Off to a good start: environmental imprinting in the childbirth period

Our organism and the expression of our genetic inheritance are conditioned by the environment. This is demonstrated by experimental models on animals, but more and more evidence shows similarities also in humans. Evidence now supports that neonatal and maternal health also depends on the interactions between the environment and the DNA itself. Even though the DNA sequence remains the same over the years, some genetic traits of human beings can be affected by the silencing or activation of some nucleotide sequences, for example by DNA methylation. Today, epigenetics is much more important than we used to think in 1942 when Waddington used the word “epigenetics” for the first time. The environment can modify DNA sequence methylation, affecting protein production and the phenotype. Examples of how epigenetics affects childbirth phenomenon are given and mechanisms are discussed. Four biological mechanisms of epigenetics are presented: genomic imprinting and silencing of the paternal set of chromosomes, the unpredictable “on/off” expression patterns of wild type genes, paramutations, and alternative states of protein folding. Some genes are triggered by stress, maternal nutrition, drugs (namely oxytocin, fentanyl), childbirth modalities, labor, environmental behavior, microorganism colonization. Imprinting theory is a good scientific basis, to explain the permanence of some biological effects at a considerable time after birth. Imprinting is an important mechanism of DNA expression, and different types of imprinting are described. The consequences of antibiotic use in the childbirth period are discussed, along with the importance of awareness in the use of antibiotics for maternal prophylaxis. Prenatal antibiotics and cesarean sections do affect neonatal microbiome considerably and, therefore, may be the causes of inflammatory intestinal disorders, asthma, obesity, diabetes. Mode of delivery, labor, breastfeeding, and skin-to-skin practice are strictly related to future neonatal health, and the effects are shown here. One of the most important factors to explain the diseases mentioned above is probably the lack of “bacterial contamination” through the birth canal. However, this mechanism cannot be the only one to act, and, in fact, here we also discuss other mechanisms that contribute to the development of future pathologies. Last but not least, the culture and education of the operators, as well as maternal and providers’ attendance behavior during childbirth,  can change the relative outcomes of children’s long-term health

The association of high-sensitivity c-reactive protein and other biomarkers with cardiovascular disease in patients treated for HIV: a nested case–control study

Background: Elevated high-sensitivity C-reactive protein (hsCRP) increases the risk of cardiovascular disease (CVD) in the general population, but its role as a predictive marker in HIV-positive patients remains unclear. Aim of the study was to evaluate whether hsCRP or other biomarkers are independent predictors of CVD risk in HIV-infected patients.Methods: Retrospective, nested case-control study. HIV-positive men and women (35-69 years of age) receiving combination antiretroviral therapy (cART) were included. Cases (n = 35) had a major CVD event. Controls (n = 74) free from CVD events for at least 5 years from starting ART were matched on diabetes and smoking. HsCRP, D-dimer, P-selectin, interleukin-6 (IL-6), tissue plasminogen activator, plasminogen activator inhibitor-1 levels were measured.Results: High hsCRP was associated with CVD risk, independently of traditional cardiovascular risk factors, HIV replication and the type of ART received at the time of sampling (adjusted odds ratio 8.00 [1.23-51.94] comparing >3.3 mg/L with <0.9 mg/L; P = 0.03). Higher IL-6 and P-selectin levels were also independently associated with increased CVD risk, although the association was weaker than for hsCRP. Higher total cholesterol and lower HDL cholesterol increased CVD risk, independent of hsCRP.Conclusion: hsCRP may be a useful additional biomarker to predict CVD risk in HIV-infected patients receiving cART

Liver fibrosis is associated with cognitive impairment in HIV-positive patients

Introduction: The aim of our study was to investigate the potential relationship between liver fibrosis (LF) and cognitive performance in HIV+ patients. Materials and Methods: We performed a cross-sectional cohort study by consecutively enrolling HIV+ patients during routine outpatient visits at two clinical centres in Italy. Subjects with decompensated liver disease were excluded. All subjects underwent a comprehensive neuropsychological battery exploring memory, attention, psychomotor speed and language; cognitive impairment was defined as at least two abnormal [1.5 SD below the mean for appropriate norms] cognitive domains. LF was explored by calculating FIB4 index; in a subgroup of patients, LF was also assessed by transient elastography. Factors associated with cognitive impairment were investigated by logistic regression models. Results: A total of 413 patients [77% males, median age 46 (IQR 39–52), 17% with past AIDS-defining events, 19% past IDU, 3% with diabetes, 94% on cART, 90% with HIV RNA <50 copies/mL, 18% co-infected with HCV] were enrolled. Seventeen patients (4%) had FIB4 >3.25 and 14/129 (3%) had liver stiffness >14KPa. Forty-seven patients (11%) were diagnosed with cognitive impairment. At multivariate analyses patients with FIB4 >1.45 showed a higher risk of cognitive impairment in comparison with those with lower values (OR 2.19, 95% CI 1.02–4.72; p=0.044) after adjusting for education (OR 0.79, 95% CI 0.71–0.88; p<0.001), past IDU (OR 1.69, 95% CI 0.67–4.23; p=0.264), diabetes (OR 2.35, 95% CI 0.62–8.86; p=0.207), HIV RNA <50 copies/mL (OR 0.47, 95% CI 0.19–1.14; p=0.095) and HCV co-infection (OR 0.88, 95% CI 0.33–2.39; p=0.807). Analyzing any single cognitive domain, a higher risk of abnormal psychomotor speed was associated with fibroscan score >14KPa in comparison with fibroscan score <7KPa (OR 285.07; 95% CI 2.42–33574.06; p=0.020) after adjusting for education (OR 0.54, 95% CI 0.31–0.92; p=0.024), age (for 10 years increase) (OR 2.03, 95% CI 0.55–7.53; p=0.288), past IDU (OR 4.43, 95% CI 0.35–7.57; p=0.526), HIV RNA <50 copies/mL (OR 0.01, 95% CI 0.00–0.18; p=0.003), HIV history (for 1 year increase) (OR 0.96, 95% CI 0.83–1.12; p=0.641), CD4 cells count at nadir (OR 1.10, 95% CI 0.56–2.16; p=0.779), and HCV co-infection (OR 0.06; 95% CI 0.00–1.93; p=0.113). Conclusions: In HIV-infected patients higher LF, estimated through non-invasive methods, is associated to a higher risk of cognitive impairment

Prevalence of osteoporosis and predictors of low BMD in a cohort of HIV-1-infected patients in Rome: features of a population at high risk

Introduction: Ageing of HIV-infected patients led to an increasing rate of osteopenia and osteoporosis. The cause is multifactorial, including virus activity, drug toxicity and host factors. The aim of our analysis is to quantify this issue according to our department experience and to evaluate predictors of low BMD. Materials and Methods: HIV-1-infected patients, on stable HAART, were consecutively enrolled in this cross-sectional study and underwent DEXA. We analyzed the prevalence and evaluated predictors of low BMD in our population. Results: We collected data from 208 patients, 148 of whom were male, with 49 years median age (IQR 24.1–68.3). About 39% of patients were heterosexuals, 33.7 MSM and 12.5% were IDU, 40.4% were smokers. Caucasians were 93.3%, and 13.9% were co-infected with HCV virus. Around 6.7% of patients were on their first HAART regimen and all of them started TDF. Their median time of HAART exposure was 1.17 years (IQR 0.8–1.6). Conversely, median time of HAART exposure of multi-experienced patients was 8.5 years (IQR 3.1–12.0). We stratified DEXA results for patients on first-line regimen versus multi-experienced one. We found that 42.9% of patients on first-line HAART had low BMD of lumbar spine and 7.1% had osteoporosis. Regarding the multi-experienced group of patients, lumbar spine osteopenia was observed in 36.6% of patients and 15.5% of them had osteoporosis. Median age of patients with low BMD of lumbar spine was 45.6 (IQR 24.1–68.3) for patients on first-line regimen and 49.8 years for multi-experienced (IQR 44.2–54.0) regimen. We found similar data for BMD of hip, but no patients in the first group had hip osteoporosis. We also analyzed predictors of low BMD in our population. MSM patients showed a 3.4-fold higher risk to have osteoporosis of lumbar spine (OR 3.41, CI 1,105–9,269, p=0.03). As expected, we found that non-Caucasian patients had 13.5-fold higher risk to have osteoporosis of the hip (OR 13.52, CI 1.5–122.7, p=0.02). Exposure to HAART was also evaluated, but no predictors were found. Conclusions: Our data confirm how osteoporosis is highly prevalent and occurs earlier in HIV-infected patients. Antiretrovirals play a crucial role. In our experience loss of BMD can occur within a year of treatment, when almost half of our patients starting TDF had a low BMD. MSM patients have a higher risk to develop spine osteoporosis and non-Caucasian patients are more likely to have hip osteoporosis. We remark the importance of BMD assessment for HIV-infected patients especially during their first months of treatment

Hydroethanolic Extract of Prunus domestica L.: Metabolite Profiling and In Vitro Modulation of Molecular Mechanisms Associated to Cardiometabolic Diseases

High consumption of fruit and vegetables has an inverse association with cardiometabolic risk factors. This study aimed to chemically characterize the hydroethanolic extract of P. domestica subsp. syriaca fruit pulp and evaluate its inhibitory activity against metabolic enzymes and production of proinflammatory mediators. Ultra-high-performance liquid chromatography high-resolution mass spectrometry(UHPLC-HRMS) analysis showed the presence of hydroxycinnamic acids, flavanols, and glycoside flavonols, while nuclear magnetic resonance(NMR) analysis showed, among saccharides, an abundant presence of glucose. P. domestica fruit extract inhibited &alpha;-amylase, &alpha;-glucosidase, pancreatic lipase, and HMG CoA reductase enzyme activities, with IC50 values of 7.01 mg/mL, 6.4 mg/mL, 6.0 mg/mL, and 2.5 mg/mL, respectively. P. domestica fruit extract inhibited lipopolysaccharide-induced production of nitrite, interleukin-1 &beta; and PGE2 in activated J774 macrophages. The findings of the present study indicate that P. domestica fruit extracts positively modulate in vitro a series of molecular mechanisms involved in the pathophysiology of cardiometabolic diseases. Further research is necessary to better characterize these properties and their potential application for human health

Raman Microspectroscopy Detection and Characterisation of Microplastics in Human Breastmilk

The widespread use of plastics determines the inevitable human exposure to its by-products, including microplastics (MPs), which enter the human organism mainly by ingestion, inhalation, and dermal contact. Once internalised, MPs may pass across cell membranes and translocate to different body sites, triggering specific cellular mechanisms. Hence, the potential health impairment caused by the internalisation and accumulation of MPs is of prime concern, as confirmed by numerous studies reporting evident toxic effects in various animal models, marine organisms, and human cell lines. In this pilot single-centre observational prospective study, human breastmilk samples collected from N. 34 women were analysed by Raman Microspectroscopy, and, for the first time, MP contamination was found in 26 out of 34 samples. The detected microparticles were classified according to their shape, colour, dimensions, and chemical composition. The most abundant MPs were composed of polyethylene, polyvinyl chloride, and polypropylene, with sizes ranging from 2 to 12 &micro;m. MP data were statistically analysed in relation to specific patients&rsquo; data (age, use of personal care products containing plastic compounds, and consumption of fish/shellfish, beverages, and food in plastic packaging), but no significant relationship was found, suggesting that the ubiquitous MP presence makes human exposure inevitable

Plastic and Placenta: Identification of Polyethylene Glycol (PEG) Compounds in the Human Placenta by HPLC-MS/MS System

The placenta is a crucial interface between the fetus and the maternal environment. It allows for nutrient absorption, thermal regulation, waste elimination, and gas exchange through the mother&rsquo;s blood supply. Furthermore, the placenta determines important adjustments and epigenetic modifications that can change the phenotypic expression of the individual even long after birth. Polyethylene glycol (PEG) is a polyether compound derived from petroleum with many applications, from medicine to industrial manufacturing. In this study, for the first time, an integration of ultra-high-performance liquid chromatography (UHPLC) coupled with mass spectrometry (MS) was used to detect suites of PEG compounds in human placenta samples, collected from 12 placentas, originating from physiological pregnancy. In 10 placentas, we identified fragments of PEG in both chorioamniotic membranes and placental cotyledons, for a total of 36 samples

Deeply in plasticenta: presence of microplastics in the intracellular compartment of human placentas

Highlights: What are the main findings? For the first time, microplastics were detected and localized by electron microscopy in human placentas. The presence of microplastics was correlated with ultrastructural alterations of some cell organelles in placental tissue, mainly in the syncytiotrophoblast. What is the implication of the main finding? Microplastics in human placentas could contribute to the activation of pathological traits, such as oxidative stress, apoptosis, and inflammation. Microplastics in human placentas may cause long-term effects on human health. Microplastics (MPs) are defined as plastic particles smaller than 5 mm. They have been found almost everywhere they have been searched for and recent discoveries have also demonstrated their presence in human placenta, blood, meconium, and breastmilk, but their location and toxicity to humans have not been reported to date. The aim of this study was twofold: 1. To locate MPs within the intra/extracellular compartment in human placenta. 2. To understand whether their presence and location are associated with possible structural changes of cell organelles. Using variable pressure scanning electron microscopy and transmission electron microscopy, MPs have been localized in ten human placentas. In this study, we demonstrated for the first time the presence and localization in the cellular compartment of fragments compatible with MPs in the human placenta and we hypothesized a possible correlation between their presence and important ultrastructural alterations of some intracytoplasmic organelles (mitochondria and endoplasmic reticulum). These alterations have never been reported in normal healthy term pregnancies until today. They could be the result of a prolonged attempt to remove and destroy the plastic particles inside the placental tissue. The presence of virtually indestructible particles in term human placenta could contribute to the activation of pathological traits, such as oxidative stress, apoptosis, and inflammation, characteristic of metabolic disorders underlying obesity, diabetes, and metabolic syndrome and partially accounting for the recent epidemic of non-communicable diseases. © 2022 by the authors