Dyssynchronous Left Ventricular Activation is Insufficient for the Breakdown of Wringing Rotation

Cardiac resynchronization therapy is a valuable tool to restore left ventricular function in patients experiencing dyssynchronous ventricular activation. However, the non-responder rate is still as high as 40%. Recent studies suggest that left ventricular torsion or specifically the lack thereof might be a good predictor for the response of cardiac resynchronization therapy. Since left ventricular torsion is governed by the muscle fiber orientation and the heterogeneous electromechanical activation of the myocardium, understanding the relation between these components and the ability to measure them is vital. To analyze if locally altered electromechanical activation in heart failure patients affects left ventricular torsion, we conducted a simulation study on 27 personalized left ventricular models. Electroanatomical maps and late gadolinium enhanced magnetic resonance imaging data informed our in-silico model cohort. The angle of rotation was evaluated in every material point of the model and averaged values were used to classify the rotation as clockwise or counterclockwise in each segment and sector of the left ventricle. 88% of the patient models (n = 24) were classified as a wringing rotation and 12% (n = 3) as a rigid-body-type rotation. Comparison to classification based on in vivo rotational NOGA XP maps showed no correlation. Thus, isolated changes of the electromechanical activation sequence in the left ventricle are not sufficient to reproduce the rotation pattern changes observed in vivo and suggest that further patho-mechanisms are involved

TRSP is dispensable for the Plasmodium pre-erythrocytic phase

Plasmodium sporozoites deposited in the skin following a mosquito bite must migrate and invade blood vessels to complete their development in the liver. Once in the bloodstream, sporozoites arrest in the liver sinusoids, but the molecular determinants that mediate this specific homing are not yet genetically defined. Here we investigate the involvement of the thrombospondin-related sporozoite protein (TRSP) in this process using knockout Plasmodium berghei parasites and in vivo bioluminescence imaging in mice. Resorting to a homing assay, trsp knockout sporozoites were found to arrest in the liver similar to control parasites. Moreover, we found no defects in the establishment of infection in mice following inoculation of trsp knockout sporozoites via intravenous and cutaneous injection or mosquito bite. Accordingly, mutant sporozoites were also able to successfully invade hepatocytes in vitro. Altogether, these results suggest TRSP may have a redundant role in the completion of the pre-erythrocytic phase of the malaria parasite. Nonetheless, identifying molecules with paramount roles in this phase could aid in the search for new antigens needed for the design of a protective vaccine against malaria.We would like to thank: Prof. Anabela Cordeiro da Silva from the IBMC/i3S for the exceptional hosting conditions; Dr. Ana Xavier Carvalho from the IBMC/i3S for the critical reading of the manuscript; the team of the CEPIA from Institut Pasteur, Paris, for providing the Anopheles stephensi female mosquitos. The following reagents were obtained through BEI Resources, NIAID, NIH: (a) Plasmid pL0001, for Transfection in Plasmodium berghei, MRA-770, contributed by Andrew P. Waters; (b) Hybridoma 3D11 Anti-Plasmodium berghei 44-Kilodalton Sporozoite Surface Protein (Pb44), MRA-100, contributed by Victor Nussenzweig. This work was supported by funds from project Norte-01-0145-FEDER-000012 - Structured program on bioengineered therapies for infectious diseases and tissue regeneration, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through FEDER. This work also received funds from the Fundação para a Ciência e Tecnologia (FCT)/Ministério da Educação e Ciência (MEC) co-funded by FEDER (EXPL/JTAVARES-IF/00881/2012/CP0158/CT0005,EXPL/IMI-MIC/1331/ 2013) under the Partnership agreement PT2020, through the Research Unit No. 4293. J.T. is an Investigator FCT funded by National funds through FCT and co-funded through European Social Fund within the Human Potential Operating Programme. D.M.C., M.S. and A.R.T. are funded by FCT individual fellowships SFRH/ BD/123734/2016, SFRH/BD/133485/2017 and SFRH/BD/133276/2017 respectively). The authors acknowledge the support of the BioSciences Screening i3S Scientific Platform, member of the PPBI (PPBI-POCI-01-0145-FEDER-022122)

Percepção Social da Indisciplina

Este trabalho aborda a percepção social dos professores sobre a indisciplina na escola, pensada como uma questão atrelada aos estudos sobre o pensamento dos professores. Inicialmente abordamos o conceito de indisciplina, partindo de uma leitura etimológica do termo disciplina e recorremos às concepções propostas por alguns teóricos desse assunto. Em seguida, exploramos algumas perspectivas teóricas sobre a percepção da indisciplina escolar, pensada como um processo de construção social que fala sobre a formação de professores. Ao final, articulamos questões sobre a percepção da indisciplina, a cultura escolar e a formação de professores, em que propomos repensar a formação dos professores em relação à indisciplina, articulada com a tarefa de reinventar a escola

UV cross-linked polyvinylpyrrolidone electrospun fibres as antibacterial surfaces

Many bacteria become progressively more resistant to antibiotics and it remains a challenging task to control their overall levels. Polymers combined with active biomolecules come to the forefront for the design of antibacterial materials that can address this encounter. In this work, we investigated the photo-crosslinking approach of UV-sensitive benzophenone molecule (BP) with polyvinylpyrrolidone (PVP) polymer within electrospun fibres. The BP and PVP solutions allowed fabricating polymer mats that were subsequently functionalised with antibacterial lysozyme. The physical properties of the crosslinked electrospun fibres were investigated by scanning electron microscopy and atomic force microscopy. The average diameter of the obtained fibres decreased from 290 ± 50 nm to 270 ± 70 nm upon the addition of the crosslinking molecules and then to 240 ± 80 nm and 180 ± 90 nm after subsequent crosslinking reaction at an increasing time: 3 and 5 h, respectively. The peak force quantitative nanomechanical mapping (PF-QNM) indicated the increase of DMT modulus of obtained cross-linked fibres from 4.1 ± 0.8 GPa to 7.2 ± 0.5 GPa. Furthermore, the successful crosslinking reaction of PVP and BP solution into hydrogels was investigated in terms of examining photo-crosslinking mechanism and was confirmed by rheology, Raman, Fourier transform infrared and nuclear magnetic resonance. Finally, lysozyme was successfully encapsulated within cross-linked PVP-BP hydrogels and these were successfully electrospun into mats which were found to be as effective antibacterial agents as pure lysozyme molecules. The dissolution rate of photo cross-linked PVP mats was observed to increase in comparison to pure PVP electrospun mats which opened a potential route for their use as antibacterial, on-demand, dissolvable coatings for various biomedical applications

The usefulness of His bundle pacing in a heterogeneous population of patients with impaired left ventricular systolic function

Background: His bundle pacing (HBP) maintains a physiological activation pattern of ventricular activation, and in patients with intraventricular conduction delay (IVCD) it can normalize wide QRS duration. Methods: A total of 181 patients from the HBP registry were enrolled into a the study, which was conducted at the Department of Electrocardiology in Katowice, Poland. The patients had left ventricular ejection fraction (LVEF) < 50% and were implanted between November 2015 and April 2019. The HBP indications were as follows: 1) bradycardia and atrioventricular conduction disturbances with expected high pacing burden, 2) IVCD, LVEF ≤ 35%, with an indication for resynchronization therapy, 3) the need to upgrade to resynchronization therapy due to pacing-induced cardiomyopathy. Pacing parameters and echocardiographic and clinical data were assessed for up to 2 years of follow-up (FU). Results: His bundle pacing was successful in 154 (85.1%) patients. Eighty-two patients completed a 6-month FU. The mean age was 70.6 ± 9.23 years, and 79% were males. At 6 months FU LVEF improved from 35.3 ± 8.22% to 43.1 ± 10.14% (p < 0.0001), and indexed left ventricular end-systolic volume (LVESVi) decreased from 63.1 ± 25.21 mL/m2 to 51.9 ± 22.79 mL/m2 (p < 0.0001). In 53.1%, the LVESVi reduction was greater than 15%. The improvement in LVEF and LVESVi was also observed after 24 months of FU. Conclusions: His bundle pacing in permanently paced patients when LVEF is reduced below 50% is associated with improvement in LVEF and reverse left ventricle remodeling

Electrical Conductivity and Morphology Study of Polyaniline Powder Synthesised with Various Doping Ions

Powdered polyaniline (PANI) was synthesised chemically with different doping anions namely hydrochloric acid, sulphuric acid and para-toluenesulfonic acid (pTSA). Two-step synthetic procedure was utilised at low temperature. The highest reaction efficiency was found for chlorine-doped PANI. Structural characterization with FTIR revealed the vibration bands characteristicto formation of the emeraldine salt. The surface morphology of doped PANIs was studied by SEM images which showed near globular shape and porous structures with different size of the aggregated particles. They were smaller for Cl-- or pTS--doped PANI while for SO4 2- the size was markedly larger. The XRD patterns revealed that there are ordered regions especially for pTS- doped PANI, while the highest conductivity value was recorded for Cl- doped one followed by organic pTS- doped and SO4 2- doped one