Preliminary study on the role of human defensins, interleukins and PCSK9 in early and late preeclampsia.

The lack of reliable methods for preeclampsia (PE) early diagnosis limits the opportunities for timely prevention, diagnosis and treatment. This study aims to identify the alterations of biochemical parameters and the immune system activity to build a panel of markers that can support preeclampsia diagnosis. For this study, we recruited 30 pregnant women: 10 healthy pregnant women (CTR); 10 pregnant women with early preeclampsia (EP); 10 pregnant women with late preeclampsia (LP). We evaluated lipid profile and, by gene expression, we assessed PCSK9, IL-2, IL-6, IL-8, IL-10, TNF-α and TGF-ß. Moreover, we evaluated both the serum and gene levels of the defensins HBD-1, HBD-2, HBD-4 and HNP-1. Our results showed an increase in gene expression levels of IL-6 and IL-8 in EP compared to LP (IL-6: median 11.7 vs 3.3, p = 0.005; IL-8: median 634.1 vs 214.1, p = 0.013) and to CTR (IL-6: median 11.7 vs 0.5, p < 0.001; IL-8: median 634.1 vs 225.6, p = 0.012), highlighting a massive activation of immune system in case of more severe preeclampsia. Furthermore, higher serum levels of HBD1 in LP compared to CTR (median: 278.8 vs 67.8, p = 0.005) and to EP (median: 278.8 vs 68.6, p = 0.001) might indicate that the same immune system puts in action protective actions to prevent adverse outcome in these cases. Finally, gene expression levels of PCSK9 decreased significantly in women with EP compared to controls and to LP (median: 0.2 vs 0.9, p = 0.010; median: 0.2 vs 1.2, p = 0.012), causing a decrease in circulating LDL-c necessary for the synthesis of placental hormones.

Controlled ovarian stimulation leads to cardiovascular changes in patients undergoing in vitro fertilization.

OBJECTIVE: To study hemodynamic changes along controlled ovarian stimulation in women undergoing in vitro fertilization. STUDY DESIGN: Prospective observational cohort study conducted at Mother and Child Department of University Hospital Federico II, in Naples, Italy, between April 2021 and July 2022. Sixty-eight infertile patients undergoing controlled ovarian stimulation with gonadotropin, antagonist protocol and a fresh embryo transfer were included. Haemodynamic assessment was carried out using UltraSonic Cardiac Output Monitor at baseline (T1), estradiol peak (T2), fresh embryo-transfer day (T3). To evaluate relationships between quantitative variables and groups a Student T test for independent data was assessed. One-way analysis of variance (ANOVA) was used to determine the differences between the means of three time points (T1, T2 and T3) for quantitative variables. A mixed-model analysis of variance (ANOVA) was used to determine the differences between groups, among time points (T1, T2 and T3). RESULTS: Sixty-eight patients were included. Significant differences over the three time points have been observed for CO (f = 3.78 l/min; p = 0.025), SVI (f = 3.56 ml/m2;p = 0.013), and RSVI (f = 4.84 dscm-5 m2; p = 0.009). No significant differences in trends have been found between beta hCG positive and beta hCG negative groups. There were no significant differences in maternal hemodynamic parameters at time-point T3 between patients treated with hCG 10,000 UI and with Triptorelin. Patients considered at increased risk of hyperstimulation reported a significant increase in SVI at baseline (26.9 ± 9.0 mL/m2 vs 21.9 ± 7.0 mL/m2; p = 0.010). CONCLUSION: According to the results of our study, during controlled ovarian stimulation with antagonist protocol, patients undergo significant changes in maternal cardiovascular parameters over a very short period.

Adherence to physical activity among pregnant women in Southern Italy: results of a cross-sectional survey.

PROBLEM: Knowledge about physical activity in pregnancy is limited compared to general population and several approaches have been used to evaluate duration and intensity of physical activity during pregnancy. BACKGROUND: Although physical activity can contribute to maternal and fetal well-being, more than half of women stopped their physical activity because of pregnancy. AIM: To evaluate the adherence to physical activity of low-risk pregnant women by adapting an Italian version of the PPAQ. METHODS: PPAQ was administered to women with singleton uneventful pregnancies between May and December 2022. The intensity of physical activity was calculated using activity's metabolic equivalent (MET). FINDINGS: Respondents spent 8.5 hours/week during the third trimester in all the types of activities included in the questionnaire, and the majority of METs were spent in household/caregiving activities (91.7 METs-h/week). Only 2,6 % of women reported they spent at least 150 minutes per week in moderate-intensity sport/exercise activity. One-hundred-forty-one women (37.2 %) reported they have been counselled by a midwife or an obstetrician regarding the importance of physical activity in pregnancy and 164 participants (43.3 %) declared that have been advised in favour of bed rest at least once in the current pregnancy. DISCUSSION: Our results showed that a very small percentage was regularly involved in sport/exercise activities. CONCLUSION: The engagement in physical activity of pregnant women during the third trimester is still very low and specific policies to improve exercise in pregnancy should be warrantied.

Maternal Reassurance, Satisfaction, and Anxiety after First-Trimester Screening for Aneuploidies: Comparison between Contingent Screening and Universal Cell-Free DNA Testing.

BACKGROUND: This study aims to evaluate maternal reassurance, satisfaction, and anxiety after two different strategies for the first-trimester screening for aneuploidies. METHODS: Patients between 11 + 3 and 13 + 6 weeks of gestation attending the first-trimester screening at Department of Mother and Child, University Hospital Federico II, Naples, Italy have been recruited and randomly allocated to contingent screening or universal cell-free fetal DNA testing (cffDNA). Questionnaires to measure reassurance, satisfaction, and anxiety have been filled twice: (Q1) after randomization and (Q2) after receiving results. Anxiety was measured by an Italian-version short form of the state scale of the Spielberger State-Trait Anxiety Inventory (STAI); child-related anxiety was measured by the 11-item Pregnancy-Related Anxiety Questionnaire-Revised Regardless of Parity (PRAQ-R2 scale); fear of bearing a physically or mentally handicapped child was measured considering only four items (item 4, 9, 10, and 11) of the PRAQ-R2 scale. RESULTS: 431 patients were recruited: 205 (49%) were randomized in the contingent screening arm, 226 (51%) in the cfDNA arm. Maternal reassurance, satisfaction, and anxiety were not different in the two groups. CONCLUSION: A contingent screening for aneuploidies in the first trimester seems able to ensure the same maternal reassurance and satisfaction as a cfDNA analysis in the low-risk population and to not affect maternal anxiety.

Unveiling therapeutic potentials and exploring maternal-fetal health benefits of metformin in pregnancy: A scoping review.

This scoping review synthesizes evidence on metformin's use during pregnancy, encompassing diverse conditions like gestational diabetes, type 1 and type 2 diabetes, polycystic ovary syndrome (PCOS), and obesity. Metformin demonstrates comparable efficacy to insulin in gestational diabetes, positive outcomes in type 2 diabetes pregnancies, and potential benefits in reducing complications. The review highlights nuances in its effects across conditions, indicating advantages such as reduced risk of macrosomia and cesarean section in gestational diabetes. However, its prophylactic role in preventing gestational diabetes and associated complications remains inconclusive. In obese pregnant women, mixed results are observed, with potential benefits in reducing pre-eclampsia risk. Metformin shows promise in preventing preterm birth and late miscarriage in PCOS pregnancies. Categorizing patient subgroups is crucial for identifying advantages, especially in gestational diabetes and type 2 diabetes. Challenges arise from study heterogeneity, necessitating standardized indications for dosage, timing, and postpartum follow ups. Efforts to identify patient characteristics influencing metformin efficacy are crucial for tailored therapy. Although metformin emerges as a viable option in complicated pregnancies, comprehensive research, standardized protocols, and subgroup identification efforts will enhance clinical utility, ensuring evidence-based therapies and optimal maternal and fetal outcomes. Bridging existing knowledge gaps remains imperative for advancing metformin's role in pregnancy management.

Gardnerella vaginalis and Trichomonas vaginalis infections as risk factors for persistence and progression of low-grade precancerous cervical lesions in HIV-1 positive women.

Gardnerella vaginalis (GV) and Trichomonas vaginalis (TV) infections have been proposed as risk factors for persistence and/or progression of low-grade cervical precancerous lesions (CIN1/L-SIL). In patients with Human Immunodeficiency Virus (HIV), who have an increased baseline risk of CIN1/L-SIL progression, the role of GV and TV is undefined. We aimed to investigate the prognostic impact of GV and TV infections on CIN1/L-SIL in HIV-positive women. HIV-1-positive women with L-SIL were retrospectively included. The risk of persistence or progression in the case of any infection (primary outcome), only GV (GV+), only TV (TV+), or GV and TV coinfection (secondary outcomes) was calculated compared to women with no GV or TV infections (NI), by using relative risk (RR) and multivariate logistic regression, with a significant p-value>0.05;. One hundred and ninety-two patients were included (18.2 %GV+, 15.6 %TV+, 5.2 % coinfection, 60.9 %NI); 58 CIN1/L-SIL showed persistence and 46 progression. RR for persistence/progression of CIN1/L-SIL in the case of any infection was 1.56 (1.21-2.01; p = 0.0006) compared to NI. RR for persistence alone was 1.91 (1.25-2.09; p = 0.0026) in GV+, 1.2 (0.63-2.3; p = 0.5736) in TV+, and 2.06 (1.09-3.9; p = 0.0254) in coinfection. RR for progression alone was 1.94 (1.06-3.4; p = 0.0311) in GV+, 2.14 (1.25-3.67; p = 0.0058) in TV+, and 2.73 (1.39-5.37; p = 0.0036) in coinfection. On multivariate analysis, the presence of any infection was significantly associated with persistence/progression (p = 0.002), GV + with persistence (p = 0.019) and TV + with progression (p = 0.016). In conclusion, GV infection is a risk factor for persistence of CIN1/L-SIL in HIV-positive women, while TV infection is a risk factor for progression. Women with these infections may require a closer and more careful follow-up of CIN1/L-SIL.

Gardnerella vaginalis and Trichomonas vaginalis infections and the risk of persistence or progression of low-grade cervical intraepithelial neoplasia.

Gardnerella vaginalis (GV) and Trichomonas vaginalis (TV) infections have been proposed as risk factors for persistence or progression of low-grade precancerous cervical lesions (CIN1/L-SIL). However, their role is still undefined. We aimed to assess if GV and TV infections affect the risk of persistence/progression of CIN1/L-SIL. A retrospective cohort study was performed to assess the risk of CIN1/L-SIL persistence or progression, persistence alone and progression alone in patients with GV and/or TV infections (GV + and/or TV+), only GV (GV+), only TV (TV+), or GV and TV coinfections compared to patients without these infections. Relative risk (RR) with 95 % confidence intervals (CI) was adopted (significant p-value>0.05). Two hundred and seventy patients were included. RR for CIN1/L-SIL persistence or progression was 1.63 in GV + and/or TV+ (p = 0.02), 1.99 in GV+ (p = 0.0008), 0.25 in TV+ (p = 0.32), 1.78 in coinfection (p = 0.26). RR for persistence was 1.55 in GV + and/or TV+ (p = 0.1), 2.179 in GV+ (p = 0.0013), 0.32 in TV+ (p = 0.41), 0.45 in coinfection (p = 0.55). RR for progression was 1.92 in GV + and/or TV+ (p = 0.22), 1.34 in GV+ (p = 0.68), 1.16 in TV+ (p = 0.91), 8.39 in coinfection (p = 0.0002). In conclusion, GV infection may be a risk factor for CIN1/L-SIL persistence. TV infection alone does not significantly affect the risk of persistence or progression of such lesions, while it may greatly increase the risk of progression when associated with GV infection.

Determinants of FDI Localization in China: A County-Level Analysis for the Pharmaceutical Industry.

Foreign direct investments (FDIs) have been widely recognized as a crucial feature of the Chinese industrial development process. Over the past decades, China has been attracting huge amounts of inward FDIs as a consequence of both spontaneous market dynamics and place-based preferential policies at the sub-national level. However, the Chinese market exhibits large dissimilarities in terms of FDI localization across territories that are worth investigating at a more disaggregated level. In this regards, our study explores the determinants of attraction of inward FDIs in China, at the county level. It focuses on the pharmaceutical industry and attempts to assess whether factors related to location advantages, agglomeration dynamics, information cost effects and environmental regulation costs affect foreign firms' localization choices as well as invested amounts in that location. By means of discrete choice models, our paper confirms the findings of the prevalent literature about the positive effects of location advantages on pharmaceutical FDI attraction. Different from our expectations, a higher proportion of foreign enterprises do not stimulate significant effects on FDI localization, while preferential policies and sectoral agglomeration are positively correlated with the localization of pharmaceutical foreign firms. Finally, our results suggest that investing firms tend to avoid areas with strict environment regulation.

Pharmaceutical Industry in Vietnam: Sluggish Sector in a Growing Market.

Vietnam is a fast growing economy in the Asian region with a significantly high population (over 92 million in 2015). Although still expanding (about 1.1% on average during 2000-2015), the Vietnamese population is considered to be entering the ageing stage at a very high rate. The rapid expansion of the middle-income urban class and the ageing people ratio have dramatically pushed up the demand for healthcare goods, particularly in terms of pharmaceutical products. Since the early 1990s the government has addressed the necessities of rising demand for healthcare products by formulating a series of policies aimed at promoting the development of the pharmaceutical industry. However, the implementation of such policies does not seem to have been completely efficient given that the country still needs to import up to 90% of its pharmaceutical consumption. This paper aims to explore the development of the pharmaceutical industry during the years 1990-2015 and to identify a series of weaknesses in the government promotion of the industry. Future developments will also be discussed on how the Vietnamese pharmaceutical industry could increase its participation in the regional supply chain, which is currently being dominated by big players like India and China.