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Purpose: To develop an open-source prototype of myocardial T1 mapping (Open-MOLLI) to improve accessibility to cardiac T1 mapping and evaluate its repeatability. With Open-MOLLI, we aim to enable faster implementation and testing of sequence modifications and to facilitate inter-scanner and cross-vendor reproducibility studies., Methods: Open-MOLLI is an inversion-recovery sequence using a balanced SSFP (bSSFP) readout, with inversion and triggering schemes based on the 5(3)3 MOLLI sequence, developed in Pulseq. Open-MOLLI and MOLLI sequences were acquired in the ISMRM/NIST phantom and 21 healthy volunteers. In 18 of those subjects, Open-MOLLI and MOLLI were repeated in the same session (test-retest)., Results: Phantom T1 values were comparable between methods, specifically for the vial with reference T1 value most similar to healthy myocardium T1 (T1 vial3  = 1027 ms): T1 MOLLI  = 1011 ± 24 ms versus T1 Open-MOLLI  = 1009 ± 20 ms. In vivo T1 estimates were similar between Open-MOLLI and MOLLI (T1 MOLLI  = 1004 ± 33 ms vs. T1 Open-MOLLI  = 998 ± 52 ms), with a mean difference of -17 ms (p = 0.20), despite noisier Open-MOLLI weighted images and maps. Repeatability measures were slightly higher for Open-MOLLI (RC MOLLI  = 3.0% vs. RC Open-MOLLI  = 4.4%)., Conclusion: The open-source sequence Open-MOLLI can be used for T1 mapping in vivo with similar mean T1 values to the MOLLI method. Open-MOLLI increases the accessibility to cardiac T1 mapping, providing also a base sequence to which further improvements can easily be added and tested., (© 2024 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: Enabling fast and accessible myocardial T 1 mapping is crucial for extending its clinical application. We introduce Open-MOLLI-SMS combining simultaneous multi-slice (SMS) with auto-calibration and variable-rate selective excitation (VERSE)-multiband pulses to obtain all slices in a fast single-shot T 1 mapping sequence., Methods: Open-MOLLI-SMS was developed by integrating SMS with the open-source method Open-MOLLI previously implemented in Pulseq. Three methods were integrated for Open-MOLLI-SMS: (1) auto-calibration blip patterns to ensure consistency between the data and coil information; (2) a blipped-balanced SSFP (bSSFP) readout to induce controlled aliasing in parallel imaging shifts without disturbing the bSSFP frequency response; and (3) a VERSE-multiband pulse for minimizing the achievable TR and the specific absortion rate (SAR) impact of SMS. Two (SMS2) or three (SMS3) slices were excited simultaneously and encoded with an in-plane acceleration factor of 2. Experiments were performed in the International Society for Magnetic Resonance in Medicine/National Institute of Standards and Technology phantom and five healthy volunteers., Results: Phantom results show accurate T 1 estimates for reference values between 400 to 2200 ms. Artifacts were visible for Open-MOLLI-SMS3 but not replicated in vivo. In vivo Open-MOLLI-SMS (T 1 SMS2  = 993 ± 10 ms; T 1 SMS3  = 1031 ± 17 ms) provided similar values to mean T 1 single-band Open-MOLLI estimates (T 1 Open-MOLLI  = 1005 ± 47 ms). Open-MOLLI-SMS2 provided the closest estimates to the reference., Conclusion: This proof-of-principle implementation study demonstrates the feasibility of speeding up T 1 -mapping acquisitions and increasing coverage by combining auto-calibration strategies with a blipped-bSFFP readout and VERSE multiband RF excitation pulses. The proposed methodology was built on the Open-MOLLI mapping sequence, which provides a fast means for prototyping and enables open-source sharing of the method., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Objective: Our objective was to study the relationship between epilepsy and autoimmune diseases in two different types of epilepsy: idiopathic generalized epilepsies (IGEs) and mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS). The contribution of the human leukocyte antigen (HLA) system to this relationship was analyzed., Methods: Adult patients with IGEs and MTLE-HS at a tertiary epilepsy center were consecutively enrolled between January 2016 and December 2020., Results: A total of 664 patients, 422 with IGEs and 242 with MTLE-HS, were included. Patients with IGEs were 15 years younger, on average, than patients with MTLE-HS (p < .001). The frequency of autoimmune diseases was 5.5% (n = 23) and 4.5% (n = 11) in patients with IGEs and MTLE-HS, respectively (p = .716). The mean age of autoimmune disease onset was 20 ± 15.6 years in patients with IGEs and 36.7 ± 16.5 years in patients with MTLE-HS (p < .05). Clinical manifestations of autoimmune diseases preceded epilepsy onset in 30.4% of patients with IGEs (i.e., in early childhood); in the other patients, epilepsy appeared before autoimmune disease onset. In all but one patient with MTLE-HS and autoimmune diseases, the autoimmune diseases appeared after epilepsy onset from adolescence onward., Significance: Our study indicates two relationship patterns: a bidirectional association between IGEs and autoimmune diseases and a unidirectional relationship between MTLE-HS and autoimmune diseases. The involvement of genetic susceptibility factors (such as the HLA system), autoinflammatory mechanisms, female sex, and antiseizure medications in these relationships are discussed., (© 2023 International League Against Epilepsy.)

With an ageing world population and ~20% of adults in Europe being affected by bone diseases, there is an urgent need to develop advanced regenerative approaches and biomaterials capable to facilitate tissue regeneration while providing an adequate microenvironment for cells to thrive. As the main components of bone are collagen and apatite mineral, scientists in the tissue engineering field have attempted in combining these materials by using different biomimetic approaches to favour bone repair. Still, an ideal bone analogue capable of mimicking the distinct properties (i.e., mechanical properties, degradation rate, porosity, etc.) of cancellous bone is to be developed. This review seeks to sum up the current understanding of bone tissue mineralisation and structure while providing a critical outlook on the existing biomimetic strategies of mineralising collagen for bone tissue engineering applications, highlighting where gaps in knowledge exist., (© 2022 The Authors. Biopolymers published by Wiley Periodicals LLC.)

A new rutin copper(II) complex (R-Cu2) was prepared and characterized by spectroscopic methods and elemental analysis. The effects of rutin and R-Cu2 were evaluated on the prevention of hypercholesterolemia in animals feed with high-cholesterol diet (HCD) for 8 weeks. The animals (n = 5) were neither fed with HCD nor treated (control group), or were treated with vehicle, 10 mg/kg simvastatin, rutin (16 and 160 μmol/kg), and R-Cu2 (16 and 160 μmol/kg) administered orally. Total cholesterol (TC) levels were significantly increased (p < .01) in all HCD groups. In rutin and R-Cu2 groups, it was observed a discrete, but not significant, TC and LDL-induced increase inhibition compared with vehicle-treated group. R-Cu2 treatment significantly decreased (p < .05) plasma triglycerides compared with the vehicle-treated group. All groups receiving treatments maintained the malondialdehyde at normal levels. Serum NO levels were reduced in animals treated with rutin and R-Cu2 compared with the vehicle-treated group. In addition, the results also showed that the groups treated with rutin and R-Cu2 reduced significantly (p < .01), the number of neutrophils and prevented histological changes in all evaluated liver zones. R-Cu2 group maintained the ALT, AST, and ALP enzymes at normal levels. Thus, the effects of R-Cu2 in modulating inflammation and protecting liver damage were confirmed. PRACTICAL APPLICATIONS: Rutin, a plant-derived flavonoid, is one of phenolic compounds well known as a nutraceutical due to its antioxidant and anti-inflammatory properties. Findings of this study demonstrate the effects of both rutin and R-Cu2 in modulating inflammation and protecting liver damage in hypercholesterolemic rats. However, some effects analyzed became more evident in R-Cu2. Thereby, it was shown that the synthesis of a new flavonoid compound (R-Cu2) could be applied as a nutraceutical benefit option to prevent hypercholesterolemia condition., (© 2021 Wiley Periodicals LLC.)

Novel liquid supports for enzyme immobilization and reuse based on aqueous biphasic systems (ABS) constituted by cholinium-based ionic liquids (ILs) and polymers for the degradation of dyes are here proposed. The biocatalytic reaction for dye decolorization using laccase occured in the biphasic medium, with the enzyme being "supported" in the IL-rich phase and the dye and degradation products being enriched in the polymer-rich phase. An initial screening of the laccase activity in aqueous solutions of ABS constituents, namely cholinium dihydrogen citrate ([Ch][DHC]), cholinium dihydrogen phosphate ([Ch][DHP]), cholinium acetate ([Ch][Acet]), polypropylene glycol 400 (PPG 400), polyethylene glycol 400 (PEG 400) and K 2 HPO 4 was carried out. Compared to the buffered control, a relative laccase activity of up to 170%, 257%, and 530% was observed with PEG 400, [Ch][DHP], and [Ch][DHC], respectively. These ABS constituents were then investigated for the in situ enzymatic biodegradation of the Remazol Brilliant Blue R (RBBR) dye. At the optimized conditions, the ABS constituted by PPG 400 at 46 wt% and [Ch][DHC] at 16 wt% leads to the complete degradation of the RBBR dye, further maintaining the enzyme activity. This ABS also allows an easy immobilization, recovery, and reuse of the biocatalyst for six consecutive reaction cycles, achieving a degradation yield of the dye of 96% in the last cycle. In summary, if properly designed, high enzymatic activities and reaction yields are obtained with ABS as liquid supports, while simultaneously overcoming the safety and environmental concerns of conventional organic solvents used in liquid-liquid heterogeneous reactions, thus representing more sustainable biocatalytic processes., (© 2021 Wiley Periodicals LLC.)

Antigen B (EgAgB) is a phosphatidylcholine (PC)-rich lipoprotein of Echinococcus granulosus s.l. larva, potentially capable of modulating the activation of various myeloid cells, including macrophages. As C-reactive protein (CRP) can act as an innate receptor with ability to bind the phosphocholine moiety of PC in lipoproteins, we investigated whether EgAgB and CRP could interact during cystic echinococcosis infection (CE), and how CRP binding could affect the modulation activities exerted by EgAgB on macrophages. To that end, we firstly investigated the occurrence of CRP induction during human CE. We found that 61% of CE patients, but none of healthy donors, exhibited serum CRP levels higher than 10 mg/mL, suggesting that CRP can be induced during the chronic phase of CE. Furthermore, human CRP was capable of binding specifically to EgAgB with high affinity (0.6 ± 0.1 nM); this binding was Ca 2+ -dependent and involved the phosphocholine moiety of PC, but not EgAgB8/1, EgAgB8/2 or EgAgB8/3 apolipoproteins. Finally, CRP presence altered the modulation exerted by EgAgB on the cytokine response of LPS-activated macrophages. Overall, our results suggest that CRP presence during CE may contribute to a complex scenario of interactions between EgAgB and myeloid cells, influencing the cytokine response induced during macrophage activation., (© 2018 John Wiley & Sons Ltd.)

Among all plant derivates, essential oils (EOs) have gained the attention of many scientists. Diterpenes, a family of components present in some EO, are becoming a milestone in the EOs world. The goal of this review is to describe a scenario of diterpenes taking into health-consumption deportment. Previous studies revealed that diterpenes have antioxidant, antimicrobial, antiviral, antiprotozoal, cytotoxic, anticancer, antigenotoxic, antimutagenic, chemopreventive, antiinflammatory, antinociceptive, immunostimulatory, organoprotective, antidiabetic, lipid-lowering, antiallergic, antiplatelet, antithrombotic, and antitoxin activities. In conclusion, diterpenes may be an immense featuring concern in pharmaceutical consumption from a drug discovery point of view. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Cystic echinococcosis is the infection by the larvae of cestode parasites belonging to the Echinococcus granulosus sensu lato species complex. Local host responses are strikingly subdued in relation to the size and persistence of these larvae, which develop within mammalian organs as 'hydatid cysts' measuring up to tens of cm in diameter. In a context in which helminth-derived immune-suppressive, as well as Th2-inducing, molecules garner much interest, knowledge on the interactions between E. granulosus molecules and the immune system lags behind. Here, we discuss what is known and what are the open questions on E. granulosus molecules and structures interacting with the innate and adaptive immune systems, potentially or in demonstrated form. We attempt a global biological approach on molecules that have been given consideration primarily as protective (Eg95) or diagnostic antigens (antigen B, antigen 5). We integrate glycobiological information, which traverses the discussions on antigen 5, the mucin-based protective laminated layer and immunologically active preparations from protoscoleces. We also highlight some less well-known molecules that appear as promising candidates to possess immune-regulatory activities. Finally, we point out gaps in the molecular-level knowledge of this infectious agent that hinder our understanding of its immunology., (© 2015 John Wiley & Sons Ltd.)

Background: The MTHFR rs1801131A>C and rs1801133C>T variants have been analyzed as putative genetic risk factors for oral clefts within various populations worldwide., Methods: To test the role of these polymorphisms in nonsyndromic cleft lip with or without cleft palate (NSCL/P) in the Brazilian population, we conducted a study combining a Family-Based Association Test (transmission disequilibrium test) and a structured association analysis (case-control study) based on the individual ancestry proportions. The rs1801131 and rs1801133 were initially analyzed in 197 case-parent trios by transmission disequilibrium test, and polymorphisms showing significant association with NSCL/P were subsequently studied in independent sample composed of 318 isolated samples of NSCL/P and 598 healthy controls in a case-control approach. Genomic ancestry was characterized by a set of 40 biallelic short insertion/deletion markers., Results: A strong overtransmission of the T allele of rs1801133 was observed in case-parent trios of NSCL/P (p = 0.002), but no preferential parent-of-origin transmission was detected. No association of rs1801131 polymorphism with NSCL/P was observed. The structured case-control analysis supported that the T allele was significantly more frequent in the NSCL/P group (odds ratio: 1.37; 95% CI: 1.12-1.69; p = 0.002) than in the control group. Both polymorphisms were in linkage disequilibrium (D' = 0.94 and r(2)  = 0.79), and haplotype-transmission disequilibrium test for allelic combination of rs1801131 and rs1801133 showed a significant overtransmission of haplotype A-T to the affected NSCL/P offspring (p = 0.001)., Conclusion: Our findings provide evidences for the involvement of rs1801133 in the development of NSCL/P in the Brazilian population., (© 2015 Wiley Periodicals, Inc.)

Purpose: Acute pain occurs in over 50% of hospitalized children. The accuracy of this diagnosis has been underexplored in the literature, as has the role of training to implement pain assessment. This study analyzed the accuracy of acute pain diagnoses after the implementation of a systematic evaluation of pain (study intervention)., Method: The sample was divided into: pre- and postintervention. The Nursing Diagnosis Accuracy Scale, which scores accuracy as null, low, moderate, or high, was used., Results: In the postimplementation, acute pain was diagnosed more often. However, accuracy only improved in the moderate category., Conclusion: Diagnosis of acute pain increased in the postimplementation period, but accuracy did not., Implications: The development of strategies for improvement of diagnostic accuracy is warranted., (© 2012, The Authors International Journal of Nursing Knowledge © 2012, NANDA International.)

Objective: To evaluate the effect of bupivacaine on muscle force and histology. We hypothesize that bupivacaine will worsen the muscle's physiological activity., Setting: Controlled laboratory experiment., Methods: Bupivacaine (0.5 mL, 0.5%) was injected into the mid belly and distal portions of the right gastrocnemius in 32 Wistar male rats (the left gastrocnemius was used as a control). After 5, 14, 21, and 28 days, in groups of 4, muscle force was evaluated and the animals were euthanized by an overdose of anesthetic for histologic evaluation. One-way analysis of variance was used to analyze data from force and weight measurements. Only the values of P < .05 were considered to be statistically significant., Results: Bupivacaine causes a process of degeneration-regeneration of the muscle fibers and it also causes a reduction in muscle force, which is significant at 2 and 3 weeks and does not normalize at 4 weeks. The muscle injury is obvious after 5 days, and the degenerative process is predominant at 2 and 3 weeks. We found an increase in muscle mass in the acute phase and a decrease in muscle force., Conclusion: Although our results do not allow a direct clinical application, we believe that caution should be warranted when intramuscular bupivacaine is used., (Copyright © 2011 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.)

The larva of the cestode Echinococcus granulosus (hydatid cyst) is protected by the acellular laminated layer (LL). The mechanisms that make this thick coat a poor activator of host complement are incompletely understood. The structure binds, through unknown motifs, the host regulator of the alternative complement pathway (ACP), factor H. A second potential mechanism of ACP regulation, the inhibition of factor B activation, was detected in assays employing purified components (Immunopharmacology 42 : 91). The inhibitor was subsequently identified as myo-inositol hexakisphosphate (InsP(6)), which in the form of nano-deposits is a major component of the LL (Biochem J 362 : 297; J Cell Biochem 93 : 1272; FEBS J 273 : 3192). In this report we show that colloidal InsP(6 )solids inhibit factor B activation, through adsorption and associated impairment of C3b binding. However, this interaction is not relevant in the presence of serum proteins. In serum, InsP(6) deposits instead bind C1q, and initiate complement activation. This activation is curtailed through efficient C3b inactivation, previously shown to be entirely factor H-dependent, and now observed to be independent of the InsP(6) deposits. Therefore the complement resistance of the LL must be based on functional factor H binding sites present on the mucin-based meshwork that is its other major constituent.

Objective: To compare uterine artery pulsatility index (PI) and flow velocity wave (FVW) patterns between women with no history of abortion and women with recurrent pregnancy loss of unexplained cause., Method: A cross-sectional study was conducted with 43 women with recurrent pregnancy loss and 43 women with no history of abortion and at least 1 child born at term (control group). Transvaginal ultrasonography with uterine artery Doppler evaluation was performed in the second phase of the menstrual cycle to calculate the PI and analyze the FVW pattern., Results: The women with recurrent pregnancy loss had a significantly higher uterine artery PI than those in the control group (2.71+/-0.54 and 2.30+/-0.44, respectively), as well as a higher incidence of FVWs of the A and B types., Conclusion: Compared with the control group, a higher PI and a higher incidence of FVW of the A and B types--and thus a higher uterine artery impedance--were found among women with recurrent pregnancy loss.

Eosinophils are locally recruited during the establishment and chronic phases of cystic hydatidosis. This study provides evidence that eosinophil cationic protein (ECP), one of the major components of eosinophil granules, can damage Echinococcus granulosus protoscoleces (PSC). The toxicity of ECP was investigated in vitro by following parasite viability in the presence of this protein. ECP was found to damage PSC at micromolar concentrations; the effect was blocked by specific antibodies and heparin, and was more severe than the one caused by similar concentrations of RNase A, suggesting that the cationic nature of ECP, and not its ribonuclease activity, is involved in toxicity. This observation may highlight the capacity of eosinophils to control secondary hydatidosis, derived from PSC leakage from a primary cyst. To further assess the relevance of the previous result during infection, the presence of eosinophil proteins was investigated in human hydatid cysts. ECP was found to be strongly associated with the laminated layer of the cyst wall, and present at micromolar concentrations in the hydatid fluid. Overall, these results demonstrate that eosinophils degranulate in vivo at the host-parasite interface, and that the released ECP reaches concentrations that could be harmful for the parasite.

Calculations of molecular polarizabilities require basis sets capable of accurately describing the responses of the electrons to an external perturbation. Unfortunately, basis sets that yield suitable quantitative results have traditionally been all-electron sets with large numbers of primitives, making their use computationally intractable even for moderately sized systems. We present a systematic augmentation of the effective core potential basis set of Stevens et al. [J Chem Phys 81, 12 (1984), Can J Chem 70, 612 (1992)] for 39 main group elements based on the procedure used to construct diffuse and polarization functions in the well-known Sadlej basis sets [Collec Czech Chem Comm 53, 1995 (1988)]. Representative calculations have been performed and we have shown that results to within 1% of all-electron calculations using the Sadlej basis set can be obtained for <1-35% of the computational cost using this new basis set.

The larval stage of the parasite Echinococcus granulosus causes hydatid disease. The hydatid cyst is potentially capable of activating host complement, since it is a large, persistent, carbohydrate-rich structure, coated with host immunoglobulins, and localized in the host's internal organs. Nonetheless, in vitro studies have suggested that the cyst surface, the hydatid cyst wall (HCW), is a poor complement activator. In this study, we assessed the occurrence of in vivo complement activation on the hydatid cyst by measuring the levels of two complement activation products, C3d and complexes bearing a C9 activation neoepitope (TCC/MAC), in extracts from HCW of human origin. Low amounts of C3d and TCC/MAC were found in HCW in comparison with their levels in normal human plasma and activated human sera, suggesting that in vivo complement activation on HCW is efficiently down-regulated. This regulation may contribute to limit host inflammation which has been observed to correlate with parasite degeneration and death.

The aim of this work was to investigate the contribution of complement C5-mediated mechanisms, with an emphasis on inflammation, to host defences against Echinococcus granulosus hydatid disease. Thus, we compared the systemic and local inflammatory responses induced by the parasite, and the outcome of infection, between congenic C5-sufficient (B10.D2 n/SnJ) and C5-deficient (B10.D2 o/SnJ) mice challenged with protoscoleces. Indirect evidence of in-vivo complement activation during the establishment phase was obtained; infection induced serum amyloid P and eosinophil responses which were dependent on C5. Early recruitment of polymorphonuclear cells was not dependent on the presence of C5. The higher capacity of C5-sufficient mice to recruit eosinophils was also observed during the cystic phase of infection, and mice recruiting more eosinophils developed lower parasite masses. Analysis of the outcome of infection after 8 months showed that C5-sufficient mice were more resistant to infection than C5-deficient mice in terms of individuals with no cysts; this trend was not statistically significant. In addition, C5-deficient mice developed higher numbers of large (> 5 mm in diameter) cysts and higher cyst weights than C5-sufficient mice indicating that C5-mediated mechanisms are detrimental for parasite growth. Taken together, our results suggest that complement, through C5-mediated effectors, contributes to host defences by both restricting the establishment of infection and controlling the growth of established cysts. This contribution may, at least partially, be associated with the ability of C5a to promote eosinophil infiltration.

In the present study we have investigated and compared in vitro the specific complement (C) activating activity of three metacestode preparations of Echinococcus granulosus. Extracts from hydatid cyst fluid (HCF-ext), protoscoleces (PSC-ext) and hydatid cyst membrane (HCM-ext) activated human C producing C3 conversion and generating the C5b6 complex and the terminal C complex (TCC). HCM-ext showed much lower C activating activity than PSC-ext and HCF-ext. Moreover, its ability to generate C5b6 and TCC was lower than its ability to convert C3. On the other hand, PSC-ext and HCF-ext proved to be good C activators when their specific C activating activities were compared with that of inulin. However, PSC-ext produced lower levels of TCC than those produced by HCF-ext, in spite of the fact that both produced practically the same levels of C3d and C5b6. These results may be consistent with the existence of several mechanisms of C modulation involved in the defence of the parasite against host C damage.

In the present study we have investigated the fluid phase activation of the complement (C) alternative pathway by Echinococcus granulosus sheep hydatid cyst fluid (SHCF) and its higher molecular weight fraction (SHCF-I) by quantitating the formation of both the terminal C intermediary C5b6 complex and the terminal C complex (TCC). Our results show that in vitro C activation progresses beyond the C5 step suggesting that potentially lytic complexes may be generated in vivo. In addition, SHCF and SHCF-I glucidic moieties are probably involved in C activation since 80% and 86% of SHCF and SHCF-I activity respectively was destroyed by periodate oxidation. Furthermore, partial deglycosylation with Peptide N-Glycosidase F of SHCF-I which had been digested with Pronase E, released an active fraction (MW < 14 KDa) which bound to Soybean agglutinin, suggesting that N-linked oligosaccharides containing alpha- or beta-linked N-acetyl galactosamine play a role in C activation by SHCF.