Timing Matters: Ultra-Early and Early versus Late Thromboprophyaxis Following Spontaneous Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis.

Spontaneous intracerebral hemorrhage (ICH) represents a critical and potentially devastating medical event resulting from the rupture of intracerebral vessels. Patients afflicted with ICH face an increased risk of venous thromboembolism (VTE) due to factors such as immobility. However, determining the ideal timing for initiating venous thromboembolism thromboprophylaxis (TP) remains uncertain, as it may carry the potential risk of exacerbating hematoma expansion. Thus, our objective was to ascertain the optimal timing for initiating TP following ICH through a comprehensive systematic review and meta-analysis.This systematic review and meta-analysis were performed following the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines, considering outcomes based on the time of intervention: Ultra early (UEPT) < 24 h, Early (EPT) < 48 h, Late (LPT) > 48 h to perform an analysis on hematoma expansion and mortality.Of 2.777 Hematoma expansion was not more frequent in the 440 patients receiving UEPT/EPT (n = 440) versus 565 receiving LPT (Odds ratio (OR) 0.94 (95% CI; 0.62 to 1.43; I2 = 0%)). Similarly, mortality was not lower in the 293 received UEPT or EPT versus 477 receiving LPT (OR 0.63 (95% CI; 0.39 to 1.0; I2 = 0%).This study, through a systematic review and meta-analysis, conclusively found no difference in intracranial hematoma expansion and/or increased mortality between the use of heparin in the early thromboprophylaxis (< 48 h) group compared to the late thromboprophylaxis (> 48 h) group. Implementing this approach in the management of spontaneous cerebral hemorrhage could facilitate progress towards more optimal care protocols.

Immunogens in Balamuthia mandrillaris: a proteomic exploration.

Balamuthia mandrillaris is the causative agent of granulomatous amoebic encephalitis, a rare and often fatal infection affecting the central nervous system. The amoeba is isolated from diverse environmental sources and can cause severe infections in both immunocompromised and immunocompetent individuals. Given the limited understanding of B. mandrillaris, our research aimed to explore its protein profile, identifying potential immunogens crucial for early granulomatous amoebic encephalitis diagnosis. Cultures of B. mandrillaris and other amoebas were grown under axenic conditions, and total amoebic extracts were obtained. Proteomic analyses, including two-dimensional electrophoresis and mass spectrometry, were performed. A 50-kDa band showed a robust recognition of antibodies from immunized BALB/c mice; peptides contained in this band were matched with elongation factor-1 alpha, which emerged as a putative key immunogen. Besides, lectin blotting revealed the presence of glycoproteins in B. mandrillaris, and confocal microscopy demonstrated the focal distribution of the 50-kDa band throughout trophozoites. Cumulatively, these observations suggest the participation of the 50-kDa band in adhesion and recognition mechanisms. Thus, these collective findings demonstrate some protein characteristics of B. mandrillaris, opening avenues for understanding its pathogenicity and developing diagnostic and therapeutic strategies.

How to perform an anastomosis following a low anterior resection by transanal total mesorectal excision surgery: from top to bottom techniques.

AIM: The aim was to describe the range of possibilities and our group's clinical outcomes when performing different types of anastomosis during transanal total mesorectal excision (taTME). METHOD: A retrospective analysis was performed based on four taTME series from 2016 to 2021. Inclusion criteria were patients with rectal cancer in whom a sphincter-saving low anterior resection by taTME was performed. Four different techniques were employed for the anastomosis construction: (A) abdominal view, (B) transanal view, (C) hand-sewn coloanal anastomosis and (D) pull-through. Intra-operative and postoperative data were collected and compared. RESULTS: A total of 161 patients were included. Tumour height was lower in groups C and D (4 [3-5] vs. 7 [6-8] group A vs. 6 [5-7] group B, P = 0.000), requiring a hand-sewn anastomosis. A transanal extraction of the specimen was more commonly performed in groups C and D (over 60% vs. 30% in groups A and B, P = 0.000). The rate of temporary stoma was similar between groups A, B and C (ranging from 84% to 98%) but was significantly lower in group D (P = 0.000). The overall rate of complications was similar between groups; however, group D had longer length of stay (15 days vs. 5-6 in groups A, B and C, P = 0.026). CONCLUSION: Every type of anastomosis construction after a taTME procedure seems to be safe and feasible and should be chosen based on surgeon's experience, tumour height and the length of the rectal cuff after the rectal transection. Colorectal surgeons should be familiar with these techniques in order to choose the one that benefits each patient the most.

UAV-Based Smart Educational Mechatronics System Using a MoCap Laboratory and Hardware-in-the-Loop.

Within Industry 4.0, drones appear as intelligent devices that have brought a new range of innovative applications to the industrial sector. The required knowledge and skills to manage and appropriate these technological devices are not being developed in most universities. This paper presents an unmanned aerial vehicle (UAV)-based smart educational mechatronics system that makes use of a motion capture (MoCap) laboratory and hardware-in-the-loop (HIL) to teach UAV knowledge and skills, within the Educational Mechatronics Conceptual Framework (EMCF). The macro-process learning construction of the EMCF includes concrete, graphic, and abstract levels. The system comprises a DJI Phantom 4, a MoCap laboratory giving the drone location, a Simulink drone model, and an embedded system for performing the HIL simulation. The smart educational mechatronics system strengthens the assimilation of the UAV waypoint navigation concept and the capacity for drone flight since it permits the validation of the physical drone model and testing of the trajectory tracking control. Moreover, it opens up a new range of possibilities in terms of knowledge construction through best practices, activities, and tasks, enriching the university courses.

Exogenous activation and inhibition of plasminogen/plasmin activity during in vitro maturation of bovine cumulus-oocyte complexes: A biological and spectroscopic approach.

This study deals with the effect of plasminogen/plasmin on the in vitro maturation (IVM) of bovine cumulus-oocyte complexes (COCs). Exogenous plasminogen activator streptokinase (SK) added to the IVM medium revealed similar values of cumulus expansion and oocyte nuclear maturation compared to controls (standard IVM medium). However, a decrease in both determinations was observed in COCs matured with the supplementation of ɛ-aminocaproic acid (ɛ-ACA), a specific plasmin inhibitor. After in vitro fertilization, no differences were observed in either cleavage or blastocyst rates between SK and control groups; however, ε-ACA treatment caused a decrease in both developmental rates. Zona pellucida (ZP) digestion time decreased in the SK group while it increased in the ε-ACA group. Raman microspectroscopy revealed an increase in the intensity of the band corresponding to the glycerol group of sialic acid in the ZP of oocytes matured with SK, whereas ZP spectra of oocytes treated with ɛ-ACA presented similarities with immature oocytes. The results indicate that although treatment with SK did not alter oocyte developmental competence, it induced modifications in the ZP of oocytes that could modify the folding of glycoproteins. Plasmin inhibition impairs oocyte maturation and has an impact on embryo development, thus evidencing the importance of this protease during IVM.

Oncological safety of transanal total mesorectal excision (TaTME) for rectal cancer: mid-term results of a prospective multicentre study.

BACKGROUND: There is no consensus regarding the gold standard technique for rectal cancer as Total Mesorectal Excision (TME) may be safely performed either by open or minimally invasive surgery. The laparoscopic approach, however, may carry technical difficulties. For this reason, a novel technique has emerged in the last decade combining a dual laparoscopic dissection (abdominal and transanal) to perform the TME technique (TaTME). When focusing on oncological outcomes, there is a lack of literature regarding mid-long term results. The aim of this study is to evaluate the mid-term oncological impact of TaTME for treating rectal cancer. METHODS: A prospective multicentre study was performed in four tertiary centres including consecutive patients who underwent TaTME for mid-low rectal cancer by the same group of experienced surgeons. The analysed data included pathological results on the quality of TME and mid-term oncological outcomes. RESULTS: In total, 173 patients were included throughout a study period of 6 years. Our series included 70% males and 68% of patients with neoadjuvant treatments. The median follow-up was 23 [15-37.5] months. Regarding pathological results, a complete TME was achieved in 72.8%, while circumferential and distal margins were affected in 1.4 and 1.1%, respectively. Five patients developed local recurrences (3%) and 8.1% presented distant disease during the follow-up. The 2-year disease-free survival and the overall survival rates were 88% and 95%, respectively. CONCLUSIONS: There is currently a lack of evidence in the literature regarding TaTME and oncological outcomes with no data available from randomized clinical trials. In the meantime, the reported results from different multicentre series are controversial. This study showed positive mid-term outcomes at 2 years of follow-up and supported notable oncological outcomes with TaTME. However, it must be emphasized that previous experience in minimally invasive and transanal surgeries is essential for surgeons before intending to perform TaTME.

A DNA aptamer for binding and inhibition of DNA methyltransferase 1.

DNA methyltransferases (DNMTs) are enzymes responsible for establishing and maintaining DNA methylation in cells. DNMT inhibition is actively pursued in cancer treatment, dominantly through the formation of irreversible covalent complexes between small molecular compounds and DNMTs that suffers from low efficacy and high cytotoxicity, as well as no selectivity towards different DNMTs. Herein, we discover aptamers against the maintenance DNA methyltransferase, DNMT1, by coupling Asymmetrical Flow Field-Flow Fractionation (AF4) with Systematic Evolution of Ligands by EXponential enrichment (SELEX). One of the identified aptamers, Apt. #9, contains a stem-loop structure, and can displace the hemi-methylated DNA duplex, the native substrate of DNMT1, off the protein on sub-micromolar scale, leading for effective enzymatic inhibition. Apt. #9 shows no inhibition nor binding activity towards two de novo DNMTs, DNMT3A and DNMT3B. Intriguingly, it can enter cancer cells with over-expression of DNMT1, colocalize with DNMT1 inside the nuclei, and inhibit the activity of DNMT1 in cells. This study opens the possibility of exploring the aptameric DNMT inhibitors being a new cancer therapeutic approach, by modulating DNMT activity selectively through reversible interaction. The aptamers could also be valuable tools for study of the functions of DNMTs and the related epigenetic mechanisms.

HelpResponder-System for the Security of First Responder Interventions.

Firefighter's interventions under dense smoke and flames are hazardous and ideally need an efficient in-advance geo-located actuation plan. The existing communication and sensing technologies should be customized, optimized, and integrated to better know the conditions (flame locations, air condition) before and during the rescue team's interventions. In this paper, we propose a firefighter intervention architecture, which consists of several sensing devices (flame detectors, carbon dioxide air content) a navigation platform (an autonomous ground wheeled robot), and a communication/localization network (BLE IoT network) that can be used before and during an intervention in rescue or fire extinguishing missions even for indoor or confined spaces. The paper's key novelty presents our integrated solution, giving some key implementation details and an intensive experimentation campaign in two real firefighter scenarios with real controlled fires. Results carried out in these real indoor scenarios are presented to demonstrate the feasibility of the system. A fire detection system is proposed to improve fire focus in real time and moving in confined spaces with no visibility and physical references. The results obtained in the experimentation show the proposal's effectiveness in locating the fire focus's position and orientation reducing time and risk exposure. This kind of location-aware fire integrated systems would significantly impact the speed and security of first responder interventions.

Protective effects of 17-ß-oestradiol and phytoestrogen on age-induced oxidative stress and inhibition of surfactant synthesis in rat type II pneumocytes.

Epidemiological data suggest protective effects of oestrogen and phytoestrogen on lung tissue. This study aimed to elucidate the role of 17-ß-oestradiol and phytoestrogen in age-related inhibition of surfactant synthesis and oxidative stress in rat type II pneumocytes. Forty male and 66 female Wistar rats were used. Female rats were randomly kept intact or ovariectomized at age 12 months. At age 22 months, ovariectomized rats received 17-ß-oestradiol, soy extract, or no treatment. Oxidative stress markers CO, NO, cGMP and lipid peroxide (LPO), antioxidant enzymes and phosphatidylcholine (PC) were measured in cultured type II pneumocytes isolated at ages 2, 14, 18, 22 and 24 months. Old, male and ovariectomized rats showed significantly higher CO, NO, cGMP and LPO and lower PC content and antioxidant enzymes. 17-ß-oestradiol and phytoestrogen significantly reversed these effects. In conclusion, aging and oestrogen deprivation decreased PC synthesis and altered the redox status in type II pneumocytes, which were partially restored by 17-ß-oestradiol or soy supplementation.

The impact of SARS-CoV-2 infection on the surgical management of colorectal cancer: lessons learned from a multicenter study in Spain.

OBJECTIVE: the aim of the study was to analyze the management of colorectal cancer (CRC) patients diagnosed with CRC or undergoing elective surgery during the period of the SARS-CoV-2 pandemic. MATERIAL AND METHODS: a multicenter ambispective analysis was performed in nine centers in Spain during a four-month period. Data were collected from every patient, including changes in treatments, referrals or delays in surgeries, changes in surgical approaches, postoperative outcomes and perioperative SARS-CoV-2 status. The hospital's response to the outbreak and available resources were categorized, and outcomes were divided into periods based on the timeline of the pandemic. RESULTS: a total of 301 patients were included by the study centers and 259 (86 %) underwent surgery. Five hospitals went into phase III during the peak of incidence period, one remained in phase II and three in phase I. More than 60 % of patients suffered some form of change: 48 % referrals, 39 % delays, 4 % of rectal cancer patients had a prolonged interval to surgery and 5 % underwent neoadjuvant treatment. At the time of study closure, 3 % did not undergo surgery. More than 85 % of the patients were tested preoperatively for SARS-CoV-2. A total of nine patients (3 %) developed postoperative pneumonia; three of them had confirmed SARS-CoV-2. The observed surgical complications and mortality rates were similar as expected in a usual situation. CONCLUSIONS: the present multicenter study shows different patterns of response to the SARS-CoV-2 pandemic and collateral effects in managing CRC patients. Knowing these patterns could be useful for planning future changes in surgical departments in preparation for new outbreaks.

In Vitro Screening of the Open-Source Medicines for Malaria Venture Malaria and Pathogen Boxes To Discover Novel Compounds with Activity against Balamuthia mandrillaris.

Balamuthia mandrillaris is an under-reported, pathogenic free-living amoeba that causes Balamuthia amoebic encephalitis (BAE) and cutaneous skin infections. Although cutaneous infections are not typically lethal, BAE with or without cutaneous involvement is usually fatal. This is due to the lack of drugs that are both efficacious and can cross the blood-brain barrier. We aimed to discover new leads for drug discovery by screening the open-source Medicines for Malaria Venture (MMV) Malaria Box and MMV Pathogen Box, with 800 compounds total. From an initial single point screen at 1 and 10 µM, we identified 54 hits that significantly inhibited the growth of B. mandrillarisin vitro Hits were reconfirmed in quantitative dose-response assays and 23 compounds (42.6%) were confirmed with activity greater than miltefosine, the current standard of care.

Surface features can deeply affect artificial grammar learning.

Three experiments explored the extent to which surface features explain discrimination between grammatical and non-grammatical strings in artificial grammar learning (AGL). Experiment 1 replicated Knowlton and Squire's (1996) paradigm using either letter strings as in the original study, or an analogous set of color strings to further explore if learning was affected by type of stimuli. Learning arose only with letter strings, but the results were mostly due to the discrimination of non-grammatical strings containing highly salient illegal features. Experiments 2 and 3 tested a new grammar devised to control for those features. Experiment 2 showed reduced grammar learning effects, and again only for letter materials. Experiment 3 explored the effect of additional practice with letter stimuli, and found increased learning only in the spaced practice condition, though additional practice also produced more explicit knowledge. These findings call for further research on the boundary conditions of learning in AGL paradigms.

Does incidental sequence learning allow us to better manage upcoming conflicting events?

Recent proposals emphasize the role of learning in empirical markers of conflict adaptation. Some of these proposals are rooted in the assumption that contingency learning works not only on stimulus-response events but also on covert processes such as selective attention. In the present study, we explored how these learning processes may apply to trial-to-trial modulations of selective attention, mirroring the sequential nature of congruency sequence effects. Two groups of participants performed a four-choice Stroop task in which the color to which they responded on each trial acted as a probabilistic predictor either of the external response to be emitted on the next trial, or the congruency level (and therefore control demands) on the next trial. The results showed clear effects of sequence learning for external responses, but no evidence of learning about sequential stimulus-conflict associations. The implications of these results are discussed in relation to other learning-based phenomena of conflict adaptation and suggest that learning of stimulus-control associations is strongly constrained by event boundaries.

Asymmetrical effects of control on the expression of implicit sequence learning.

As an automatic process, implicit learning effects have been characterized as inflexible and largely tied to the reinstatement of the acquisition context. However, implicit learning transfer has been observed under certain conditions, depending on the changes introduced between training and transfer. Here, we assess the hypothesis that transfer is specifically hindered by those changes that increase the control demands required by the orienting task with respect to those faced over training. Following on previous results by Jiménez et al. (J Exp Psychol Learn Memory Cognit 32(3):475-490, 2006), which showed that the learning acquired over a standard serial reaction time task was not transferred to conditions requiring a more demanding search task, we explored the impact of symmetrical training and transfer conditions, and showed that sequence learning survived such transfer. Four additional experiments designed to assess transfer to either lower or higher control demands confirmed that the expression of learning was selectively hindered by those transfer conditions requiring higher levels of control demands. The results illustrate how implicit sequence learning can be indirectly subjected to cognitive control.

Increasing control improves further control, but it does not enhance memory for the targets in a face-word Stroop task.

Recent research on the dynamics between attentional and memory processes have outlined the idea that applying control in a conflicting situation directly leads to enhanced episodic memory of the processed information. However, in spite of a small subset of studies supporting this claim, the majority of the evidence in the field seems to support the opposite pattern. In this study, we used a face-word Stroop task to enforce different control modes either from trial to trial or in an item-specific manner. Both manipulations of congruency proved to be effective in making participants' responses to conflicting stimuli more efficient over time by applying a trial-specific control mode. However, these manipulations had no impact on memory performance on a surprise recognition memory test. To our knowledge, this is the first attempt at measuring the memory consequences of the application of specific control modes at the trial level. The results reported here call for caution and possibly reconceptualization of the relationship between cognitive control and memory.

ggroups: an R package for pedigree and genetic groups data.

BACKGROUND: R is a multi-platform statistical software and an object oriented programming language. The package archive network for R provides CRAN repository that features over 15,000 free open source packages, at the time of writing this article (https://cran.r-project.org/web/packages, accessed in October 2019). The package ggroups is introduced in this article. The purpose of this package is providing functions for checking and processing the pedigree, calculation of the additive genetic relationship matrix and its inverse, which are used to study the population structure and predicting the genetic merit of animals. Calculation of the dominance relationship matrix and its inverse are also covered. A concept in animal breeding is genetic groups, which is about the inequality of the average genetic merits for groups of unknown parents. The package provides functions for the calculation of the matrix of genetic group contributions (Q). Calculating Q is computationally demanding, and depending on the size of the pedigree and the number of genetic groups, it might not be feasible using personal computers. Therefore, a computationally optimised function and its parallel processing alternative are provided in the package. RESULTS: Using sample data, outputs from different functions of the package were presented to illustrate a real experience of working with the package. CONCLUSIONS: The presented R package is a free and open source tool mainly for quantitative geneticists and ecologists, who deal with pedigree data. It provides numerous functions for handling pedigree data, and calculating various pedigree-based matrices. Some of the functions are computationally optimised for large-scale data.

Sensor Fusion Algorithm Using a Model-Based Kalman Filter for the Position and Attitude Estimation of Precision Aerial Delivery Systems.

In this research, we focus on the use of Unmanned Aerial Vehicles (UAVs) for the delivery of payloads and navigation towards safe-landing zones, specifically on the modeling of flight dynamics of lightweight vehicles denoted Precision Aerial Delivery Systems (PADSs). While a wide range of nonlinear models has been developed and tested on high-end applications considering various degrees of freedom (DOF), linear models suitable for low-cost applications have not been explored thoroughly. In this study, we propose and compare two linear models, a linearized version of a 6-DOF model specifically developed for micro-lightweight systems, and an alternative model based on a double integrator. Both linear models are implemented with a sensor fusion algorithm using a Kalman filter to estimate the position and attitude of PADSs, and their performance is compared to a nonlinear 6-DOF model. Simulation results demonstrate that both models, when incorporated into a Kalman filter estimation scheme, can determine the flight dynamics of PADSs during smooth flights. While it is validated that the double integrator model can adequately operate under the proposed estimation scheme for up to small acceleration changes, the linearized model proves to be capable of reproducing the nonlinear model characteristics even during moderately steep turns.

Velocity Sensor for Real-Time Backstepping Control of a Multirotor Considering Actuator Dynamics.

A real-time implementation of a control scheme for a multirotor, based on angular velocity sensors for the actuators, is presented. The control scheme is composed of two loops: an inner loop for the actuators and an outer loop for the unmanned aerial vehicle (UAV). The UAV control algorithm is designed by means of the backstepping technique and a robust sliding mode differentiator, and the actuator control strategy is based on a standard proportional-integral-derivative (PID) controller. A robust exact differentiator, based on high order sliding modes, is used to estimate the complex derivatives present in the proposed control law. As the measurements of the propeller's angular velocities are required for the control law, velocity sensors are mounted in the axles of the rotors to retrieve them and a signal conditioning stage is implemented. In addition, dynamical models for the actuators of the aircraft were calculated by means of transfer functions obtained via experimental measurements in a test bench developed for this purpose. This test bench permits to characterize the parameters of the transfer functions by comparing the forces computed using the nominal parameter to the measured forces. To this end, it is assumed that the loads in the actuators of the vehicle are insignificant during flight. The effectiveness of the proposed sensor, its signal conditioning, and the overall control scheme are validated by means of simulation results and real-time experiments.

IoT Smart Parking System Based on the Visual-Aided Smart Vehicle Presence Sensor: SPIN-V.

Humanity is currently experiencing one of the short periods of transition thanks to novel sensing solutions for smart cities that bring the future to today. Overpopulation of cities demands the development of solid strategic plannings that uses infrastructure, innovation, and technology to adapt to rapid changes. To improve mobility in cities with a larger and larger vehicle fleet, a novel sensing solution that is the cornerstone of a smart parking system, the smart vehicular presence sensor (SPIN-V, in its Spanish abbreviation), is presented. The SPIN-V is composed of a small single-board computer, distance sensor, camera, LED indicator, buzzer, and battery and devoted to obtain the status of a parking space. This smart mobility project involves three main elements, namely the SPIN-V, a mobile application, and a monitoring center, working together to monitor, control, process, and display the parking space information in real-time to the drivers. In addition, the design and implementation of the three elements of the complete architecture are presented.

Educational Mechatronics and Internet of Things: A Case Study on Dynamic Systems Using MEIoT Weather Station.

This paper presents the design and development of an IoT device, called MEIoT weather station, which combines the Educational Mechatronics and IoT to develop the required knowledge and skills for Industry 4.0. MEIoT weather station connects to the internet, measures eight weather variables, and upload the sensed data to the cloud. The MEIoT weather station is the first device working with the IoT architecture of the National Digital Observatory of Intelligent Environments. In addition, an IoT open platform, GUI-MEIoT, serves as a graphic user interface. GUI-MEIoT is used to visualize the real-time data of the weather variables, it also shows the historical data collected, and allows to export them to a csv file. Finally, an OBNiSE architecture application to Engineering Education is presented with a dynamic system case of study that includes the instructional design carried out within the Educational Mechatronics Conceptual Framework (EMCF) to show the relevance of this proposal. This work main contribution to the state of art is the design and integration of the OBNiSE architecture within the EMCF offering the possibility to add more IoT devices for several smart domains such as smart campus, smart cities, smart people and smart industries.