategies to mitigate gonadal damage, including GnRH agonists, AMH, imatinib, melatonin, sphingolipid metabolites, G-CSF, mTOR inhibitors, AS101, and LH. These therapies, paired with existing fertility preservation methods, could safeguard reproductive and hormonal functions and improve the quality of life for young cancer patients. Despite the progress made in recent years in understanding gonadotoxic mechanisms, gaps remain due to questionable reliance on mouse models and the lack of models replicating human ovarian dynamics. Long-term studies are vital for wider analyses and exploration of protective strategies based on various animal models and clinical trials. It is essential to verify that these substances do not hinder the anti-cancer effectiveness of treatments or cause lasting DNA changes in granulosa cells, raising the risk of miscarriages and infertility. Full article

In China, grandparents play a significant role in childrearing. This study aims to identify latent profiles of intergenerational parenting styles and explore their impact on grandchildren’s behavioral outcomes. A total of 1432 Chinese children (M_age = 12.58 years; 45.25% boys) completed questionnaires assessing perceived grandparenting styles, while fathers and mothers independently reported their own parenting practices. Latent Profile Analysis (LPA) identified three distinct parenting profiles: “Grandparents Positive–Parents Negative” (GP–PN, 18.37%), “Grandparents Positive–Parents Positive” (GP–PP, 59.15%), and “Grandparents Negative–Parents Positive” (GN–PP, 22.48%). Regression analyses revealed that the number of siblings, grade level, and grandparent type could significantly predict profile membership. Notably, consistent and positive intergenerational parenting styles were associated with fewer problem behaviors in children. Furthermore, the relationship between parenting profiles and problem behaviors was mediated by the quality of the grandparent–parent relationship. These findings suggested that grandparents and parents should coordinate their parenting styles when raising grandchildren together. Full article

Objectives: This study aimed to evaluate the effects of AMCOP^® elastodontic appliances on cephalometric parameters of skeletal divergence and upper airway dimensions in growing patients, comparing treated individuals with an untreated control group. Methods: A total of 60 subjects (30 treated with AMCOP^® devices and 30 controls) were selected, with mean ages of 8.67 ± 1.3 and 9.19 ± 0.8 years, respectively. The AMCOP^® appliances, designed for mixed dentition, were worn for 1 h during the day and throughout the night for 6–8 months. Cephalometric analyses were conducted at the beginning (T0) and end (T1) of treatment. Statistical analyses were performed using multivariable linear regression models to assess changes in skeletal and airway parameters, with significance set at p < 0.05. Results: Significant reductions were observed in Ans-Snp^Go-Gn (p = 0.0351), SN^Go-Gn (p = 0.0091), and FMA (p < 0.001) in the treated group compared to controls, indicating improved mandibular rotation. Upper airway spaces (SPAS, MAS, IAS) increased significantly, suggesting enhanced airway patency. Regression models confirmed the positive impact of AMCOP^® therapy on skeletal and airway outcomes, particularly in subjects with pronounced vertical discrepancies. Conclusions: AMCOP^® elastodontic devices effectively promote anterior mandibular rotation and reduce mandibular plane inclination in hyperdivergent patients, contributing to balanced craniofacial growth. The expansion of pharyngeal spaces indicates potential respiratory benefits. Future research is needed to confirm long-term stability and address variability in treatment response. Full article

Pulmonary arterial hypertension (PAH) is a rare, progressive, and incurable disease characterized by an elevated pulmonary blood pressure, extensive remodeling of the pulmonary vasculature, increased pulmonary vascular resistance, and culminating in right ventricular failure. Mitochondrial dysfunction has a major role in the pathogenesis of PAH and secondary right ventricular failure, and its targeting may offer therapeutic benefit. In this study, we provide proof-of-concept for the use of the mitochondrially active drug SUL-150 to treat PAH. PAH was induced in rats by monocrotaline, followed by the placement of an aortocaval shunt one week later. The mitoprotective compound SUL-150 (~6 mg·kg⁻¹·day⁻¹) or vehicle was administered intraperitoneally via osmotic minipump for 28 days, implanted at the time of aortocaval shunt placement. Vehicle-treated PAH rats had dyspnea and showed pulmonary artery remodeling with increased responsiveness to phenylephrine, in addition to remodeling of the intrapulmonary arterioles. SUL-150 administration mitigated the dyspnea and the remodeling responses. Vehicle-treated PAH rats developed right ventricular hypertrophy, fibrosis, and failure. SUL-150 administration precluded cardiomyocyte hypertrophy and inhibited ventricular fibrogenesis. Right ventricular failure in vehicle-treated PAH rats induced mitochondrial loss and dysfunction associated with a decrease in mitophagy. SUL-150 was unable to prevent the mitochondrial loss but improved mitochondrial health in the right ventricle, which culminated in the preservation of right ventricular function. We conclude that SUL-150 improves PAH-associated morbidity by the amelioration of pulmonary vascular remodeling and right ventricular failure and may be considered a promising therapeutic candidate to slow disease progression in pulmonary arterial hypertension and secondary right ventricular failure. Full article

In agricultural practice, in addition to determining the nitrogen (N_f) dose, it is necessary to effectively control its effect on currently grown crops. Meeting these conditions requires not only the use of phosphorus (P) and potassium (K), but also nutrients such as magnesium (Mg) and sulfur (S). This hypothesis was verified in a single-factor field experiment with winter wheat (WW) carried out in the 2015/2016, 2016/2017, and 2017/2018 growing seasons. The experiment consisted of seven variants: absolute control (AC), NP, NPK-MOP (K as Muriate of Potash), NPK-MOP+Ki (Kieserite), NPK-KK (K as Korn–Kali), NPK-KK+Ki, and NPK-KK+Ki+ES (Epsom Salt). The use of K as MOP increased grain yield (GY) by 6.3% compared to NP. In the NPK-KK variant, GY was 13% (+0.84 t ha⁻¹) higher compared to NP. Moreover, GYs in this fertilization variant (FV) were stable over the years (coefficient of variation, CV = 9.4%). In NPK-KK+Ki+ES, the yield increase was the highest and mounted to 17.2% compared to NP, but the variability over the years was also the highest (CV ≈ 20%). The amount of N in grain N (GN) increased progressively from 4% for NPK-MOP to 15% for NPK-KK and 25% for NPK-KK+Ki+ES in comparison to NP. The nitrogen harvest index was highly stable, achieving 72.6 ± 3.1%. All analyzed NUE indices showed a significant response to FVs. The PFP-N_f (partial factor productivity of N_f) indices increased on NPK-MOP by 5.8%, NPK-KK by 12.9%, and NPK-KK+Ki+ES by 17.9% compared to NP. The corresponding N_f recovery of N_f in wheat grain was 47.2%, 55.9%, and 64.4%, but its total recovery by wheat (grain + straw) was 67%, 74.5%, and 87.2%, respectively. In terms of the theoretical and practical value of the tested indexes, two indices, namely, NUP (nitrogen unit productivity) and NUA (nitrogen unit accumulation), proved to be the most useful. From the farmer’s production strategy, FV with K applied in the form of Korn–Kali proved to be the most stable option due to high and stable yield, regardless of weather conditions. The increase in the number of nutritional factors optimizing the action of nitrogen in winter wheat caused the phenomenon known as the “scissors effect”. This phenomenon manifested itself in a progressive increase in nitrogen unit productivity (NUP) combined with a regressive trend in unit nitrogen accumulation (NUA) in the grain versus the balance of soil available Mg (Mg_b). The studies clearly showed that obtaining grain that met the milling requirements was recorded only for NUA above 22 kg N t⁻¹ grain. This was possible only with the most intensive Mg treatment (NPK-KK+Ki and NPK-KK+Ki+ES). The study clearly showed that three of the six FVs fully met the three basic conditions for sustainable crop production: (i) stabilization and even an increase in grain yield; (ii) a decrease in the mass of inorganic N in the soil at harvest, potentially susceptible to leaching; and (iii) stabilization of the soil fertility of P, K, and Mg. Full article

The development of lightweight composites with superior mechanical properties and electromagnetic interference (EMI) shielding performance is essential for various structural and functional applications. This study investigates the effect of hybrid nanocarbon (graphene nanosheet (GNS) and carbon nanotube (CNT)) reinforcements on the properties of magnesium (Mg) matrix composites. Specifically, the GNS-CNT hybrid, which forms a three-dimensional interconnected network structure, was analyzed and compared to composites reinforced with only GNSs or CNTs. The objective was to determine the benefits of hybrid reinforcements on the mechanical strength and EMI shielding capability of the composites. The results indicated that the GNS-CNT/Mg composite, at a nanocarbon content of 0.5 wt.% and a GNS-CNT ratio of 1:2, achieved optimal performance, with a 55% increase in tensile strength and an EMI shielding effectiveness of 70 dB. The observed enhancements can be attributed to several key mechanisms: effective load transfer, which promotes tensile twinning, along with improved impedance matching and multiple internal reflections within the GNS-CNT network, which enhance absorption loss. These significant improvements position the composite as a promising candidate for advanced applications requiring high strength, toughness, and efficient electromagnetic shielding, providing valuable insights into the design of high-performance lightweight materials. Full article

Objectives: Research on the immunocastration vaccine is of great significance for animal management. In this study, the gonadotropin-releasing hormone (GnRH) ferritin nanoparticle vaccine was constructed using Spy Catcher-Spy Tag (SC-ST) as a delivery system; Methods: The Spy Catcher was constructed to fuse with the expression vector pET-30a-SF of ferritin nanoparticles. Two polypeptides, STG1: Spy Tag-GnRH I-PADRE and STG2: Spy Tag-GnRH I-GnRH II, coupled to SF in vitro to form two nanoparticles, were designed and synthesized to detect castration effects in mice. We mixed them with the adjuvant MONTANIDE ISA 206 VG to explore the adjuvant’s effect on immunogenicity; Results: All immunized groups produced anti-GnRH specific antibodies after the second immunization, which was significantly higher in the immunized group and the combined adjuvant group than in the control group, and the immune response could still be detected at the 12th week. The concentrations of testosterone, follicle-stimulating hormone, and luteinizing hormone in serum were significantly decreased. The number of sperm in the epididymis of mice in each immune group was significantly reduced, and the rate of sperm deformity was high; Conclusions: The two ferritin-based GnRH nanoparticles developed in this study can significantly cause testicular atrophy, decreased gonadal hormone concentration, decreased sperm count, and increased deformity rate in male mice. These findings provide experimental evidence supporting their potential application in animal immunocastration. Full article

This essay argues for the reciprocal benefits of joining the new theories of matter emerging out of critical posthumanism and the psychedelic drugs currently experiencing a so-called “renaissance” in global north societies. While the former’s twin emphasis on relationality and embodiment is perfectly suited to capture and ground the ontological, epistemological, and ethical implications of psychedelic experiences of interconnectedness and transformation, these substances are in turn powerful companions through which to enact a “posthuman phenomenology” that helps us with the urgent task to “access, amplify, and describe” our deep imbrication with our more-than-human environments. In other words, I argue that while the “new materialism” emerging out of posthumanism can help elaborate a psychedelic rationality, psychedelics can in turn operate as educators in materiality. It is from this materialist perspective that we can best make sense of psychedelics’ often touted potential for social transformation and the enduring suspicion that they are somehow at odds with the “ontoepistemological order” of modernity. From this point of view, I contend that a crucial critical move is to push against the common trope that this opposition is best expressed as a turn from the narrow scientific and “consumerist materialism” of modern Western societies to more expansive “spiritual” worldviews. Pushing against this science-–spirituality binary, which in fact reproduces modern “indivi/dualism” by confining psychedelic experience inside our heads, I argue instead that what is in fact needed to think through and actualize such potentials is an increased attention to our material transcorporeality. In a nutshell, if we want psychedelics to inform social change, we must be more, not less, materialist—albeit by redefining matter in a rather “weird”, non-reductive way and by redefining consciousness as embodied. By the end of the essay, attaching psychedelics to a new materialism will enable us to formulate a “material spirituality” that establishes psychedelics’ political value less in an idealistic or cognitive “politics of consciousness” and more in a “materialization of critique”. Full article

Long-term storage may induce lipid oxidation in brown rice and impact its utilization in animal diets. One-day-old male Ross 308 broiler chickens (with an initial body weight of 20 g) were randomly divided into three groups: corn-based diet (Corn), fresh brown rice-based diet (BR1) and stored brown rice-based diet (BR6), with 8 replicates of 10 birds per pen, in a 42-day feeding trial. The results showed that lipid oxidation indexes increased and fatty acid composition changed significantly in BR6 (p < 0.05). The dietary replacement of corn with brown rice showed no effects on growth performance of broilers (p > 0.05). However, palmitic acid and oleic acid increased, and stearic acid, linoleic acid and docosadienoic acid decreased in the broiler breast muscle of the BR1 and BR6 groups (p < 0.05). Ileum antioxidant enzyme activities increased in the BR1 and BR6 groups compared to the Corn group (p < 0.05), and the activities of α-amylase, trypsin, chymotrypsin and lipase decreased in the BR6 group compared to the BR1 and Corn groups (p < 0.05). Also, compared to the BR1 group, the overall expression of metabolites involved in drug metabolism—cytochrome P450, GnRH secretion and the estrogen signaling pathway in broiler ileum were down-regulated in the BR6 group (p < 0.05). In conclusion, the lipid oxidation of stored brown rice decreased digestive enzyme activities and changed metabolic characteristics in the ileum of broilers. While replacing corn with brown rice did not affect broiler growth performance, it reduced the contents of unsaturated and essential fatty acids in breast muscle and enhanced the ileal antioxidant functions of broilers. Full article

Kallmann syndrome (KS) is a form of hypogonadotropic hypogonadism (HH) characterized by gonadotropin-releasing hormone (GnRH) deficiency and anosmia due to defective neuronal migration. While traditionally considered irreversible, cases of spontaneous improvement of HH have been reported, suggesting residual GnRH neuronal function in some individuals. We present a case of a 29-year-old man with KS who exhibited spontaneous recovery of endogenous testosterone production following the cessation of long-term androgen therapy without the use of alternative hormonal agents. After ceasing testosterone therapy for several months, the patient’s total testosterone levels normalized (407–424 ng/dL), accompanied by increased secondary sexual characteristics, stable gonadotropin levels, and normal testicular volume. Persistent anosmia was noted, suggesting that restoration of reproductive endocrine function can occur independently of olfactory recovery. Genetic testing identified heterozygous mutations in PCSK1 and HS6ST1, genes implicated in GnRH regulation and KS pathogenesis. This case highlights the potential role of genetic variation in spontaneous HH improvement and underscores the need for individualized management strategies, including periodic reassessment of gonadal function and fertility potential. Further research is needed to elucidate the mechanisms driving spontaneous HH improvement, identify predictive biomarkers of reversibility, and explore therapeutic strategies that may promote endogenous GnRH activity in select patients with KS. Full article

This study investigated the effects of dietary Gonadotropin-releasing hormone (GnRH) and domperidone on the reproductive performance of Devario devario during a 40-day trial. Five treatment groups received varying doses of GnRH (100, 50, 25, 12.5 µg/kg body weight) in combination with domperidone (50, 25, 12.5, 6.25 mg/kg body weight), embossed in a gel-based diet alongside a control group without the exogenous hormones. Reproductive performance was examined by measuring the gonadosomatic index, fecundity, reproductive hormone levels, and histological features of the gonads, blood parameters, and antioxidant enzyme activity. The T1 group (100 µg GnRH + 50 mg domperidone) exhibited the highest GSI in both sexes. The histological analysis of testes from T1, T2 (50 µg GnRH + 25 mg domperidone), and T3 (25 µg GnRH + 12.5 mg domperidone) groups revealed an increased presence of late-stage spermatids and spermatozoa. In females, the T2 group produced the highest proportion of advanced-stage oocytes and demonstrated the greatest absolute fecundity (1300 ± 23 eggs). However, the control group showed the highest fertilization and hatching rates. Testosterone levels were significantly elevated in the T3 group, while vitellogenin levels increased in the T1 and T2 groups. Antioxidant enzyme activity varied, with the T1 group displaying higher superoxide dismutase activity in gills and liver, and the T2 group showing increased SOD activity in muscle and brain. Improvements in haematological parameters were observed across all treatments. These results suggest that an optimal dose of 50 µg GnRH + 25 mg domperidone can enhance reproductive performance in D. devario. Full article

Background/Objectives: Glomerulonephritis (GNs) is a heterogeneous group of inflammatory kidney diseases. Novel genetic methods have revealed some disease-causing and susceptibility genes underlying primary and secondary GNs. We aimed to investigate the presence of the single nucleotide polymorphisms (SNPs) rs12917707, found in the UMOD gene, and rs17319721, found in the SHROOM3 gene, as well as different polymorphisms in immune system genes in a group of children with GN. Method: The study included 71 children with GN (40 with primary and 31 with secondary GN) and 119 healthy children (HC). SNPs of the UMOD (rs12917707), SHROOM3 (rs17319721), IL10 (rs1800871 and rs3024505), IL6 (rs1800795), IL12B (rs3212227), IL23R (rs11209026 and rs1800896), and TNF (rs361525 and rs1800629) genes were genotyped. Results: The median age of the patients was 8 years at the onset of GN and 14 years at sampling. Allele A for rs1800629 in the TNF gene was more common in patients with GN in comparison to HCs (p = 0.009), followed by the difference in genotype distributions (p = 0.021), where AA and GA genotypes were more prevalent in patients. We found a statistically significant difference in haplotype distributions between patients and HCs for TNF, with GN patients having the GGAG haplotype more frequently and HCs having GGGG (p < 0.05). No correlation between the investigated SNPs and patient clinical characteristics (disease onset, primary or secondary GN, severity of disease, occurrence of remission, and presence of hypertension) was observed. Conclusions: An association between the TNF gene and different types of GN was noticed in children with GN. This may help us to understand the pathogenesis of these disorders and develop new treatments to cover the unmet needs of children with GN. Full article

Natural-fiber-reinforced polypropylene (PP) composites are gaining increasing interest as lightweight, sustainable alternatives for various packaging and applications. This study investigates the effect of filler addition sequence on the mechanical, morphological, thermal, and dynamic mechanical properties of PP-based composites reinforced with graphite nanoplatelets (GnP) and kenaf fiber (KF). Two filler incorporation sequences were evaluated: GnP/KF/PP (GnP initially mixed with KF before PP addition) and GnP/PP/KF (KF added after mixing GnP with PP). The GnP/KF/PP composite exhibited superior mechanical properties, with tensile strength and flexural strength increasing by up to 25% compared to the control, while GnP/PP/KF showed a 13% improvement. SEM analyses revealed that initial mixing of GnP with KF significantly improved filler dispersion and interfacial bonding, enhancing stress transfer within the composite. XRD and DSC analyses showed reduced crystallinity and lower crystallization temperatures in the addition of KF due to restricted polymer chain mobility. Thermal stability assessed by TGA indicated minimal differences between the composites regardless of filler sequence. DMA results demonstrated a significantly higher storage modulus and enhanced elastic response in the addition of KF, alongside a slight decrease in glass transition temperature (T_g). The results emphasize the importance of optimizing filler addition sequences to enhance mechanical performance, confirming the potential of these composites in sustainable packaging and structural automotive applications. Full article