Originally conceived as a mechanism to enable a trustless cryptocurrency-Bitcoin, blockchain has since unbound itself from its original purpose as an increasing number of industries and stakeholders' ...eye the technology as an attractive alternative to solve existing business solutions as well as disrupt mature industries. This paper presents a systematic literature review of the blockchain technology, tracking its increase in popularity in relation to similar technologies, such as cryptocurrencies and Bitcoin. The objective of this paper is to identify the current standing of the blockchain technology within the literature while also identifying the major fields of study and areas of application for which blockchain offers a valuable solution. This paper finds that unique features to the blockchain, such as privacy, security, anonymity, decentralization, and immutability, provide valuable benefits to various fields and subjects. This paper also finds that exploring the application of blockchain has only begun with some limited studies in areas, such as the Internet of Things, energy, finance, healthcare, and government, that also stand to benefit disproportionately from its implementation.
Spontaneous preterm birth (PTB) and preterm prelabor rupture of membranes (pPROM) are major pregnancy complications often associated with a fetal inflammatory response. Biomolecular markers of this ...fetal inflammatory response to both infectious and non-infectious risk factors and their contribution to PTB and pPROM mechanism are still unclear. This study examined fetal membrane production, activation and mechanistic properties of high mobility group box 1 (HMGB1) as a contributor of the non-infectious fetal inflammatory response.
HMGB1 transcripts and active HMGB1 were profiled in fetal membranes and amniotic fluids collected from PTB and normal term birth. In vitro, normal term not in labor fetal membranes were exposed to lipopolysaccharide (LPS) and water soluble cigarette smoke extract (CSE). HMGB1-transcripts and its protein concentrations were documented by RT-PCR and ELISA. Recombinant HMGB1 treated membranes and media were subjected to RT-PCR for HMGB1 receptors, mitogen activated protein kinase pathway analysis, cytokine levels, and Western blot for p38MAPK.
HMGB1 expression and its active forms were higher in PTB and pPROM than normal term membranes and amniotic fluid samples. Both LPS and CSE enhanced HMGB1 expression and release in vitro. Fetal membrane exposure to HMGB1 resulted in increased expression of TLR2 and 4 and dose-dependent activation of p38MAPK-mediated inflammation.
HMGB1 increase by fetal membrane cells in response to either oxidative stress or infection can provide a positive feedback loop generating non-infectious inflammatory activation. Activation of p38MAPK by HMGB1 promotes development of the senescence phenotype and senescence associated sterile inflammation. HMGB1 activity is an important regulator of the fetal inflammatory response regardless of infection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cardiovascular disease (CVD) is the leading cause of death in women. Because women generally present with more atypical symptoms of CVD than do men and because underlying CVD risk factors are often ...present for years before the onset of CVD, it is important to use innovative ways to identify women who should undergo CVD risk screening at a younger age. Pregnancy and the postpartum period afford us that opportunity, given that the development of certain pregnancy complications (hypertensive disorders of pregnancy, gestational diabetes, preterm birth, delivery of a neonate with fetal growth restriction, and significant placental abruption) can reliably identify women with underlying, often unrecognized, CVD risk factors. Women with one or more of these pregnancy complications should be identified at the time of delivery and referred for regular follow-up. This would ideally take the form of a multidisciplinary clinic including clinicians and allied health specialists to carry out physical and biochemical screening and counseling regarding lifestyle modification and possible therapeutic interventions. Longer-term follow-up and recommendations should be individualized based on findings and risks. There is also an opportunity for future pregnancy counseling and discussion about the importance of weight loss between pregnancies, initiation of a routine involving physical activity, use of preconception folic acid, and the potential initiation of low-dose aspirin for those women at risk for future preeclampsia and fetal growth restriction or the use of progesterone for women at risk for preterm labor. The link between pregnancy complications and future CVD affords us with the earliest opportunity for CVD risk assessment for health preservation and disease prevention.
With more than one third of pregnancies in the United States being delivered by cesarean and the growing knowledge of morbidities associated with repeat cesarean deliveries, the Eunice Kennedy ...Shriver National Institute of Child Health and Human Development, the Society for Maternal-Fetal Medicine, and the American College of Obstetricians and Gynecologists convened a workshop to address the concept of preventing the first cesarean delivery. The available information on maternal and fetal factors, labor management and induction, and nonmedical factors leading to the first cesarean delivery was reviewed as well as the implications of the first cesarean delivery on future reproductive health. Key points were identified to assist with reduction in cesarean delivery rates including that labor induction should be performed primarily for medical indication; if done for nonmedical indications, the gestational age should be at least 39 weeks or more and the cervix should be favorable, especially in the nulliparous patient. Review of the current literature demonstrates the importance of adhering to appropriate definitions for failed induction and arrest of labor progress. The diagnosis of "failed induction" should only be made after an adequate attempt. Adequate time for normal latent and active phases of the first stage, and for the second stage, should be allowed as long as the maternal and fetal conditions permit. The adequate time for each of these stages appears to be longer than traditionally estimated. Operative vaginal delivery is an acceptable birth method when indicated and can safely prevent cesarean delivery. Given the progressively declining use, it is critical that training and experience in operative vaginal delivery are facilitated and encouraged. When discussing the first cesarean delivery with a patient, counseling should include its effect on future reproductive health.
Recent evidence supports the use of an early, short course of glucocorticoids in patients with COVID-19 who require mechanical ventilation or oxygen support. As the number of coronavirus disease 2019 ...(COVID-19) cases continues to increase, the number of pregnant women with the disease is very likely to increase as well. Because pregnant women are at increased risk for hospitalization, intensive care unit admission, and mechanical ventilation support, obstetricians will be facing the dilemma of initiating maternal corticosteroid therapy while weighing its potential adverse effects on the fetus (or neonate if the patient is postpartum and breastfeeding). Our objective is to summarize the current evidence supporting steroid therapy in the management of patients with acute respiratory distress syndrome and COVID-19 and to elaborate on key modifications for the pregnant patient.
Oxidative stress (OS)-induced senescence of the amniochorion has been associated with parturition at term. We investigated whether telomere fragments shed into the amniotic fluid (AF) correlated with ...labor status and tested if exogenous telomere fragments (T-oligos) could induce human and murine amnion cell senescence. In a cross-sectional clinical study, AF telomere fragment concentrations quantitated by a validated real-time PCR assay were higher in women in labor at term compared to those not in labor. In vitro treatment of primary human amnion epithelial cells with 40 μM T-oligos (TTAGGG2) that mimic telomere fragments, activated p38MAPK, produced senescence-associated (SA) β-gal staining and increased interleukin (IL)-6 and IL-8 production compared to cells treated with complementary DNA sequences (Cont-oligos, AATCCC2). T-oligos injected into the uteri of pregnant CD1 mice on day 14 of gestation, led to increased p38MAPK, SA-β-gal (SA β-gal) staining in murine amniotic sacs and higher AF IL-8 levels on day 18, compared to saline treated controls. In summary, term labor AF samples had higher telomere fragments than term not in labor AF. In vitro and in situ telomere fragments increased human and murine amnion p38MAPK, senescence and inflammatory cytokines. We propose that telomere fragments released from senescent fetal cells are indicative of fetal cell aging. Based on our data, these telomere fragments cause oxidative stress associated damages to the term amniotic sac and force them to release other DAMPS, which, in turn, provide a sterile immune response that may be one of the many inflammatory signals required to initiate parturition at term.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Our objective was to determine the amniotic fluid-derived exosomal proteomic profile in patients who had spontaneous preterm birth (PTB) or preterm premature rupture of membranes (pPROM) compared ...with those who delivered at term. A cross-sectional study of a retrospective cohort was used to quantify and determine the protein content of exosomes present in amniotic fluid, in PTB or pPROM, and normal term labor (TL) or term not in labor (TNIL) pregnancies. Exosomes were isolated by differential centrifugation and quantified using nanocrystals (Qdot) coupled to CD63 and placental alkaline phosphatase (PLAP) by fluorescence nanoparticle tracking analysis. The exosomal proteomic profile was identified by liquid chromatography-tandem mass spectrometry, and a small ion library was constructed to quantify the proteomic data by Sequential Window Acquisition of All Theoretical analysis. Ingenuity Pathway Analysis determined canonical pathways and biofunctions associated with dysregulated proteins. Amniotic fluid exosomes have similar shape and quantity regardless of the conditions; however, the PLAP/CD63 ratios for TL, PTB, and pPROM were significantly higher (∼3.8-, ∼4.4-, and ∼3.5-fold, respectively) compared with TNIL. The PLAP/CD63 ratio was also significantly higher (∼1.3-fold) in PTB compared with pPROM. Biological functions primarily indicated nonspecific inflammatory response regardless of condition, but unique profiles were also identified in cases (PTB and pPROM) compared with term. Amniotic fluid exosomes provide information specific to normal and abnormal parturition. Inflammatory marker enrichment and its uniqueness in term and preterm pregnancies support the value of exosomes in determining underlying physiology associated with term and preterm parturition.
Coronavirus disease 2019 (COVID-19) is a novel infectious disease that started in Wuhan, China, and has rapidly spread all across the world. With limited ability to contain the virus and relatively ...high transmissibility and case fatality rates, governmental institutions and pharmaceutical companies are racing to find therapeutics and vaccines that target this novel coronavirus. However, once again, pregnant and breastfeeding women are excluded from participating in clinical trials during this pandemic. This “protection by exclusion” of pregnant women from drug development and clinical therapeutic trials, even during epidemics and pandemics, is not unprecedented. Moreover, it is both misguided and not justifiable and may have excluded them from potentially beneficial interventions. This is another missed opportunity to obtain pregnancy-specific safety and efficacy data, because therapeutics developed for men and nonpregnant women may not be generalizable to pregnant women. Therefore, we recommend and urge the scientific community and professional societies that, without clear justification for exclusion, pregnant women should be given the opportunity to be included in clinical trials for COVID-19 based on the concepts of justice, equity, autonomy, and informed consent.
Aging is associated with the onset of several diseases in various organ systems; however, different tissues may age differently, rendering some of them dysfunctional sooner than others. Placental ...membranes (fetal amniochorionic membranes) protect the fetus throughout pregnancy, but their longevity is limited to the duration of pregnancy. The age-associated dysfunction of these membranes is postulated to trigger parturition. Here, we investigated whether cellular senescence-the loss of cell division potential as a consequence of stress-is involved in placental membrane function at term. We show telomere reduction, p38 MAPK activation, increase in p21 expression, loss of lamin B1 loss, increase in SA-β-galactosidase , and senescence-associated secretory phenotype (SASP) gene expression in placental membranes after labor and delivery (term labor TL) compared to membranes prior to labor at term (term, not-in-labor TNIL). Exposing TNIL placental membranes to cigarette smoke extract, an oxidative stress inducer, also induced markers of cellular senescence similar to those in TL placental membranes. Bioinformatics analysis of differentially expressed SASP genes revealed HMGB1 signaling among the top pathways involved in labor. Further, we show that recombinant HMGB1 upregulates the expression of genes associated with parturition in myometrial cells. These data suggest that the natural physiologic aging of placental tissues is associated with cellular senescence and human parturition.
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