Primary Biliary Cholangitis: a Rare Diagnosis During Pregnancy

Primary biliary cholangitis is an autoimmune disease that mostly affects women. It is uncommon in women of childbearing age and the diagnosis during pregnancy is rare and can be challenging. Described here is a case of primary biliary cholangitis first manifesting during pregnancy, with the onset of pruritus, jaundice, biochemical liver abnormalities and positive antimitochondrial antibodies. Although treatment with ursodeoxycholic acid was started at the time of diagnosis, there was a progressive worsening of cholestatic biochemical markers throughout pregnancy. In addition, fasting hyperglycemia with polyhydramnios was diagnosed, consistent with gestational diabetes. She had a spontaneous preterm delivery at 31 weeks of gestation, of a newborn who was admitted to the neonatal intensive care unit but who subsequently had no long-term sequelae of preterm delivery. A maternal postpartum flare occurred. Treatment with ursodeoxycholic acid was well tolerated during pregnancy and lactation.info:eu-repo/semantics/publishedVersio

Improving Protein Template Recognition by Using Small-Angle X-Ray Scattering Profiles

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Small-angle x-ray scattering (SAXS) is able to extract low-resolution protein shape information without requiring a specific crystal formation. However, it has found little use in atomic-level protein structure determination due to the uncertainty of residue-level structural assignment. We developed a new algorithm, SAXSTER, to couple the raw SAXS data with protein-fold-recognition algorithms and thus improve template-based protein-structure predictions. We designed nine different matching scoring functions of template and experimental SAXS profiles. The logarithm of the integrated correlation score showed the best template recognition ability and had the highest correlation with the true template modeling (TM)-score of the target structures. We tested the method in large-scale protein-fold-recognition experiments and achieved significant improvements in prioritizing the best template structures. When SAXSTER was applied to the proteins of asymmetric SAXS profile distributions, the average TM-score of the top-ranking templates increased by 18% after homologous templates were excluded, which corresponds to a p-value < 10(-9) in Student's t-test. These data demonstrate a promising use of SAXS data to facilitate computational protein structure modeling, which is expected to work most efficiently for proteins of irregular global shape and/or multiple-domain protein complexes.1011127702781National Science Foundation [1027394]National Institute of General Medical Sciences [GM083107, GM084222]Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)National Science Foundation [1027394]National Institute of General Medical Sciences [GM083107, GM084222]CNPq [140377/2008-5

QUADRATIC FBSDE WITH GENERALIZED BURGERS' TYPE NONLINEARITIES, PERTURBATIONS AND LARGE DEVIATIONS

We discuss BSDE with drivers containing nonlinearities of the type p(y)|z | and p(y)|z|2 with p a polynomial of any degree. Sufficient con-ditions are given for existence and uniqueness of solutions as well as comparison results. We then connect the results to the Markovian FBSDE setting, discussing applications in the theory of PDE pertur-bation and stating a result concerning a large deviations principle for the first component of the solution to the BSDE

Biodegradable polymer‐Metal‐Organic Framework (MOF) composites for controlled and sustainable pesticide delivery

Due to high surface area, loading capacity, and selectivity, Metal-Organic Frameworks (MOFs) have shown much promise recently for potential applications in extraction and delivery of agrochemicals for environmental remediation and sustainable release, respectively. However, application of MOFs for pesticide delivery in wider agricultural context can be restricted by their granular form. Herein, an alternative approach is studied using biodegradable polymer-MOF composites to address this limitation. The loading and release of a widely used pesticide, 2,4-dichloropheoxycetic acid (2,4-D), is studied using two MOFs, UiO-66 and UiO-66-NH2, and the 2,4-D-loaded MOFs are incorporated into biodegradable polycaprolactone composites for convenient handling and minimizing runoff. The MOFs are loaded by in-situ, and post-synthetic methods, and characterised thoroughly to ensure successful synthesis and loading of 2,4-D. The pesticide release studies are performed on the MOFs and composites in distilled water, and analysed using UV-Vis spectroscopy, demonstrating sustained-release of 2,4-D over 16 days. The loaded MOF samples show high loading capacity, with up to 45 wt% for the in-situ loaded UiO-66. Release kinetics show more sustained release of 2,4-D from UiO-66-NH2 compared to UiO-66, which can be due to supramolecular interactions between the NH2 group of UiO-66-NH2 and 2,4-D. This is further supported by computational studies

Bayesian molecular clock dating of species divergences in the genomics era

It has been five decades since the proposal of the molecular clock hypothesis, which states that the rate of evolution at the molecular level is constant through time and among species. This hypothesis has become a powerful tool in evolutionary biology, making it possible to use molecular sequences to estimate the geological ages of species divergence events. With recent advances in Bayesian clock dating methodology and the explosive accumulation of genetic sequence data, molecular clock dating has found widespread applications, from tracking virus pandemics, to studying the macroevolutionary process of speciation and extinction, to estimating a timescale for Life on Earth

Poly-l-Lactic Acid Nanofiber–Polyamidoamine Hydrogel Composites: Preparation, Properties, and Preliminary Evaluation as Scaffolds for Human Pluripotent Stem Cell Culturing

none13siGualandi, Chiara; Bloise, Nora; Mauro, Nicolò; Ferruti, Paolo; Manfredi, Amedea; Sampaolesi, Maurilio; Liguori, Anna; Laurita, Romolo; Gherardi, Matteo; Colombo, Vittorio; Visai, Livia; Focarete, Maria Letizia; Ranucci, ElisabettaGualandi, Chiara; Bloise, Nora; Mauro, Nicolò; Ferruti, Paolo; Manfredi, Amedea; Sampaolesi, Maurilio; Liguori, Anna; Laurita, Romolo; Gherardi, Matteo; Colombo, Vittorio; Visai, Livia; Focarete, Maria Letizia; Ranucci, Elisabett

Higher Expression of CCL2, CCL4, CCL5, CCL21, and CXCL8 Chemokines in the Skin Associated with Parasite Density in Canine Visceral Leishmaniasis

Several previous studies correlated immunopathological aspects of canine visceral leishmaniasis (CVL) with tissue parasite load and/or the clinical status of the disease. Recently, different aspects of the immune response in Leishmania-infected dogs have been studied, particularly the profile of cytokines in distinct compartments. However, the role of chemokines in disease progression or parasite burdens of the visceralising species represents an important approach for understanding immunopathology in CVL. We found an increase in inflammatory infiltrate, which was mainly composed of mononuclear cells, in the skin of animals presenting severe forms of CVL and high parasite density. Our data also demonstrated that enhanced parasite density is positively correlated with the expression of CCL2, CCL4, CCL5, CCL21, and CXCL8. In contrast, there was a negative correlation between parasite density and CCL24 expression. These findings represent an advance in the knowledge of the involvement of skin inflammatory infiltrates in CVL and the systemic consequences and may contribute to developing a rational strategy for the design of new and more efficient prophylactic tools and immunological therapies against CVL