The effect of menopause hypoestrogenism on osteogenic differentiation of periodontal ligament cells (PDLC) and stem cells (PDLCs): A systematic review

(1) Background: Menopause is a physiological condition typified by drastic hormonal changes, and the effects of this transition have long-term significant clinical implications on the general health, including symptoms or physical changes. In menopausal women, the periodontium can be affected directly or through neural mechanism by oestrogen (E2) deficiency. The majority of the biological effects of E2 are modulated via both oestrogen receptor-α (ERα) and oestrogen receptor-β (ERβ). There is evidence that hypoestrogenism has a substantial impact on the aetiology, manifestation and severity of periodontitis, via the regulation of the expression of osteoproges-terin and RANKL in human periodontal ligament cells through ERβ. However, the mechanistic understanding of oestrogen in periodontal status has been partially clarified. The aim of this paper was to synopsize the recent scientific evidence concerning the link between the menopause and periodontitis, through the investigation of physio-pathological impact of the oestrogen deficiency on osteogenic differentiation of PDLSCs and PDLSC, as well as the dynamic change of ERα and ERβ. (2) Methods: Search was conducted for significant studies by exploring electronic PubMed and EMBASE databases, and it was independently performed by two researchers. All studies on the impact of oestrogen level on alveolar bone resorption were searched from 2005 to July 2020. Data selection was in concordance with PRISMA guidelines. (3) Results: Eight studies met the criteria and were included in this systematic review. All studies reported that oestrogen deficiency impairs the osteogenic and osteoblastic differentiation of PDL cells and oestrogen affects the bone formation capacity of cells. Seven studies were conducted on animal samples, divided into two groups: the OVX animals and animals who received the sham operation. (4) Conclusions: There is a multitude of data available showing the influence of menopause on periodontal status. However, the evidence of this line to investigation needs more research and could help explain the physiological linkage between menopause state and periodontal disease

autotaxin a possible new biological marker of endometrial cancer

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Prenatal diagnosis of a lean umbilical cord: A simple marker for the fetus at risk of being small for gestational age at birth

Objective. The purpose of this study was to investigate whether the prenatal diagnosis of a 'lean' umbilical cord in otherwise normal fetuses identifies fetuses at risk of being small for gestational age (SGA) at birth and of having distress in labor. The umbilical cord was defined as lean when its cross-sectional area on ultrasound examination was below the 10th centile for gestational age. Method. Pregnant women undergoing routine sonographic examination were included in the study. Inclusion criteria were gestational age greater than 20 weeks, intact membranes, and singleton gestation. The sonographic cross-sectional area of the umbilical cord was measured in a plane adjacent to the insertion into the fetal abdomen. Umbilical artery Doppler waveforms were recorded during fetal apnea and fetal anthropometric parameters were measured. Results. During the study period, 860 patients met the inclusion criteria, of whom 3.6% delivered a SGA infant. The proportion of SGA infants was higher among fetuses who had a lean umbilical cord on ultrasound examination than among those with a normal umbilical cord (11.5% vs. 2.6%, p < 0.05). Fetuses with a lean cord had a risk 4.4-fold higher of being SGA at birth than those with a normal umbilical cord. After 25 weeks of gestation, this risk was 12.4 times higher when the umbilical cord was lean than when it was of normal size. The proportion of fetuses with meconium-stained amniotic fluid at delivery was higher among fetuses with a lean cord than among those with a normal umbilical cord (14.6% vs. 3.1%, p < 0.001). The proportion of infants who had a 5-min Apgar score < 7 was higher among those who had a lean cord than among those with normal umbilical cord (5.2% vs. 1.3%, p < 0.05). Considering only patients admitted in labor with intact membranes and who delivered an appropriate-for-gestational-age infant, the proportion of fetuses who had oligohydramnios at the time of delivery was higher among those who had a lean cord than among those with a normal umbilical cord (17.6% versus 1.3%, p < 0.01). Conclusion. We conclude that fetuses with a lean umbilical cord have an increased risk of being small for gestational age at birth and of having signs of distress at the time of delivery

Exploring the role of Fusobacterium nucleatum in preterm birth: A narrative review

In recent years, substantive attention has been drawn to the relationship between oral microbiome homeostatic equilibrium disruption and systemic health, demonstrating the negative impacts of this reciprocal biological interplay. Increasingly, there is a concern over the potential noxious effect of oral microbiome dysbiosis on obstetric poor outcomes, focusing on preterm birth. This epidemiological observation remains unexplained, although biologically plausible mechanism has been proposed. Intrauterine infection has long been associated with adverse pregnancy, when the elicitation of an immune response is determinant. There is evidence that Fusobacterium nucleatum (FN), a Gram-negative anaerobe ubiquitous in the oral cavity, infects the mouse placenta originating in the decidua basalis. Based on the current data in literature, we performed a review to provide resources for the explanation of the potential impact of microbiome dysbiosis on poor obstetric outcomes, focusing on the role of FN

Respiratory Syncytial Virus: New Challenges for Molecular Epidemiology Surveillance and Vaccination Strategy in Patients with ILI/SARI.

Abstract: Several respiratory pathogens are responsible for influenza-like illness (ILI) and severe respiratory infections (SARI), among which human respiratory syncytial virus (hRSV) represents one of the most common aetiologies. We analysed the hRSV prevalence among subjects with ILI or SARI during the five influenza seasons before the emergence of SARS-CoV-2 epidemic in Sicily (Italy). Respiratory specimens from ILI outpatients and SARI inpatients were collected in the framework of the Italian Network for the Influenza Surveillance and molecularly tested for hRSV-A and hRSV-B. Overall, 8.1% of patients resulted positive for hRSV. Prevalence peaked in the age-groups &lt;5 years old (range: 17.6–19.1%) and ≥50 years old (range: 4.8–5.1%). While the two subgroups co-circulated throughout the study period, hRSV-B was slightly predominant over hRSV-A, except for the season 2019–2020 when hRSV-A strongly prevailed (82.9%). In the community setting, the distribution of hRSV subgroups was balanced (47.8% vs. 49.7% for hRSV-A and hRSV-B, respectively), while most infections identified in the hospital setting were caused by hRSV-B (69.5%); also, this latter one was more represented among hRSV cases with underlying diseases, as well as among those who developed a respiratory complication. The molecular surveillance of hRSV infections may provide a valuable insight into the epidemiological features of ILI/SARI. Our findings add new evidence to the existing knowledge on viral aetiology of ILI and SARI in support of public health strategies and may help to define high-risk categories that could benefit from currently available and future vaccines

Exercise training improves vascular function in patients with Alzheimer’s disease

Purpose: Vascular dysfunction has been demonstrated in patients with Alzheimer’s disease (AD). Exercise is known to positively affect vascular function. Thus, the aim of our study was to investigate exercise-induced effects on vascular function in AD. Methods: Thirty-nine patients with AD (79 ± 8&nbsp;years) were recruited and randomly assigned to exercise training (EX, n = 20) or control group (CTRL, n = 19). All subjects performed 72 treatment sessions (90&nbsp;min, 3 t/w). EX included moderate–high-intensity aerobic and strength training. CTRL included cognitive stimuli (visual, verbal, auditive). Before and after the 6-month treatment, the vascular function was measured by passive-leg movement&nbsp;test (PLM, calculating the variation in blood flow: ∆peak; and area under the curve: AUC) tests, and flow-mediated dilation (FMD, %). A blood sample was analyzed for vascular endothelial growth factor (VEGF). Arterial blood flow (BF) and shear rate (SR) were measured during EX and CTRL during a typical treatment session. Results: EX group has increased FMD% (+ 3.725%, p ' 0.001), PLM ∆peak (+ 99.056&nbsp;ml/min, p = 0.004), AUC (+ 37.359AU, p = 0.037) and VEGF (+ 8.825&nbsp;pg/ml, p = 0.004). In the CTRL group, no difference between pre- and post-treatment was found for any variable. Increase in BF and SR was demonstrated during EX (BF + 123%, p ' 0.05; SR + 134%, p ' 0.05), but not during CTRL treatment. Conclusion: Exercise training improves peripheral vascular function in AD. These ameliorations may be due to the repetitive increase in SR during exercise which triggers NO and VEGF upregulation. This approach might be included in standard AD clinical practice as an effective strategy to treat vascular dysfunction in this population

The RNA-binding protein MEX3A is a prognostic factor and regulator of resistance to gemcitabine in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer. Most patients present with advanced disease at diagnosis, which only permits palliative chemotherapeutic treatments. RNA dysregulation is a hallmark of most human cancers, including PDAC. To test the impact of RNA processing dysregulation on PDAC pathology, we performed a bioinformatics analysis to identify RNA-binding proteins (RBPs) associated with prognosis. Among the 12 RBPs associated with progression-free survival, we focused on MEX3A because it was recently shown to mark an intestinal stem cell population that is refractory to chemotherapeutic treatments, a typical feature of PDAC. Increased expression of MEX3A was correlated with higher disease stage in PDAC patients and with tumor development in a mouse model of PDAC. Depletion of MEX3A in PDAC cells enhanced sensitivity to chemotherapeutic treatment with gemcitabine, whereas its expression was increased in PDAC cells selected upon chronic exposure to the drug. RNA-sequencing analyses highlighted hundreds of genes whose expression is sensitive to MEX3A expression, with significant enrichment in cell cycle genes. MEX3A binds to its target mRNAs, like cyclin-dependent kinase 6 (CDK6), and promotes their stability. Accordingly, knockdown of MEX3A caused a significant reduction in PDAC cell proliferation and in progression to the S phase of the cell cycle. These findings uncover a novel role for MEX3A in the acquisition and maintenance of chemoresistance by PDAC cells, suggesting that it may represent a novel therapeutic target for PDAC

Non-invasive scoring of cellular atypia in keratinocyte cancers in 3D LC-OCT images using Deep Learning

Diagnosis based on histopathology for skin cancer detection is today's gold standard and relies on the presence or absence of biomarkers and cellular atypia. However it suffers drawbacks: it requires a strong expertise and is time-consuming. Moreover the notion of atypia or dysplasia of the visible cells used for diagnosis is very subjective, with poor inter-rater agreement reported in the literature. Lastly, histology requires a biopsy which is an invasive procedure and only captures a small sample of the lesion, which is insufficient in the context of large fields of cancerization. Here we demonstrate that the notion of cellular atypia can be objectively defined and quantified with a non-invasive in-vivo approach in three dimensions (3D). A Deep Learning (DL) algorithm is trained to segment keratinocyte (KC) nuclei from Line-field Confocal Optical Coherence Tomography (LC-OCT) 3D images. Based on these segmentations, a series of quantitative, reproducible and biologically relevant metrics is derived to describe KC nuclei individually. We show that, using those metrics, simple and more complex definitions of atypia can be derived to discriminate between healthy and pathological skins, achieving Area Under the ROC Curve (AUC) scores superior than 0.965, largely outperforming medical experts on the same task with an AUC of 0.766. All together, our approach and findings open the door to a precise quantitative monitoring of skin lesions and treatments, offering a promising non-invasive tool for clinical studies to demonstrate the effects of a treatment and for clinicians to assess the severity of a lesion and follow the evolution of pre-cancerous lesions over time.© 2022. The Author(s)

Inter- and intra-observer variability in Sonographic measurements of the cross-sectional diameters and area of the umbilical cord and its vessels during pregnancy

Background. The purpose of the study was to evaluate inter- and intra-observer variability in sonographic measurements of the cross-sectional area of the umbilical cord and the diameters of its vessels in low-risk pregnancies of 12 to 40 weeks of gestation. Methods. A prospective cross sectional study was performed in 221 pregnant women at different gestational ages. Measurements were carried out also by a second observer to evaluate inter-observer variability and repeated once again by the first observer to assess intra-observer variability. The linear correlation between the measurements (Spearman's coefficient of correlation) and their reliability through the intraclass correlation coefficient (ICC), the Cronbach's alpha coefficient and the limits of agreement proposed by Bland and Altman were evaluated. Results. The results showed that inter-observer and intra-observer variability did not show any significant difference between examiners. A good linear correlation between the measurements and reliability was obtained, with values of R, ICC and Cronbach's alpha all above the standard limits. Conclusion. It is possible to conclude that inter- and intra-observer variability in the measurements of the umbilical cord and its vessels was small; their reliability and agreement were good. © 2008 Barbieri et al; licensee BioMed Central Ltd