A Preliminary Report Regarding the Morphological Changes of Nano-Enabled Pharmaceutical Formulation on Human Lung Carcinoma Monolayer and 3D Bronchial Microtissue.

Background and Objectives: Nowadays, the development of enabled pharmaceutical nanoparticles of solid lipid type is continuously growing, because they have the potential to be used for targeted drug release leading to an increased effect of chemotherapy, being used in lung cancer nano-diagnosis and nano-therapy. The current study reports the preliminary results obtained regarding the biological effect of a new nano-enabled pharmaceutical formulation in terms of its cytotoxic and biosafety profile. Materials and Methods: The pharmaceutical formulations consist of solid lipid nanoparticles (SLN) obtained via the emulsification-diffusion method by loading green iron oxide nanoparticles (green-IONPs) with a pentacyclic triterpene (oleanolic acid-OA). Further, a complex biological assessment was performed, employing three-dimensional (3D) bronchial microtissues (EpiAirwayTM) to determine the biosafety profile of the SLN samples. The cytotoxic potential of the samples was evaluated on human lung carcinoma, using an in vitro model (A549 human lung carcinoma monolayer). Results: The data revealed that the A549 cell line was strongly affected after treatment with SLN samples, especially those that contained OA-loaded green-IONPs obtained with Ocimum basilicum extract (under 30% viability rates). The biosafety profile investigation of the 3D normal in vitro bronchial model showed that all the SLN samples negatively affected the viability of the bronchial microtissues (below 50%). As regards the morphological changes, all the samples induce major changes such as loss of the surface epithelium integrity, loss of epithelial junctions, loss of cilia, hyperkeratosis, and cell death caused by apoptosis. Conclusions: In summary, the culprit for the negative impact on viability and morphology of 3D normal bronchial microtissues could be the too-high dose (500 µg/mL) of the SLN sample used. Nevertheless, further adjustments in the SLN synthesis process and another complex in vitro evaluation will be considered for future research.

Current Trends in Diagnosis and Treatment Approach of Diabetic Retinopathy during Pregnancy: A Narrative Review.

Diabetes mellitus during pregnancy and gestational diabetes are major concerns worldwide. These conditions may lead to the development of severe diabetic retinopathy during pregnancy or worsen pre-existing cases. Gestational diabetes also increases the risk of diabetes for both the mother and the fetus in the future. Understanding the prevalence, evaluating risk factors contributing to pathogenesis, and identifying treatment challenges related to diabetic retinopathy in expectant mothers are all of utmost importance. Pregnancy-related physiological changes, including those in metabolism, blood flow, immunity, and hormones, can contribute to the development or worsening of diabetic retinopathy. If left untreated, this condition may eventually result in irreversible vision loss. Treatment options such as laser therapy, intravitreal anti-vascular endothelial growth factor drugs, and intravitreal steroids pose challenges in managing these patients without endangering the developing baby and mother. This narrative review describes the management of diabetic retinopathy during pregnancy, highlights its risk factors, pathophysiology, and diagnostic methods, and offers recommendations based on findings from previous literature.

Recent Advances in Diagnosis and Treatment Approaches in Fungal Keratitis: A Narrative Review.

Fungal keratitis represents a potentially sight-threatening infection associated with poor prognosis, as well as financial burden. Novel diagnostic methods include polymerase-chain-reaction (PCR)-based approaches, metagenomic deep sequences, in vivo confocal microscopy, and antifungal susceptibility testing. The ideal therapeutic approaches and outcomes have been widely discussed in recent times, with early therapy being of the utmost importance for the preservation of visual acuity, minimizing corneal damage and reducing the scar size. However, combination therapy can be more efficacious compared to monotherapy. Understanding the pathogenesis, early diagnosis, and prevention strategies can be of great importance. In this narrative, we discuss the recent progress that may aid our understanding of the diagnosis, treatment, and prevention of mycotic keratitis.

The Impact of the COVID-19 Pandemic on Depressive Disorder with Postpartum Onset: A Cross-Sectional Study.

BACKGROUND: COVID-19 has led to a global health crisis that is defining for our times and one of the greatest challenges to emerge since World War II. The potential impact of the pandemic on mental health should not be overlooked, especially among vulnerable populations such as women who gave birth during the COVID-19 pandemic. MATERIALS AND METHODS: The study is a cross-sectional survey conducted from 1 March 2020 to 1 March 2023, during the period of the SARS-CoV-2 (COVID-19) pandemic, based on a retrospective evaluation of 860 postpartum women. The screening tool used to assess symptoms of postpartum depression was the Edinburgh Postnatal Depression Rating Scale (EPDS) questionnaire. The questionnaire was completed both in the Obstetrics and Gynaecology Clinical Sections I and II of the "Pius Brînzeu" County Emergency Hospital in Timisoara, Romania, and online using Google Forms. RESULTS: The highest severity of postpartum depression symptoms was observed during the COVID-19 pandemic. The results of the study conducted during the period of the SARS-CoV-2 pandemic (COVID-19) showed that the prevalence of major postpartum depressive disorder (EPDS ≥ 13) was 54.2% (466 patients), while 15.6% (134) had minor depressive disorder (10 < EPDS ≤ 12) in the first year after delivery. Comparing these results with those obtained in research conducted before the onset of the pandemic period showed an alarming increase in the prevalence of postpartum depression. The risk factors associated with postpartum depression included the type of delivery, level of education, socio-economic conditions, health status, age, background, and personal obstetric history (number of abortions on demand, parity). CONCLUSIONS: The effects of the pandemic on mental health are of particular concern for women in the first year after childbirth. Observing these challenges and developing effective measures to prepare our health system early can be of great help for similar situations in the future. This will help and facilitate effective mental health screening for postpartum women, promoting maternal and child health.

Variations in NT-proBNP Levels in Pregnant Patients with and without SARS-CoV-2 Infection: Consequences for the Newborns.

BACKGROUND: NT-proBNP (N-terminal pro-brain natriuretic peptide) has a high negative predictive value for ruling out heart failure, a disorder linked with volume overload of the ventricles, and is used for diagnosis, prognosis, and risk stratification. Pregnancy causes in healthy women changes in physical and hemodynamic parameters and appears to be a risk factor for severe COVID-19 illness. The purpose of this study is to highlight the significance of monitoring NT-proBNP levels during pregnancy, particularly in patients who were infected with COVID-19 during pregnancy or were infected with the virus while giving birth. The findings of this comparative research indicate the importance of NT-proBNP in terms of foetal prognosis and birthweight. METHODS: We collected blood samples to measure NT-proBNP concentrations from a cohort of 186 pregnant patients divided into two groups based on the presence of SARS-CoV-2 viral infection. RESULTS: Elevated NT-proBNP had an unfavourable implication on the newborn birth weight and Apgar score and expressed its influence on lower values. CONCLUSIONS: We consider that NT-proBNP testing in pregnant patients, especially those with COVID-19 infection, can be relevant and be used as a predictive marker to be taken into consideration when it comes to management, outcome, and treatment regarding pregnant patients and their newborns.

NT-proBNP-Possible Prognostic Marker in Pregnant Patients with Associated Cardiovascular Risk Factors and SARS-CoV-2 Infection.

BACKGROUND: N-terminal pro brain-type natriuretic peptide (NT-proBNP) is a practical biomarker in the clinical pathologies where the ventricle is under stress and particularly stretched in the general population. The study aims to compare the value of NT-proBNP and its importance in the prognosis and severity of the cases involving pregnant patients with SARS-CoV-2 infection and cardiovascular risk factors to those of low-risk pregnant patients, mainly by analysing their symptoms, administered medication, days of hospitalization and severity of the viral disease. METHODS: The study included a total of eighty-three pregnant patients who underwent natural birth or caesarean section at out hospital. NT-proBNP levels were analyzed at hospital admission as a potential cardiovascular marker. A comparative analysis was performed between pregnant patients with cardiovascular risk factors and pregnant patients without cardiovascular risk factors regarding NT-proBNP values. RESULTS: Pregnant patients with SARS-CoV-2 infection and cardiovascular risk factors had higher values of NT-proBNP in comparison to pregnant patients without cardiovascular risk factors. CONCLUSIONS: NT-proBNP testing in pregnant patients with SARS-CoV-2 infection can be a relatively important marker to be taken into consideration when it comes to the management, treatment and outcome of the cases, especially when it comes to women with associated cardiovascular risk factors.

Lipid Profile Variations in Pregnancies with and without Cardiovascular Risk: Consequences for Both Mother and Newborn.

Background: Maternal cardiovascular risk and its implications can have significant repercussions for both the mother and the child. This study compares the lipid profiles of two distinct groups of pregnant women, those with and without cardiovascular risk, to shed light on its effects on maternal and outcomes for newborns. Materials and Methods: This study enrolled 86 pregnant women, dividing them into two groups: Group 1 (n = 46, healthy pregnancies) and Group 2 (n = 40, pregnancies with cardiovascular risk factors). The data collected included maternal demographics, smoking history, pre-existing pathologies, and a range of laboratory measures. Neonatal outcomes were also recorded. Results: Group 2 showed a significant increase in the percentage of newborns with abnormal APGAR scores (p-value < 0.0001), congenital abnormalities (p-value < 0.0001), severe prematurity (p-value < 0.0001), and neonatal mortality rates (p-value < 0.0001), as well as differences in birth weight (p-value = 0.0392) and therapy usage (surfactant: p-value < 0.001, steroids p-value = 0.004, and antibiotics p-value < 0.001). Regarding laboratory measures, Group 2 exhibited significantly elevated levels of total cholesterol, LDL-C (p-value < 0.0001), ApoB (p-value < 0.0001), Lp(A) (p-value = 0.0486), triglycerides (p-value < 0.0001), and hs-CRP (p-value = 0.0300). Discussion: These results underscore the elevated risk associated with pregnancies complicated by cardiovascular risk factors. Group 2 demonstrated a more concerning clinical profile, with a higher prevalence of detrimental neonatal outcomes and different lipid and inflammatory profiles, signifying a potential pathophysiological link. Conclusions: The differential lipid profiles and adverse neonatal outcomes in pregnancies with cardiovascular risks highlight the urgency of effective risk stratification and management strategies in this population.

Hypertensive Disorders of Pregnancy: Assessing the Significance of Lp(a) and ApoB Concentrations in a Romanian Cohort.

Background: This research delves into the association between altered lipid profiles and hypertensive disorders of pregnancy (HDP), shedding light on cardiovascular implications in maternal health. Methods: A cohort of 83 pregnant women was studied, with 48.19% diagnosed with HDP. This investigation primarily focused on Apolipoprotein B (ApoB) and Lipoprotein(a) (Lp(a)) as indicators of cardiovascular health. A comparative examination was conducted to determine discrepancies in the ApoB and Lp(a) levels between standard pregnancies and those presenting with HDP. Results: Significant elevations in ApoB (p value = 0.0486) and Lp(a) (p value < 0.0001) levels were observed in pregnant women with HDP compared to their counterparts with typical pregnancies. The pronounced link between heightened ApoB and Lp(a) concentrations and HDP persisted, even considering pregnancy's distinct physiological conditions. Conclusions: Our research accentuates the crucial role of early detection and specialized handling of cardiovascular risks in expectant mothers, especially those predisposed to HDP. The study indicates ApoB and Lp(a)'s potential as reliable markers for gauging cardiovascular threats during gestation. Furthermore, our findings suggest an integrative care approach and guidance for pregnant women, aspiring to enhance cardiovascular health in the postpartum phase.

Maternal Fever and Reduced Fetal Movement as Predictive Risk Factors for Adverse Neonatal Outcome in Cases of Congenital SARS-CoV-2 Infection: A Meta-Analysis of Individual Participant Data from Case Reports and Case Series.

OBJECTIVES: To determine risk factors for primary and secondary adverse neonatal outcomes in newborns with congenital SARS-CoV-2 infection. DATA SOURCES: PubMed/MEDLINE and Google Scholar from January 2020 to January 2022. STUDY ELIGIBILITY CRITERIA: newborns delivered after 24 weeks of gestation with confirmed/possible congenital SARS-CoV-2 infection, according to standard classification criteria. METHODS: Execution of the IPD analyses followed the PRISMA-IPD statement. Univariate non-parametric tests compared numerical data distributions. Fisher's exact or Chi-square test determined categorical variables' statistical significance. Multivariate logistic regression revealed risk factors for adverse neonatal outcome. RESULTS: Maternal fever was associated with symptomatic congenital infection (OR: 4.55, 95% CI: 1.33-15.57). Two-thirds of women that reported decreased fetal movements were diagnosed with IUFD (p-value = 0.001). Reduced fetal movement increased the risk of intrauterine fetal death by 7.84 times (p-value = 0.016, 95% CI: 2.23-27.5). The risk of stillbirth decreased with gestational age at the time of maternal infection (p-value < 0.05, OR: 0.87, 95% CI: 0.79-0.97). CONCLUSIONS: Maternal fever and perception of reduced fetal movement may be predictive risk factors for adverse pregnancy outcome in cases with congenital SARS-CoV-2 infection.

Comparative Analysis of Neonatal Effects in Pregnant Women with Cardiovascular Risk versus Low-Risk Pregnant Women.

BACKGROUND: Cardiovascular diseases are a leading cause of mortality and morbidity worldwide. Pregnancy imposes unique physiological changes on a woman's cardiovascular system. MATERIALS AND METHODS: A cohort of 68 participants, comprising 30 pregnant women with cardiovascular risk and 38 without cardiovascular risk, was recruited for this study. These participants were prospectively followed during their pregnancies from 2020 to 2022 at the Obstetrics and Gynecology Department of the "Pius Brînzeu" Emergency County Clinical Hospital in Timisoara, Romania. All women included in this study underwent cesarean section deliveries at the same medical facility. Data regarding the gestational weeks at delivery, birth weight, and Apgar scores assessed by neonatologists were collected for each participant. Statistical analyses were performed to compare the neonatal effects between the two groups. RESULTS: The results of this study revealed significant differences between the groups in terms of Apgar scores (p = 0.0055), gestational weeks (p = 0.0471), and baby birth weight (p = 0.0392). CONCLUSION: The findings underscore the importance of considering maternal cardiovascular health as a potential determinant of neonatal outcomes. Further research is needed to elucidate the underlying mechanisms and develop strategies for optimizing neonatal outcomes in high-risk pregnancies.

The Effects of Vitamin D Supplementation before 20 Weeks of Gestation on Preeclampsia: A Systematic Review.

Preeclampsia is a leading cause of maternal and fetal morbidity and mortality worldwide. The role of vitamin D supplementation during early pregnancy in the prevention of preeclampsia remains unclear. Our objective was to synthesize and critically appraise the available evidence from observational and interventional studies to determine the effects of early pregnancy vitamin D supplementation on the risk of preeclampsia. A systematic review was conducted in March 2023 using PubMed, Web of Science, Cochrane, and Scopus databases, including literature published up to February 2023. In adherence to PRISMA guidelines, a structured and systematic search strategy was employed. A total of five studies were included in the review, encompassing 1474 patients. Overall, vitamin D supplementation during early pregnancy was associated with a reduced incidence of preeclampsia in all studies (ORs ranging from 0.26 to 0.31), while others showed an increased risk of preeclampsia with low vitamin D levels during the first trimester (ORs of 4.60, 1.94, and 2.52). However, other studies found no significant protective effect but good overall safety for various vitamin D dosages administered during the first trimester. Nevertheless, variations in vitamin D dosage, the timing of supplementation, and definitions of vitamin D insufficiency may have contributed to the inconsistencies in the observed outcomes. Some studies reported significant secondary outcomes, such as a reduction in blood pressure, preterm labor, and improved neonatal outcomes, such as birth weight. The evidence from this systematic review suggests that early pregnancy vitamin D supplementation may have a role in reducing the risk of preeclampsia. However, inconsistencies in the timing of supplementation, dosages, and methodological differences between studies highlight the need for further research to determine the optimal supplementation strategy and to clarify the relationship between vitamin D and preeclampsia risk.

Linking Pregnancy and Long-Term Health: The Impact of Cardiovascular Risk on Telomere Shortening in Pregnant Women.

Background and Objectives: Telomeres are repetitive DNA sequences located at the end of chromosomes that play a crucial role in maintaining chromosomal stability. Shortening of telomeres has been associated with an increased risk of cardiovascular disease. The aim of this study was to investigate whether the length of telomeres in pregnant women with cardiovascular risk is shorter compared to those without cardiovascular risk. Materials and Methods: A total of 68 participants were enrolled, including 30 pregnant women with cardiovascular risk and 38 without cardiovascular risk, who were followed-up during their pregnancy between 2020 and 2022 at the Obstetrical and Gynecology Department of the "Pius Brînzeu" Emergency County Clinical Hospital in Timisoara, Romania. All included women underwent delivery via cesarean section at the same medical institution. The telomere length was measured in each participant using quantitative Polymerase chain reaction (PCR). Results: The results showed that the telomere length was negatively correlated with cardiovascular risk in pregnant women, with significantly shorter telomeres observed in the cardiovascular risk group (mean telomere length = 0.3537) compared to the group without cardiovascular risk (mean telomere length = 0.5728) (p = 0.0458). Conclusions: These findings suggest that cardiovascular risk during pregnancy may be associated with accelerated telomere shortening, which could have implications for the long-term health of both the mother and the child. Further research is needed to investigate the potential mechanisms underlying this association and to identify interventions that may mitigate the negative effects of cardiovascular risk on the telomere length during pregnancy.

A Comparative Analysis of NT-proBNP Levels in Pregnant Women and the Impact of SARS-CoV-2 Infection: Influence on Birth Outcome.

BACKGROUND: The cardiac biomarker NT-proBNP is released by the ventricles in response to increased cardiac wall tension, showing cardiac activity in heart failure. The primary objective of this comparative study was to analyze the variations of NT-proBNP levels among pregnant patients and to determine the potential influence of SARS-CoV-2 infection on these values. Secondly, the study focused on NT-proBNP levels and their influence on the type of birth. METHODS: Blood samples were taken from 160 pregnant mothers in order to determine, through the solid-phase enzyme-linked immunosorbent assay (ELISA) method, the NT-proBNP concentrations from the plasma. The cohort was separated into two distinct groups based on SARS-CoV-2 diagnostic results: negative to the infection, and positive to the infection. RESULTS: The SARS-CoV-2-positive group of patients presented with higher levels of NT-proBNP and had higher rates of cesarean sections. (4) Conclusions: Our research highlights the crucial relationship between elevated NT-proBNP values and the mode of giving birth, natural delivery or cesarean section, and also the influence of SARS-CoV-2 viral infection and this biomarker.

High Concentrations of Aspartame Induce Pro-Angiogenic Effects in Ovo and Cytotoxic Effects in HT-29 Human Colorectal Carcinoma Cells.

Aspartame (ASP), an artificial sweetener abundantly consumed in recent years in an array of dietary products, has raised some concerns in terms of toxicity, and it was even suggested a link with the risk of carcinogenesis (colorectal cancer), though the present scientific data are rather inconclusive. This study aims at investigating the potential role of aspartame in colorectal cancer by suggesting two experimental approaches: (i) an in vitro cytotoxicity screening in HT-29 human colorectal carcinoma cells based on cell viability (Alamar blue assay), cell morphology and cell migration (scratch assay) assessment and (ii) an in ovo evaluation in terms of angiogenic and irritant potential by means of the chorioallantoic membrane method (CAM). The in vitro results showed a dose-dependent cytotoxic effect, with a significant decrease of viable cells at the highest concentrations tested (15, 30 and 50 mM) and morphological cellular changes. In ovo, aspartame (15 and 30 mM) proved to have a pro-angiogenic effect and a weak irritant potential at the vascular level. These data suggest new directions of research regarding aspartame's role in colorectal cancer.

Hormone treatment and UVB exposure influences on female mice regarding skin physiological parameters, biochemical parameters and organ histology.

Females require at a certain period of life the administration or supplementation of specific hormones (estrogen, progesterone), for various needs, such as: prevention of unwanted pregnancies, decreased menstrual bleeding, dysmenorrhea and pelvic pain in endometriosis, alleviation of symptoms associated with menopause, regulation of certain skin processes related to acne or aging and others. Also, hormones could act as oncogenes being known eloquent examples of estrogens labeled both as promoters of cell specific alteration or as mutagenic agents. The use of hormones and exposure to solar radiation is expected to cause a number of adverse changes to the body, especially due to their association with malignant processes. The current study was purported as a basis for understanding certain processes that occur with the administration of hormones and exposure to ultraviolet B (UVB) radiation. The animal model was made on healthy adult female BALB∕c mice, which were separated into groups and treated with Ethinylestradiol (EES), Levonorgestrel (LNG) and their combination in the presence of UVB radiation. Changes in skin physiological parameters were analyzed by non-invasive methods, biochemical parameters related to changes in blood circulating system were evaluated by standard methods and histopathological analysis was conducted to point out the changes at the level of the internal body. Measurement of skin parameters such as erythema, melanin, skin hydration, has highlighted some changes in hormone-treated and exposed to UVB radiation groups which were significant only in the case of erythema. Biochemical parameters showed variations in terms of liver enzymes in groups treated with active substances. Histologically, aspects of internal organs revealed significant changes in the group treated with EES and LNG and exposed to UVB radiation.