Obstetric antiphospholipid syndrome: A recent classification for an old defined disorder

Obstetric antiphospholipid syndrome (APS) is nowbeing recognized as a distinct entity fromvascular APS. Pregnancy morbidity includes N3 consecutive and spontaneous early miscarriages before 10 weeks of gestation; at least one unexplained fetal death after the 10thweek of gestation of a morphologically normal fetus; a premature birth before the 34thweek of gestation of a normal neonate due to eclampsia or severe pre-eclampsia or placental insufficiency. It is not well understood how antiphospholipid antibodies (aPLs), beyond their diagnostic and prognostic role, contribute to pregnancy manifestations. Indeed aPL-mediated thrombotic events cannot explain the obstetric manifestations and additional pathogenic mechanisms, such as a placental aPL mediated complement activation and a direct effect of aPLs on placental development, have been reported. Still debated is the possible association between aPLs and infertility and the effect of maternal autoantibodies on non-vascular manifestations in the babies. Combination of low dose aspirin and unfractionated or low molecular weight heparin is the effective treatment in most of the cases. However, pregnancy complications, in spite of this therapy, can occur in up to 20% of the patients. Novel alternative therapies able to abrogate the aPL pathogenic action either by interfering with aPL binding at the placental level or by inhibiting the aPL-mediated detrimental effect are under active investigation

Synthetic PreImplantation Factor (PIF) prevents fetal loss by modulating LPS induced inflammatory response

Maternal control of inflammation is essential during pregnancy and an exaggerated response is one of the underlying causes of fetal loss. Inflammatory response is mediated by multiple factors and Toll-like receptors (TLRs) are central. Activation of TLRs results in NALP-3 mediated assembly of apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1 into the inflammasome and production of pro-inflammatory cytokines IL-1\u3b2 and IL-18. Given that preventing measures are lacking, we investigated PreImplantation Factor (PIF) as therapeutic option as PIF modulates Inflammation in pregnancy. Additionally, synthetic PIF (PIF analog) protects against multiple immune disorders. We used a LPS induced murine model of fetal loss and synthetic PIF reduced this fetal loss and increased the embryo weight significantly. We detected increased PIF expression in the placentae after LPS insult. The LPS induced serum and placenta cytokines were abolished by synthetic PIF treatment and importantly synthetic PIF modulated key members of inflammasome complex NALP-3, ASC, and caspase-1 as well. In conclusion our results indicate that synthetic PIF protects against LPS induced fetal loss, likely through modulation of inflammatory response especially the inflammasome complex. Given that synthetic PIF is currently tested in autoimmune diseases of non-pregnant subjects (clinicaltrials.gov, NCT02239562), therapeutic approach during pregnancy can be envisioned

Low-molecular-weight heparins induce decidual heparin-binding epidermal growth factor–like growth factor expression and promote survival of decidual cells undergoing apoptosis Nicoletta Di

Objective: To evaluate the effects of low-molecular-weight heparins (LMWHs) on decidual heparin-binding epidermal growth factor–like growth factor (HB-EGF) expression/secretion and on TNF-a–induced decidual apoptosis. Design: Experimental study. Setting: Department of Obstetrics and Gynecology, Universita Cattolica del Sacro Cuore, Rome, Italy. Patient(s): Cultures of primary decidual cells isolated from human term placenta. Intervention(s): The effects of LMWHs (tinzaparin and enoxaparin) on decidual HB-EGF expression and secretion were investigated by Western blot analysis and ELISA, respectively. TNF-a–induced decidual apoptosis was evaluated by annexin V staining, terminal deoxynucleotide transferase– mediated dUTP nick-end labeling (TUNEL) assay, and caspase activities. Main Outcome Measure(s): Decidual HB-EGF expression/secretion and apoptotic rate induced by TNF-a were investigated. Result(s): Tinzaparin enhanced decidual HB-EGF expression and secretion. TNF-a reduced the number of viable cells by inducing apoptosis. Simultaneous addition of LMWHs (primarily tinzaparin) blocked the increase in annexin V– and TUNEL-positive cells and reduced the amount of caspase activities. Conclusion(s): Both LMWHs induced a significant increase in decidual HB-EGF expression/secretion and reduced TNF-a–induced decidual apoptosis. Tinzaparin demonstrated higher efficacy. (Fertil Steril 2012;97:169–77. 2012 by American Society for Reproductiv

Effect of Low Molecular Weight Heparins (LMWHs) on antiphospholipid Antibodies (aPL)-mediated inhibition of endometrial angiogenesis

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by vascular thrombosis and/or pregnancy morbidity in the presence of circulating antiphospholipid antibodies (aPL). Different pathogenic mechanisms for aPL-mediated pregnancy failure have been proposed. In particular a direct effect of aPL on both maternal and fetal side of the placental tissue has been reported, since their reactivity with \u3b22-glycoprotein I (\u3b22GPI) makes them adhere to trophoblast and human endometrial endothelial cell (HEEC) membranes. \u3b22GPI can be recognized by aPL that, once bound, interfere with both trophoblast functions and with the HEEC differentiation.APS patients can be successfully treated with Low Molecular Weight Heparin (LMWH). Recent reports suggest that LMWH acts through mechanisms alternative to its well known anticoagulant effect, because of its ability to bind \u3b22GPI. In our previous studies, we showed that LMWH is able to reduce the aPL binding to trophoblasts and restore cell invasiveness and differentiation. So far, however, no study has described its effects on endometrial angiogenesis.The aim of our research was to evaluate whether two LMWHs, tinzaparin and enoxaparin, have an effect on the aPL-inhibited endometrial angiogenesis. This prompted us to investigate: (i) in vitro HEEC angiogenesis through a Matrigel assay; (ii) VEGF secretion by ELISA; (iii) matrix metalloproteinase-2 (MMP-2) activity by gelatin zymography; (iv) Nuclear Factor-\u3baB (NF-\u3baB) DNA binding activity by colorimetric assay; (v) STAT-3 activation by a sandwich-ELISA kit. Furthermore, using an in vivo murine model we investigated the LMWHs effects on angiogenesis.We demonstrated that the addition of LMWHs prevents aPL-inhibited HEEC angiogenesis, both in vitro and in vivo, and is able to restore the aPL inhibited NF-\u3baB and/or STAT-3 activity, the VEGF secretion and the MMPs activity.The demonstration of a beneficial role for LMWHs on the aPL-inhibited HEEC angiogenesis might provide additional mechanisms whereby this treatment protects early pregnancy in AP

Advances in Electronic-Nose Technologies Developed for Biomedical Applications

The research and development of new electronic-nose applications in the biomedical field has accelerated at a phenomenal rate over the past 25 years. Many innovative e-nose technologies have provided solutions and applications to a wide variety of complex biomedical and healthcare problems. The purposes of this review are to present a comprehensive analysis of past and recent biomedical research findings and developments of electronic-nose sensor technologies, and to identify current and future potential e-nose applications that will continue to advance the effectiveness and efficiency of biomedical treatments and healthcare services for many years. An abundance of electronic-nose applications has been developed for a variety of healthcare sectors including diagnostics, immunology, pathology, patient recovery, pharmacology, physical therapy, physiology, preventative medicine, remote healthcare, and wound and graft healing. Specific biomedical e-nose applications range from uses in biochemical testing, blood-compatibility evaluations, disease diagnoses, and drug delivery to monitoring of metabolic levels, organ dysfunctions, and patient conditions through telemedicine. This paper summarizes the major electronic-nose technologies developed for healthcare and biomedical applications since the late 1980s when electronic aroma detection technologies were first recognized to be potentially useful in providing effective solutions to problems in the healthcare industry

Aprendizajes y prácticas educativas en las actuales condiciones de época: COVID-19

“Esta obra colectiva es el resultado de una convocatoria a docentes, investigadores y profesionales del campo pedagógico a visibilizar procesos investigativos y prácticas educativas situadas en el marco de COVI-19. La misma se inscribe en el trabajo llevado a cabo por el equipo de Investigación responsable del Proyecto “Sentidos y significados acerca de aprender en las actuales condiciones de época: un estudio con docentes y estudiantes de la educación secundarias en la ciudad de Córdoba” de la Facultad de Filosofía y Humanidades. Universidad Nacional de Córdoba. El momento excepcional que estamos atravesando, pero que también nos atraviesa, ha modificado la percepción temporal a punto tal que habitamos un tiempo acelerado y angustiante que nos exige la producción de conocimiento provisorio. La presente publicación surge como un espacio para detenernos a documentar lo que nos acontece y, a su vez, como oportunidad para atesorar y resguardar las experiencias educativas que hemos construido, inventado y reinventando en este contexto. En ella encontrarán pluralidad de voces acerca de enseñar y aprender durante la pandemia. Este texto es una pausa para reflexionar sobre el hacer y las prácticas educativas por venir”.Fil: Beltramino, Lucia (comp.). Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Escuela de Archivología; Argentina

A synthetic peptide corresponding to the 550–585 region of α-dystroglycan binds β-dystroglycan as revealed by NMR spectroscopy

AbstractWe have probed the binding of a synthetic peptide corresponding to the region 550–585 of the α subunit of dystroglycan with a recombinant protein fragment corresponding to the N-terminal extracellular region of β-dystroglycan (654–750), using NMR in solution. In a 30:1 molar ratio, the peptide binds to the recombinant protein fragment in the fast/intermediate exchange regime. By monitoring the peptide intra-residue HN–Hα peak volumes of the 2D TOCSY NMR spectra, both in the absence and in the presence of the recombinant fragment, we determined the differential binding affinities of each amino acid. We found that the residues in the region 550–565 (SWVQFNSNSQLMYGLP) are more influenced by the presence of the protein, whereas the C-terminal portion is marginally involved. These NMR results have been confirmed by solid-phase binding assays

Thyroid autoimmunity and recurrent miscarriage

PROBLEM: To investigate the role of antithyroid autoantibodies (ATA) in recurrent miscarriage (RM). METHODS: In this case-control study, a total of 160 women with RM and 100 healthy women were investigated for the presence of serum ATA directed against thyreoglobulin (TG-Ab), thyroid peroxidase (TPO-Ab) and TSH receptor (TSHr-Ab), which were determined by either chemiluminescence or radioimmunoassay. RESULTS: Antithyroid autoantibodies were detected in 46 (28.75%) women with RM and in 13 (13%) women of the control group (P < 0.05). The frequencies for TG-Ab and TPO-Ab were higher in RM than in control women. Among the women of RM group, 91.3% of ATA+ women were positive also for other autoantibodies. The majority of study women were euthyroid. CONCLUSIONS: Antithyroid autoantibodies, particularly TG-Ab, are associated with RM and could be an expression of a more general maternal immune system abnormality leading to RM. ATA could have a role in RM irrespective of thyroid hormone statu

Adipokines: New Emerging Roles in Fertility and Reproduction

Adipose tissue is a specialized endocrine and paracrine organ producing specific factors called adipokines. It is well known that adipokines balance is fundamental to prevent obesity, metabolic syndrome, and cardiovascular diseases. During the last years, new roles of adipokines have been emerging in the field of fertility and reproduction. Although the literature is still quite controversial, this review serves to resume current knowledge on this topic. Alterations in adipokine levels or in their mechanism of action are associated with fertility impairment and pregnancy diseases, as well as with obesity, metabolic syndrome, and cardiovascular diseases. Normal levels of adipokines are fundamental to maintain integrity of hypothalamus-pituitary-gonadal axis, regular ovulatory processes, successful embryo implantation, and physiologic pregnancy. More efforts are needed to understand the mechanisms and to the extent to which adipokine changes are involved in the impairment of fertility and pregnancy outcome, to find possible medical treatments. Target Audience: Obstetricians & Gynecologists, Family Physicians Learning Objectives: After completion of this educational activity, the obstetrician/gynecologist should be better able to demonstrate current knowledge in the research field of adipokines in fertility and reproduction; evaluate the central role of metabolism balance in good pregnancy outcome; and apply new perspectives of studies