Background and Objectives: The purpose of this study was to assess the bleeding that occurs during the first weeks of gestation and its implications throughout pregnancy. Secondarily, we studied the associated complications that appeared and tried to identify possible risk factors that could serve to select women at a greater risk of adverse outcomes that could benefit from an early diagnosis and improved monitoring. Materials and Methods: We selected all the women who consulted for first trimester metrorrhagia in the Emergency Department of the Hospital QuirónSalud in Malaga over the year 2015. We refer to first trimester metrorrhagia as that which occurs until week 12+6. Once the pregnant women were identified, we studied certain risk factors already present prior to the gestation and others associated with the gestation and its evolution. Results: After reviewing the visits to the obstetrics and gynecology emergency department, we selected those patients that met the inclusion criteria, resulting in a sample of 696 patients that we followed up. The average age of our patients was 34.1 years, with an average number of visits to the hospital of 1.67, most of them between the 5th and 8th weeks of pregnancy. 45.3% of these pregnancies resulted in a first trimester miscarriage, mainly between weeks 6 and 8. We tried to establish associations in order to identify possible risk factors, finding a relationship between increased maternal age and a higher risk of first trimester pregnancy loss, which rises as maternal age increases (33,37 4,316 years vs 35,01 4,740 years). This increase in risk is proportional to the increase in age. We made subgroups of women over 35 and over 40 and confirmed that increased age led to worse outcomes. We also studied several gestational complications and concluded that they appeared more frequently among older women. These complications include prematurity (33.11 vs 34.48 years), gestational diabetes (33.11 vs 36.06 years) and preeclampsia (33.25 vs 35 years). We reviewed the obstetric history of pregnant women whose gestation resulted in miscarriage and found that 50.5% of them had previously had another loss. Conclusions: Comparing the results with data from the general population, we found that the rate of first trimester miscarriage is up to 3 times higher among women who present bleeding during the first weeks of gestation compared to those who do not develop this complication. Maternal age is a risk factor for first trimester pregnancy loss and for the development of complications associated with pregnancy.

Recurrent pregnancy loss (RPL) affects around 2 % of women of reproductive age. Primary RPL is defined by ≥2 pregnancy losses and no normal birth delivery. In secondary RPL, the losses are after a normal pregnancy and delivery. Most cases have no clear aetiology, although primary cases are the most complex. Several gene polymorphisms have been associated with RPL. Some polymorphisms are increased in women of Asian or Caucasian race. In admixed RPL populations, the information on possible genetic links is scarce and contradictory. The study aimed to assess the frequency of two SNP in different enzymes involved in medical conditions observed during pregnancy. Microsomal epoxy hydrolase (mEPH) is involved in detoxifying xenobiotics. It is present in ovaries, and it is hormonally regulated. The endothelial nitric oxide synthase forms nitric oxide from arginine and is involved in vascular tone. Two SNPs, rs1051740 and rs1799983, were assessed. The study included 26 controls and 63 primary RPL patients. Significant differences were observed in the frequencies of both SNP (p<0.05). The frequency of mutated alleles was higher in patients. Double mutated homozygotes were encountered only in RLP patients (p<0.05). Genetic polymorphisms rs1051740 and rs1799983 may be involved in primary RPL in the Venezuelan admix population. Genetic studies could provide crucial information on the aetiology of primary RPL.

Recent research emphasises the importance of Artificial Intelligence applications as supporting tools for students in higher education. Simultaneously, an intensive exchange of views has started in the public debate in the international educational community. However, for a more proper use of these applications, it is necessary to investigate the factors that explain their intention and actual use in the future. With the Unified Theory of Acceptance and Use of Technology (UTAUT2) model, this work analyses the factors influencing students' use and intention to use artificial intelligence technology. For this purpose, a sample of 199 Greek students at the School of Humanities and Social Sciences from the University of Patras participated in a survey. The findings highlight that expected performance, habit, and enjoyment of these Artificial Intelligence applications are key determinants influencing teachers' intentions to use them. Moreover, behavioural intention, habit, and facilitating conditions explain the usage of these Artificial Intelligence applications. The study did not reveal any moderating effects. The limitations, practical implications, and proposed directions for future research based on these results are discussed.

Selenium is essential for the synthesis and function of various selenoenzymes, such as glutathione peroxidases, selenoprotein P, and thioredoxin reductase, which play an important role in both antioxidant defense and limiting oxidative damage. Associations between serum selenium concentration and obstetric complications as well as pregnancy outcomes has been reported in many studies. The aim of this study was to determine whether the dietary intake of selenium, its concentration in serum and the activity of glutathione peroxidase in subsequent trimesters of pregnancy affect the birth condition of newborns assessed on the basis of the Apgar score in the 1st and 5th minute of life, birth weight, body length and head and chest circumference in physiological and complicated pregnancy course. Twenty-seven pregnant women at a mean age 29.6 ± 4.8 years from the Lower Silesia region of Poland were recruited to the study, 55% of studied group had pregnancy complications. The mean reported Se intake and serum selenium content for Polish pregnant women was in the first trimester – 56.53 μg/day and 43.75 μg/l, the second trimester – 61.79 μg/day and 41.77 μg/l and the third trimester – 58.37 μg/day and 42.13 μg/l, respectively. In the subgroup of pregnant women with a physiological pregnancy course, a weak, although statistically significant, positive correlation was found in the first trimester between Se intake and the length (R=0.48, p=0.019) and birth weight of newborns (R=0.472, p=0.022), and in the second trimester with the APGAR score at 1 (R=0.680, p=0.005) and 5 minutes (R=0.55, p=0.033), as well as in the third trimester with th APGAR score at 1 minut (R=0.658, p=0.019). The GPX value had a strong positive correlation with the APGAR score at 1 min. (R=0.650, p=0.008) in the second trimester and with the birth weight of the newborns (R=0.598, p=0.039) in the third trimester. There was no correlation between newborns' birth measurements and serum selenium concentration. In the subgroup of pregnant women with pregnancy complications, a strong, statistically significant, negative correlation was found between Se intake in the second trimester and gestational age (R=-0.618, p=0.032), and in the third trimester, a positive correlation between Se concentration in serum and head circumference (R=0.587, p=0.021). The obtained results indicate that there is a relationship between the maternal selenium status during pregnancy, both in terms of the intake of this element, its serum concentration as well as the glutathione peroxidase activity, and the anthropometric parameters of the newborn, such as birth weight, length and APGAR score, especially in the group with physiological course of pregnancy, but when pregnancy complications occur, these relationships lose their importance.

Introduction: The emergency of the SARS-CoV-2 virus spread and its subsequent global pan-demic have raised significant concerns regarding its impact on pregnancy outcomes. This review aims to summarize the emerging data on the risk of preterm delivery in pregnant women infected with SARS-CoV-2. Materials and Methods: A systematic search was conducted from March 2020 to December 2023 using PubMed, following PRISMA guidelines. Studies correlating maternal COVID-19 infection with preterm birth were included. Results: Thirteen studies were analyzed, indicating a higher incidence of preterm birth in SARS-CoV-2 positive pregnant women compared to controls. The average incidence rate of pre-term birth in infected patients was 18.5%, with a median of 12.75%, while non infected women showed an average incidence of preterm birth of 10% with a median of 8.2%. Discussion: Studies suggest an association between SARS-CoV-2 infection during pregnancy and increased risk of preterm birth and cesarean section. Severity of symptoms and underlying comorbidities further elevate this risk. Notably, infections during the third trimester pose the highest risk of preterm birth. Conclusion: Preventing SARS-CoV-2 infection during pregnancy is crucial to mitigate adverse obstetric outcomes. Close monitoring and tailored interventions for infected pregnant women, particularly those in later trimesters and with comorbidities, are imperative to reduce the risk of preterm birth and improve maternal-fetal outcomes.

Recipients of uterus transplantation have unique factors that may increase their risk of cervical insufficiency. This report describes a uterus transplant recipient with cervical insufficiency resulting in two second-trimester miscarriages. After McDonald cerclages (one that failed), she underwent an interval transabdominal cerclage and delivered a healthy term child in her third pregnancy. The longitudinal information of this case provides observations from which we can propose testable hypotheses that address venous outflow and inflammation. This case also suggests that there could be a role for prophylactic cerclage placement at the time of transplantation.

The aim of this study was to develop and validate a predictive early tooth loss multivariable model for periodontitis patients before periodontal treatment. A total of 544 patients seeking periodontal care at a university dental hospital were enrolled in the study. Teeth extracted after periodontal diagnosis and due to periodontal reasons were recorded. Clinical and sociodemographic variables were analyzed, considering the risk of short-term tooth loss. This study followed the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines for development and validation, with two cohorts considered as follows: 455 patients in the development phase and 99 in the validation phase. As a result, it was possible to compute a predictive model based on tooth type and clinical attachment loss. The model explained 25.3% of the total variability and correctly ranked 98.9% of the cases. The final reduced model area under the curve (AUC) was 0.809 (95% Confidence Interval (95% CI): 0.629 - 0.989) for the validation sample and 0.920 (95% CI: 0.891 - 0.950) for the development cohort. The established model presented adequate prediction potential of early tooth loss due to periodontitis. This model may have clinical and epidemiologic relevance towards the prediction of tooth loss burden.

Consumption of coffee by women early in their pregnancy has been viewed as potentially increasing the risk of miscarriage, low birth weight, and childhood leukemias. Many of these reports of epidemiologic studies have not acknowledged the potential biases inherent in studying the relationship between early-pregnancy-coffee consumption and subsequent events. I discuss five of these biases, recall bias, misclassification, residual confounding, reverse causation, and publication bias. Each might account for claims that attribute adversities to early-pregnancy-coffee consumption. To what extent these biases can be avoided remains to be determined. At a minimum, they need to be acknowledged wherever they might account for what is reported.

Hemangioblasts give rise to endothelial progenitor cells (EPCs), which also express the cell surface markers CD133 and C-kit. They may differentiate into the outgrowth endothelial cells (OECs) that control neovascularization in the developing embryo. Reduced levels of EPC in circulation have been linked to human cardiovascular disorders, according to numerous studies. Furthermore, preeclampsia and senescence have been linked to levels of EPCs produced from cord blood. Uncertainties surround how preeclampsia affects the way EPCs function. It is reasonable to speculate that preeclampsia may have an impact on the function of fetal EPCs during the in utero period; however, given the present literature's suggestion that maternal vasculopathies, including preeclampsia, damage fetal circulation. Additionally, the differentiation potential and general activity of EPCs may serve as an indicator of the health of the fetal vascular system since they promote neovascularization and repair during pregnancy. Thus, the purpose of this review is to compare, through assessment of their quantity, differentiation potency, angiogenic activity, and senescence, the angiogenic function of fetal EPCs obtained from cord blood for normal and pregnancy problems. This will shed light on the relationship between the angiogenic function of fetal EPCs and pregnancy complications, which could have an effect on the management of long-term health issues like metabolic and cardiovascular disorders in offspring with abnormal vasculature development.

Hepatitis E virus (HEV) is a common cause of acute hepatitis worldwide, accounting for approximately 25% of deaths among pregnant women. We previously reported that pregnancy serum facilitates HEV replication in vitro. However, the differences in host cells with HEV infection induced by pregnancy serum and fetal bovine serum (FBS) are unclear. In this study, differentially expressed proteins were identified in HEV-infected hepatoma cells (HepG2) supplemented with different sera by using isobaric tags for relative and absolute quantitation. Proteomic analysis indicated that HEV infection significantly induced 1014 differentially expressed proteins in HEV-infected HepG2 cells when supplemented with FBS compared with pregnancy serum. Further validation by Western blot confirmed that filamin A, heat-shock proteins 70 and 90, Cytochrome c, and Thioredoxin were associated with HEV infection. This comparative analysis provides an important basis to further investigate HEV pathogenesis in pregnant women and HEV replication.

Brain pathological changes impair cognition early in disease etiology. There is an urgent need for understanding aging-linked mechanisms of early memory loss to develop therapeutic strategies and prevent the development of cognitive impairment. Tusc2, also named Fus1, is a mitochondrial-resident protein regulating Ca2+ fluxes to and from mitochondria impacting overall health. We reported that Tusc2-/- female mice develop chronic inflammation and age prematurely, causing age- and gender-dependent spatial memory deficits at 5 m.o. Therefore, we investigated Tusc2-dependent mechanisms of memory impairment in mice, comparing changes in resident and brain-infiltrating immune cells. Interestingly, Tusc2-/- female mice demonstrated proinflammatory increase in astrocytes, IFN-γ expression in CD4+T cells and Granzyme-B in CD8+T cells. We also found fewer FOXP3+ T-regulatory cells and Ly49G+ NK and Ly49G+ NKT cells in female Tusc2-/- brain, suggesting a weakened anti-inflammatory response. Moreover, Tusc2-/- hippocampi exhibited Tusc2- and sex-specific protein changes associated with brain plasticity, including mTOR activation, and Calbindin and CamKII dysregulation affecting intracellular Ca2+ dynamics. Overall, data suggest that dysregulation of Ca2+-dependent processes and proinflammatory brain microenvironment heighten in Tusc2-/- mice could underlie cognitive impairment. Thus, strategies to modulate the brain’s Tusc2-, Ca2+, and mitochondria-dependent pathways should be explored to improve cognitive health.

The Dph1•Dph2 heterodimer from yeast is a radical SAM (RS) enzyme that generates the 3-amino-3-carboxy-propyl (ACP) precursor for diphthamide, a clinically relevant modification on eukaryotic elongation factor 2 (eEF2). ACP formation requires SAM cleavage and atypical Cys-bound Fe-S clusters in each Dph1 and Dph2 subunit. Intriguingly, the first Cys residue in each motif locates next to another, ill-defined cysteine that we show in-here is conserved across eukaryotes. As judged from structural modeling, the orientation of these tandem cysteine motifs (TCM) suggests a candidate Fe-S cluster ligand role. Hence, we generated by site-directed DPH1 and DPH2 mutagenesis, Dph1•Dph2 variants with cysteines from each TCM replaced individually or in combination by serines. Assays diagnostic for diphthamide formation in vivo reveal that while single substitutions in the TCM of Dph2 cause mild defects, double mutations almost entirely inactivate the RS enzyme. Based on enhanced Dph1 and Dph2 subunit instability in response to cycloheximide chases, the variants with Cys substitutions in their cofactor motifs are particularly prone to protein degradation. In sum, we identify a fourth functionally cooperative Cys residue within the Fe-S motif of Dph2 and show that the Cys-based cofactor binding motifs in Dph1 and Dph2 are critical for the structural integrity of the dimeric RS enzyme in vivo.

The emotion of disgust protects individuals against pathogens, and it has been found that during pregnancy, it is elevated. Physiological mechanisms discussed in relation to these changes include immune markers and progesterone levels. The aim of this study is to assess the association between steroids and disgust in pregnancy. In a sample of 179 pregnant women, we have analyzed blood serum steroid concentrations and measured disgust sensitivity by text-based questionnaires in the first and third trimester. We found positive correlations between disgust sensitivity and the levels of C19 steroids, including testosterone, but also its precursors in the Δ5 pathway (androstenediol, DHEA, and their sulfates) and the Δ4 pathway (androstenedione). Furthermore, positive correlations between disgust sensitivity and 5α/β-reduced C19 steroid metabolites were consistently present in both trimesters. In the first trimester, we found a positive association between disgust sensitivity and 17-hydroxypregnanolone as well as some estrogens. In the third trimester, we have observed positive associations between disgust sensitivity and cortisol as well as immunoprotective Δ5 C19 7α/β-hydroxy-steroids. Our study has thus shown that disgust sensitivity is positively correlated with immunomodulatory steroids, and in the third trimester, steroids may reflect potential maternal anxiety-related symptoms.

This study addresses the implementation of the International Financial Reporting Standard 9 (IFRS 9) in the European Union as of January 1, 2018, replacing the International Accounting Standard 39 (IAS 39) to introduce a new model for recognizing Loan Loss Provisions (LLP) based on Expected Credit Loss (ECL). This model responds to criticisms of the former Incurred Credit Loss (ICL) system for its inability to reflect credit losses in a timely manner, potentially exacerbating the effects of financial crises (Bushman &amp; Williams, 2015; Gebhardt &amp; Novotny-Farkas, 2011). The study focuses on the effects of adopting the ECL model on the level of Loan Loss Allowances (LLA) in loans, own equity, and the Common Equity Tier 1 (CET1) ratio across 13 Portuguese commercial banks. A mean comparison test is used to evaluate scenarios before and after the application of the ECL model, highlighting the importance of regulator actions and the adequacy of loss recognition policies, including the effects of Regulation (EU) 2017/2395 of December 12. The results obtained demonstrate significant negative impacts on the net values of loans, own equity, and the CET1 ratio upon adopting the IFRS 9 ECL model, due to the widespread increase in LLAs.

Background: In this study, we aimed to evaluate the effect of s-FLT-1 and PlGF concentrations in women in the first trimester of pregnancy on the pulsatility index of the ductus venosus and the right and left uterine arteries. Methods: A total of 108 pregnant women in their first trimester were included in the study, with 87 assigned to the experimental group and 21 to the control group. Ultrasound examination were performed to measure the uterine artery pulsatility index, resistance index, ductus venosus pulsatility index, and blood sampling levels of biomarkers such as b-HCG; PAPP-A; s-FLT-1 and PlGF. Results: There was a significant negative relationship between PAPP-A concentration and the risk of fetal growth restriction, and a significant negative relationship between PlGF concentration and the risk of preeclampsia and fetal growth restriction in women in their first trimester of pregnancy. There was also a significant positive relationship between sFLT-1/PLGF ratio and the risk of developing preeclampsia. No significant relationships were found between the concentrations of biomarkers beta-HCG, PAPP-A, sFLT-1, PlGF, and any of the parameters PIUARt, PIUALt, Mean uterine arteries, and DVPI. Summary: In conclusion, this study did not find conclusive evidence to support the hypothesis that beta-HCG, PAPP-A, s-FLT-1, and PlGF concentrations in women in the first trimester of pregnancy have a significant effect on the Pulsatility Index of the ductus venosus and the Right and left Uterine Arteries. Further research is needed to investigate these potential associations.

The Internet of Things (IoT) is a concept based on the integration of various devices and methods of communication to exchange information in order to contribute to the improvement of everyday life, business and environment. This paper focuses on the establishment of a modern Internet of Things platform to ensure secure collection, processing and storage of data, under unexpected events. This platform establishes reliable connectivity which enhance system uptime; the key to success when implementing an IoT strategy. For this purpose, we proposed a hybrid approach combining different connectivity technologies to ensure the availability and smooth operation of the system and the prevention of data loss in unforeseen cases.

Periodontitis is a chronic inflammatory disease which results in the destruction of the tooth’ s supporting tissues and the alveolar bone resorption. The complement becomes a major link between infection and inflammatory pathology including periodontitis. Gingipians as important virulence factors of P. gingivalis have the activity of C5 convertase, could cleave C5 into fully functional C5a to activate C5aR. The above process could be blocked by the C5aR antagonist (PMX-53) to suppress local periodontal inflammation, and then achieves the purpose of treatment of periodontitis. Nanoparticles incorporated within gelatin are promising carrier system for drug delivery in recent years. This study aimed to investigate whether gelatin nanoparticles loaded with PMX-53 prevents alveolar bone resorption in miniature swines model of periodontitis. Four miniature swines were placed ligatures around the maxillary and mandibular fourth premolar and first molar on both sides for seven weeks to induce periodontitis. Then, animals were assigned randomly to four groups: minocycline-treated group, gelatin with PMX53-treated group, gelatin-treated group and a sham control group. They were treated with 1ml related drugs respectively, into gingival sulcusl for 4 times at one-week intervals. We showed that local treatments with gelatin nanoparticles loaded with PMX-53 could inhibit alveolar bone loss of periodontitis. Our study revealed that gelatin nanoparticles loaded with PMX-53 prevented alveolar bone resorption miniature swines model of periodontitis. In addition, provided proof-of-concept for local targeting of gelatin nanoparticles loaded with PMX-53 as a powerful candidate for the treatment of periodontitis.

This literature review paper delves into the synergies between Climate-Smart Agriculture (CSA) and the effective management of food losses. With the escalating challenges posed by climate change and the pressing need to address food security concerns, the intersection of these two critical domains becomes paramount for sustainable agricultural practices. The review explores existing research on the implementation of climate-smart agricultural techniques and their impact on mitigating food losses throughout the agricultural value chain. The paper synthesizes findings related to climate-resilient crop varieties, precision farming, water-use efficiency, and sustainable soil management, highlighting their contributions to reducing post-harvest losses and enhancing overall food security. In addition to summarizing current knowledge, this paper identifies gaps in the literature and proposes avenues for future research. This review serves as a foundation for researchers, policymakers, and practitioners seeking to contribute to the advancement of climate-smart agriculture and the reduction of food losses, paving the way for a more sustainable and resilient global food system.

Background: Ankle fractures, comprising about 10% of musculoskeletal injuries, pose a significant healthcare burden with an increasing incidence, particularly among an aging population. This study focuses on isolated Danis-Weber type B fractures. Recent trends lean towards surgical intervention for anatomical restoration, quicker recovery, albeit with associated complications. This report aims to assess the safety and efficacy of NewClip narrow locking plate system with early weight bearing in treating isolated fibular fractures. Methods: The study includes patients with Danis-Weber type B fractures surgically treated with NewClip narrow locking plate system. Exclusions involved nondisplaced fractures, open fractures, or those requiring additional fixation.Results: Fifteen patients were enrolled in this study. Minor complications, including wound swelling, were observed in two cases. The Visual Analogue Scale (VAS) for pain exhibited a steady decline postoperatively, with almost complete resolution by the third month. At three months, the FAOS demonstrated excellent results, and final follow-up at twelve months revealed complete osseous healing without complications.Conclusions: The use of this type of plates in treating isolated fibular fractures with early weight bearing shows promising results in terms of fracture healing, pain resolution, and functional outcomes warranting further investigation with larger cohorts.

Serological human birth cohort studies have identified maternal infection during pregnancy as a risk factor for development of disorders such as Autism Spectrum Disorder and schizophrenia in offspring. Similarly, in experiments using animal models, maternal immune activation (MIA) has been shown to alter neuroanatomical and behavioral development in offspring. This study employs magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) in conjunction with behavioral assays to refine our understanding of the impact of MIA on neurobiological development in exposed animals. On gestational day nine, pregnant dams were injected with either polyinosinic:polycytidylic acid (POL) to induce MIA or saline (SAL) as a control. Whole-brain MRI, localized proton MRS, and behavioral tests (open field, three chambered social approach, and prepulse inhibition) were acquired at two timepoints, during adolescence (postnatal day [PND] 35) and adulthood (PND 60). Whole-brain voxel-wise volumetric analyses revealed that MIA offspring exhibited altered volume in the hippocampus and caudate putamen (CPu) between adolescence and early adulthood. MRS data were assessed at each timepoint separately; MIA offspring during early adulthood but not adolescence exhibited trending reductions in γ-aminobutyrate (GABA) (p = 0.06) and myo-inositol (Ins) (p = 0.08) compared to saline controls. However, these metabolite differences did not reach levels of significance, even before multiple comparison corrections. Open field testing revealed that during adolescence, MIA offspring displayed a more anxious phenotype than controls wherein they spent less time in the anxiogenic center zone of the open field arena (p < 0.007), but this difference normalized by adulthood. There were no significant differences in sociability preference, novelty preference, or prepulse inhibition comparing the groups. Results suggest that early gestational exposure to MIA results in subtle neuroanatomical changes in the trajectories of development, trending behavioral changes in adolescent offspring, and slight neurochemical changes in young adult offspring. Maternal infection alone may not be enough; additional genetic or environmental risk factors may be required to elicit the more typical symptoms of neuropsychiatric disorders.

(1) Background: Ectopic pregnancy (EP) is when fertilized ovum implanted outside of uterine cavity. The incidence was 1.5% to 2.0% of all pregnancies [1, 2]. EP decreases fertility ability [3]. This study focused on the pregnancy rate after EP and various parameters influencing pregnancy. (2) Methods: The data was extracted from National Health Insurance Research Database (NHIRD) during 2000-2013. The study group enrolled women with one EP history. Those who did not have EP was put into the control group. Chi-square/Fisher exact test was performed on category variable and t-test was used on continue variables. (3) Results: The EP group had a higher cumulative rate of conceive, 41.55% than control group, 37.14% and 1.16 times higher risk in developing pregnancy (P&lt;0.001). The conceiving rate was lower than the control group in the first 5 years, but higher than the control group in the 10th to 14th years. (4) Conclusions: The fecundability after EP is lower at the beginning, but regained after long term follow.

A large core size and bending resistance are very important properties of mid-infrared energy transfer fibers, but large core sizes usually lead to a deterioration of bending properties. A negative-curvature nested node-free anti-resonant hollow-core fiber (AR-HCF) based on quartz is proposed. It was made by adding a nested layer to a previous AR-HCF design to provide an additional anti-resonance region while keeping the gap between adjacent tubes strictly correlated to the core diameter to produce a node-free structure. These features improve the fiber’s bending resistance while achieving a larger core diameter. The simulation results show that the radial air-glass anti-resonant layer is increased by the introduction of the nested anti-resonant tube, and the weak interference overlap between the fiber core and the cladding mode is reduced, so the fiber core’s limiting loss and the sensitivity to bending are effectively reduced. When the capillary wall thickness t of the fiber is 0.71 μm, the core diameter D is 70 μm, the ratio of the inner diameter of the cladding capillary to the core diameter d/D is 0.62, and the diameter of the nested tube is d0=29 μm, the fiber has a lower limiting loss at the wavelength of 2.79 μm, and the limiting loss is 3.28×10-4 dB/m. At the same time, the optimized structure also has good bending resistance. When the bending radius is 30 mm, the bending loss is only 4.72×10-2 dB/m. To our knowledge, this is the first research to achieve an anti-bending low-loss micro-structure hollow fiber with a bending radius of less than 30 mm in the 2.79 μm band. An anti-bending low-loss anti-resonant hollow-core fiber with this structure constitutes a reliable choice for the light guiding system of a 2.79 μm band erbium laser therapy instrument.

Abstract Peripartum depression (PPD) is a major complication of pregnancy and many risk factors have been associated with its development, including dysfunctional coping strategies and insecure attachment styles, both during pregnancy and postpartum. The aim of our study was to investigate the role of coping strategies in mediating the relationship between women’s attachment style and PPD in pregnancy, and one week after childbirth, in a large cohort of women. We hypothesized that the relationship between anxious and avoidant attachment and PPD would be mediated by use of maladaptive coping strategies. The assessment instruments were Edinburgh Postnatal Depression Scale (EPDS), Brief Coping Orientation for Problem Experiences (COPE), Experiences in Close Relationship Scale (ECR). The results indicated that the effect of insecure attachment styles (anxious and avoidant attachment) on antepartum depressive symptomatology was partially mediated by dysfunctional coping styles. Anxious attachment has also an indirect significant effect on postpartum depression through emotional coping; however, avoidant attachment does not seem to be significantly related to postpartum depression. Our findings revealed that not only it is important to consider attachment in understanding PPD but also that coping plays an important role in these relationships. These findings would help a preventive coping-based intervention strategy to enhance the capacity of women with insecure attachment styles to use more adaptive coping during and after pregnancy.

This paper aims to address the exponential stability and stabilization problems for a class of delayed nonlinear Markov jump systems under randomly occurring Denial-of-Service (DoS) attack and packet loss. Firstly, the stochastic characteristics of DoS attack and packet loss are depicted by the attack success rate and packet loss rate. Secondly, a Period Observation Window (POW) method and a hybrid-input strategy are proposed to compensate for the impact of DoS attack and packet loss on the system. Thirdly, A Dynamic Event-triggered Mechanism (DETM) is introduced to save more network resources and ensure the security and reliability of systems. Then, by constructing a general common Lyapunov functional and combining with the DETM and other inequality analysis techniques, the less conservative stability and stabilization criteria for the underlying systems are derived. In the end, the effectiveness of our result is verified through a numerical example.

Severe early childhood caries remains the most common chronic disease affecting children. Its multifactorial etiology has established a controversy about which risk factors were more significant to its development. Therefore our study aimed through meticulous statistical analysis to arrange the “well agreed upon” common risk factors in order of significance, to aid the clinician in tailoring an adequate preventive program for this affected age group. The study reshuffled the risk factors contributing to severe early childhood caries and placed them in the order of their significance as follows: snacking of sugary food several times a day, increased number of siblings to 3 or more, night feeding, child self-employed brushing, mother caries experience, 2 siblings, on demand feeding, once/day sugary food, sharing utensils, 1 Sibling, male gender, father’s education, late first child dental visit, brushing time, mother’s education, no dental visit, decreased brushing frequency & no night brushing.

Sweat rate and electrolyte losses have a large inter-individual variability, a personalized approach to hydration can overcome this issue to meet an individual’s needs. This study aimed to investigate the effects of personalized hydration strategy (PHS) on fluid balance and intermittent exercise performance. Twelve participants conducted 11 laboratory visits including a VO2max test and two 5-day trial arms under normothermic (NOR) or hyperthermic (HYP) environmental conditions. Each arm began with 3-day of familiarization exercise following by two random exercise trials with a either PHS or control (CON). Then, participants crossed-over to the second arm for: NOR+PHS, NOR+CON, HYP+PHS, and HYP+CON. The PHS was prescribed according to participants’ fluid and sweat sodium losses. CON drank ad-libitum of commercially-available electrolyte solution. Exercise trials consisted of two phases: 1) 45min constant workload; 2) high-intensity intermittent exercise (HIIT) until exhaustion. PHS had a significantly greater fluid intake compared to CON. HYP+CON produced the lowest sweat sodium concentration. HYP+PHS had a lower thirst perception and a longer HIIT compared to HYP+CON. Thus, PHS reinforces fluid intake and successfully optimizes hydration status, regardless of environmental conditions. PHS may be or is an important factor to preventing negative physiological consequences during high-intensity exercise in the heat.

A large diversity of epigenetic factors, such as microRNAs and histones modifications, are known to be capable of regulating gene expression without altering DNA sequence itself. In particular, miR-1 is considered the first essential microRNA in cardiac development. In this study, miR-1 potential role in early cardiac chamber differentiation is analyzed through specific signaling pathways. For this, we performed in chick embryos functional experiments by means of miR-1 microinjections into the posterior cardiac precursors -of both primitive endocardial tubes- committed to sinoatrial region fates. Subsequently, embryos were subjected to whole mount in situ hybridization, immunohistochemistry and RT-qPCR analysis. As a relevant nov-elty, our results revealed that miR-1 increases Tbx5, Gata4 and AMHC1, while this microRNA diminishes Mef2c expression, during early differentiation of cardiac sinoatrial region. Further-more, we observed in this developmental context that miR-1 upregulates CRABPII and RARß, and downregulates CRABPI, which are three crucial factors in retinoic acid signaling pathway. Interestingly, we also noticed that miR-1 directly interacts with HDAC4 and Calmodulin, as well as with Erk2/MAPK1, which are three key factors actively involved in Mef2c regulation. Our study shows, for the first time, a key role of miR-1 as an epigenetic regulator in early differenti-ation of cardiac sinoatrial region through orchestrating opposite actions between retinoic acid and Mef2c, fundamental to properly assign cardiac cells to their respective heart chambers. A better understanding of those molecular mechanisms modulated by miR-1 will definitely help in fields applied to therapy and cardiac regeneration and repair.

This paper analyzes and compares models for predicting average magnet losses in interior permanent-magnet motors with fractional-slot concentrated windings due to harmonics in the armature reaction (assuming sinusoidal phase currents). Particularly, loss models adopting different formulations and solutions to the Helmholtz equation to solve for the eddy currents are compared to a simpler model relying on an assumed eddy-current distribution. Boundaries in terms of magnet dimensions and angular frequency are identified (numerically and using an identified approximate analytical expression) to aid the machine designer whether the more simple loss model is applicable or not. The assumption of a uniform flux-density variation (used in the loss models) is also investigated for the case of V-shaped and straight interior permanent magnets. Finally, predicted volumetric loss densities are exemplified for combinations of slot and pole numbers common in automotive applications.

A case-crossover study examined how PM_2.5 from Asian Dust Storms (ADS) affects the number of emergency room (ER) admissions for cardiovascular diseases (CVDs) and respiratory diseases (RDs). Our data indicated that PM_2.5 concentration from ADS was highly correlated with ER visits for CVDs and RDs. The odds ratios (OR) increased by 2.92 (95% CI: 1.22-5.08) and 1.86 (95% CI: 1.30-2.91) per increase 10 µg/m³ in PM_2.5 levels, for CVDs and RDs, respectively. A 10 µg/m³ increase in PM_2.5 from ADSs was significantly associated with increase in ER visits for CVDs among those 65 years of age and older (an increase of 2.77 in OR) and for females (an increase of 3.09 in OR). In contrast, PM_2.5 levels had a significant impact on RD ER visits among those under 65 years of age (OR=1.77). The risk of ER visits for CVDs increased on the day when the ADS occurred in Taiwan and the day after (lag 0 and lag 1); the corresponding risk increase for RDs only increased on the fifth day after the ADS (lag 5). In Taiwan’s late winter and spring, the severity of ER visits for CVDs and RDs increases. Environmental protection agencies should employ an early warning system for ADS to reduce high-risk groups’ exposure to PM_2.5.

Subchondral bone loss is an important pathological feature of early-stage temporomandibular joint (TMJ) osteoarthritis (OA). Previous studies focused mainly on the bone resorption by osteoclasts in early-stage OA, but the bone formation feature has not drawn enough attention. Sema4D/Plexin-B1 is a pair of molecules expressed by osteoclast/osteoblast, which is capable of inhibiting bone formation by osteoblasts. The present study found that subchondral bone loss in early-stage TMJ OA was accompanied by up-regulated expression of Sema4D in cartilage and subchondral bone and Plexin-B1 in subchondral bone. Reducing Sema4D level could inhibit the subchondral bone loss and cartilage degeneration of early-stage TMJ OA. In vitro, results revealed that Sema4D could reduce the expression of osteocalcin (OCN) and alkaline phosphatase (ALP), and increase the migrating capability of Plexin-B1-positive osteoblasts. Our results revealed that elevated Sema4D expression in early-stage TMJ OA might decrease the bone formation activity of osteoblasts in the subchondral bone by binding to Plexin-B1 expressed by osteoblasts. Inhibiting Sema4D/Plexin-B1 signaling in the early-stage OA holds promise as a strategy for new therapeutic approaches to osteoarthritis.

Background: Assessing the impact of bone health clinical management in breast cancer (BC) patients receiving adjuvant endocrine therapy and designing a personalized clinical pathway to reduce bone loss, in an Italian research hospital. Methods: The primary endpoint was to assess (through the process improvement organizational method) the clinical pathway that post-surgical BC patients prescribed with endocrine therapy undergo to prevent bone loss. The secondary endpoint was to design a personalized clinical pathway for a prompt implementation of guidelines, to assess and possibly prescribe antiresorptive therapy. Results: During the first year of the new diagnostic therapeutic assistance pathway execution, an 60% increase in Dual-Energy X-ray Absorptiometry evaluations within 30 days and a 39.5% increase in antiresorptive therapy prescription within 90 days (since prescription of endocrine therapy) were shown, thus increasing patients’ compliance. Conclusion: Case managers and bone health specialists in this context can improve patients’ adherence to therapies and bone health, helping physicians to expand their collaboration.

The information on the land use and soil conservation practice based on year 2006, 2010 and 2014, hence offering an opportunity to model the impacts of land use change on erosion, deposition and surface water runoff. Limitation in the use of hydrological models had been their inability to handle the large amount of input data that describe the heterogeneity of the natural system. In this study, a procedure that takes into account soil conservation practice based on the land use change, the response of soil erosion and sediment export from the George Town Conurbation catchment area, and average annual sediment yields were estimated for each grid cell of the watershed to identify the critical erosion areas of rural and urban planning proposes. Average annual sediment yield and data on a grid basis estimated using Universal Soil Loss Equation (USLE) and an emerging technology represented by Geographic Information System (GIS) used as a tool to produce a map for erosion rate. The changing of the land use from forest to agriculture and then to an urban area is a challenging task to research on land use demand for population, and environmental impact assessment is important for the planning of natural resources management, allowing research the modification of land use properly and implement more sustainable for long term management strategies. The challenge is to formulate strategies that would promote an integrated approach to the land use planning at an appropriate level as to address the issues that arose. Modelling for creating urban growth boundary for the George Town Conurbation must have to be controlled surface runoff and soil loss and sediment export from land use of the George Town Conurbation catchment.

Familial Alzheimer’s disease (FAD) can be caused by mutations in PSEN1 that encodes presenilin-1, a component of the gamma-secretase complex that cleaves amyloid precursor protein. Alterations in calcium (Ca2+) homeostasis and glutamate signaling are implicated in the pathogenesis of FAD, however it has been difficult to assess in humans whether or not these phenotypes are the result of amyloid or tau pathology. This study aimed to assess early calcium and glutamate phenotypes of FAD by measuring the Ca2+ response of induced pluripotent stem cell (iPSC)-derived neurons bearing PSEN1 mutations to glutamate and the ionotropic glutamate receptor agonists NMDA, AMPA and kainate compared to isogenic control and healthy lines. The data shows that in early neurons, even in the absence of amyloid and tau phenotypes, FAD neurons exhibit increased Ca2+ responses to glutamate and AMPA, but not NMDA or kainate. Together this suggests that PSEN1 mutations alter Ca2+ and glutamate signaling as an early phenotype of FAD.

The question of how to conceive of the relation between the pregnant female and the embryo has become a recent focus of debate in the philosophical literature. Here we consider this problem in the context of current debates on individuality in the philosophy of biology by looking at how pregnancy is individuated in different disciplinary contexts. Firstly, we review different notions of biological individuality in the literature, examine how each of them applies to the case of pregnancy, and claim that recent work on the evolution of eutherian reproduction offers insights for new criteria for rethinking the individuality of pregnancy. Then, we reconstruct the main assumptions underlying the established biological account of pregnancy. Finally, we develop an alternative account based on the hypothesis that pregnancy is an evolved relational novelty and maintain that pregnant females are conceived as historical reproductive individuals. In the final section before the conclusions, we discuss how the historical reproductive biological individuality of pregnancy differs from, and coexists with, other views of individuality, and examine some of its consequences.

This work investigated the isothermal holding time dependence of the densification, microstructure, weight loss and tensile properties of Fe-Mn-Si powder compacts. Elemental Fe, Mn and Si powder mixtures with a nominal composition of Fe-28Mn-3Si (in weight percent) were ball milled for 5h and subsequently pressed under a uniaxial pressure of 400 MPa. The compacted Fe-Mn-Si powder mixtures were sintered at 1200 ℃ for 0, 1, 2 and 3 h, respectively. In general, the density, weight loss and tensile properties increased with the increase of isothermal holding time. A significant increase in density, weight loss and tensile properties occurred in the compacts isothermally holding for 1 h, as compared to those with no isothermal holding. However, further extension of isothermal holding time (2 and 3 h) only played a limited role in promoting the density and tensile properties. The weight loss of the sintered compacts was mianly caused by the sublimation of Mn in Mn depletion region on the surface layer of the sintered Fe-Mn-Si compacts. The length of the Mn depletion region increased as isothermal holding time increased. A single α-Fe phase was detected on the surface of all the sintered compacts, and the locations beyond the Mn depletion region were comprised of a dual dominant γ-austenite and minor ε-martensite.

Hypertensive diseases of pregnancy (HDP) represent a global clinical challenge, affecting 5-10% of women and leading to complications for both maternal well-being and fetal development. At the heart of these complications is endothelial dysfunction, with oxidative stress emerging as a pivotal causative factor. The reduction in nitric oxide (NO) bioavailability is a vital indicator of this dysfunction, culminating in blood pressure dysregulation. In the therapeutic context, although antihypertensive medications are commonly used, they come with inherent concerns related to maternal-fetal safety, and a percentage of women do not respond to these therapies. Therefore, alternative strategies that directly address the pathophysiology of HDP are required. This article focuses on the potential of the nitrate-nitrite-NO pathway, abundantly present in dark leafy greens and beetroot, as an alternative approach to treating HDP. The objective of this review is to discuss the prospective antioxidant role of nitrate. We hope our discussion paves the way for using nitrate to improve endothelial dysfunction and control oxidative stress, offering a potential therapy for managing HDP.

Recent years have seen an increased interest in the role of oxidative stress (OS) in pregnancy. Pregnancy inherently heightens susceptibility to OS, a condition fueled by a systemic inflam-matory response which culminates in an elevated presence of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the circulatory system. The amplified OS in pregnancy can trigger a series of detrimental outcomes such as underdevelopment, abnormal placental function, and a host of pregnancy complications, including pre-eclampsia, embryonic resorp-tion, recurrent pregnancy loss, fetal developmental anomalies, intrauterine growth restriction, and in extreme instances, fetal death. The body’s response to mitigate the uncontrolled increase in RNS/ROS levels involves trace elements that take part in non-enzymatic and enzymatic defense mechanisms, namely, copper (Cu), zinc (Zn), manganese (Mn), iron (Fe), and selenium (Se). Determination of ROS concentrations poses a challenge due to their short lifespan, prompting the use of marker proteins, including malondialdehyde (MDA), superoxide dis-mutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), lipid peroxidation (LPO), catalase (CAT), and glutathione (GSH). These markers, indicative of redox stress intensity, can offer indirect assessments of pregnancy complications. Given the limitations in conducting experimental studies on pregnant women, animal models serve as valuable substitutes for in-depth research. This review delves into the mechanism of OS in pregnancy and underscores the pivotal role of markers in its evaluation.

Abstract: Background/Objectives: There are indications that the microbial composition of the maternal mucosal surfaces is associated with adverse events during pregnancy. The aim of this review is to investigate the link between vaginal microbiome alterations and gestational com-plications risk. Methods: This comprehensive literature review was performed using Medline and Scopus databases. The following search algorithm was used "Pregnancy Complications"[Mesh] AND (Vagin*) and after literature screening 44 studies were included in the final review. Results: The studies that were included investigated the association between vaginal microbial composi-tion and preterm birth, miscarriage, preeclampsia, ectopic pregnancy, gestational diabetes mellitus, chorioamnionitis and preterm premature rupture of membranes. In most of the studies, it was well established that increased microbial diversity is associated with these conditions. Also, the depletion of Lactobacillus species is linked to most of the gestational complication, while the increased relative abundance and especially L. crispatus may exerts a protective effect in favor of the pregnant woman. Several pathogenic taxa including Gardnerella, Prevotella, Sneathia, Bac-terial Vaginosis-Associated Bacteria-2, Atopobium and Megasphera seem to be correlated to higher maternal morbidity. Conclusions: Vaginal microbiome aberrations seem to have an as-sociation with pregnancy related adverse events, but more high-quality homogenous studies are necessary to reliably verify this link.

The adverse relationship between viral hepatitis and pregnancy in developing countries was seen as a reflection of retrospective biased hospital-based data collection by the West. However, the discovery of HEV from an epidemic of non-A, non-B hepatitis in Kashmir and documenting increased incidence and severity of hepatitis E in pregnancy from a house-to-house survey unmasked the unholy alliance. Among the family of HEV’s, genotype (gt)-1, with a unique ORF4-encoded protein enhancing viral polymerase activity and viral replication, is the sole HEV that shows this adverse relationship. The epidemics caused by HEV-gt1 and not by HEV-gt2 show adverse relationship with pregnancy. The pathogenesis of the unholy alliance is complex and at present not well understood. Possibly multiple factors play a role in causing severe liver disease in the mother including: infection, replication and damage to the maternal-foetal interface by HEV-gt1; vertical transmission of HEV to foetus causing severe foetal/neonatal hepatitis; and combined viral and hormone related immune dysfunction of diverse nature in the mother promoting viral replication. Management is multidisciplinary and needs a close watch for the development and management of ALF. Preliminary data suggest beneficial maternal outcomes by early termination of pregnancy in patients with lower grades of encephalopathy.

Metformin use in pregnancy is increasing worldwide as randomised controlled trial (RCT) evidence is emerging demonstrating its safety and efficacy. The Metformin in Gestational Diabetes (MiG) RCT changed practice in many countries demonstrating that metformin had similar pregnancy outcomes to insulin therapy with less maternal weight gain and a high degree of patient acceptability. A multicentre RCT is currently assessing the addition of metformin to insulin in pregnant women with type 2 diabetes. RCT evidence is also available for the use of metformin for women with Polycystic Ovarian Syndrome and for non-diabetic women with obesity. No evidence of an increase in congenital malformations or miscarriages has been observed even when metformin is started before pregnancy and continued to term. Body composition and metabolic outcomes at two, seven and nine years have now been reported for the offspring of mothers treated in the MiG study. In this review, we will briefly discuss the action of metformin and then consider the evidence from the key clinical trials.

Kinesiophobia (fear of movement) has been recognized as a significant barrier to recovery and rehabilitation in patients after total knee arthroplasty (TKA). Our goal was to identify predictors of kinesiophobia and examine its correlation with early functional outcomes in TKA recipients. On the first and fifth postoperative days (POD1 and POD5), we evaluated pain using the International Pain Outcomes Questionnaire (IPO-Q) and created multidimensional pain composite scores (PCS). Pain Composite Score-total (PCStotal) assesses the overall impact of pain, taking into account outcomes of pain intensity, pain-related interference with function, and emotions and side effects. Functional status on POD 5 was determined by the Barthel index, 6-minute walking test, and knee range of motion. Kinesiophobia was measured on POD5 using the Tampa Scale for Kinesiophobia (TSK) and multivariable logistic regression was used to assess factors associated with kinesiophobia. Among 75 TKA patients, 27% exhibited kinesiophobia. The final regression model highlighted PCStotal on POD5 (OR=6.2, CI=1.9-19.9), PCStotal (OR=2.1, CI=1.2-3.8) on POD1, and the intensity of chronic pain before surgery (OR=1.4, CI=1.1-2.1) as significant kinesiophobia predictors. On POD5, those with kinesiophobia showed increased dependency, slower gait, and poorer knee extension recovery. This study highlights the importance of identifying and addressing kinesiophobia in TKA patients to optimize functional outcomes and improve recovery. Also, it is important to assess not only pain intensity but also the physical and emotional interference caused by pain, which can contribute to the development of kinesiophobia.

Abstract: Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (KATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset hyperinsulinemic hypoglycemia caused by ABCC8 gene mutations. In the first patients, which presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330- 1)del] correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C&gt;T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine) PET/CT was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance and of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH.

Hypertensive disorders of pregnancy (HDP), including preeclampsia (PE) and gestational hypertension (GH), are major causes of maternal and fetal morbidity and mortality. This review elucidates the role of regulatory T cells (Tregs) in the immunological aspects of HDP and explores their therapeutic potential. Tregs, known for maintaining immune tolerance, are crucial in pregnancy to prevent immune-mediated rejection of the fetus. In HDP, Treg numbers and function imbalance are observed, correlating with disease severity. The review highlights that Tregs contribute to immunological adaptation in normal pregnancy, ensuring fetal acceptance and placental development. In contrast, HDP is associated with Treg dysfunction, marked by decreased numbers and impaired regulatory capacity, leading to inadequate immune tolerance and abnormal placental development. This dysfunction is particularly evident in PE, where Tregs fail to adequately modulate the maternal immune response against fetal antigens, contributing to the pathophysiology of the disorder. Therapeutic interventions aiming to modulate Treg activity represent a promising avenue for HDP management. Studies in animal models and limited clinical trials suggest that enhancing Treg functionality could mitigate HDP symptoms and improve pregnancy outcomes. However, the review acknowledges the complexity of translating these findings into effective clinical therapies, given the multifactorial nature of HDP and the intricate regulatory mechanisms of Tregs. In conclusion, while the precise role of Tregs in HDP is still being unravelled, their central role in immune regulation during pregnancy is indisputable. Further research is needed to fully understand the mechanisms by which Tregs contribute to HDP and to develop targeted therapies that can safely and effectively harness their regulatory potential for treating hypertensive diseases of pregnancy.

The most prevalent musculoskeletal disorder of childhood with unclear aetiology is Growing Pains (GPs). Anatomic deformities and factors that change bone turnover are implicated in GPs pathophysiology. Perinatal risk factors alter the bone metabolism affecting the bone mineral density and content. The aim of our study was to analyze the relationship between GPs, knock knees and perinatal factors. The examined population consisted of 276 children aged 3-7 years. Among them 10 pairs of dizygotic twins were evaluated. The data were collected by using a combination of semi-structured questionnaires, clinical examinations and medical charts of the children and the obstetric history of the mothers. 78 children presented GPs meeting Peterson’s criteria. Genu valgum severity was a significant factor for GPs manifestation and for their increased frequency and intensity. Subsequently, perinatal factors regarding gestational age, Apgar score, head circumference (lower than 33cm) and birth length or weight (smaller than 50 cm and 3000gr, respectively) made a remarkable contribution to the development of GPs. Conversely, antenatal corticosteroid treatment, increased maternal age and maternal smoking during pregnancy were not predictive for the disorder. Our data are potentially supportive for the “bone strength” theory and for the contribution of anatomical disturbances in GPs appearance.

PURPOSE: Breast cancer tumors frequently have intratumor heterogeneity. Tumors with high intratumor heterogeneity have caused therapeutic resistance and have human epidermal growth factor receptor 2 (HER2) heterogeneity in response to HER2-targeted therapies. This study aimed to investigate whether high HER2 heterogeneity levels were clinically related to poor prognosis for HER2-targeted adjuvant therapies resistance in primary breast cancers. METHODS: This study included patients with primary breast cancer (n = 251) treated with adjuvant HER2-targeted therapies. HER2 heterogeneity was manifested by the shape of HER2 fluorescence in situ hybridization amplification (FISH) distributed histograms with HER2 gene copy number within a tumor sample. Those heterogeneity classified each tumor into the biphasic grade graph (high heterogeneity [HH]) group and the monophasic grade graph (low heterogeneity [LH]) group. Both groups were evaluated for disease-free survival (DFS) and overall survival (OS) for a median of ten years of annual follow-up. RESULTS: Of 251 patients with HER2-positive breast cancer, 46 (18.3%) and 205 (81.7%) were classified into the HH and LH groups, respectively. The HH group had more distant metastases and a poorer prognosis than the LH group (DFS: P < 0.001 (HH:63% vs LH:91% at 10 years), and OS: P = 0.012 (HH:78% vs LH:95% at 10 years). CONCLUSION: High HER2 heterogeneity is a poor prognostic factor in patients with HER2-positive breast cancer. A novel approach of heterogeneity, which is manifested by the shape of HER2 FISH distributions, might be clinically useful in the prognosis prediction of patients after HER2 adjuvant therapy.

Purpose: In recent years, there has been an increasing interest in simultaneous hip and knee arthroplasty compared to staged procedures. The aim of this study was to clarify some controversies and show the safety for the patients by comparing the transfusion rate, postoperative hemoglobin drop, length of stay (LOS), in-hospital complications, 30-day readmissions, and early functional outcome after simultaneous and staged hip and knee arthroplasty. Methods: We conducted a retrospective trial that included all patients who were undergoing primary TKA, THA, and UKA by one single surgeon in a high-volume arthroplasty center between 2017 and 2020 as a simultaneous or staged procedure. Staged bilateral arthroplasties were performed within 12 months and were stratified by the time between procedures. Data was acquired through the electronic files at the OCM. For functional outcome, we compared the ability of the patients to walk independently on the ward and the ability to walk a set of stairs alone which was daily recorded by the attending physiotherapist. Results: In total 305 patients were assessed for eligibility and included in this clinical trial. 145 patients were allocated to the staged arthroplasty group. That group was subdivided in a hip and a knee group, whereas the knee group was split in TKA and unicompartmental knee arthroplasty (UKA). The second staged procedure was performed within 12 months of the first procedure.160 patients were allocated to the simultaneous arthroplasty group. This group was also subdivided into a hip and knee group, whereas the knee group was split again into a TKA and UKA group. No statistical difference was found between the two groups regarding demographic data. Primary outcome measurements: There is no significant difference in transfusion rate or complication rate. Secondarily: No correlation was found between the Hb-drop and the functional outcome as well as the length of stay (LOS). Walking the stairs showed a significant difference in the knee group. Conclusion: We observed no significant differences in transfusion rate, in-hospital complications, as well as readmission rate. The early functional outcome showed no significant difference in mobility for all groups. Simultaneous arthroplasty for knee or hip is as safe as a staged procedure, with no higher risk for the patient and his outcome, in a high-volume center.

Background and Objectives: The purpose of this study was to investigate whether early surfactant administration affects the status of ductus arteriosus (DA) in preterm infants ≤32 weeks of gestational age (GA) within 24 hours of birth. Materials and Methods: It is a prospective study conducted from March 15, 2022, to November 15, 2023, in a tertiary academic center. In-born infants ≤ 32 weeks of gestation (n = 88) were enrolled. The study group was further divided into surfactant (n=44) and non-surfactant (n=44) subgroups. Results: 76% of the preterm infants who received surfactant therapy (RRR = 0.839) recorded an increase in Kindler Score at 24 hours of life (1-RR = 1-0.24 = 76%). Surfactant administration was significantly associated with decreased pre-ductal diastolic pressure (29.9 mmHg vs. 34.8 mmHg, p=0.0231), post-ductal diastolic pressure (28.7 mmHg vs. 32.2 mmHg, p=0.0178) pre-ductal MAP (41.6 mmHg vs. 46.5 mmHg, p=0.0210) post-ductal MAP (41.0 mmHg vs. 45.3 mmHg, p=0.0336). There were no significant changes in ductus arteriosus parameters at 24 hours of life. Conclusions: Early surfactant administration does not affect the status of ductus arteriosus in preterm infants ≤32 weeks of gestational age at 24 hours of life.

Although a growing number of evidence emphasizes superior of VATS over conventional thoracotomy, still is little known about early postoperative diaphragm muscle function after lobectomy via these two approahces. To fill the gap in existing literature, we conducted comparative study between VATS and conventional thoracotomy in terms of postoperative diaphragm muscle function, assessing its contractility, strength, magnitude of effort and potential risk of dysfunction such as: atrophy and paralysis. A total of 59 patients (30 after VATS), who underwent anatomical pulmonary resection at our institution, were enrolled into this study. The control group was consisted of 28 health subjects without medical condition could contribute to diaphragm dysfunction. Diaphragm muscle was assessed before and after surgery using ultrasonography. We found that both surgical approaches were associated with postoperative impairment of diaphragm muscle function - compared to baseline data. Postoperative reduction of diaphragm contraction was demonstrated in all of 59 patients. In case of control group, the differences between measurements were no observed. We noted that lobectomy via thoracotomy was linked with greater percentage of patients with diaphragm paralysis or/and atrophy that VATS. Similar findings were observed in refer to diaphragm magnitude effort, as well as, diaphragm contraction strength, where minimal invasive surgery was associated with better diaphragm function parameters - in comparison to thoracotomy. Disturbance of diaphragm work was reported both at operated and non-operated side. Upper right and left lobectomy was connected with greater diaphragm function impairment than other segments. In conclusion, VATS technique seems to be less invasive than conventional thoracotomy providing a better postoperative function of a main respiratory muscle.

Dysregulation of cartilage homeostasis and the changes in the density and the architecture of the subchondral bone were postulated as a potent mechanically pathological activity contributing to osteoarthritis (OA) pathogenesis. Extracorporeal shockwave therapy (ESWT) is a new, none invasive and effective method in the treatment of animal OA model. In the current study, we demonstrated that shockwave induced the expression of protein-disulfide isomerase-associated 3 (Pdia-3) which is a multifunctional protein hypothesized to be a significant mediator for 1α,25-Dihydroxyvitamin D3 (1α,25(OH)₂D₃) signaling pathway using two-dimensional electrophoresis. Histological analysis and quantitative polymerase chain reaction (qPCR) were verified and observed that the expression of Pdia-3 at 2 weeks was significantly higher than that of any other group at 4 weeks, 8 weeks, and 12 weeks post-shockwave treatment in early OA knee of rat. The other factors of the 1α,25(OH)₂D₃ rapid membrane signaling pathway including extracellular signal-regulated protein kinases 1 (ERK1), osteopontin (OPG), alkaline phosphatase (ALP), and matrix metallopeptidase 13 (MMP13) were measured and significantly increased by qPCR at 2 weeks post-shockwave treatment in early OA knee. Our proteomic data revealed significant Pdia-3 expression in microenvironments of joint tissue that could be actively responded to ESWT, which may potentially regulate biological function of chondrocytes and osteoblasts in the treatment of OA knee.

This study investigates the effects of subclinical hypothyroidism and BDNF on telomere length in T1DM mothers and their neonates. Methods: In this prospective cohort study, 70 pregnant women with T1DM were enrolled. Subclinical hypothyroidism during the first trimester was characterized by elevated thyroid-stimulating hormone (TSH) levels ranging from 2.5 to 5.0mIU/L alongside normal free thyroxine (FT4) concentrations. Participants were stratified into two groups based on TSH levels: a maternal subclinical hypothyroid group (SHG, n=35) and a maternal euthyroid group (ETG, n=35). Leukocyte telomere length (LTL) measurements were conducted using whole blood samples from the mothers and umbilical veins. Results: The maternal LTL mean was 1.7 (SD=1.1), which was significantly shorter than the neonatal telomeres, with a mean of 2.3 SD (1.2). A significant correlation was observed between maternal and neonatal LTL (r=0.750, p&lt;0.001). A positive association was found between neonatal LTL and BDNF levels in maternal circulation [β=0.421 (95% CI 0.536; 1.873; p=0.001)]. Neonatal LTL was negatively associated with gestational weight gain [β=-0.266 (95% CI-0.138; -0.009)], and with TSH in the first trimester [β=-0.237; (95% CI -0.493; - 0.010)]. Notably, neonates in the SHG exhibited shorter LTL, with a mean of 2.1 (1.0), compared to those in the ETG, who had a mean LTL of 2.7 (1.4). A positive association was found between maternal LTL and BDNF levels in maternal circulation [β=0.523 (95% CI 0.790; 1.950; P&lt;0.001)]. Maternal LTL was negatively associated with gestational weight gain [β=-0.259 (95% CI -0.122; -0.010)], and with TSH in the first trimester [β=-0.231; (95% CI -0.422; - 0.015)]. Conclusions: Genetic factors affect neonatal LTL. Maternal subclinical hypothyroidism reduces neonatal LTL. The link between maternal and neonatal LTL and BDNF reveals the complex endocrine-neurotrophic interaction in T1DM telomere dynamics.

Cytomegalovirus (CMV) infection is the most common congenital infection worldwide, affecting between 0.7% and 1% of all live births. Approximately 11% of infected newborns are symptomatic at birth, and between 30% and 40% of these are at risk of developing long-term neurological sequelae. Until recently, the lack of an effective treatment did not justify universal testing of pregnant women. In recent years, however, valacyclovir at a dose of 8 g/day has been shown to be effective in preventing vertical transmission, and ganciclovir has been shown to be effective in preventing long-term sequelae in the treatment of symptomatic neonates. The aim of this article is to review congenital CMV infection, from its epidemiology to its treatment, using the most recent studies in the literature, and to help in the decision to modify protocols for universal testing of pregnant women according to the possibilities of each locality.

Objective Ovarian pregnancy is a rare but well-known pathology. However, pathophysiology, diagnosis and treatment are not clearly established. Data sources. All case reports published in Pubmed from Nov 2011 till Nov 2022. Study eligibility criteria. A systematic review and 2 case reports of ovarian pregnancy Study appraisal and synthesis methods. Not applicable Results Ovarian pregnancies occur in 8% of women without or blocked oviducts and in 23% on the other side than the corpus luteum and the symptoms of ovarian pregnancies are not specific. Therefore ovarian pregnancy has to be suspected in all women with abdominal bleeding. As for extrauterine pregnancies, the presence of an intrauterine pregnancy does not rule out an ovarian pregnancy. Surgical excision is the preferred treatment. Important is that in women with both an intra-uterine and an ovarian pregnancy, care should be taken not to damage the corpus luteum. Conclusions Ovarian pregnancies can occur in women with blocked tubes, on the other side of the corpus luteum, in the presence of an intrauterine pregnancy, and even when pregnancy tests or tranvaginal ultrasonography are negative. The diagnosis being difficult to exclude, a laparoscopy is indicated in all women with intra-abdominal bleeding, keeping in mind that an intra-uterine pregnancy cannot be exluded and that a corpus luteum need to be respected.

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the chief concern of the international community in almost no time. As of May 9th, 2021, more than 150 million cases and 3.2 million deaths have been recorded. Considering the early struggle in treating COVID-19 patients, the researchers and clinicians have decided to try the previously available drugs according to their mechanisms of action. Hence, many antivirals, antibiotics, antiparasitics, and antipyretics have been proposed. Pregnant women, fetuses, and infants are known high-risk populations that are threatened during disease outbreaks. Therefore, this article reviews the safety of potential drugs for COVID-19 patients during pregnancy and breastfeeding.

Inflammatory Bowel Disease (IBD) presents distinct challenges during pregnancy due to its influence on maternal health and pregnancy outcomes. This literature review aims to dissect the existing scientific evidence on pregnancy in women with IBD and provide evidence-based recommendations for clinical management. A comprehensive search was conducted across scientific databases, selecting clinical studies, systematic reviews, and other pertinent resources. Numerous studies have underscored an increased risk of complications during pregnancy for women with IBD, including preterm birth, low birth weight, neonates small for gestational age, and congenital malformations. Nevertheless, it's evident that proactive disease management before and throughout pregnancy can mitigate these risks. Continuation of IBD treatment during pregnancy and breastfeeding is deemed safe with agents like thiopurines, anti-TNF, vedolizumab, or ustekinumab. However, there's a call for caution when combining treatments due to the heightened risk of severe infections in the first year of life. For small molecules, their use is advised against in both scenarios. Effective disease management, minimizing disease activity, and interdisciplinary care are pivotal in attending to women with IBD. The emphasis is placed on the continual assessment of maternal and infant outcomes and an expressed need for further research to enhance the understanding of the ties between IBD and adverse pregnancy outcomes.

Background. Pregnancy rates in women on dialysis have increased in the last decades, thus making it a topic of growing interest. The rarity of this event is predominantly due to fertility problems and to the high rates of pregnancy failure including stillbirth, fetal and neonatal deaths [1]. Methods. We conducted a narrative review of existent literature in order to analyse the major issues about pregnancy on dialysis to give the reader a full updated prospective about this topic which, even if not common, is becoming more and more frequent. Results. Even if recently acquired knowledge has improved diagnosis and treatment of dialysis pregnancies focusing on several aspects, pregnancy on dialysis remains a great challenge for obstetricians and should be managed by a multidisciplinary expertise team. Conclusion. Dialysis in pregnancy may be necessary for women previously affected by end stage renal disease (ESRD) becoming pregnant, or in case of acute renal injury presenting for the first time during gestation or, again in case of existent renal pathology worsening during pregnancy and requiring dialysis. Although some evidence suggests that more intensive dialysis regimens are correlated with better obstetric outcomes, the optimal therapeutic protocol still remains to be established.

The global food system has three recognized challenges: (a)increasing the availability of food consumption, (b) reducing food loss, and (c) reducing food waste. The increasing demand for food consumption, increasing quantity of food loss, and corresponding increase in food waste are resulting in serious health, aesthetic, social, economic, and environmental problems due to a lack of appropriate planning and management. Despite its importance, there is no clear, concise, and comprehensive definition of food consumption, loss, and waste. Generally, food consumption, food loss, and food waste are dealt with separately. This article presents a logically constructed ontological framework of food consumption, loss, and waste. It gives equal importance to all three aspects of global food management. The systematic ontological framework is general, and the analysis can be applied to any country. The framework deconstructs the combinatorial complexity of the problem and explicates the pathways to manage the consumption, loss, and waste. The ontological framework encapsulates 19*8*7*4*5*6 = 25,536 possible components of the challenge. A critical analysis based on available data using the framework will help to develop strategies to deal with the problem. It can help to discover the gaps and to find ways to bridge the gaps. It is novel to conceptualize food consumption, loss, and waste together.

An observational cohort study of patients diagnosed with endometrial cancer (EC) stage IA G1, or atypical endometrial hyperplasia (AHE), undergoing organ-preserving treatment, was conducted. Objective of the study: to determine CDO1, PITX2, and CDH13 gene methylation levels in early endometrial cancer and atypical hyperplasia specimens obtained before organ-preserving treatment in the patients with adequate response and with insufficient response to hormonal treatment. Materials and methods: 41 endometrial specimens obtained during diagnostic uterine curettage in women with EC (n=28) and AEH (n=13), willing to preserve reproductive function, were studied; 18 specimens of endometrial cancer IA stage G1 from peri- and early postmenopausal women (comparison group) were included in the study. The control group included 18 endometrial specimens from healthy women obtained by diagnostic curettage for missed abortion and/or intrauterine adhesions. Methylation levels were analyzed using the modified MS-HRM method. Results: All 13 women with AEH had complete response (CR) to medical treatment. In the group undergoing organ-preserving treatment for uterine cancer IA stage G1 (n=28), 14 patients had complete response (EC CR group) and 14 had not (non-CR). It was found that all groups had statistically significant differences in CDO1 gene methylation levels with the control group (p&lt;0.001) except for the EC CR group (p=0.21). The p-value of difference between EC CR and EC non-CR groups was &lt;0.001. The differences in PITX2 gene methylation levels between the control and study groups were also significantly different (p&lt;0.001), except for AEH group (p=0.21). For the difference between EC CR and EC non-CR groups, the p-value was 0.43. For CDH13 gene methylation levels, statistically significant differences were found between the control and EC non-CR groups (p&lt;0.001), and the control and EC comparison groups (p=0.005). When comparing the EC CR group with EC non-CR group, the p-value for this gene was &lt;0.001. Simultaneous assessment of CDO1 and CDH13 genes methylation allowed to accurately distinguish between EC CR and EC non-CR groups (AUC=0.96). Conclusion: Assessment of CDO1 and CDH13 gene methylation in endometrial specimens from patients with endometrial cancer (IA stage G1), planned for medical treatment, can predict the treatment outcome.

Lung cancer is the leading cause of cancer related mortality worldwide. In order to improve its overall survival, early diagnosis is required. Since current screening methods still face some pitfalls, such as high false positive rates for low-dose computed tomography, researchers are still looking for early biomarkers to complement existing screening techniques in order to provide a safe, faster and more accurate diagnosis. Biomarkers are biological molecules found in body fluids, such as plasma, that can be used to diagnose a condition or disease. Metabolomics has already shown to be a powerful tool in the search for cancer biomarkers since cancer cells are characterised by impaired metabolism, resulting in an adapted plasma metabolite profile. The metabolite profile can be determined using nuclear magnetic resonance, or NMR. Although metabolomics and NMR metabolite profiling of blood plasma are still under investigation, there is already evidence for its potential for early-stage lung cancer diagnosis, therapy response, and follow-up monitoring. This review highlights some key breakthroughs in this research field, where the most significant biomarkers will be discussed in relation with their metabolic pathways and in light of the altered cancer metabolism.

Herein, we examined the effects of weather parameters and individual clinicodemographic risk factors on hemorrhagic stroke (HS) incidence, severity on admission, and disability at discharge in a harsh desert climate. In a retrospective design we studied patients admitted to a stroke unit in Arab Emirates in 2016-2019. With a distributed lag nonlinear model we explored immediate and delayed effects of weather on stroke incidence. Supervised machine learning was used to build models predictive of scores in NIHSS and mRS scales. We assessed model performance by calculating ROC AUC, F1 scores, specificity, and sensitivity. HS risk increased after a significant change in any weather parameter. The risk was reduced below baseline after 1-week adjustment to environmental changes. Climate input from the previous 3 days yielded reliable classification models. Humidex was a better predictor of severity than air temperature, whereas body mass index, age, and time of day at stroke onset were the strongest clinical predictors. Weather parameters before admission were stronger predictors of disease severity than individual clinical factors. We addressed limitations of previous studies by analyzing a full set of climate parameters: ambient temperature, relative humidity, humidex, atmospheric pressure, and wind speed. Predictive models may help to optimize patient management and develop preventative strategies.

Maize is an important staple food crop in sub-Saharan Africa (SSA). However, the average grain yield on farmers’ fields falls considerably short of the demand of the region’s population. In addition, the normal endosperm maize widely consumed in SSA is deficient in vitamin A. Drought, a consequence of climate change, is a major constraint to maize production, resulting in seasonal low grain yield in farmers’ fields. The objectives of this study were to assess the performance of newly developed extra-early maturing provitamin A hybrids under managed drought and well-watered conditions, compare the outcomes of multiple trait base-index and multi-trait genotype-ideotype distance index selection procedures, and identify drought-tolerant hybrids with stable performance across contrasting environments for commercialization in SSA. One hundred and ninety provitamin A hybrids and six checks were evaluated under managed drought and well-watered conditions at Ikenne for two seasons between 2021 and 2023. A 14*14-lattice design was used for the field evaluations under both research conditions. Drought stress was achieved by the complete withdrawal of irrigation water 25 days after planting. Results revealed significant differences among the hybrids under drought and well-watered conditions. Grain yield, ears per plant, and plant aspect under managed drought were correlated to the same traits under well-watered conditions suggesting that the expression of these traits is governed by common genetic factors. Twenty-nine hybrids were identified as top-performing drought-tolerant hybrids by the multiple trait base index and multiple-trait genotype–ideotype distance index. Of the selected outstanding 29 hybrids, 34% were derived from crosses involving the tester TZEEIOR 197, demonstrating the outstanding genetic potential of this inbred line. Further analysis of the 29 selected hybrids revealed TZEEIOR 509 × TZEEIOR 197 as the hybrid that combined the most drought-tolerant adaptive traits. However, the hybrids TZEEIOR 526 × TZEEIOR 97, TZEEIOR 384 × TZEEIOR 30, TZEEIOR 515 × TZEEIOR 249, TZEEIOR 510 × TZEEIOR 197, TZEEIOR 479 × TZEEIOR 197, and TZEEIOR 458 × TZEEIOR 197 were identified as the most stable hybrids across drought and well-watered conditions. These hybrids should be extensively tested in multi-location trials for deployment and commercialization in SSA.

Background: One challenge in implant dentistry is to reduce marginal bone resorption to avoid long-term esthetic and biological complications. Sub-gingival implant placement has been suggested as a suitable strategy. Methods: 38 healthy patients were enrolled to receive bone level (BL – Control group) or 2 mm sub-crestal (SC - Test group) conical connection, platform-switched implants. An immediate tissue level abutment was used in the Test group by following a One Time Abutment (OTA) restorative procedure. Marginal Bone Modification (MBM) was calcu-latied on standardized radiographs at surgery (T0), loading (T1), and 6 months (T2) and 12 months after loading (T3), and cathegorised in Bone Loss (BL) if the resorption occurred below the implant neck and Bone Remodeling (BR) if above. Pocket probing depth (PPD), Bleeding on probing (BoP) and Plaque Index (PI) were also collected. Results: The mean MBM in the test group after 12 months was 0.61mm, compared to 0.52mm in the control group. However, no BL was observed in the test group, as the MBM completely occurred above the implant neck as BR, whilst in the control group MBM corresponded in total to BL. The average PPD was 2.38mm in the test group and 3.04mm in the control group after 12 months, BoP 50% and 43%, PI 33% and 19.44% respectively. Conclusions: Sub-crestal conical connection, platform-switched implants could be a suitable clinical choice to avoid BL with exposure of the treated implants surfaces.

When training deep neural networks tasks, the most popular choices are cross-entropy loss. On the other hand, in general speaking, a decent loss function can take on shapes that are considerably more flexible and ought to be adapted for different activities and datasets. In most of the classification tasks, generally if the true class is not correctly recognized by the network (top1), that class is placed among the five classes with the highest probability (top5). This shows that the network does not necessarily recognize the correct class with a low probability, but a class similar to it (such as 3 vs. 8 in mnist) assigns a higher probability and this causes a mistake in that task. Accordingly, we proposed a loss function deals with the error of class that the neural network incorrectly recognized as correct, in addition to the correct class error. We call our proposed loss as False Positive Loss (FPL), with the intention of viewing and designing loss functions not only through the utilization of true class but also through the utilization of the value of false positive classes. One of the core properties of our proposed loss is full adaptability, which makes False Positive Loss be fully capable of getting reformulated by using other widely used loss functions formulas based on the task or the need of the users. Extensive experimental results demonstrate that our suggested loss function outperforms other well-known losses on a variety of tasks and datasets. As can be observed, the performance of our False Positive Loss is superior to that of the cross-entropy loss when it comes to tasks involving 2D picture classification. We have compared our loss with cross entropy as the most common classification loss function on some models (such as ResNet-18, ResNet-50 and Efficientnet-V2) through classification known as a basic computer vision task. with both random or pre-trained initial weights. As a result, in some cases the models with our loss outperform the same tasks with cross entropy from the viewpoint of some metric (i.e. accuracy and FP). For example, the resnet-50 on cifar-10 dataset with random initialization indicated a top1 accuracy of 94.93 with cross entropy and 95.25 with our loss, while for top5 accuracy the results are 99.86 and 99.87, respectively.

Abnormalities in sperm nuclei and chromatin can interfere with normal fertilization, embryonic development, implantation, and pregnancy. We aimed in this study to determine the impact of H2BFWT gene variants in sperm DNA on ICSI outcomes in couples undergoing ART treatment. One hundred and nineteen partners were divided into pregnant (G1) and non-pregnant (G2) groups. After semen analysis, complete DNA was extracted from purified sperm samples. The sequence of the H2BFWT gene was amplified by PCR and then subjected to Sanger sequencing. The results showed that there are three mutations in this gene: rs7885967, rs553509 and rs578953. rs553509 and rs578953 showed significant differences in the distribution of alternative and reference alleles between G1 and G2 (P = 0.0004 and P = 0.0020, respectively). However, there was no association between these SNPs and the studied parameters. This study is the first to shed light on the connection between H2BFWT gene variants in sperm DNA and pregnancy after ICSI therapy. This is a pilot study, so further investigations about these gene variants at the transcriptional and translational levels, in a larger cohort of patients, are needed to determine its functional consequences and to understand the mechanism of how the pregnancy is affected by sperm DNA.

During the last decades, a growing number of studies have shown that infections during pregnancy have an important impact on both pregnant women and their fetuses. Our goal was to identify newborns from pregnancies with SARS-CoV-2 infection and to investigate the extension of neonatal complications using cardiac, abdominal and cerebral ultrasonography, hearing testing and indirect ophthalmoscopy. By contrast, neonates whose mothers were vaccinated against COVID-19 during pregnancy and those from pathology-free pregnancies have been examined. A total of 458 newborns were included, over a period of 10 months, divided into 3 groups, COVID-19 group, vaccine group and control group. Although 6 cardiac malformations were found in the COVID-19 group, no correlation was made compared to the vaccine and control group (p=0.07). Grade 1 intraventricular hemorrhage and hypoxic ischemic encephalopathy were the most prevalent among neonates from mothers with SARS-CoV-2 infection (p=0.002 and p&lt;0.001, respectively). The kidney anomaly found to be most frequent in this group was grade 1 unilateral hydronephrosis (p&lt;0.001). COVID-19 disease during the gestational period had no effect on the auditory or visual function. Despite the fact that our observations are relevant, further studies investigating the effects of SARS-CoV-2 infection during pregnancy and the neonatal outcomes are necessary.

Lung cancer remains the main cause of global cancer-related deaths. Currently low-dose computed tomography (LD-CT) shows a 20% reduction of mortality. However, its clinical suitability is hindered by cost, radiation, and some false positives. Thus, the discovery non-invasive and less-expensive biomarker is urgent needed. In this scenario, proteins released in biological fluids could be considered interesting biomarkers for their role in cancer development. We conducted a pioneering case-control pilot study aimed at assessing the usefulness of Raf Kinase Inhibitory Protein (RKIP) and its phosphorylated form (pRKIP) as potential early-stage lung cancer biomarkers. Urine and Blood samples of two consecutive and independent cohorts of lung cancer patients and healthy controls were screened by means of a novel experimental ELISA assay designed to evaluate both forms of the biomarker. Although urinary levels of RKIP were not statistically different between the lung cancer group and high-risk healthy group, serum ones instead increased significantly in early stage LC patients and permitted to discriminate LC patients from both low-risk (HS) and high-risk healthy subjects (HR-HS) with an overall 93% accuracy (AUC 0.93) when LC was compared to HS and 74% (AUC 0.73) when it was compared to high-risk group. Of note, the analysis of RKIP/pRKIP ratio also showed a high accuracy (90% - AUC 0.95) in discriminating LC patients from HS and more importantly, it allowed to identify LC patients compared to HR-HS, with a higher accuracy (79% - AUC 0.79) than RKIP alone. We hypothesize that serum RKIP levels may be correlated to the activation of the immune systems against the tumor during the first phases of its development. Our study identified a preliminary, non-invasive, RKIP and pRKIP profile able to discriminate with high specificity and sensitivity the early-stage lung cancer patients from high-risk Healthy Subjects. These results, although preliminary, suggest the utility of measuring RKIP/pRKIP as potential new screening test for lung cancer and provide the basis for future validation studies.

In the brain, astrocytes regulate shape and functions of the synaptic and vascular compartments through a variety of released factors and membrane-bound proteins. An imbalanced astrocyte activity can therefore have drastic negative impacts on brain development, leading to the onset of severe pathologies. Clinical and pre-clinical studies show alterations in astrocyte cell number, morphology, molecular makeup and astrocyte-dependent processes in different affected brain regions in neurodevelopmental (ND) and neuropsychiatric (NP) disorders. Astrocytes proliferate, differentiate and mature during the critical period of early postnatal brain development, a time window of elevated glia-dependent regulation of a proper balance between synapse formation/elimination, which is pivotal in refining synaptic connectivity. Therefore, any intrinsic and/or extrinsic factors altering these processes during the critical period may result in an aberrant synaptic remodelling and onset of mental disorders. The peculiar bridging position of astrocytes between synaptic and vascular compartments further allows them to “compute” the brain state and consequently secrete factors in the bloodstream, which may serve as diagnostic biomarkers of distinct healthy or disease conditions.Here, we collect recent advancements regarding astrogenesis and astrocyte-mediated regulation of neuronal network remodelling during early postnatal critical periods of brain development, focusing on synapse elimination. We then propose alternative hypotheses for an involvement of aberrancies in these processes in the onset of ND and NP disorders. In light of the well-known differential prevalence of certain brain disorders between males and females, we also discuss putative sex-dependent influences on these neurodevelopmental events.From a translational perspective, understanding age- and sex-dependent astrocyte-specific molecular and functional changes may help to identify biomarkers of distinct cellular (dys)functions in health and disease, favouring the development of diagnostic tools or the selection of tailored treatment options for male/female patients.

Background: Early postoperative airway management after laryngo-tracheal surgery is crucial. Acute respiratory failure due to glottis’ oedema may occur, requiring reintubation. This can prolong ventilatory assistance, jeopardizing the anastomosis. To date, only judicious steroid administration and fluid management are available to avoid more invasive procedures. High-Flow-Oxygen-Therapy(HFOT) is a noninvasive O2 support method providing humidification, warmed air, Positive-End-Expiratory-Pressure(AIRVO2). No data exist about HFOT use to prevent early complications after laryngo-tracheal surgery. Methods: Between Sept.2020-Sept.2022, 107 consecutive patients underwent laryngo-tracheal surgery received HFOT(Group A). Data and long-term results were compared with those of 80 patients operated between Sept.2018-Aug.2020(Group B), when HFOT was not available. All patients were operated in a single center. No pre- or post-operative settings changed, except for HFOT introduction. We analyzed and compared the risk for “delayed” reintubation (unexpected reintubation within the first 24-48 hours after extubating/laryngeal mask removal) in the two groups. Results: No patients reported HFOT-related adverse events. Control group(B) presented “delayed” reintubation in 37% (p= 0.027), Intensive Care Unit admission in 67%(p=0.005) and longer hospital stay(p=0.001) compared to HFOT group(A). Minor complications rate was 3% in both group and overall mortality was 0%. Re-stenosis was described in 4.6% of HFOT group, without a statistically significant difference (p=0.7006). Conclusions: Our study is the first to investigate HFOT use in patients undergoing laryngo-tracheal surgery, potentially representing a consistent innovation in the peri-operative management of these patients. With the limit of a retrospective series, we would suggest HFOT use for preventing post-operative reintubation rate, possibly reducing ICU admission and hospital stay.

Background: Asthma is a very prevalent disease with special characteristics during pregnancy, however little is known about its relation to the psychological wellbeing of women in this period; We aimed to know whether depression and anxiety symptoms are more frequent in asthmatic pregnant women. (2) Methods: Family Apgar (week 20), Edinburgh (weeks 20 and 32) and STAI (week 32) tests were administered to 738 pregnant women (81 asthmatics) in the NELA birth cohort; (3) Results: There were no significant differences between asthmatic and non-asthmatic pregnant women in any of the different tests at any of the time points. The mean? scores for the different tests and timepoints between asthmatic and non-asthmatic pregnant women were: Apgar 20, 17.9±2.2 vs. 10.0±2.2; Edinburgh 20, 6.7±4.2 vs. 6.9±4.3; Edinburgh 32, 5.9±4.4 vs. 5.6±4.3; and STAI 32, 16.7±8.4 vs. 15.8±8.3. The proportion of pregnant women out of the normal range score for any of the tests and time points was also similar in both populations. (4) Conclusions: Asthma is not associated with the psychological wellbeing among pregnant women.

Spiral steroids (SS) are a newly discovered type of steroid. Originally, they were described as cardiotonic glycosides because they cross-reacted with digoxin-specific antibodies (Digoxin-Like-Materials-DLM). SS differ from the classical steroids in several ways: [a] they are steroid phosphodiester conjugates and displace digoxin from digoxin-specific antibodies, [b] in contrast to all other steroids, cholesterol is not a precursor, [c] SS have more than 21 carbon atoms; the extra atoms form a 5th ring which includes a lactone, [d] SS bind to NaK-ATPase in membranes rather than receptors in the nucleus. SS have been identified by HPLC- mass spectroscopy in extracts from mammals, birds, and oysters but were not detected in plant extracts. Overall, SS seem to be key components in regulating potassium electrolytes during pregnancy and its related diseases – specifically pre-eclampsia and necrotizing enterocolitis.

The research paper provides a mathematical framework for understanding phase shift in wave phenomena, bridging theoretical foundations with real-world applications. It emphasizes the importance of phase shift in physics and engineering, particularly in fields like telecommunications and acoustics. Key equations are introduced to explain phase angle, time delay, frequency, and wavelength relationships. The study also introduces the concept of time distortion due to a 1° phase shift, crucial for precise time measurements in precision instruments. The research also addresses infinitesimal wave energy loss related to phase shift, enriching our understanding of wave behavior, and impacting scientific and engineering disciplines.

Hearing loss in infancy leads to preventable speech, language, and cognitive developmental delay [1, 2]. Sensorineural hearing loss (SNHL) is caused by damages, problems, or issues related to the inner ear such as the cochlea with or without the auditory nerve; cranial nerve VIII, involvement. There are three anatomic areas which include the outer ear: composed of the auricle and external auditory canal and the middle ear: which includes the tympanic membrane, ossicles, and the middle ear space, the inner ear: composed of the cochlea, semi-circular canals, and internal auditory canals. The unique anatomical shape of the auricle catches the incoming sound waves to send them down the external auditory canal. Hearing risk assessment should be part of all health visits while regular hearing screening checks are done for all children from 4 to 21 years [1, 2]. Assessment of hearing loss includes history, physical examination and specific hearing assessment tests.

Many aging adults experience some form of hearing problems that may arise from auditory peripheral damage. However, it has been increasingly acknowledged that hearing loss is not only a dysfunction of the auditory periphery but results from changes within the entire auditory system, from periphery to cortex. Damage to the auditory periphery is associated with an increase in neural activity at various stages throughout the auditory pathway. Here, we review neurophysiological evidence of hyperactivity, auditory perceptual difficulties that may result from hyperactivity, and outline open conceptual and methodological questions related to the study of hyperactivity. We suggest that hyperactivity alters all aspects of hearing – including spectral, temporal, spatial hearing – and, in turn, impairs speech comprehension when background sound is present. By focusing on the perceptual consequences of hyperactivity and the potential challenges of investigating hyperactivity in humans, we hope to bring animal and human electrophysiologists closer together to better understand hearing problems in older adulthood.

The article discusses early diagnosis and intervention for developmental delays in children, emphasizing the role of specialized services and personnel in supporting recovery and development. It presents findings from a pilot project initiated in Bucharest, aiming to assess the incidence of developmental delays in children aged 1-3 years in selected kindergartens, including ASD. The study involved children, parents, and specialists, utilizing systematic behavior observation (SBO) and semi-structured interviews. Results indicate that out of 613 evaluated children, 81 received specialized control recommendations, with 4 cases showing potential risk of ASD. Additionally, 8 children were diagnosed with autism. The incidence of autism in children aged 1-3 years was 1 in 51. Although exploratory, these findings suggest a model of good practice for future early diagnosis campaigns nationally. Conclusively, the study underscores the importance of early diagnosis and intervention for developmental delays, advocating for a responsive community and emphasizing the significance of national-level efforts to address these issues effectively.

Iodine is essential for thyroid hormones synthesis and normal neurodevelopment; however, 60% of pregnant women do not meet the WHO recommended intake. Using a qualitative design, we explored perceptions, awareness and experiences of pregnancy nutrition, focusing on iodine. Women in the perinatal period (n=48) were interviewed and filled in a food frequency questionnaire for iodine. Almost all participants achieved the recommended 150 μg/day intake for non-pregnant adults (99%), but only 81% met the increased demands of pregnancy (250 μg/day). Most were unaware of the importance, sources and recommendations of iodine intake. Attitudes to dairy products consumption were positive (e.g. helps with heartburn; easy to increase). Increased fish consumption was considered less achievable, with barriers around taste, smell, heartburn and morning sickness. Community midwives were the main recognised provider of dietary advice. The dietary advice received focused most often on multivitamin supplements rather than food sources. Analysis highlighted a clear theme of commitment to change behaviour, motivated by pregnancy, with desired focus on user-friendly documentation and continued involvement of the health services. The study highlights the importance of redirecting advice on dietary requirements in pregnancy and offers practical suggestions from women in the perinatal period as the main stakeholder group.

(1) Background: Sudden Infant Death Syndrome (SIDS) represents unexplained and sudden deaths during the sleep of infants under one year of age, despite thorough investigation. Screening for prolonged QTc or Long QT Syndrome (LQTS) should be conducted on all newborns to reduce the incidence of SIDS. Neonatal electrocardiogram (ECG) could identify congenital heart defects (CHD) early, especially those not detected at birth. Infants with prolonged QT intervals typically undergo genetic analysis for Long QT Syndrome; (2) Methods: The study involved infants aged 20-40 days, born clinically healthy, with initial ECG screening. Infants with prenatal diagnoses or signs/symptoms of CHD identified immediately after birth, as well as those who underwent ECG or echocardiogram for other clinical or historical indications, were excluded from the study. The data were analyzed using SPSS version 22.0; (3) Results: Of the 42,200 infants involved, 2,245 were enrolled, with 39.9% being males. Subsequently, 164 children (37.8% males) with prolonged QT intervals underwent further diagnostic investigations. Genetic mutations were identified in 11 out of 18 tested children. The most common mutations were LQT1 (54.5%), LQT2 (36.4%), and LQT3 (1 patient). Medications used included propranolol (39.8%), nadolol (22.2%), inderal (11.1%), metoprolol (11.1%), and no treatment (16.7%). The most common abnormalities were focal right bundle branch block (54.5%), left axis deviation (9.2%), and nonspecific ventricular repolarization abnormalities (7.1%). Multiple anomalies were found in 0.47% of children with focal right bundle branch block. Structural abnormalities were associated with specific features in 267 patients (11.9%), primarily isolated patent foramen ovale (PFO) at 61.4%; (4) Conclusions: The screening has proven effective in early diagnosing Long QT Syndrome and other cardiac rhythm anomalies, with additional benefits in detecting mutations and/or QTc prolongations in family members. Identifying other ECG abnormalities and congenital heart malformations further enhances the benefits of the screening.

Objectives Assess rates of adverse events (AE) after COVID-19 vaccines experienced by women of reproductive age, focusing on pregnancy and menstruation, using data collected by the US Centers for Disease Control and Prevention (CDC) Vaccine Adverse Events Reporting System (VAERS) database. Design Population-based retrospective cohort study. Setting US and global entries in US Centers for Disease Control and Prevention (CDC) Vaccine Adverse Events Reporting System (VAERS). Participants CDC VAERS entries from January 1, 1998 to June 30, 2022. Interventions None. Main Outcome Measures A proportional reporting ratio analysis is performed using data in the VAERS system comparing adverse events (AE) reported post-COVID-19 vaccines with that of post-Influenza vaccines. Results COVID-19 vaccines, when compared to the Influenza vaccines, are associated with a significant increase in AE with all proportional reporting ratios of > 2.0: menstrual abnormalities, miscarriage, fetal chromosomal abnormalities, fetal malformation, fetal cystic hygroma, fetal cardiac disorders, fetal arrhythmias, fetal cardiac arrest, fetal vascular malperfusion, fetal growth abnormalities, fetal abnormal surveillance, fetal placental thrombosis, low amniotic fluid, preeclampsia, premature delivery, preterm premature rupture of membrane, fetal death/stillbirth, and premature baby death (all p values were much smaller than 0.05). When normalized by time-available, doses-given, or persons-received, all COVID-19 vaccine AE far exceed the safety signal on all recognized thresholds. Conclusions Pregnancy complications and menstrual abnormalities are significantly more frequent following COVID-19 vaccinations than Influenza vaccinations. A worldwide moratorium on the use of COVID-19 vaccines in pregnancy is advised until randomized prospective trials document safety in pregnancy and long-term follow-up in offspring.

There is limited data on pregnancy outcomes in Pompe Disease (PD) resulting from deficiency of the lysosomal enzyme acid alpha-glucosidase. Late-onset PD is characterized by progressive proximal muscle weakness and decline of respiratory function secondary to the involvement of the respiratory muscles. In a cohort of twenty-five females, the effects of both PD on the course of pregnancy and the effects of pregnancy on PD were investigated. Reproductive history, course of pregnancy, use of Enzyme replacement therapy (ERT), PD symptoms, and outcomes of each pregnancy were obtained through a questionnaire. Among 20 subjects that reported one or more pregnancies, one subject conceived while on ERT and continued therapy through two normal pregnancies with worsening of weakness during pregnancy and improvement postpartum. While fertility was not affected, pregnancy may worsen symptoms, or cause initial symptoms to arise. Complications with pregnancy or birth were not higher, except for an increase in the rate of stillbirths (3.8% compared to the national average of 0.2-0.7%). Given small sample size and possible bias of respondents being only women who have been pregnant, further data may be needed to better analyze the effects of pregnancy on PD, and the effects of ERT on pregnancy outcomes.

Background: Circulating rare cells participate in breast cancer evolution as systemic components of the disease and thus, are a source of theranostic information. Exploration of cancer-associated rare cells is in its infancy. We determined the validity of a rare-cell detection platform and demonstrated the usefulness of a certain rare cell subset as a novel approach to characterize the breast cancer system. Methods: Linearity of the Rarmax® platform was established using a spike-in approach. The platform includes red blood cell lysis, leukocyte depletion and high-resolution fluorescence image recording. Rare cell analysis was conducted on 28 samples (before and after surgery) from 14 patients with breast cancer, 20 healthy volunteers and 9 non-cancer control volunteers. In-depth identification of rare cells, including circulating tumor cells, endothelial-like cells, erythroblasts and inflammation-associated cells, was performed using a phenotype and morphology-based classification system. Results: The platform performed linearly over a range of 5-950 spiked cells, with an average recovery of 84.6%. Circulating epithelial and endothelial-like cell subsets have been demonstrated to be associated with or independent of cancer with tumor presence. Furthermore, certain cell patterns may be associated with treatment-related adverse effects. The sensitivity in detecting tumor-presence and cancer-associated abnormality before surgery was 50% and 85.7%, respectively and the specificity was 100% and 96.6%, respectively. Conclusion: The present study supports the idea of a cancer-associated rare cell abnormality to represent tumor entities as well as systemic cancer. The latter is independent of the apparent clinical cancer.

Steroid hormones have diverse roles in pregnancy; some, such as progesterone and its metabolites, help stabilise pregnancy and can very likely influence the stability of pregnancy and the onset of labour. Changes and disorders in steroidogenesis may be involved in several pregnancy pathologies, such as premature delivery, preeclampsia, and intrahepatic cholestasis. To date, only a few studies have performed steroid analysis in multiple pregnancies. However, these studies offered a limited analysis of the steroidome in children and mothers with multiple pregnancies. Our team and a team from the Department of Steroids and Proteofactors of the Institute of Endocrinology in Prague investigated multiple pregnancies regarding the biosynthesis, transport, and effects of steroids. We recruited two groups of patients: pregnant women with multiple pregnancies as the study group and singleton pregnancies as the control group. Blood samples were drawn from the participants and analysed. Information about the mother, foetus, delivery, and newborn was extracted from medical records. The data were then analysed. The gestational age of twin pregnancies during delivery ranged from 35+3 to 39+3 weeks, while it was 38+1 to 41+1 weeks for the controls. Our findings provide answers to questions regarding the steroidome in multiple pregnancies.

Granulomatous mastitis is a benign disease with a clinical presentation similar to that of breast cancer, and is most commonly observed in women of childbearing age. Although it has been suggested that autoimmune diseases are involved in its pathogenesis, no specific treatments have been established. The occurrence of this disease during pregnancy has rarely been reported. Our patient was a 37-year-old woman. She was pregnant and manifested a dichorionic, diamniotic placenta. At 24 weeks of gestation, the patient experienced a sensation of hardness in her left breast. Mastitis was suspected, and she was treated with cephem antibiotics. Simultaneously, she was diagnosed with erythema nodosum in the extremities. As her symptoms did not improve, an incisional drainage was performed. Bacterial cultures were obtained at 31 weeks of gestation, and Corynebacterium kroppenstedtii was detected. An elective cesarean section was performed at 37 weeks of gestation, and the baby was delivered safely. After delivery, a needle biopsy was performed, and the patient was diagnosed with granulomatous mastitis. She was completely cured with prednisolone after weaning. In this case, the patient's condition was maintained through incision and drainage; and antibiotic, anti-inflammatory, and analgesic drugs during pregnancy. This approach was chosen, taking into consideration the potential side effects of steroids. After delivery, breastfeeding and steroidal therapy proved to be effective in treating the condition.

Caesarean scar ectopic pregnancy (CSEP) is an uncommon form of ectopic pregnancy. This review defines types of CSEP, discusses pathophysiology, clinical presentation and diagnosis and compares common treatment options and outcomes. The pathophysiology is not yet fully understood. One third of patient are asymptomatic. In symptomatic patients vaginal bleeding and pelvic pain which is usually misdiagnosed as threatened or missed abortion. The main principles of treatment for CSEP are early diagnose, quick management, and maintain reproductive function as much as possible. Up to date; no consensus or guidelines for the treatment and management of CSEP. Management of CSEP depends on the clinical presentation and gestational age. Significant controversy exists regarding management, for this reason, several factors should be considered including age of the patient, myometrial thickness, clinical symptoms, hemodynamic status, fertility preservation.

The comparison of group means in latent variable models plays a vital role in empirical research in the social sciences. The present article discusses extensions of invariance alignment and Haberman linking concerning the choice of linking functions for comparisons of many groups. Robust linking functions are proposed for invariance alignment and robust Haberman linking that are particularly suited to item response data under partial invariance. In a simulation study, it is shown that both linking approaches have comparable performance, and in some conditions, the newly proposed robust Haberman linking outperforms invariance alignment.

In this paper, we consider an economy, in which consumers exhibit unrealistic optimism, and show that such an economy is more likely to undergo early recessions and underinvestment rather than experiencing bubbles or overinvestment. In this model, each consumer incorrectly believes that a negative aggregate preference shock will hit all other consumers, but not herself. When consumers have such an unrealistic optimism, the output price must fall prematurely before the aggregate shock occurs. The reason is that if the price does not plummet today, all consumers would postpone making purchases by falsely expecting that an arbitrage opportunity will arise in the future when the aggregate shock hits the economy, in which case, the output market cannot clear. We also show that the government has the potential to improve welfare of the economy by providing subsidies, if the government judiciously selects the right timing for intervention.

The objective of this study was to compare the mental well-being of French women who were and were not pregnant during the first COVID-19 pandemic lockdown. We performed a nationwide online quantitative survey including all women between 18 and 45 years of age during the second and third weeks of global lockdown (March 25–April 07, 2020). The main outcome measures was the mental well-being measured by the Warwick-Edinburgh Mental Well-Being Scale (WEMWBS). This study analysed 275 responses from pregnant women and compared them with those from a propensity score–matched sample of 825 non-pregnant women. The median WEMWBS score was 49.0 and did not differ by pregnancy status. Women living in urban areas reported better well-being, while those with sleep disorders or who spent more than an hour a day watching the news reported poorer well-being. During the first lockdown in France, women had relatively low mental well-being scores, with no significant difference between pregnant and non-pregnant women. More than ever, health-care workers need to find a way to maintain their support for women’s well-being. Minor daily annoyances of pregnancy, such as insomnia, should not be trivialised because they are a potential sign of poor well-being.

Background Cesarean scar ectopic pregnancies are a rare form of extrauterine pregnancies, yet their incidence has increased along with the rise in the number of cesarean deliveries. As with other ectopic pregnancies, cesarean scar ectopic pregnancies pose a greater risk for maternal hemorrhage and ultimately maternal mortality. Case presentation We present a series of clinical cases of cesarean scar ectopic pregnancy diagnosed by transvaginal ultrasonography. Each patient received an individualized treatment: the rate of success depended on the particular maternal condition in each case. Due to the low frequency of this entity, there are no clear protocols for its treatment and thus there are numerous options for treatment and follow up: expectant management, medical therapy, surgical intervention, uterine artery embolization or a combined approach. Each method has different levels of success and is dependent on the surgeon’s skill and patient presentation. The transvaginal ultrasound is necessary to obtain the fine details of the gestation sac and its relation to the scar and must be followed by a meticulous abdominal scan with a full bladder. Conclusion Herein, we present a rare pathological phenomenon whose frequency is on the rise, and for which transvaginal ultrasound and flow doppler provide high diagnostic accuracy. Early diagnosis of cesarean scar ectopic pregnancies offers treatment options to that may help avoid uterine rupture and bleeding, thus preserving the uterus and future fertility.

Dietary components are important for the structural and functional development of the brain. Among these, docosahexaenoic acid,22:6n-3 (DHA) is critically required for the structure and development of the growing fetal brain in utero. DHA is the major n-3 long-chain fatty acid in brain gray matter representing about 15% of all fatty acids in the human frontal cortex. DHA affects neurogenesis, neurotransmitter, synaptic plasticity & transmission, and signal transduction in the brain. Studies in animals and humans show that adequate levels of DHA in neural membranes are important for cortical astrocyte maturation and vascular coupling, and helps cortical glucose uptake and metabolism. In addition, specific metabolites of DHA are bioactive molecules that protect tissues from oxidative injury and stress in the brain. A low DHA level in the brain results in behavior changes and is associated with learning problems and memory deficits. In humans, the third trimester-placental supply of maternal DHA to the growing fetus is critically important as the growing brain obligatory requires DHA during this window period. Besides, DHA is also involved in the early placentation process, essential for placental development. This underscores the critical importance of maternal DHA intake for the structural and functional development of the brain. This review describes DHA's multiple roles during gestation, lactation, and the consequences of its lower intake during pregnancy and postnatally on the children's brain development and function.

Introduction/Aim: Central sensitivity to thyroid hormones refers to the sensitivity of the hypothalamic-pituitary-thyroid (HPT) axis to changes in circulating free thyroxine (fT4). The relationship between fT4 levels and iodine intake is complex. The aim of the present study was to assess central sensitivity to thyroid hormones in pregnancy against iodine intake. Materials & Methods: One thousand one hundred two blood and urine samples were collected from pregnant women (with a mean age+SD of 30.4+4.6 years) during singleton pregnancies; women with known/diagnosed thyroid disease were excluded. Specifically, TSH & fT4 and 24-hour urinary iodine excretion (UI) were measured in each trimester and at two months postpartum. The Thyroid Feedback Quantile-based Index (TFQI) was calculated to assess central sensitivity to thyroid hormones. For the statistical analysis of TFQI by time period, analysis of variance (ANOVA) was used, while Pearson's correlation was used to assess TFQI versus UI. Results: The mean TFQI index ranged from -0.06 (first trimester) to -0.07 (two months postpartum), while the corresponding UI was 141 and 172 μg/L, respectively. The TFQI-UI correlation was negative (Pearson r: -0.325, p: 0.04 and r: -0.399, p: 0.023), for UI values over 250 μg/L, in the first and the third trimester of pregnancy, respectively. Discussion: TFQI is a new index reflecting central sensitivity to thyroid hormones. Lower TFQI indicates higher sensitivity to thyroid hormones. In our sample TFQI was inversely related to iodine intake, in the first trimester of pregnancy (the critical period of organogenesis) and the third trimester (the critical period of fetal growth). Thus, the observed changes in TFQI may reflect different ways of central action of thyroid hormones, according to the phase of pregnancy. The negative association between maternal TFQI (indicative of central sensitivity to thyroid hormone) and urine iodine levels during the third trimester of pregnancy may reflect the combined influence of maternal and fetal thyroid function. Our results are intriguing and have the potential to enhance our comprehension of the changes in the HPT axis’ function via variations in central sensitivity to thyroid hormones and its interplay with nutritional iodine status during pregnancy.

The Peripheral giant cell granuloma (PGCG) is an asymptomatic, non-neoplastic and proliferative lesion of unknown etiology. Some possible pre-disposing factors such as hormonal changes dur-ing pregnancy, have been suggested. However, the association between PGCG and pregnancy is controversial. There are few reported clinical cases of pregnancy-associated PGCG in the litera-ture, and they occurred only in the lower jaw. The present report is on a 35-year-old female pa-tient at 36 weeks of gestation who presented with a PGCG in the central and lateral incisors of the upper jaw. The management consisted of surgical excision, along with curettage of the affected bony walls. The diagnosis was based on clinical results and imaging examinations, and it was histopathologically confirmed. The patient underwent postoperative follow-up evaluations at 3, 6 and 12 months, and there were no signs of recurrence.

Pregestational and gestational diabetes mellitus are relevant complications of pregnancy and antidiabetic drugs are prescribed to obtain glycemic control and improve perinatal outcomes. The objective of this study was to highlight the prescription pattern of antidiabetics before, during and after pregnancy in Italy and to evaluate its appropriateness. A multi-database cross sectional population study using a Common Data Model was performed. In a cohort of about 450,000 women, the prescribing profile of antidiabetics seemed to be in line with the Italian standards for the treatment of GDM which currently do not recommend the use of oral antidiabetics and non-insulin injection, even if a small share of new users (up to 3.8% in the third trimester) used oral antidiabetics. A substantial variability in the prescription pattern was observed among the Italian regions considered: the highest increase was registered in Tuscany (4.2%), Umbria (3.5%) and Emilia-Romagna (2.6%) while the lowest in Lombardy (1.5%), Veneto (1.7%) and Apulia (1.7%). Analysing the prevalence of use of antidiabetics between foreign women we observed that the consumption during pregnancy was higher than Italians (second trimester: 1,8% vs 0,9%, third trimester: 3,6% vs 1,8%).

Abstract: Bariatric surgery is increasingly used in women of childbearing age due to the rising prevalence of obesity and the effectiveness and availability of this treatment. Pregnancy in women with previous bariatric surgery deserves special attention. Weight loss induced by surgery re-duces the risks that obesity poses for pregnancy. But on the other hand, decreased intake and malabsorption may increase the risk of malnutrition and micronutrient deficiency and negatively affect maternal and foetal health. The aim of this narrative review is to provide an updated anal-ysis on the impact of different bariatric surgery techniques on minerals and micronutrients status nutritional status during pregnancy and the possible effect on maternal-foetal health.

Ecological changes evoke many felt losses and types of grief. These affect sustainability efforts in profound ways. Scholarship on the topic is growing, but the relationship between general grief research and ecological grief has received surprisingly little attention. This interdisciplinary article applies theories of grief, loss, and bereavement to ecological grief. Special attention is given to research about “non-death loss” and other broad frameworks about grief. Dynamics related to both local and global ecological grief are discussed. Kinds of potential losses arising out of ecological issues are clarified with the frameworks of tangible/intangible loss, ambiguous loss, nonfinite loss, and shattered assumptions. Various possible types of ecological grief are illuminated by discussing the frameworks of chronic sorrow and anticipatory grief/mourning. Earlier scholarship about disenfranchised ecological grief is augmented by further distinctions about various forms it may take. The difficulties in defining complicated or prolonged grief in ecological context are discussed, and four types of “complicated ecological grief” are explored. Based on the findings, three special forms of ecological loss and grief are named and discussed: transitional loss and grief, lifeworld loss, and shattered dreams. The implications of the results for ecological grief scholarship, counselling and coping are briefly discussed. The results can be used by psychological and healthcare professionals and researchers, but also by members of the public who wish to reflect on their eco-emotions.

Hearing loss stands as the most prevalent sensory deficit among humans, posing a significant global health challenge. Projections indicate that by 2050, approximately 10% of the world's population will grapple with disabling hearing impairment. While approximately half of these cases have a genetic etiology, traditional interventions such as hearing aids and cochlear implants do not completely restore normal hearing. The absence of biological treatment has prompted significant efforts in recent years, with a strong focus on gene therapy to address hereditary hearing loss. Although several studies have exhibited promising recovery of common forms of genetic deafness in mouse models, existing challenges must be overcome to make gene therapy applicable in the near future. Herein, we summarize the primary gene therapy strategies employed over past years, provide an overview of the recent achievements in the preclinical studies for genetic hearing loss, and outline the current key obstacles to cochlear gene therapy.

This study proposes a method for image matching between infrared(IR)-RGB images using a deep learning network to estimate the deformation field. We propose a deformation field generator (DFG) that estimates the deformation field of the transformation matrix to match each pixel or IR image to the RGB image. DFG is a network that receives IR and RGB images as input; the output size is two channels and has the sample resolution as the input image. By warping the IR image through a grid-sampler that warps the image according to the value of the deformation field, we can obtain a warped IR image that matches the RGB image. Additionally, to check whether the warped IR image matched the RGB image, the masking images detecting the segmentation of objects were photographed in two images. Without directly comparing IR and RGB images, we proposed mask loss that warps the IR mask image through the deformation field and grid sampler and then compares the warped IR mask image with the RGB mask image. Mask loss solves the spatial similarity comparison problem with multi-modality images, such as IR and RGB images, by comparing the mask image with the same modality image as the mask image.

Mutations in epidermal growth factor receptor (EGFR) occur in about 48% of Asian and 19% of Western patients with lung adenocarcinoma (LUAD), leading to its constitutive activation and subsequent uncontrolled cell proliferation. To counteract this, tyrosine kinase inhibitors (TKIs) have been developed, targeting EGFR activity. However, the emergence of metastases and resistance mutations often undermines the durability of the treatment response. Knowledge-based mechanistic models that replicate existing clinical trial outcomes, tailored to specific population characteristics, provide invaluable assistance in designing future clinical trials. These models are particularly effective in identifying optimal responders to specific treatments, thereby enhancing therapeutic efficacy. We have developed physiologically based pharmacokinetic (PBPK) models for gefitinib and osimertinib, representing two distinct generations of EGFR TKIs, to accurately simulate the drugs’ distribution within the primary tumor and metastatic sites following oral administration. These models were integrated with a pathophysiological mechanistic model of EGFR-mutant LUAD, enabling the representation of the effects of both gefitinib and osimertinib on EGFR activation-induced signaling pathways. This comprehensive model outputs detailed evolutions of the primary tumor and each metastatic site, facilitating the evaluation of patient progression in alignment with RECIST guidelines (version 1.1). Notably, the model encapsulates the heterogeneity within the tumor, through the representation of various subclones, each characterized by unique mutation profiles, thereby reflecting differential responses to treatment. Calibration of the model was achieved using publicly available data from the NEJ002 and FLAURA clinical trials. Rigorous visual predictive checks and statistical tests were employed to ensure the proper behavior of the model. The model adeptly replicated the time to progression observed in real clinical trials in EGFR-mutant LUAD patients receiving gefitinib or osimertinib as first-line therapy. In addition, the model was able to reproduce the results from a retrospective study comparing gefitinib and osimertinib, a study that was not used to inform the model. With a consistent virtual population as a reference, the combined model facilitated a comparative analysis of the efficacy of both treatments, thereby underscoring its utility in evaluating therapeutic strategies. The faithful replication of real-world data significantly enhances the credibility of our model, rendering it a vital investigational tool for deriving pertinent insights and informing treatment strategies, particularly in identifying optimal responders to various generations of EGFR TKIs. Following its consecutive prospective validations in the FLAURA2 and MARIPOSA trials, the model is poised to facilitate the generation of synthetic control arms in future clinical trials. This advancement promises a more nuanced analysis of covariate relationships, especially when comparing investigational treatments to established standards of care. Additionally, it potentially reduces the required patient cohort size in such trials, optimizing resource utilization.

The effect of embryo reinsertion immediately after embryo flushing was studied to determine its effect on luteal function, pregnancy outcome, endometrial bacterial contamination, and embryo morphology. In Experiment 1, eight mares were used during 32 cycles (8 cycles in each group): for the first two groups, inseminated mares were flushed 8 days after ovulation and prostaglandin F2α was not administered: in group EF-ET (embryo flushing and embryo transfer) the embryo was reinserted in the same donor mare, while in the EF group, no further procedure was performed. In the third group (ET), non-inseminated mares (recipients) received a Day 8 embryo 5 to 8 days after ovulation. Progesterone concentration was measured before EF/ET and 72 h after in the 3 groups. Pregnancy diagnosis was performed within 6 days of transfer. In Experiment 2, twelve mares were used during 17 cycles in two groups: EF-ET (n=11) and ET (n=6), as in Experiment 1, except that every mare was flushed 24 h after embryo transfer to retrieve the embryo. Fewer pregnancies resulted after transfer in EF-ET cycles (0(8, 0%) than in the ET group (6/8, 75%). Progesterone concentration decreased significantly (p=0.05) 72 h after EF-ET, but not in EF or ET cycles (p>0.1). Three mares from the EF-ET showed full luteolysis and signs of endometritis. In Experiment 2, more (5/6; p=0.08) grade I embryos were recovered in the ET compared to the EF-ET group (3/7); 4 embryos were graded III-IV (were broken or had signs of degeneration) in the EF-ET group, but none in the ET group. In both groups, capsule fragments were obtained as indicative of the presence of a recently destroyed embryo in the EF-ET (n=3) and ET (n=1) groups. Positive bacterial cultures were obtained in 2/11 and 1/6 embryo flushes from the EF-ET and ET groups, respectively.

This article presents a narrative review of neonatal and paediatric complications in post-dated pregnancy and covers scientific views on the aetiology, pathology, risk factors, symptoms and complications of post-dated pregnancy. A pregnancy extending beyond 42 weeks of gestation is termed as a post term pregnancy. There are multiple complications that can occur in the perinatal period, some of the most common ones are stillbirth, asphyxia, meconium aspiration syndrome, fetal distress syndrome, etc which are found to be greater in post-dated pregnancy and hence ultimately leads to increased mortality and morbidity of the new born. Studies have shown that post-term pregnancy also causes increased risk of developing behavioural and emotional problems in children of paediatric age group. It is surprising not much importance has been given to the maternal and neonatal consequences of post- term pregnancies. It is not well understood why some women experience post-dated pregnancies. It is found that factors such as hormones and genetic build up, are responsible for causing post-term pregnancy in an obese female. The treatment and management of a post-term pregnancy still poses a challenge to clinicians in determining the right choice and right time for a particular intervention so that both mother and fetus can be prevented from having complications.

In the vaginal ecosystem there is a symbiotic relationship between the microbiota and the host, particularly Candida spp., which are considered commensals of the vaginal mucosa. During pregnancy there is an increase in hormonal secretion that alters the vaginal microbiota and favors the development of Candida infection. Several studies have shown the increased prevalence of Candida during pregnancy, as well as its association with perinatal complications and current clinical practice guidelines recommend fluconazole as the treatment of choice during pregnancy in case of infection by Candida albicans and non-albicans Candida. However, in the Mexican population, this association has not been studied. So in this study, an intentional search for colonization by Candida spp. in pregnant women who attended the obstetric triage of the Hospital Regional de Alta Especialidad de Ixtapaluca during the period from May to October 2019, and they were followed up until the end of the pregnancy. Data on age, number of pregnancies, gestational age, body mass index, and perinatal outcomes were analyzed. Of 83 patients included in the study, yeasts corre-sponding to C. albicans (12) and C. glabrata (4) were isolated in 16. In the group of patients with Candida, the maternal age range was from 15 to 36 years old, of which 7 were adolescents and 2 with advanced maternal age, with an average of 2 gestations, the range of body mass index was from 19.3 to 42.4, of which 4 were overweight and 7 obese. Perinatal complications were observed in three patients, one presented chorioamnionitis and in two the neonates were small for gestational age. No association was found between colonization by Candida spp. and the number of preg-nancies, gestational age, body mass index or perinatal results. However, it was found that age (adolescence) may be a risk factor for the development of vulvovaginitis during pregnancy.

Twin pregnancies are highly undesirable in dairy cattle; they compromise the health and wellbeing of a cow, and its incidence dramatically impairs the farm economy. Recently, a genomic prediction for twin pregnancies has been developed. The objective of this study was to assess cow, environmental and management risk factors affecting the incidence of twin pregnancies in high-producing dairy cows in their first lactation, with special emphasis placed on the genomic prediction values for twin pregnancy. Our study population of primiparous cows proved valuable in identifying factors other than genomic predictive values influencing the twin pregnancy rate. The odds ratio for twin pregnancy was 0.85 (p &lt;0.0001) for each unit of a prediction value increase, 3.5 (p = 0.023) for cows becoming pregnant during the negative photoperiod, and 0.33 (p = 0.016) for cows producing ≥42 kg of milk at AI, compared to the remaining cows producing &lt;42kg of milk. As a general conclusion, the practical implication of our findings is that genomic prediction values can identify the risk of twin pregnancy at herd level. Given the cumulative effect of genomic selection, selecting for animals with reduced genetic risk of twin pregnancies can contribute to reduce its incidence in dairy herds.

Background: The rising prevalence of obesity has a significant impact on obstetrics practice regarding maternal and perinatal complications includes recurrent miscarriage, pregnancy-induced hypertension, preeclampsia, gestational diabetes, and prolonged labor. Objective: To assess the impact of obesity on pregnancy and neonatal outcomes among Saudi women. Methods: The study was conducted at King Abdul-Aziz Medical City, Jeddah. Design: A cross-sectional retrospective design. A total number of 186 participants were recruited from July to Dec.2018 according to eligibility criteria. The data were collected retrospectively by a review of the chart records of the labor and delivery department. Results: The mean (SD) age of participants was 31.94(5.67) years old; two-thirds were in obesity class1. There was a significant association between obesity and pre-existing thyroid disease and induced hypertension class3. However, episiotomy showed that obesity class3 was significantly different from obesity class2. Conclusion: This study concludes obesity affects the outcomes of pregnant Saudi associations between obesity and preeclampsia, perineal tears, and episiotomy variables, and other variables reflect no associations. Recommendations: Further studies are needed to generalize the results. This study endorses the pregnant women start the antenatal follow-up from 1st trimester so, the data will be available on the system for research.

Pregnancy-induced hypertension and preeclampsia are associated with significant maternal and fetal mortality. A better understanding of those diseases, delineation of molecular pathomechanism, and efficient treatment development are some of the most urgent tasks in obstetrics and gynecology. Recent findings indicate a crucial role of inflammation in the development of hypertension and preeclampsia. Although the mechanism is very complex and needs further explanation, it appears that high levels of cholesterol, urate, and glucose activates NLRP3 inflammasome, which produces IL-1β, IL-18 and gasdermin D. Production of these proinflammatory chemokines is a beginning of local and general inflammation, what results in sympathetic outflow, angiotensin II production, proteinuria, hemolysis, liver damage, immunothrombosis, and coagulopathy. NLRP3 inflammasome is a critical complex in the mediation of inflammatory response, which makes it crucial for the development of pregnancy-induced hypertension and preeclampsia, as well as its complications, such as placental abruption and HELLP syndrome. Herein presented the article delineate molecular mechanisms of those processes, indicating directions of future advance.