Altered Glycosylation Contributes to Placental Dysfunction Upon Early Disruption of the NK Cell-DC Dynamics

Immune cells [e. g., dendritic cells (DC) and natural killer (NK) cells] are critical players during the pre-placentation stage for successful mammalian pregnancy. Proper placental and fetal development relies on balanced DC-NK cell interactions regulating immune cell homing, maternal vascular expansion, and trophoblast functions. Previously, we showed thatin vivodisruption of the uterine NK cell-DC balance interferes with the decidualization process, with subsequent impact on placental and fetal development leading to fetal growth restriction. Glycans are essential determinants of reproductive health and the glycocode expressed in a particular compartment (e.g., placenta) is highly dependent on the cell type and its developmental and pathological state. Here, we aimed to investigate the maternal and placental glycovariation during the pre- and post-placentation period associated with disruption of the NK cell-DC dynamics during early pregnancy. We observed that depletion of NK cells was associated with significant increases of O- and N-linked glycosylation and sialylation in the decidual vascular zone during the pre-placental period, followed by downregulation of core 1 and poly-LacNAc extended O-glycans and increased expression of branched N-glycans affecting mainly the placental giant cells and spongiotrophoblasts of the junctional zone. On the other hand, expansion of DC induced a milder increase of Tn antigen (truncated form of mucin-type O-glycans) and branched N-glycan expression in the vascular zone, with only modest changes in the glycosylation pattern during the post-placentation period. In both groups, this spatiotemporal variation in the glycosylation pattern of the implantation site was accompanied by corresponding changes in galectin-1 expression. Our results show that pre- and post- placentation implantation sites have a differential glycopattern upon disruption of the NK cell-DC dynamics, suggesting that immune imbalance early in gestation impacts placentation and fetal development by directly influencing the placental glycocode

Parents' understanding about newborn screening

A Triagem Neonatal, mais conhecida como o Teste do Pezinho, é uma estratégia de saúde pública que visa à prevenção de seqüelas, como o retardo mental provocado por hipotireoidismo congênito e fenilcetonúria. Estas patologias apresentam-se freqüentemente assintomáticas nos primeiros meses de vida da criança. Entretanto, se forem diagnosticadas precocemente, existe alta probabilidade do tratamento prevenir suas graves conseqüências. O público-alvo da triagem são os recém-nascidos de 0 a 30 dias de vida, e os seus cuidadores primários desempenham papel crucial para que a prevenção ocorra. O objetivo desse trabalho foi fazer um levantamento das características da clientela atendida por um serviço de referência em Triagem Neonatal localizado na cidade de Belém-PA, e avaliar a compreensão dos pais e/ou cuidadores sobre a importância da realização do Teste do Pezinho. Aplicou-se um questionário para 200 participantes que concordaram em responder a um roteiro de entrevista e foi verificado se houve retorno para buscar o resultado do teste. Os resultados indicaram que a maioria dos participantes não possuía um bom entendimento sobre a importância do teste como recurso para promover prevenção em saúde da criança.Newborn screening, known mainly as PKU and CH screening or Guthrie test, is a public health strategy which aims at the prevention of mental sequels provoked by congenital hypothyroidism and phenylketonuria. These diseases do not usually cause symptoms during the first months of the child's life. However, if they are diagnosed precociously, there is a high probability that the treatment prevents its serious consequences. The test is performed in infants during their first 30 days of life, and their primary caregivers play a crucial role so that prevention occurs. The objective of this work was to study the characteristics of the people being assisted by a service of excellence in Newborn Screening located in the city of Belém, state of Pará, and to evaluate the understanding of parents and/or caregivers about the importance of the Guthrie Test. A questionnaire was applied to 200 participants, who had previously agreed to answer an interview script, and it was verified whether they returned to check the result of the test. The results indicated that most of the participants were not aware of the importance of the test as a resource to promote prevention in child's health

Virus-Templated Near-Amorphous Iron Oxide Nanotubes

© 2016 American Chemical Society. We present a simple synthesis of iron oxide nanotubes, grown under very mild conditions from a solution containing Fe(II) and Fe(III), on rod-shaped tobacco mosaic virus templates. Their well-defined shape and surface chemistry suggest that these robust bionanoparticles are a versatile platform for synthesis of small, thin mineral tubes, which was achieved efficiently. Various characterization tools were used to explore the iron oxide in detail: Electron microscopy (SEM, TEM), magnetometry (SQUID-VSM), diffraction (XRD, TEM-SAED), electron spectroscopies (EELS, EDX, XPS), and X-ray absorption (XANES with EXAFS analysis). They allowed determination of the structure, crystallinity, magnetic properties, and composition of the tubes. The protein surface of the viral templates was crucial to nucleate iron oxide, exhibiting analogies to biomineralization in natural compartments such as ferritin cages

The emerging role of virtual reality as an adjunct to procedural sedation and anesthesia: a narrative review

Over the past 20 years, there has been a significant reduction in the incidence of adverse events associated with sedation outside of the operating room. Non-pharmacologic techniques are increasingly being used as peri-operative adjuncts to facilitate and promote anxiolysis, analgesia and sedation, and to reduce adverse events. This narrative review will briefly explore the emerging role of immersive reality in the peri-procedural care of surgical patients. Immersive virtual reality (VR) is intended to distract patients with the illusion of “being present” inside the computer-generated world, drawing attention away from their anxiety, pain, and discomfort. VR has been described for a variety of procedures that include colonoscopies, venipuncture, dental procedures, and burn wound care. As VR technology develops and the production costs decrease, the role and application of VR in clinical practice will expand. It is important for medical professionals to understand that VR is now available for prime-time use and to be aware of the growing body in the literature that supports VR.info:eu-repo/semantics/publishedVersio

Using immersive virtual reality distraction to reduce fear and anxiety before surgery

Presurgical anxiety is very common and is often treated with sedatives. Minimizing or avoiding sedation reduces the risk of sedation-related adverse events. Reducing sedation can increase early cognitive recovery and reduce time to discharge after surgery. The current case study is the first to explore the use of interactive eye-tracked VR as a nonpharmacologic anxiolytic customized for physically immobilized presurgery patients. Method: A 44-year-old female patient presenting for gallbladder surgery participated. Using a within-subject repeated measures design (treatment order randomized), the participant received no VR during one portion of her preoperative wait and interactive eye-tracked virtual reality during an equivalent portion of time in the presurgery room. After each condition (no VR vs. VR), the participant provided subjective 0–10 ratings and state–trait short form Y anxiety measures of the amount of anxiety and fear she experienced during that condition. Results: As predicted, compared to treatment as usual (no VR), the patient reported having 67% lower presurgical anxiety during VR. She also experienced “strong fear” (8 out of 10) during no VR vs. “no fear” (0 out of 10) during VR. She reported a strong sense of presence during VR and zero nausea. She liked VR, she had fun during VR, and she recommended VR to future patients during pre-op. Interactive VR distraction with eye tracking was an effective nonpharmacologic technique for reducing anticipatory fear and anxiety prior to surgery. The results add to existing evidence that supports the use of VR in perioperative settings. VR technology has recently become affordable and more user friendly, increasing the potential for widespread dissemination into medical practice. Although case studies are scientifically inconclusive by nature, they help identify new directions for future larger, carefully controlled studies. VR sedation is a promising non-drug fear and anxiety management technique meriting further investigation.info:eu-repo/semantics/publishedVersio

Potential red-flag identification of colorectal adenomas with wide-field fluorescence molecular endoscopy

Adenoma miss rates in colonoscopy are unacceptably high, especially for sessile serrated adenomas / polyps (SSA/Ps) and in high-risk populations, such as patients with Lynch syndrome. Detection rates may be improved by fluorescence molecular endoscopy (FME), which allows morphological visualization of lesions with high-definition white-light imaging as well as fluorescence-guided identification of lesions with a specific molecular marker. In a clinical proof-of-principal study, we investigated FME for colorectal adenoma detection, using a fluorescently labelled antibody (bevacizumab-800CW) against vascular endothelial growth factor A (VEGFA), which is highly upregulated in colorectal adenomas. Methods: Patients with familial adenomatous polyposis (n = 17), received an intravenous injection with 4.5, 10 or 25 mg of bevacizumab-800CW. Three days later, they received NIR-FME. Results: VEGFA-targeted NIR-FME detected colorectal adenomas at all doses. Best results were achieved in the highest (25 mg) cohort, which even detected small adenomas ( < 3 mm). Spectroscopy analyses of freshly excised specimen demonstrated the highest adenoma-to-normal ratio of 1.84 for the 25 mg cohort, with a calculated median tracer concentration in adenomas of 6.43 nmol/mL. Ex vivo signal analyses demonstrated NIR fluorescence within the dysplastic areas of the adenomas. Conclusion: These results suggest that NIR-FME is clinically feasible as a real-time, red-flag technique for detection of colorectal adenomas

Definitions, Criteria and Global Classification of Mast Cell Disorders with Special Reference to Mast Cell Activation Syndromes: A Consensus Proposal

Activation of tissue mast cells (MCs) and their abnormal growth and accumulation in various organs are typically found in primary MC disorders also referred to as mastocytosis. However, increasing numbers of patients are now being informed that their clinical findings are due to MC activation (MCA) that is neither associated with mastocytosis nor with a defined allergic or inflammatory reaction. In other patients with MCA, MCs appear to be clonal cells, but criteria for diagnosing mastocytosis are not met. A working conference was organized in 2010 with the aim to define criteria for diagnosing MCA and related disorders, and to propose a global unifying classification of all MC disorders and pathologic MC reactions. This classification includes three types of `MCA syndromes' (MCASs), namely primary MCAS, secondary MCAS and idiopathic MCAS. MCA is now defined by robust and generally applicable criteria, including (1) typical clinical symptoms, (2) a substantial transient increase in serum total tryptase level or an increase in other MC-derived mediators, such as histamine or prostaglandin D 2, or their urinary metabolites, and (3) a response of clinical symptoms to agents that attenuate the production or activities of MC mediators. These criteria should assist in the identification and diagnosis of patients with MCAS, and in avoiding misdiagnoses or overinterpretation of clinical symptoms in daily practice. Moreover, the MCAS concept should stimulate research in order to identify and exploit new molecular mechanisms and therapeutic targets. Copyright (C) 2011 S. Karger AG, Base

Hantavirus pulmonary syndrome in northwestern Argentina : circulation of Laguna Negra virus associated with Calomys callosus

The purpose of this study was to characterize the hantaviruses circulating in northwestern Argentina. Human and rodent studies were conducted in Yuto, where most cases of hantavirus pulmonary syndrome (HPS) occur. Partial virus genome sequences were obtained from the blood of 12 cases of HPS, and from the lungs of 4 Calomys callosus and 1 Akodon simulator. Phylogenetic analysis showed that three genotypes associated with HPS circulate in Yuto. Laguna Negra (LN) virus, associated with C. laucha in Paraguay, was identified for the first time in Argentina; it was recovered from human cases and from C. callosus samples. The high sequence identity between human and rodent samples implicated C. callosus as the primary rodent reservoir for LN virus in Yuto. The genetic analysis showed that the Argentinian LN virus variant differed 16.8% at the nucleotide level and 2.9% at the protein level relative to the Paraguayan LN virus. The other two hantavirus lineages identified were the previously known Bermejo and Orán viruses.Fil: Levis, Silvana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas Dr. Julio Maiztegui; Argentina.Fil: Garcia, Jorge. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas Dr. Julio Maiztegui; Argentina.Fil: Pini, Noemí. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas Dr. Julio Maiztegui; Argentina.Fil: Calderón, Gladys. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas Dr. Julio Maiztegui; Argentina.Fil: Ramírez, Josefina. Hospital San Miguel; Argentina.Fil: Bravo, Daniel. Hospital Oscar Orías; Argentina.Fil: St. Jeor, Stephen. University of Nevada. Department of Microbiology; Estados Unidos.Fil: Ripoll, Carlos. Dirección de Epidemiología. San Salvador de Jujuy, Jujuy; Argentina.Fil: Bego, Mariana. University of Nevada. Department of Microbiology; Estados Unidos.Fil: Lozano, Elena. Hospital San Miguel; Argentina.Fil: Barquez, Rubén. Fundación Miguel Lillo; Argentina.Fil: Ksiazek, Thomas G. Centers for Disease Control and Prevention. Special Pathogens Branch; Estados Unidos.Fil: Enria, Delia. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas Dr. Julio Maiztegui; Argentina

Proteomic Interrogation of Human Chromatin

Chromatin proteins provide a scaffold for DNA packaging and a basis for epigenetic regulation and genomic maintenance. Despite understanding its functional roles, mapping the chromatin proteome (i.e. the “Chromatome”) is still a continuing process. Here, we assess the biological specificity and proteomic extent of three distinct chromatin preparations by identifying proteins in selected chromatin-enriched fractions using mass spectrometry-based proteomics. These experiments allowed us to produce a chromatin catalog, including several proteins ranging from highly abundant histone proteins to less abundant members of different chromatin machinery complexes. Using a Normalized Spectral Abundance Factor approach, we quantified relative abundances of the proteins across the chromatin enriched fractions giving a glimpse into their chromosomal abundance. The large-scale data sets also allowed for the discovery of a variety of novel post-translational modifications on the identified chromatin proteins. With these comparisons, we find one of the probed methods to be qualitatively superior in specificity for chromatin proteins, but inferior in proteomic extent, evidencing a compromise that must be made between biological specificity and broadness of characterization. Additionally, we attempt to identify proteins in eu- and heterochromatin, verifying the enrichments by characterizing the post-translational modifications detected on histone proteins from these chromatin regions. In summary, our results provide insights into the value of different methods to extract chromatin-associated proteins and provide starting points to study the factors that may be involved in directing gene expression and other chromatin-related processes

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis