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Introduction: Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder characterized by hyperandrogenism, insulin resistance, and menstrual irregularities, leading to infertility in many women. Emerging evidence suggests intermittent fasting (IF), particularly time-restricted feeding (TRF), may improve reproductive and metabolic outcomes in women with PCOS by addressing core pathophysiological mechanisms. This systematic review examines the impact of IF on fertility and reproductive hormones in women with PCOS. Methods: A systematic search was conducted in PubMed, Scopus, and Cochrane Library using predefined search terms related to intermittent fasting, fertility, and PCOS. Eligible studies published between 2014 and 2024 were identified following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria targeted primary research evaluating the effects of IF on reproductive outcomes, menstrual irregularities, and metabolic parameters in women with PCOS. Data extraction and quality assessment were performed using the Caldwell framework. Results: Three studies were included in the review. TRF interventions led to significant improvements in menstrual regularity, with 33–40 % of participants reporting normalized cycles. Reductions in total testosterone, free androgen index, anti-Müllerian hormone (AMH), and luteinizing hormone (LH) levels were observed, alongside increased sex hormone-binding globulin (SHBG). TRF also improved insulin sensitivity, reduced body weight, and decreased inflammatory markers, all of which contribute to enhanced reproductive outcomes. Key outcomes included a 9 % reduction in testosterone levels, 26 % reduction in the free androgen index (FAI), and significant improvements in menstrual regularity (33–40 %). Conclusions: Intermittent fasting, particularly TRF, shows potential as a non-pharmacological intervention to improve reproductive health and fertility in women with PCOS. By targeting hyperandrogenism, insulin resistance, and menstrual irregularities, TRF offers a promising lifestyle approach. However, larger randomized controlled trials with long-term follow-up are needed to confirm these findings and establish IF as a standard therapeutic option for PCOS management.

This article explores the chaotic violence in Nathaniel Lee's tragedies, which, while clearly originating in the sovereign, by its sheer excess and blindness, is hypostasised as a motor of history. In Lee, violence is a reflection of the political anxieties surrounding the Exclusion Crisis but it is also intrinsic to the way he understands the nature of political life; in reality, it is constitutive of the very exercise of power. Drawing on Giorgio Agamben's Homo Sacer I argue that sovereign violence is inscribed in a most savage form as the very foundation of the civil community, and, therefore, its autonomisation, as in Lee's early plays, is only apparent. In Lucius Junius Brutus: Father of His Country (1680) the extreme sovereign assault on human life fully discloses its politically defined character because it is emblematically performed in the name of the institution of a new body politic, the Republic. Keywords: Agamben, Exclusion Crisis, fatherhood, Lee, social contract, sovereign, Much of the unsettling effect of Nathaniel Lee's tragedies, and their peculiar fascination, lies in their pervasive chaotic violence which, while clearly originating in the sovereign, at some point appears [...]

Abstract Background Non-invasive prenatal testing (NIPT) has been widely adopted for the detection of fetal aneuploidies and microdeletion syndromes, nevertheless, limited clinical utilization has been reported for the non-invasive prenatal screening of monogenic diseases. In this study, we present the development and validation of a single comprehensive NIPT for prenatal screening of chromosomal aneuploidies, microdeletions and 50 autosomal recessive disorders associated with severe or moderate clinical phenotype. Results We employed a targeted capture enrichment technology powered by custom TArget Capture Sequences (TACS) and multi-engine bioinformatics analysis pipeline to develop and validate a novel NIPT test. This test was validated using 2033 cell-fee DNA (cfDNA) samples from maternal plasma of pregnant women referred for NIPT and paternal genomic DNA. Additionally, 200 amniotic fluid and CVS samples were used for validation purposes. All NIPT samples were correctly classified exhibiting 100% sensitivity (CI 89.7–100%) and 100% specificity (CI 99.8–100%) for chromosomal aneuploidies and microdeletions. Furthermore, 613 targeted causative mutations, of which 87 were unique, corresponding to 21 monogenic diseases, were identified. For the validation of the assay for prenatal diagnosis purposes, all aneuploidies, microdeletions and point mutations were correctly detected in all 200 amniotic fluid and CVS samples. Conclusions We present a NIPT for aneuploidies, microdeletions, and monogenic disorders. To our knowledge this is the first time that such a comprehensive NIPT is available for clinical implementation.

Abstract Introduction Non-Invasive Prenatal Testing (NIPT) for fetal aneuploidies using cell-free DNA (cfDNA) has been widely adopted in clinical practice due to its improved accuracy. A number of NIPT tests have been developed and validated. The purpose of this study is to evaluate the performance of the Veracity NIPT test for sex chromosome aneuploidy (SCA) detection in singleton pregnancies, autosomal aneuploidy detection in twin pregnancies and evaluation of Veracity clinical performance under routine NIPT conditions in a diverse cohort. Methods Blinded retrospective study in singleton pregnancies (n = 305); blinded retrospective and prospective study in twin pregnancies (n = 306) and prospective evaluation of clinical performance in singleton and twin pregnancies (n = 10564). Results Validation study results for the detection of SCAs in singleton pregnancies exhibited 100% sensitivity and specificity and correctly classified 7 (45,X), 4 (47,XXY), 2 (47,XXX) and 1 (47,XYY) cases. Validation study results for autosomal aneuploidy detection in twin pregnancies exhibited 100% sensitivity and specificity and correctly classified 3 trisomy 21, 1 trisomy 18 and 1 trisomy 13 samples. Clinical performance evaluation of Veracity was performed in 10564 pregnancies with median gestational age of 13 weeks, median maternal age 35 years and median gestational weight of 64 kg. Based on confirmation feedback the PPV for trisomies 21, 18 and 13 was estimated at 100% (95% CI, 92–100%), 100% (95% CI, 69–100%) and 71% (95% CI, 29–96%), respectively. Estimated PPV for Monosomy X was 57% (95%CI, 18–90%), while the NPV for SCA detection was estimated at 100% (95% CI, 99.94–100%). Conclusion Veracity NIPT test is based on a very powerful, highly accurate methodology that can be safely applied in the clinical setting.

The neonatal MK-801 model of schizophrenia has been developed based on the neurodevelopmental and NMDA receptor hypofunction hypotheses of schizophrenia. This animal model is generated with the use of the NMDA receptor antagonist, MK-801, during different temporal windows of postnatal life of rodents leading to behavioral defects in adulthood. However, no studies have examined the role of specific postnatal time periods in the neonatal MK-801 (nMK-801) rodent model and the resulting behavioral and neurobiological effects. Thus, the goal of this study is to systematically investigate the role of NMDA hypofunction, during specific temporal windows in postnatal life on different cognitive and social behavioral paradigms, as well as various neurobiological effects during adulthood. Both female and male mice were injected intraperitoneally (i.p.) with MK-801 during postnatal days 7–14 (p7–14) or 11–15 (p11–15). Control mice were injected with saline during the respective time period. In adulthood, mice were tested in various cognitive and social behavioral tasks. Mice nMK-801-treated on p7–14 show impaired performance in the novel object, object-to-place, and temporal order object recognition (TOR) tasks, the sociability test, and contextual fear extinction. Mice nMK-801-treated on p11–15 only affects performance in the TOR task, the social memory test, and contextual fear extinction. No differences were identified in the expression of NMDA receptor subunits, the synapsin or PSD-95 proteins, either in the prefrontal cortex (PFC) or the hippocampus (HPC), brain regions significantly affected in schizophrenia. The number of parvalbumin (PV)-expressing cells is significantly reduced in the PFC, but not in the HPC, of nMK-801-treated mice on p7–14 compared to their controls. No differences in PV-expressing cells (PFC or HPC) were identified in nMK-801-treated mice on p11–15. We further examined PFC function by recording spontaneous activity in a solution that allows up state generation. We find that the frequency of up states is significantly reduced in both nMK-801-treated mice on p7–14 and p11–15 compared to saline-treated mice. Furthermore, we find adaptations in the gamma and high gamma activity in nMK-801-treated mice. In conclusion, our results show that MK-801 treatment during specific postnatal temporal windows has differential effects on cognitive and social behaviors, as well as on underlying neurobiological substrates.