Prenatal maternal stress during the COVID-19 pandemic and infant regulatory capacity at 3 months: A longitudinal study.

The COVID-19 pandemic is a global traumatic experience for citizens, especially during sensitive time windows of heightened plasticity such as pregnancy and neonatal life. Pandemic-related stress experienced by mothers during pregnancy may act as an early risk factor for infants' regulatory capacity development by altering maternal psychosocial well-being (e.g., increased anxiety, reduced social support) and caregiving environment (e.g., greater parenting stress, impaired mother-infant bonding). The aim of the present longitudinal study was to assess the consequences of pandemic-related prenatal stress on infants' regulatory capacity. A sample of 163 mother-infant dyads was enrolled at eight maternity units in northern Italy. They provided complete data about prenatal stress, perceived social support, postnatal anxiety symptoms, parenting stress, mother-infant bonding, and infants' regulatory capacity at 3 months of age. Women who experienced emotional stress and received partial social support during pregnancy reported higher anxious symptoms. Moreover, maternal postnatal anxiety was indirectly linked to the infants' regulatory capacity at 3 months, mediated by parenting stress and mother-infant bonding. Dedicated preventive interventions should be delivered to mothers and should be focused on protecting the mother-infant dyad from the detrimental effects of pandemic-related stress during the COVID-19 healthcare emergency.

Growth Curve, Morphological and Molecular Characterization of Two Strains of Trypanosoma cruzi (Kinetoplastida, Trypanosomatidae) isolated from Triatoma sherlocki (Hemiptera, Reduviidae, Triatominae).

BACKGROUND: Trypanosoma cruzi presents great variability in morphology, virulence, pathogenicity, avoidance of the host immune system, and antigenic constitution, associated with different clinical manifestations of the disease. METHODS: Two strains of T. cruzi were cultivated in liver infusion tryptose to determine growth kinetics, morphometry and molecular characterization using restriction fragment length polymorphism polymerase chain reaction. RESULTS: The biological parameters showed sharp growth by the 7th day. Morphologically, both strains showed short and thin forms and were classified as Group I. CONCLUSION: Group TcI presents cardiac manifestations and T. sherlocki is adapting to the home environment, requiring attention to future problems.

Hydroxymethylnitrofurazone (NFOH) decreases parasitaemia, parasitism and tissue lesion caused by infection with the Bolivia Trypanosoma cruzi type I strain in Swiss and C57BL/6 mice

Abstract The chemical hydroxymethylation of the antimicrobial nitrofurazone leads to the prodrug NFOH, also increases the anti-T. cruzi activities (in vitro and in vivo), as well as showed non-genotoxic (Ames and micronucleus assays). In the present study, we assessed the anti-T. cruzi effect of the NFOH In vivo - in acute Swiss and C57Bl/6 experimental Chagas models. The treatment started at 5 days post-infection during 20 consecutive days (orally, once day, 150mg/kg), and the parasitaemia as well as histopathology analysis were performed. In both experimental murine models, NFOH was able to reduce parasitemia blood avoiding parasitic reactivation, during immunosuppression period (dexamethasone 5mg/kg, 14 days), in 100% of the mice, and decrease tissue parasite nests, demonstrating absence of amastigote forms in all organs (100%) analyzed, data similar to benznidazole (BZN). Therefore, the results shown here pointing to the NFOH as promising compound for further preclinical studies, being a high potential drug to effective and safe chemotherapy to Chagas disease.

Depression and Anxiety in Mothers Who Were Pregnant During the COVID-19 Outbreak in Northern Italy: The Role of Pandemic-Related Emotional Stress and Perceived Social Support.

The COVID-19 pandemic is a collective trauma that is threatening citizens' mental health resulting in increased emotional stress, reduced social support, and heightened risk for affective symptoms. The present study aimed to investigate the effects of antenatal pandemic-related emotional stress and perceived social support on the symptoms of depression and anxiety of mothers who were pregnant during the initial COVID-19 outbreak in northern Italy. A sample of 281 mothers was enrolled at eight maternity units in the first hotspot region of the COVID-19 outbreak in northern Italy. Participants filled out online questionnaires assessing the direct or indirect exposure to the SARS-CoV-2 virus, pandemic-related stress, perceived social support, as well as symptoms of depression and anxiety. Depressive and anxious symptomatology was above clinical concern, respectively, in 26 and 32% of the respondents. Mothers who reported no exposure to SARS-CoV-2 during pregnancy and those who reported at least one direct or indirect exposure did not differ in terms of affective symptoms. Continuous scores and risk for severe depression and anxiety were positively associated with prenatal pandemic-related emotional stress and negatively linked with perceived social support during pregnancy. Women who become mothers during the COVID-19 emergency may be at high risk for affective problems. Dedicated preventive programs are needed to provide adequate preventive support and care for maternal mental health during and after the COVID-19 pandemic.

Hidden pandemic: COVID-19-related stress, SLC6A4 methylation, and infants' temperament at 3 months.

The COVID-19 pandemic represents a collective trauma that may have enduring stress effects during sensitive periods, such as pregnancy. Prenatal stress may result in epigenetic signatures of stress-related genes (e.g., the serotonin transporter gene, SLC6A4) that may in turn influence infants' behavioral development. In April 2020, we launched a longitudinal cohort study to assess the behavioral and epigenetic vestiges of COVID-19-related prenatal stress exposure in mothers and infants. COVID-19-related prenatal stress was retrospectively assessed at birth. SLC6A4 methylation was assessed in thirteen CpG sites in mothers and infants' buccal cells. Infants' temperament was assessed at 3-month-age. Complete data were available from 108 mother-infant dyads. Greater COVID-19-related prenatal stress was significantly associated with higher infants' SLC6A4 methylation in seven CpG sites. SLC6A4 methylation at these sites predicted infants' temperament at 3 months.

Differentiation of Rhodnius neglectus and Rhodnius prolixus (Hemiptera: Reduviidae: Triatominae) by multiple parameters.

INTRODUCTION: The genus Rhodnius in the subfamily Triatominae comprises 20 species, which can transmit Trypanosoma cruzi and Trypanosoma rangeli. Due to the development of molecular techniques, Triatominae species can now be characterized by mitochondrial and nuclear markers, making it possible to verify and/or correct the existing data on these species. The results achieved in this study provide a more detailed and accurate differentiation of the Rhodnius species, helping the establishment of a more appropriate classification. METHODS: Data collection was performed by DNA analysis, morphological and morphometric studies to distinguish four populations of R. neglectus and four of R. prolixus. Phylogenetic data were compared to morphological and morphometric data. RESULTS: The analysis of Cytb fragments suggests that the four colonies designated to Rhodnius neglectus as well as those of R. prolixus were correctly identified. CONCLUSIONS: The morphological characters observed in the specimens of the colonies originally identified as R. prolixus and R. neglectus, such as the presence or absence of collar in the eggs, the patterns of the median process of the pygophore, and anterolateral angle, are consistent with the species. Geometric morphometrics also show an intraspecific variability in R. prolixus.

Measuring the Outcomes of Maternal COVID-19-related Prenatal Exposure (MOM-COPE): study protocol for a multicentric longitudinal project.

INTRODUCTION: COVID-19 is a highly infectious respiratory disease that rapidly emerged as an unprecedented epidemic in Europe, with a primary hotspot in Northern Italy during the first months of 2020. Its high infection rate and rapid spread contribute to set the risk for relevant psychological stress in citizens. In this context, mother-infant health is at risk not only because of potential direct exposure to the virus but also due to high levels of stress experienced by mothers from conception to delivery. Prenatal stress exposure associates with less-than-optimal child developmental outcomes, and specific epigenetic mechanisms (eg, DNA methylation) may play a critical role in mediating this programming association. METHODS AND ANALYSIS: We present the methodological protocol for a longitudinal, multicentric study on the behavioural and epigenetic effects of COVID-19-related prenatal stress in a cohort of mother-infant dyads in Northern Italy. The dyads will be enrolled at 10 facilities in Northern Italy. Saliva samples will be collected at birth to assess the methylation status of specific genes linked with stress regulation in mothers and newborns. Mothers will provide retrospective data on COVID-19-related stress during pregnancy. At 3, 6 and 12 months, mothers will provide data on child behavioural and socioemotional outcomes, their own psychological status (stress, depressive and anxious symptoms) and coping strategies. At 12 months, infants and mothers will be videotaped during semistructured interaction to assess maternal sensitivity and infant's relational functioning. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee (Pavia). Results will be published in peer-reviewed journals and presented at national and international scientific conferences. TRIAL REGISTRATION NUMBER: NCT04540029; Pre-results.

Differentiation of Rhodnius neglectus and Rhodnius prolixus (Hemiptera: Reduviidae: Triatominae) by multiple parameters

Abstract Introduction: The genus Rhodnius in the subfamily Triatominae comprises 20 species, which can transmit Trypanosoma cruzi and Trypanosoma rangeli. Due to the development of molecular techniques, Triatominae species can now be characterized by mitochondrial and nuclear markers, making it possible to verify and/or correct the existing data on these species. The results achieved in this study provide a more detailed and accurate differentiation of the Rhodnius species, helping the establishment of a more appropriate classification. Methods: Data collection was performed by DNA analysis, morphological and morphometric studies to distinguish four populations of R. neglectus and four of R. prolixus. Phylogenetic data were compared to morphological and morphometric data. Results: The analysis of Cytb fragments suggests that the four colonies designated to Rhodnius neglectus as well as those of R. prolixus were correctly identified. Conclusions: The morphological characters observed in the specimens of the colonies originally identified as R. prolixus and R. neglectus, such as the presence or absence of collar in the eggs, the patterns of the median process of the pygophore, and anterolateral angle, are consistent with the species. Geometric morphometrics also show an intraspecific variability in R. prolixus.

A new species of Rhodnius from Brazil (Hemiptera, Reduviidae, Triatominae).

A colony was formed from eggs of a Rhodnius sp. female collected in Taquarussu, Mato Grosso do Sul, Brazil, and its specimens were used to describe R. taquarussuensissp. n. This species is similar to R. neglectus, but distinct characters were observed on the head, thorax, abdomen, female external genitalia and male genitalia. Chromosomal differences between the two species were also established.

Time-domain heart rate variability in coronary artery disease patients affected by thyroid dysfunction.

Subclinical hypothyroidism and hyperthyroidism have been recognized as clinical entities with negative effects on the cardiovascular system. Moreover, the effect of treated thyroid dysfunction on parameters associated with the cardiovascular control system has been poorly investigated. In the present study we analyzed time-domain heart rate variability in coronary artery disease (CAD) patients with known thyroid diseases. Twenty-four hour ECG monitoring was performed in 344 patients with coronary artery disease (174 with thyroid dysfunction and 170 without thyroid dysfunction used as a control group), using a 3-channel tape recorder. Time domain parameters of heart rate variability (HRV) were definitely lower both in patients with subclinical hypothyroidism and subclinical hyperthyroidism than in the control group, with statistically significant differences in SDNN, RMSSD, TINN, and mean RR for both subgroups. Furthermore, patients on L-thyroxine treatment and restored euthyroidism had generally higher HRV values than patients with subclinical hypothyroidism, nevertheless SDNN, RMSSD, SDNN index, TINN, and mean RR were significantly lower when compared to those of the control group. Significant differences in HRV were also found between hyperthyroid patients under treatment and control group subjects with respect to RMSSD, TINN, and mean RR values. In conclusion, patients with cardiac disease and known thyroid disease, even when the disease is in the subclinical range or despite treatment, should be regarded as patients at additional risk conveyed by thyroid hormone disturbances.

Soluble RAGE plasma levels in patients with coronary artery disease and peripheral artery disease.

The objective of the present study was define in a relatively large patient population with coronary artery disease (CAD) whether the concomitant presence of peripheral artery disease (PAD), which is known to convey additional cardiovascular risk, was associated with different circulating levels of sRAGE with respect to CAD alone and control subjects. Clinical and laboratory parameters including the ankle brachial index (ABI) and sRAGE (enzyme-linked immunosorbent assay kit) were investigated in 544 patients with angiographically documented CAD and 328 control subjects. 213/554 CAD patients (39%) showed an ABI <0.9 associated with typical symptoms (group CAD + PAD), whereas 331 patients were free from PAD. The concentration of plasma sRAGE was significantly lower (P < 0.0001) in CAD population, with and without PAD, than in control subjects. Among CAD patients, those with PAD showed lower levels of sRAGE. The distribution of the three groups (CAD, CAD + PAD, and controls) according to sRAGE tertiles showed that lower levels were more frequent in patients with CAD and CAD + PAD, whereas higher levels were more frequently found in controls. CAD patients presenting with PAD have lower sRAGE levels than CAD patients without peripheral atherosclerosis showing that stable atherosclerotic lesions in different vascular districts are inversely related to soluble decoy receptor sRAGE.

Possible role of -374T/A polymorphism of RAGE gene in longevity.

Demographic and social changes in the last decades have resulted in improvements in health and longevity. The survival of elderly people has improved significantly and thus centenarians are becoming the fastest growing population group. Environmental, genetic, and accidental factors have influenced the human life span. Researchers have gained substantial evidence that advanced glycation end products may play an important role in the processes of physiological aging. The aim of the present study was to investigate any differences in the frequencies of -374T/A polymorphism in subjects aged >90 years and in middle-aged individuals. We observed association between the A allele and genotype homozygous for this allele (AA) with a longer life expectancy in the male population. In particular, there was a prevalence of AA genotype and A allele in long-living subjects and a prevalence of the allele T in middle-aged subjects, indicating a possible protective role of the allele A to aging. In conclusion, our results support the hypothesis that longevity is the result of a good functioning of the immune system and a presumable hyper-expression of variants of anti-inflammatory genes of immunity. The differences in the genetic regulation of inflammatory processes may influence the presence of age-related disorders.

Plasma levels of soluble receptor for advanced glycation end products and coronary atherosclerosis: possible correlation with clinical presentation.

Receptor for Advanced Glycation End-products (RAGE) is a multi-ligand receptor ubiquitous present on epithelial, neuronal, vascular and inflammatory cells, usually expressed at low levels in homeostasis and to increased degrees at sites of stress or injury. The aim of the present study was to evaluate sRAGE plasma levels in patients with Acute Coronary Syndrome (ACS) and to assess its diagnostic efficacy in identification of patients with acute events. Plasma levels of sRAGE were determined in 860 patients with Coronary Artery Disease (CAD): 530 patients presented stable angina and 330 were observed during acute ischemic event (147 with unstable angina and 183 with myocardial infarction). sRAGE plasma levels were significantly lower in patients with ACS than in patients with stable angina: [median 584 pg/mL (IQR: 266-851 pg/mL) in MI patients, median 769 pg/mL (IQR: 394-987 pg/mL) in patients with unstable angina, median 834 pg/mL (IQR 630-1005 pg/mL) in patients with stable angina; P < 0.001]. sRAGE levels did not differ among ACS patients stratified by the extent of coronary artery disease. In conclusion, this study confirm the role of sRAGE in activation and progression of inflammatory process and suggests the possibility that sRAGE can be considered an indicator of destabilization of vulnerable plaque.

Primary headache and silent myocardial ischemia in patients with coronary artery disease.

OBJECTIVE: The mechanisms by which migraine is linked to ischemic vascular disease remain uncertain and are likely to be complex. The aim of this study was to investigate the correlation between silent myocardial ischemia (SMI) and a history of documented primary headache in a large population of patients with exercise-induced myocardial ischemia. METHODS: The study involved 1,427 consecutive patients (918 symptomatic and 509 asymptomatic patients) with exercise-induced myocardial ischemia and documented coronary artery disease (CAD). RESULTS: Patients with anginal symptoms during exercise-induced myocardial ischemia had a significantly higher prevalence of primary headache than those without (41 vs. 30%, p < 0.001). Patients with angina pectoris in daily life also had greater prevalence of primary headache than those without anginal symptoms (37 vs. 20%; p < 0.0001). Symptomatic patients during percutaneous transluminal coronary angiography or myocardial infarction had a greater prevalence of primary headache than asymptomatic patients (p < 0.001 and p = 0.005, respectively). CONCLUSIONS: Our data suggest that a history of headache in CAD population is correlated to a high probability of anginal symptoms and a decreased probability of SMI. The anamnestic absence of headache requires a close monitoring for patients with risk factors for CAD, because this population seems to have a lower susceptibility to pain and the risk of developing SMI might be increased.

Coronary artery disease and depression: possible role of brain-derived neurotrophic factor and serotonin transporter gene polymorphisms.

Cardiovascular disease (CVD) and depression are two of the most common human health problems. Patients with depression have an increased risk of developing cardiovascular disease and mortality after experiencing a cardiac event. Both diseases are complex disorders that are influenced by genetic and environmental factors. Brain-derived neuro-trophic factor (BDNF) plays a critical role in regulating both vascular development and response to injury, and promotes survival, differentiation, and maintenance of neurons in the peripheral and nervous system. Evidence suggests that BDNF can enhance serotoninergic transmission. Serotonin modulates different brain functions and is known to regulate sleep, appetite, pain and inflammation. The aims of the present case-control study were to investigate the possible role of BDNF Val66Met, 5-HTTLPR and -1438 G/A polymorphisms in the development of coronary artery disease (CAD) in patients with and without depression. Regarding BDNF, our data suggest an involvement of the AA genotype in the pathogenesis of CAD in females and in the predisposition to CAD associated with depression. Furthermore, it could be argued that the GG genotype is protective against CAD in the female population and against CAD associated with depression. In our CAD population we also observed a significant increase in the L/L genotype and a decrease in the S/L genotype with respect to the controls. A higher frequency of the L allele, responsible for enhancing the efficiency of transcription, was found in CAD patients. These findings may be responsible for the increased capacity of platelet serotonin uptake previously observed in patients with CAD. Although no differences were found for genotype and allelic frequencies of the -1438 G/A polymorphism between the CAD patients and controls, we cannot exclude the possible role of this receptor in coronary artery disease.