On the time dependence of the hh-index

The time dependence of the $h$-index is analyzed by considering the average behaviour of $h$ as a function of the academic age $A_A$ for about 1400 Italian physicists, with career lengths spanning from 3 to 46 years. The individual $h$-index is strongly correlated with the square root of the total citations $N_C$: $h \approx 0.53 \sqrt{N_C}$. For academic ages ranging from 12 to 24 years, the distribution of the time scaled index $h/\sqrt{A_A}$ is approximately time-independent and it is well described by the Gompertz function. The time scaled index $h/\sqrt{A_A}$ has an average approximately equal to 3.8 and a standard deviation approximately equal to 1.6. Finally, the time scaled index $h/\sqrt{A_A}$ appears to be strongly correlated with the contemporary $h$-index $h_c$

Unified mechanism of Estrogen Action on central nervous system

17â-estradiol (E2)-induced neuroprotection is dependent upon both mitogen activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K) signaling cascades. We sought to determine whether E2 neuroprotective mechanisms are through a unified signaling cascade activated by estrogen receptor (ER)-PI3K interaction within the same population of neurons or whether E2 activation of ERK1/2 and Akt are independent signaling events in different neuron populations. Immunoprecipitation of E2 treated cortical neurons was conducted to determine a protein-protein interaction between ER and p85, the PI3K regulatory subunit. Subsequently, cortical neurons were treated with E2 alone or in presence of MAPK inhibitors or PI3K inhibitors. Results of these analyses indicated a protein-protein interaction between ER and p85 that was time-dependent and consistent with the temporal profile for generation of both Akt (pAkt) and ERK 1/2 phosphorylation (pERK 1/2). E2-induced phosphorylation of Akt, was first apparent at 10’ and maximal at 30’. Simultaneously, E2 induced pERK 1/2 was first apparent at 5-10’ and maximal at 30’. Inhibition of PI3K completely blocked E2 activation of pAkt at 10’ and 30’and blocked E2 activation of ERK1/2 at 10’. Double immunocytochemical labeling for pERK 1/2 and pAkt showed that E2 induced both signaling pathways in the same neurons. These results indicate a unified signaling mechanism of E2 action that is initiated by an interaction between ER and p85 and which leads to the coordinated activation of both pERK 1/2 and pAkt in the same population of neurons. These results are considered from an estrogen mechanism of action and a therapeutic development perspective

Macroscopic Manifestation of Microscopic Entropy Production: Space-Dependent Intermittence

We study a spatial diffusion process generated by velocity fluctuations of intermittent nature. We note that intermittence reduces the entropy production rate while enhancing the diffusion strength. We study a case of space-dependent intermittence and prove it to result in a deviation from uniform distribution. This macroscopic effect can be used to measure the relative value of the trajectory entropy.Comment: 2 postscript figures, enclose

Design, Realization, and Assessment of a High-Fidelity Physical Simulator for the Investigation of Childbirth-Induced Pelvic Floor Damage

Vaginal delivery is one of the main causes of pelvic floor damage, which can lead to short- and long-term clinical consequences called pelvic floor dysfunctions. The number of women affected by this pathology is continuously rising, representing both a medical issue and an important financial burden. Prevention represents the best strategy of care, but it requires a deep understanding of the injury mechanisms, which is currently lacking. Simulation can help to identify the main factors affecting a clinical event, reducing the need for in vivo investigations. However, current simulators poorly mimic the pelvic structures and do not provide any feedback. These limitations led to the development of an innovative high-fidelity physical simulator to study the mechanisms behind pelvic floor damage caused by vaginal delivery. Anatomically correct gynecological structures were realized using soft materials able to resemble human tissue behavior. Ad hoc stretch sensors were realized with conductive fabric and integrated into the simulator to evaluate tissue elongation caused by the passage of the fetal head. Evaluation of the simulator was carried out both in laboratory conditions and by involving expert clinicians. Gynecologists determined that the simulator is a valid teaching and training tool that is able to provide feedback on instantaneous pelvic floor elongation, thus potentially preventing induced tissue damage

Pregnancy vaccination predictive factors and uptake profiles among Italian women: A cross-sectional survey study on a large population

Objectives: To assess influenza and Tdap (tetanus, diphtheria, pertussis) vaccine coverage during pregnancy, explore key socioeconomic and maternity pathway-related predictors of vaccination, and detect specific patterns of vaccination uptake. Methods: The authors cross-sectionally analyzed self-reported data obtained from the systematic survey on the maternity pathways of Tuscany. They selected all pregnant women that completed from March 2019 to June 2022 the third-trimester questionnaire (n = 25 160), which included two dichotomous items on influenza and Tdap vaccination, as well as socioeconomic and pathway-related questions. Multilevel logistic models were performed to assess vaccination predictors and cluster analysis to identify vaccination patterns. Results: Vaccination coverage was higher for pertussis (56.5%) than for influenza (18.9%). The main predictors of vaccination were high socioeconomic status, attending private gynecologists, and receiving vaccine information. Three clusters were identified: cluster 1 included women receiving both Tdap and influenza vaccines; cluster 2 included women receiving no vaccinations; and cluster 3 included women receiving only the pertussis vaccine. Although women from cluster 3 were of middle to low education status, vaccine information was the main adherence determinant also in this group. Conclusions: Health workers and policymakers should focus on groups of pregnant women less prone to vaccination to promote vaccination information and encourage wider uptake and coverage

Driving time drives the hospital choice: choice models for pelvic organ prolapse surgery in Italy

Objective: The Italian healthcare jurisdiction promotes patient mobility, which is a major determinant of practice variation, thus being related to the equity of access to health services. We aimed to explore how travel times, waiting times, and other efficiency- and quality-related hospital attributes influenced the hospital choice of women needing pelvic organ prolapse (POP) surgery in Tuscany, Italy. Methods: We obtained the study population from Hospital Discharge Records. We duplicated individual observations (n = 2533) for the number of Tuscan hospitals that provided more than 30 POP interventions from 2017 to 2019 (n = 22) and merged them with the hospitals' list. We generated the dichotomous variable "hospital choice" assuming the value one when hospitals where patients underwent surgery coincided with one of the 22 hospitals. We performed mixed logit models to explore between-hospital patient choice, gradually adding the women's features as interactions. Results: Patient choice was influenced by travel more than waiting times. A general preference for hospitals delivering higher volumes of interventions emerged. Interaction analyses showed that poorly educated women were less likely to choose distant hospitals and hospitals providing greater volumes of interventions compared to their counterpart. Women with multiple comorbidities more frequently chose hospitals with shorter average length of stay. Conclusion: Travel times were the main determinants of hospital choice. Other quality- and efficiency-related hospital attributes influenced hospital choice as well. However, the effect depended on the socioeconomic and clinical background of women. Managers and policymakers should consider these findings to understand how women behave in choosing providers and thus mitigate equity gaps

Dehydroepiandrosterone modulates endothelial nitric oxide synthesis via direct genomic and nongenomic mechanisms.

Abstract Dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) are the major circulating steroid hormones in humans, and their levels progressively decline with age. Epidemiological studies suggest that DHEA/DHEAS concentrations may be inversely related to cardiovascular risk, but disagreement exists on this issue. Preliminary studies show that DHEA regulates vascular function, but few data have been published on the mechanisms. We show that DHEA administration to human endothelial cells triggers nitric oxide synthesis, due to enhanced expression and stabilization of endothelial nitric oxide synthase (eNOS). Additionally, DHEA rapidly activates eNOS, through a nontranscriptional mechanism that depends on ERK1/2 MAPK, but not on phosphatidylinositol 3-kinase/Akt. DHEA is not converted to estrogens or androgens by endothelial cells, and its genomic and nongenomic effects are not blocked by antagonists of the estrogen, progesterone, glucocorticoid, or androgen receptors, suggesting that DHEA acts through a specific receptor. Oral DHEA administration to ovariectomized Wistar rats dose-dependently restores aortic eNOS levels and eNOS activity, confirming the effects of DHEA in vivo. Our present data suggest that DHEA may have direct genomic and nongenomic effects on the vascular wall that are not mediated by other steroid hormone receptors, leading to eNOS activation and induction

Estetrol modulates endothelial nitric oxide synthesis in human endothelial cells

Estetrol (E4) is a natural human estrogen that is present at high concentrations during pregnancy. E4 has been reported to act as an endogenous estrogen receptor modulator, exerting estrogenic actions on the endometrium or the central nervous system but presenting antagonistic effects on the breast. Due to these characteristics, E4 is currently being developed for a number of clinical applications, including contraception and menopausal hormone therapy. Endothelial nitric oxide (NO) is a key player for vascular function and disease during pregnancy and throughout aging in women. Endothelial NO is an established target of estrogens that enhance its formation in human endothelial cells. We here addressed the effects of E4 on the activity and expression of the endothelial nitric oxide synthase (eNOS) in cultured human umbilical vein endothelial cells (HUVEC). E4 stimulated the activation of eNOS and NO secretion in HUVEC. E4 was significantly less effective compared to E2, and a peculiar concentration-dependent effect was found, with higher amounts of E4 being less effective than lower concentrations. When E2 was combined with E4, an interesting pattern was noted. E4 antagonized NO synthesis induced by pregnancy-like E2 concentrations. However, E4 did not impede the modest induction of NO synthesis associated with postmenopausal-like E2 levels. These results support the hypothesis that E4 may be a regulator of NO synthesis in endothelial cells and raise questions on its peculiar signaling in this context. Our results may be useful to interpret the role of E4 during human pregnancy and possibly to help develop this interesting steroid for clinical use

Androgens Regulate T47D Cells Motility and Invasion through Actin Cytoskeleton Remodeling

The relationship between androgens and breast cancer is controversial. Androgens have complex effects on breast cancer progression and metastasis. Moreover, androgen receptor (AR) is expressed in approximately 70 to 90% of invasive breast carcinomas, which has prognostic relevance in basal-like cancers and in triple-negative breast cancers. Recent studies have associated the actin-binding proteins of the ezrin-radixin-moesin (ERM) family with metastasis in endocrine-sensitive cancers. We studied on T47D breast cancer cells whether androgens with different characteristics, such as testosterone (T), dihydrotestosterone (DHT), and dehydroepiandrosterone (DHEA) may regulate breast cancer cell motility and invasion through the control of actin remodeling. We demonstrate that androgens promote migration and invasion in T47D via Moesin activation. We show that T and DHEA exert their actions via the AR and estrogen receptor (ER), while the non-aromatizable androgen - DHT - only recruits AR. We further report that androgen induced significant changes in actin organization with pseudopodia along with membrane ruffles formation, and this process is mediated by Moesin. Our work identifies novel mechanisms of action of androgens on breast cancer cells. Through the modulation of Moesin, androgens alter the architecture of cytoskeleton in T47D breast cancer cell and promote cell migration and invasion. These results could help to understand the biological actions of androgens on breast cancer and, eventually, to develop new strategies for breast cancer treatment

Delivery Mode Shapes the Composition of the Lower Airways Microbiota in Newborns

Radical alterations in the human microbiota composition are well-known to be associated with many pathological conditions. If these aberrations are established at the time of birth, the risk of developing correlated pathologies throughout life is significantly increased. For this reason, all newborns should begin their lives with a proper microbiota in each body district. The present study aimed at demonstrating a correlation between the mode of delivery and the development of a well-balanced microbiota in the lower airways of newborns. 44 pregnant women were enrolled in this study. Microbiological comparative analysis was carried out on tracheobronchial secretions of babies born through vaginal delivery (VD) or caesarean section (CS). All samples showed the presence of bacterial DNA, regardless of the mode of delivery. No viable cultivable bacteria were isolated from the CS samples. On the contrary, VD allowed colonization of the lower airways by alive cultivable bacteria. The identification of bacterial species revealed that Lactobacillus spp. and Bacteroides vulgatus were the most common microorganisms in the lower airways of vaginally-delivered newborns. Data obtained from quantitative PCRs showed a significantly higher total bacterial load, as well as Firmicutes and Lactobacillus spp. amount, in VD samples than CS ones, while no statistically significant difference was found in Torque Teno Virus (TTV) load between samples. Taken together, our findings confirm the hypothesis that passage through the maternal vaginal canal determines more beneficial colonization of the lower airways in newborns