Síndrome HELLP sobreposta a síndrome hemolítica-urêmica

A pregnancy complicated by typical hemolytic uremic syndrome (HUS) and hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome is reported. At 20 weeks of gestation, a case of HUS was diagnosed, with Shiga toxin-producing Escherichia coli identified. Plasmapheresis allowed continuation of the pregnancy for 5 weeks. Superimposed preeclampsia and HELLP syndrome were diagnosed after the establishment of nephrotic range proteinuria, hypertension and recurrence of hemolysis. This is a singular case, as it demonstrates that HELLP syndrome can superimpose upon HUS, a fact that can impact future research on reproductive immunology. It also reminds clinicians that the overlapping of clinical and laboratory findings in HELLP syndrome makes the diagnosis of other thrombotic microangiopathies during pregnancy a clinical challenge.info:eu-repo/semantics/publishedVersio

Tectonic and lithological controls on fluvial landscape development in Central-Eastern Portugal: Insights from long profile tributary stream analyses

This study examines the long profiles of tributaries of the Tagus and Zêzere rivers in Portugal (West Iberia) in order to provide new insights into patterns, timing, and controls on drainage development during the Quaternary incision stage. The studied streams are incised into a relict culminant fluvial surface, abandoned at the beginning of the incision stage. The streams flow through a landscape with bedrock variations in lithology (mainly granites and metasediments) and faulted blocks with distinct uplift rates. The long profiles of the analyzed streams record an older transitory knickpoint/knickzone separating (1) an upstream relict graded profile, with lower steepness and higher concavity, that reflects a long period of quasi-equilibrium conditions reached after the beginning of the incision stage, and (2) a downstream rejuvenated long profile, with steeper gradient and lower concavity, particularly for the final reach, which is often convex. The rejuvenated reaches testify to the upstream propagation of several incision waves, interpreted as the response of each stream to increasing crustal uplift and prolonged periods of base-level lowering by the trunk drainages, coeval with low sea level conditions. The morphological configurations of the long profiles enabled spatial and relative temporal patterns of incisions to be quantified. The incision values of streams flowing on the Portuguese Central Range (PCR; ca. 380–150 m) are variable but generally higher than the incision values of streams flowing on the adjacent South Portugal Planation Surface (SPPS; ca. 220–110 m), corroborating differential uplift of the PCR relative to the SPPS. Owing to the fact that the relict graded profiles can be correlated with the Tagus River T1 terrace (1.1–0.9 My) present in the study area, incision rates can be estimated (1) for the streams located in the PCR, 0.38–0.15 m/ky and (2) for the streams flowing on the SPPS, 0.22–0.12 m/ky. The differential uplift inferred in the study area supports the neotectonic activity of the bordering faults, as proposed in previous studies based upon other geological evidence

On a canonical lift of Artin's representation to loop braid groups

Each pointed topological space has an associated π-module, obtained from action of its first homotopy group on its second homotopy group. For the 3-ball with a trivial link with n-components removed from its interior, its π-module is of free type. In this paper we give an injection of the (extended) loop braid group into the group of automorphisms of . We give a topological interpretation of this injection, showing that it is both an extension of Artin's representation for braid groups and of Dahm's homomorphism for (extended) loop braid groups

Efficacy of prolonged application of low-level laser therapy combined with exercise in knee osteoarthritis: A randomized controlled double-blind study.

OBJECTIVES: To investigate the effect of prolonged low-level laser therapy application combined with exercise on pain and disability in patients with osteoarthritis of the knee. DESIGN: A randomized controlled trial. SETTING: Special rehabilitation services. SUBJECTS: Forty-three participants with knee osteoarthritis. INTERVENTION: Following initial assessment, participants were randomly allocated to the Laser group (n = 22, 44 knees) and received low-level laser therapy while the Placebo group (n = 21, 42 knees) received placebo therapy three times a week for 3 weeks. Both groups then received low-level laser therapy combined with exercise three times a week for the following 8 weeks. MAIN OUTCOME MEASURES: The primary outcome was change in knee pain and disability (Lequesne). Secondary outcomes included change in mobility (Timed Up and Go test), range of motion (goniometer), muscular strength (dynamometer), activity (Western Ontario and McMaster Universities Osteoarthritis questionnaire), and medication intake and relief. RESULTS: Mean (SD) age of participants was 63.02 (9.9) years. Pain scores at baseline, 3 weeks, 11 weeks, and 6 months follow-up were 9.1 (1.3), 2.6 (2.3), 0.2 (0.9), and 0.2 (0.8) for the Laser group and 9.5 (8.0), 7.7 (5.3), 5.6 (2.4), and 7.4 (5.0) for the Placebo group, respectively. Disability scores at baseline, 3 weeks, 11 weeks, and 6 months follow-up were 14.9 (4.7), 7.6 (4.8), 3.9 (4.2), and 3.5 (4.1) for the Laser group and 17.8 (14.7), 15.2 (11.5), 11.6 (6.4), and 15.8 (11.9) for the Placebo Group, respectively. CONCLUSION: In participants with osteoarthritis of the knee, the isolated application of low-level laser therapy in the initial 3 weeks and combined with exercises in the final 8 weeks reduced pain, disability, and intake of medication over a 6-month period

Persistence of magnetic field driven by relativistic electrons in a plasma

The onset and evolution of magnetic fields in laboratory and astrophysical plasmas is determined by several mechanisms, including instabilities, dynamo effects and ultra-high energy particle flows through gas, plasma and interstellar-media. These processes are relevant over a wide range of conditions, from cosmic ray acceleration and gamma ray bursts to nuclear fusion in stars. The disparate temporal and spatial scales where each operates can be reconciled by scaling parameters that enable to recreate astrophysical conditions in the laboratory. Here we unveil a new mechanism by which the flow of ultra-energetic particles can strongly magnetize the boundary between the plasma and the non-ionized gas to magnetic fields up to 10-100 Tesla (micro Tesla in astrophysical conditions). The physics is observed from the first time-resolved large scale magnetic field measurements obtained in a laser wakefield accelerator. Particle-in-cell simulations capturing the global plasma and field dynamics over the full plasma length confirm the experimental measurements. These results open new paths for the exploration and modelling of ultra high energy particle driven magnetic field generation in the laboratory

Full Genome Characterization of the Culicoides-Borne Marsupial Orbiviruses: Wallal Virus, Mudjinbarry Virus and Warrego Viruses

Viruses belonging to the species Wallal virus and Warrego virus of the genus Orbivirus were identified as causative agents of blindness in marsupials in Australia during 1994/5. Recent comparisons of nucleotide (nt) and amino acid (aa) sequences have provided a basis for the grouping and classification of orbivirus isolates. However, full-genome sequence data are not available for representatives of all Orbivirus species. We report full-genome sequence data for three additional orbiviruses: Wallal virus (WALV); Mudjinabarry virus (MUDV) and Warrego virus (WARV). Comparisons of conserved polymerase (Pol), sub-core-shell 'T2' and core-surface 'T13' proteins show that these viruses group with other Culicoides borne orbiviruses, clustering with Eubenangee virus (EUBV), another orbivirus infecting marsupials. WARV shares <70% aa identity in all three conserved proteins (Pol, T2 and T13) with other orbiviruses, consistent with its classification within a distinct Orbivirus species. Although WALV and MUDV share <72.86%/67.93% aa/nt identity with other orbiviruses in Pol, T2 and T13, they share >99%/90% aa/nt identities with each other (consistent with membership of the same virus species - Wallal virus). However, WALV and MUDV share <68% aa identity in their larger outer capsid protein VP2(OC1), consistent with membership of different serotypes within the species - WALV-1 and WALV-2 respectively

Application of CRISPR/Cas9 editing and digital droplet PCR in human iPSCs to generate novel knock-in reporter lines to visualize dopaminergic neurons

Human induced pluripotent stem cells (hiPSCs) have become indispensable for disease modelling. They are an important resource to access patient cells harbouring disease-causing mutations. Derivation of midbrain dopaminergic (DAergic) neurons from hiPSCs of PD patients represents the only option to model physiological processes in a cell type that is not otherwise accessible from human patients. However, differentiation does not produce a homogenous population of DA neurons and contaminant cell types may interfere with the readout of the in vitro system. Here, we use CRISPR/Cas9 to generate novel knock-in reporter lines for DA neurons, engineered with an endogenous fluorescent tyrosine hydroxylase \u2013 enhanced green fluorescent protein (TH-eGFP) reporter. We present a reproducible knock-in strategy combined with a highly specific homologous directed repair (HDR) screening approach using digital droplet PCR (ddPCR). The knock-in cell lines that we created show a functioning fluorescent reporter system for DA neurons that are identifiable by flow cytometry

The low-virulent African swine fever virus (ASFV/NH/P68) induces enhanced expression and production of relevant regulatory cytokines (IFNα, TNFα and IL12p40) on porcine macrophages in comparison to the highly virulent ASFV/L60

The impact of infection by the low-virulent ASFV/NH/P68 (NHV) and the highly virulent ASFV/L60 (L60) isolates on porcine macrophages was assessed through the quantification of IFNα, TNFα, IL12p40, TGFβ and ASFV genes by real-time PCR at 2, 4 and 6 h post-infection. Increased IFNα, TNFα and IL12p40 expression was found in infection with NHV, in which expression of TGFβ was lower than in infection with L60. Principal component analysis showed a positive interaction of cytokines involved in cellular immune mechanisms, namely IFNα and IL12p40 in the NHV infection. Quantification by ELISA confirmed higher production of IFNα, TNFα and IL12p40 in the NHV-infected macrophages. Overall, our studies reinforce and clarify the effect of the NHV infection by targeting cellular and cellular-based immune responses relevant for pig survival against ASFV infection

Kinome rewiring reveals AURKA limits PI3K-pathway inhibitor efficacy in breast cancer.

Dysregulation of the PI3K-AKT-mTOR signaling network is a prominent feature of breast cancers. However, clinical responses to drugs targeting this pathway have been modest, possibly because of dynamic changes in cellular signaling that drive resistance and limit drug efficacy. Using a quantitative chemoproteomics approach, we mapped kinome dynamics in response to inhibitors of this pathway and identified signaling changes that correlate with drug sensitivity. Maintenance of AURKA after drug treatment was associated with resistance in breast cancer models. Incomplete inhibition of AURKA was a common source of therapy failure, and combinations of PI3K, AKT or mTOR inhibitors with the AURKA inhibitor MLN8237 were highly synergistic and durably suppressed mTOR signaling, resulting in apoptosis and tumor regression in vivo. This signaling map identifies survival factors whose presence limits the efficacy of targeted therapies and reveals new drug combinations that may unlock the full potential of PI3K-AKT-mTOR pathway inhibitors in breast cancer