The exported protein PbCP1 localises to cleft-like structures in the rodent malaria parasite Plasmodium berghei

Protein export into the host red blood cell is one of the key processes in the pathobiology of the malaria parasite Plasmodiumtrl falciparum, which extensively remodels the red blood cell to ensure its virulence and survival. In this study, we aimed to shed further light on the protein export mechanisms in the rodent malaria parasite P. berghei and provide further proof of the conserved nature of host cell remodeling in Plasmodium spp. Based on the presence of an export motif (R/KxLxE/Q/D) termed PEXEL (Plasmodium export element), we have generated transgenic P. berghei parasite lines expressing GFP chimera of putatively exported proteins and analysed one of the newly identified exported proteins in detail. This essential protein, termed PbCP1 (P. berghei Cleft-like Protein 1), harbours an atypical PEXEL motif (RxLxY) and is further characterised by two predicted transmembrane domains (2TMD) in the C-terminal end of the protein. We have functionally validated the unusual PEXEL motif in PbCP1 and analysed the role of the 2TMD region, which is required to recruit PbCP1 to discrete membranous structures in the red blood cell cytosol that have a convoluted, vesico-tubular morphology by electron microscopy. Importantly, this study reveals that rodent malaria species also induce modifications to their host red blood cell

Nabiximols effect on blood pressure and heart rate in post-stroke patients of a randomized controlled study

Background: Cannabinoids may be useful to treat pain, epilepsy and spasticity, although they may bear an increased risk of cardiovascular events. This study aims to evaluate the cardiovascular safety of nabiximols, a cannabis-based drug, in patients with spasticity following stroke, thus presenting an increased cardiovascular risk. Methods: This is an ancillary study stemming from the SativexStroke trial: a randomized double-blind, placebo-controlled, crossover study aimed at assessing the effect of nabiximols on post-stroke spasticity. Patients were treated with nabiximols oromucosal spray or placebo and assessed before and after two phases of 1-month duration each. Only the phase with the active treatment was considered for each patient who completed the study. The average values of blood pressure (diastolic, systolic, differential) and heart rate from the first 5 days of the phase (lowest nabiximols dosage) were compared to the average values recorded during the last 5 days at the end of the phase (highest nabiximols dosage). Baseline comparisons between gender, stroke type and affected side and correlation between age and blood pressure and heart rate were performed. The study was registered with the EudraCT number 2016-001034-10. Results: Thirty-four patients completed the study and were included in the analysis. Thirty-one were taking antihypertensive drugs and, among these, 12 were taking beta-blockers. During the study, no arrhythmic events were recorded, blood pressure and heart rate did not show pathological fluctuations, and no cardiovascular or cerebrovascular events occurred. At baseline blood pressure and heart rate were comparable concerning gender, stroke type and affected side. A significant direct correlation emerged between differential blood pressure and age and an inverse correlation between diastolic blood pressure and age. No correlation emerged between systolic blood pressure or heart rate and age. Blood pressure and heart rate did not change during nabiximols treatment compared to the baseline condition. Conclusion: This ancillary study adds evidence that, in patients who already underwent a cerebrovascular accident, nabiximols does not determine significant blood pressure and heart rate variation or cardiovascular complications. These data support the cardiovascular safety of nabiximols, encouraging more extensive studies involving cannabinoids characterized by slow absorption rates

Habituation of somatosensory evoked potentials in patients with alzheimer’s disease and those with vascular dementia

Background and Objectives: The most prevalent dementia are Alzheimer’s disease and vascular dementia. There is evidence that cortical synaptic function may differ in these two conditions. Habituation of cortical responses to repeated stimuli is a well-preserved phenomenon in a normal brain cortex, related to an underlying mechanism of synaptic efficacy regulation. Lack of habituation represents a marker of synaptic dysfunction. The purpose of this study was to assess the habituation of somatosensory evoked potentials (SEPs) in 29 patients affected by mild-to-moderate Alzheimer’s disease (AD-type) or vascular (VD-type) dementia. Materials and Methods: All patients underwent a clinical history interview, neuropsychological evaluation, and neuroimaging examination. SEPs were elicited by electrical stimulation of the right median nerve at the wrist. Six-hundred stimuli were delivered, and cortical responses divided in three blocks of 200. Habituation was calculated by measuring changes of N20 amplitude from block 1 to block 3. SEP variables recorded in patients were compared with those recorded in 15 age-and gender-matched healthy volunteers. Results: SEP recordings showed similar N20 amplitudes in AD-type and VD-type patients in block 1, that were higher than those recorded in controls. N20 amplitude decreased from block 1 to block 3 (habituation) in normal subjects and in VD-type patients, whereas in AD-type patients it remained unchanged (lack of habituation). Conclusions: The findings suggest that neurophysiologic mechanisms of synaptic efficacy that underneath habituation are impaired in patients with AD-type dementia but not in patients with VD-type dementia. SEPs habituation may contribute to early distinction of Alzheimer’s disease vs. vascular dementia

The effect of verbal encouragement on performance and muscle fatigue in swimming

Background and Objectives: Verbal encouragement (VE) can be used to enhance performance in several sports, even though no studies have been conducted among swimmers and only a few effects have been reported in elite athletes. Besides influencing motor performance, VE is also known to enhance the physical load, thus potentially increasing the probability of developing fatigue. With this in mind, this study aimed to explore the effects of VE in swimmers in order to fill in the knowledge gap concerning the aquatic environment. Materials and Methods: Each athlete swam a maximal 200 m freestyle trial under two different conditions: one trial with VE and the other without VE. The two main outcome measures were: (1) performance velocity (m/s); and (2) muscle fatigue, investigated by means of surface electromyography. Sixty swimmers were recruited, aged 18.63 ± 3.46 years (median 18 years), 28 men (47%), and 32 women (53%), with 7.03 ± 3.9 years of experience. Results: With VE, performance significantly improved in the swim trial (p < 0.001, effect size (ES) −0.95, large). When breaking the results down into the first half (first (0–100 m) vs. the second half (100–200 m)), the ES was large in the first part (−1.11), indicating an improvement in performance. This worsened, however, in the second part of the trial (ES 0.63). In the multivariate analysis, years of experience were found to be a significant predictor of the change in overall performance (p = 0.011). There was a significant increase in muscle fatigue induced by VE, overall, and during the second half, but not during the first half of the trial. Conclusions: The present study indicates that VE during a middle-distance event (200 m) increases performance most in swimmers with little experience. However, it has a negative impact on fatigue

Not all forms of muscle hypertonia worsen with fatigue. A pilot study in para swimmers

In hypertonic muscles of patients with upper motor neuron syndrome (UMNS), investigation with surface electromyography (EMG) with the muscle in a shortened position and during passive muscle stretch allows to identify two patterns underlying hypertonia: spasticity and spastic dystonia. We recently observed in Para swimmers that the effect of fatigue on hypertonia can be different from subject to subject. Our goal was, therefore, to understand whether this divergent behavior may depend on the specific EMG pattern underlying hypertonia. We investigated eight UMNS Para swimmers (five men, mean age 23.25 ± 3.28 years), affected by cerebral palsy, who presented muscle hypertonia of knee flexors and extensors. Muscle tone was rated using the Modified Ashworth Scale (MAS). EMG patterns were investigated in rectus femoris (RF) and biceps femoris (BF) before and after two fatiguing motor tasks of increasing intensity. Before the fatiguing tasks, two subjects (#2 and 7) had spasticity and one subject (#5) had spastic dystonia in both RF and BF. Two subjects (#3 and 4) showed spasticity in RF and spastic dystonia in BF, whereas one subject (#1) had spasticity in RF and no EMG activity in BF. The remaining two subjects (#6 and 8) had spastic dystonia in RF and no EMG activity in BF. In all the 16 examined muscles, these EMG patterns persisted after the fatiguing tasks. Spastic dystonia increased (p < 0.05), while spasticity did not change (p > 0.05). MAS scores increased only in the muscles affected by spastic dystonia. Among the phenomena possibly underlying hypertonia, only spastic dystonia is fatigue-dependent. Technical staff and medical classifiers should be aware of this specificity, because, in athletes with spastic dystonia, intense and prolonged motor activity could negatively affect competitive performance, creating a situation of unfairness among Para athletes belonging to the same sports class

Medication-related osteonecrosis of the jaw. Introduction of a new modified experimental model

ABSTRACT PURPOSE : To evaluate a modified experimental model for medication-related osteonecrosis of the jaw (MRONJ) through the upper right central incisor extraction followed by intravenous bisphosphonate administration. METHODS: Forty five rats underwent the upper right central incisor tooth extraction were divided in 2 groups: Group I - experimental group, 30 rats received an intravenous administration protocol of zoledronic acid 35μg/kg into the tail vein every two weeks, totalizing four administrations, during eight weeks of administration, previously the extraction, and Group II - control group, 15 rats didn't received any medication before extraction. The groups were subdivided in postoperative periods: 14/28/42 days. Clinical analysis and microtomography were performed to verify the presence of osteonecrosis. In addition, descritive histological analysis of hematoxylin-eosin stained sections was performed to evaluate the presence of osteonecrosis or necrotic foci. RESULTS: Twelve (40%) rats, from experimental group, showed clinical signs of MRONJ (p=0.005), however, all samples showed imaginologic findings like osteolysis and loss of integrity of the cellular walls (p≤0.001). Microscopic evaluation revealed osteonecrosis areas with microbial colonies and inflammatory infiltrate (p≤0.001). In the control group, all animals presented the chronology of a normal wound healing. CONCLUSIONS: The presence of medication-related osteonecrosis of the jaw after maxillary central incisor extraction in rats. This new experimental model may be considered an option for the study of MRONJ

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background: Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods: The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results: A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion: Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)

Anti-inflammatory and healing action of oral gel containing borneol monoterpene in chemotherapy-induced mucositis in rats ( Rattus norvegicus )

ABSTRACT The aim of this study was to investigate the effect of gels containing the monoterpene borneol in induced oral mucositis using an animal model. Gels were prepared with borneol at 1.2% and 2.4% (w/w). Oral mucositis was induced by administration of three doses of 5-fluorouracil (30 mg/kg, i.p.) and injury with acetic acid (50%, v/v) soaked in filter paper applied to right cheek mucosa for 60s. Four subgroups comprising 12 animals each were formed. Six animals from each group were sacrificed at days seven and fourteen after oral mucositis induction. Mucous samples were processed and stained with hematoxylin-eosin and Masson’s Trichrome. The semiquantitative evaluation involved observation of inflammatory parameters. ImageJ® software was used in the quantitative evaluation. For statistical analyses, Two-way ANOVA, followed by Tukey’s post-test (p <0.05), were employed. Borneol 2.4% gel proved effective in the treatment of oral mucositis with statistically significant differences between groups for angiogenesis control, inflammatory cell count reduction and percentage neoformed collagen increase. The confirmation of anti-inflammatory and healing action of borneol in oral mucositis in rats renders it a good marker for predicting this activity for plant extracts rich in this substance

BIM oriented applications of structural health monitoring based on magnified digital image correlation point-clouds

Three-dimensional Digital Image Correlation (3D-DIC) gained popularity as a line-of-sight, high-resolution Structural Health Monitoring (SHM) technique. Nonetheless, 3D-DIC is still impractical when the natural frequencies and the mode shapes of the structure have to be correlated. Recently, the integration of Motion Magnification (MM) as a pre-processing tool for 3D-DIC has been explored to enhance the capabilities of DIC for structural analysis and defined a Magnified DIC (M-DIC) workflow. However, such applications do not take full advantage of the potential of the 3D-DIC to produce point-clouds informed of the dynamic properties of a structure. Hence, the definition of a straightforward workflow to manage 3D-DIC point-clouds for real-world applications should be addressed. Moreover, the large amount of raw output coming from MM and 3D-DIC combination requires appropriate tools to systematically visualise and analyse the data. In this context, Building Information Modelling (BIM) has emerged as a robust repository as well as a data management tool to store and exchange data related to the built environment, including long sequences of SHM data. This research proposes a novel Cloud to Model (C2M) tool called M-DIC2BIM that translates the Scalar Fields (SFs) of the M-DIC point-cloud directly into the faces of the BIM model instances. As a case study, a three-storey aluminium frame structure excited with broadband noise is used to validate the developed methodology. The comparison among undamaged and damaged configurations tests made the evolution of the frame's Operational Deflection Shapes (ODSs) computable by quantifying structural changes in its global and local behaviour and mapping them onto the BIM instances

Task-free functional MRI in cervical dystonia reveals multi-network changes that partially normalize with botulinum toxin

Contains fulltext : 115429.pdf (publisher's version ) (Open Access)Cervical dystonia is characterized by involuntary, abnormal movements and postures of the head and neck. Current views on its pathophysiology, such as faulty sensorimotor integration and impaired motor planning, are largely based on studies of focal hand dystonia. Using resting state fMRI, we explored whether cervical dystonia patients have altered functional brain connectivity compared to healthy controls, by investigating 10 resting state networks. Scans were repeated immediately before and some weeks after botulinum toxin injections to see whether connectivity abnormalities were restored. We here show that cervical dystonia patients have reduced connectivity in selected regions of the prefrontal cortex, premotor cortex and superior parietal lobule within a distributed network that comprises the premotor cortex, supplementary motor area, primary sensorimotor cortex, and secondary somatosensory cortex (sensorimotor network). With regard to a network originating from the occipital cortex (primary visual network), selected regions in the prefrontal and premotor cortex, superior parietal lobule, and middle temporal gyrus areas have reduced connectivity. In selected regions of the prefrontal, premotor, primary motor and early visual cortex increased connectivity was found within a network that comprises the prefrontal cortex including the anterior cingulate cortex and parietal cortex (executive control network). Botulinum toxin treatment resulted in a partial restoration of connectivity abnormalities in the sensorimotor and primary visual network. These findings demonstrate the involvement of multiple neural networks in cervical dystonia. The reduced connectivity within the sensorimotor and primary visual networks may provide the neural substrate to expect defective motor planning and disturbed spatial cognition. Increased connectivity within the executive control network suggests excessive attentional control and while this may be a primary trait, perhaps contributing to abnormal motor control, this may alternatively serve a compensatory function in order to reduce the consequences of the motor planning defect inflicted by the other network abnormalities