Stillbirth is a recognized complication of COVID-19 in pregnant women that has recently been demonstrated to be caused by SARS-CoV-2 infection of the placenta. Multiple global studies have found that ...the placental pathology present in cases of stillbirth consists of a combination of concurrent destructive findings that include increased fibrin deposition that typically reaches the level of massive perivillous fibrin deposition, chronic histiocytic intervillositis, and trophoblast necrosis. These 3 pathologic lesions, collectively termed SARS-CoV-2 placentitis, can cause severe and diffuse placental parenchymal destruction that can affect >75% of the placenta, effectively rendering it incapable of performing its function of oxygenating the fetus and leading to stillbirth and neonatal death via malperfusion and placental insufficiency. Placental infection and destruction can occur in the absence of demonstrable fetal infection. Development of SARS-CoV-2 placentitis is a complex process that may have both an infectious and immunologic basis. An important observation is that in all reported cases of SARS-CoV-2 placentitis causing stillbirth and neonatal death, the mothers were unvaccinated. SARS-CoV-2 placentitis is likely the result of an episode of SARS-CoV-2 viremia at some time during the pregnancy. This article discusses clinical and pathologic aspects of the relationship between maternal COVID-19 vaccination, SARS-CoV-2 placentitis, and perinatal death.
The environment, epigenome, and asthma Yang, Ivana V; Lozupone, Catherine A; Schwartz, David A
Journal of allergy and clinical immunology
140, Številka:
1
Journal Article
Recenzirano
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Asthma prevalence has been on the increase, especially in North America compared with other continents. However, the prevalence of asthma differs worldwide, and in many countries the prevalence is ...stable or decreasing. This highlights the influence of environmental exposures, such as allergens, air pollution, and the environmental microbiome, on disease etiology and pathogenesis. The epigenome might provide the unifying mechanism that translates the influence of environmental exposures to changes in gene expression, respiratory epithelial function, and immune cell skewing that are hallmarks of asthma. In this review we will introduce the concept of the environmental epigenome in asthmatic patients, summarize previous publications of relevance to this field, and discuss future directions.
The Ebola virus disease (EVD) outbreak that began in Kivu province of the Democratic Republic of the Congo (DRC) in July 2018 is the second largest in history. It is also the largest and most deadly ...of the ten Ebola outbreaks to occur in DRC, the country where Ebola was first identified during the 1976 Yambuku outbreak. The Kivu region is one of the most challenging locations in which to organize humanitarian assistance. It is an active conflict zone in which numerous armed groups are conducting violent acts, often directed against the inhabitants, healthcare and relief workers and peacekeepers. EVD has been especially problematic in pregnancy-previous outbreaks both in DRC and other countries have resulted in very high mortality rates among pregnant women and especially their infants, with maternal mortality in some outbreaks reaching over 90% and perinatal mortality 100%. The development and implementation of the Merck rVSV-ZEBOV vaccine for Ebola infection has been a tremendous public health advance in preventing EVD, being used successfully in both the West Africa Ebola epidemic and the Équateur DRC Ebola outbreak. But from the start of the Kivu outbreak, policy decisions had resulted in excluding pregnant and lactating women and their infants from receiving it during extensive ring vaccination efforts. In June 2019, this policy was reversed, 10 months after the start of the outbreak. Pregnant and lactating women are now permitted not only the rVSV-ZEBOV vaccine in the continuing Kivu outbreak but also the newly implemented Ad26.ZEBOV/MVA-BN vaccine.
Members of the Toll-like receptor (TLR) family are key regulators of both innate and adaptive immune responses. The function of TLRs in various human diseases has been investigated by comparison of ...the incidence of disease among people having different polymorphisms in genes that participate in TLR signaling. These studies have shown that TLR function affects several diseases, including sepsis, immunodeficiencies, atherosclerosis and asthma. As this body of data grows, it will provide new insights into disease pathogenesis as well as valuable information on the merits of various therapeutic options.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Molecular motors in cells typically produce highly directed motion; however, the aggregate, incoherent effect of all active processes also creates randomly fluctuating forces, which drive ...diffusive-like, nonthermal motion. Here, we introduce force-spectrum-microscopy (FSM) to directly quantify random forces within the cytoplasm of cells and thereby probe stochastic motor activity. This technique combines measurements of the random motion of probe particles with independent micromechanical measurements of the cytoplasm to quantify the spectrum of force fluctuations. Using FSM, we show that force fluctuations substantially enhance intracellular movement of small and large components. The fluctuations are three times larger in malignant cells than in their benign counterparts. We further demonstrate that vimentin acts globally to anchor organelles against randomly fluctuating forces in the cytoplasm, with no effect on their magnitude. Thus, FSM has broad applications for understanding the cytoplasm and its intracellular processes in relation to cell physiology in healthy and diseased states.
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•Random intracellular motion is driven by active force fluctuations in the cytoplasm•The aggregate random forces enhance motion of small proteins and large organelles•We develop force spectrum microscopy to probe aggregate random cytoplasmic forces•The aggregate random forces are larger in malignant cancer cells than benign cells
A new technique called force spectrum microscopy allows probing random active force fluctuations in the cytoplasm of living cells. These forces drive a diffusive-like mechanism of transport of organelles and proteins in the cytoplasm and are more active in cancer than in normal cells.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), is similar to two other coronaviruses, severe acute respiratory syndrome ...coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), in causing life-threatening respiratory infections and systemic complications in both children and adults. As the COVID-19 pandemic has continued to spread globally, increasing numbers of pregnant women have become infected, raising concern not only for their health but also for the health of their infants. This chapter discusses the effects of coronavirus infections, e.g., MERS, SARS, and COVID 19, on pregnancy and describes the evolving knowledge of COVID 19 among pregnant women. The physiological changes that occur in pregnancy, especially changes in the immune system, are reviewed in terms of their effect on susceptibility to infectious diseases. The effects of COVID-19 on the placenta, fetus, and neonate are also reviewed, including potential clinical outcomes and issues relating to testing and diagnosis. The potential mechanisms of vertical transmission of the virus between pregnant women and their infants are analyzed, including intrauterine, intrapartum, and postpartum infections. Several recent studies have reported the detection of SARS-CoV-2 in tissues from the fetal side of the placenta, permitting the diagnosis of transplacental infection of the fetus by SARS-CoV-2. Placentas from infected mothers in which intrauterine transplacental transmission of SARS-CoV-2 has occurred demonstrate an unusual combination of pathology findings which may represent risk factors for placental as well as fetal infection.
As evidenced from recent epidemics, both Ebola and Zika virus infection are potentially catastrophic when occurring in pregnant women. Ebola virus causes extremely high rates of mortality in both ...mothers and infants; Zika virus is a TORCH infection that produces a congenital malformation syndrome and pediatric neurodevelopmental abnormalities. Production of efficacious vaccines has been a public health priority for both infections. Unfortunately, during the clinical trials and subsequent deployment of a vaccine for the Ebola virus, pregnant and lactating women were, and continue to be, excluded from receiving the life-saving vaccine. The most serious consequence of Zika virus infection, congenital Zika syndrome, results from fetal infection during pregnancy. Thus, pregnant women have a major stake in the ongoing development of a vaccine for Zika virus. The exclusion of pregnant women from the development, clinical trials and administration of a potential Zika vaccine unfairly deprives them and their infants of the protection they need against this potentially catastrophic intrauterine infection. When creating policy about these issues, it is important to critically evaluate vaccine safety in pregnancy in the context of the substantial risk of infection for the pregnant woman and her fetus in the absence of immunization.
The number of neonates with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is increasing, and in a few there are reports of intrauterine infection.
To characterize the ...placental pathology findings in a preselected cohort of neonates infected by transplacental transmission arising from maternal infection with SARS-CoV-2, and to identify pathology risk factors for placental and fetal infection.
Case-based retrospective analysis by a multinational group of 19 perinatal specialists of the placental pathology findings from 2 cohorts of infants delivered to mothers testing positive for SARS-CoV-2: live-born neonates infected via transplacental transmission who tested positive for SARS-CoV-2 after delivery and had SARS-CoV-2 identified in cells of the placental fetal compartment by molecular pathology, and stillborn infants with syncytiotrophoblast positive for SARS-CoV-2.
In placentas from all 6 live-born neonates acquiring SARS-CoV-2 via transplacental transmission, the syncytiotrophoblast was positive for coronavirus using immunohistochemistry, RNA in situ hybridization, or both. All 6 placentas had chronic histiocytic intervillositis and necrosis of the syncytiotrophoblast. The 5 stillborn/terminated infants had placental pathology findings that were similar, including SARS-CoV-2 infection of the syncytiotrophoblast, chronic histiocytic intervillositis, and syncytiotrophoblast necrosis.
Chronic histiocytic intervillositis together with syncytiotrophoblast necrosis accompanies SARS-CoV-2 infection of syncytiotrophoblast in live-born and stillborn infants. The coexistence of these 2 findings in all placentas from live-born infants acquiring their infection prior to delivery indicates that they constitute a pathology risk factor for transplacental fetal infection. Potential mechanisms of infection of the placenta and fetus with SARS-CoV-2, and potential future studies, are discussed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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