Only the Fastest Corticospinal Fibers Contribute to ß Corticomuscular Coherence.

Human corticospinal transmission is commonly studied using brain stimulation. However, this approach is biased to activity in the fastest conducting axons. It is unclear whether conclusions obtained in this context are representative of volitional activity in mild-to-moderate contractions. An alternative to overcome this limitation may be to study the corticospinal transmission of endogenously generated brain activity. Here, we investigate in humans (N = 19; of either sex), the transmission speeds of cortical ß rhythms (∼20 Hz) traveling to arm (first dorsal interosseous) and leg (tibialis anterior; TA) muscles during tonic mild contractions. For this purpose, we propose two improvements for the estimation of corticomuscular ß transmission delays. First, we show that the cumulant density (cross-covariance) is more accurate than the commonly-used directed coherence to estimate transmission delays in bidirectional systems transmitting band-limited signals. Second, we show that when spiking motor unit activity is used instead of interference electromyography, corticomuscular transmission delay estimates are unaffected by the shapes of the motor unit action potentials (MUAPs). Applying these improvements, we show that descending corticomuscular ß transmission is only 1-2 ms slower than expected from the fastest corticospinal pathways. In the last part of our work, we show results from simulations using estimated distributions of the conduction velocities for descending axons projecting to lower motoneurons (from macaque histologic measurements) to suggest two scenarios that can explain fast corticomuscular transmission: either only the fastest corticospinal axons selectively transmit ß activity, or else the entire pool does. The implications of these two scenarios for our understanding of corticomuscular interactions are discussed.SIGNIFICANCE STATEMENT We present and validate an improved methodology to measure the delay in the transmission of cortical ß activity to tonically-active muscles. The estimated corticomuscular ß transmission delays obtained with this approach are remarkably similar to those expected from transmission in the fastest corticospinal axons. A simulation of ß transmission along a pool of corticospinal axons using an estimated distribution of fiber diameters suggests two possible mechanisms by which fast corticomuscular transmission is achieved: either a very small fraction of the fastest descending axons transmits ß activity to the muscles or, alternatively, the entire population does and natural cancellation of slow channels occurs because of the distribution of axon diameters in the corticospinal tract.

Conserved Structural Motif Identified in Peptides That Bind to Geminivirus Replication Protein Rep.

The geminivirus replication protein, Rep, has long been recognized as a high-value target for control of geminivirus infections as this protein is highly conserved and essential for viral replication and proliferation. In addition, inhibition of viral replication has been pursued through various antiviral strategies with varying degrees of success, including inhibitory peptides that target Rep. While much effort has centered around sequence characterization of the Rep protein and inhibitory peptides, detailed structural analysis has been missing. This study computationally investigated the presence of common structural features within these inhibitory peptides and if these features could inform if a particular peptide will bind Rep and/or interfere with viral replication. Molecular dynamics simulations of the inhibitory peptide library showed that simply possessing stable structural features does not inform interference of viral replication regardless of the binding of Rep. Additionally, nearly all known Rep inhibitory peptides sample a conserved ß-sheet structural motif, possibly informing structure-function relationships in binding Rep. In particular, two peptides (A22 and A64) characterized by this structural motif were computationally docked against a wide variety of geminivirus Rep proteins to determine a mechanism of action. Computational docking revealed these peptides utilize a common Rep protein sequence motif for binding, HHN-x1/2-Q. The results identified residues in both Rep and the inhibitory peptides that play a significant role in the interaction, establishing the foundation for a rational structure-based design approach for the construction of both broadly reactive and geminivirus species-specific inhibitors.

Structural, vibrational and electronic properties of α'-Ga2S3 under compression.

We report a joint experimental and theoretical study of the low-pressure phase of α'-Ga2S3 under compression. Theoretical ab initio calculations have been compared to X-ray diffraction and Raman scattering measurements under high pressure carried out up to 17.5 and 16.1 GPa, respectively. In addition, we report Raman scattering measurements of α'-Ga2S3 at high temperature that have allowed us to study its anharmonic properties. To understand better the compression of this compound, we have evaluated the topological properties of the electron density, the electron localization function, and the electronic properties as a function of pressure. As a result, we shed light on the role of the Ga-S bonds, the van der Waals interactions inside the channels of the crystalline structure, and the single and double lone electron pairs of the sulphur atoms in the anisotropic compression of α'-Ga2S3. We found that the structural channels are responsible for the anisotropic properties of α'-Ga2S3 and the A'(6) phonon, known as the breathing mode and associated with these channels, exhibits the highest anharmonic behaviour. Finally, we report calculations of the electronic band structure of α'-Ga2S3 at different pressures and find a nonlinear pressure behaviour of the direct band gap and a pressure-induced direct-to-indirect band gap crossover that is similar to the behaviour previously reported in other ordered-vacancy compounds, including ß-Ga2Se3. The importance of the single and, more specially, the double lone electron pairs of sulphur in the pressure dependence of the topmost valence band of α'-Ga2S3 is stressed.

Premovement Suppression of Corticospinal Excitability may be a Necessary Part of Movement Preparation.

In reaction time (RT) tasks corticospinal excitability (CSE) rises just prior to movement. This is preceded by a paradoxical reduction in CSE, when the time of the imperative ("GO") stimulus is relatively predictable. Because RT tasks emphasise speed of response, it is impossible to distinguish whether reduced CSE reflects a mechanism for withholding prepared actions, or whether it is an inherent part of movement preparation. To address this question, we used transcranial magnetic stimulation (TMS) to estimate CSE changes preceding 1) RT movements; 2) movements synchronized with a predictable signal (predictive timing or PT movements); and 3) self-paced movements. Results show that CSE decreases with a similar temporal profile in all three cases, suggesting that it reflects a previously unrecognised state in the transition between rest and movement. Although TMS revealed reduced CSE in all movements, the TMS pulse itself had different effects on movement times. TMS given ~200 ms before the times to move speeded the onset of RT and self-paced movements, suggesting that their initiation depends on a form of trigger that can be conditioned by external events. On the contrary, PT movements did not show this effect, suggesting the use of a different triggering strategy prioritizing internal events.

Combination of phenotype and polygenic risk score in breast cancer risk evaluation in the Spanish population: a case -control study.

BACKGROUND: In recent years, the identification of genetic and phenotypic biomarkers of cancer for prevention, early diagnosis and patient stratification has been a main objective of research in the field. Different multivariable models that use biomarkers have been proposed for the evaluation of individual risk of developing breast cancer. METHODS: This is a case control study based on a population-based cohort. We describe and evaluate a multivariable model that incorporates 92 Single-nucleotide polymorphisms (SNPs) (Supplementary Table S1) and five different phenotypic variables and which was employed in a Spanish population of 642 healthy women and 455 breast cancer patients. RESULTS: Our model allowed us to stratify two groups: high and low risk of developing breast cancer. The 9th decile included 1% of controls vs 9% of cases, with an odds ratio (OR) of 12.9 and a p-value of 3.43E-07. The first decile presented an inverse proportion: 1% of cases and 9% of controls, with an OR of 0.097 and a p-value of 1.86E-08. CONCLUSIONS: These results indicate the capacity of our multivariable model to stratify women according to their risk of developing breast cancer. The major limitation of our analysis is the small cohort size. However, despite the limitations, the results of our analysis provide proof of concept in a poorly studied population, and opens up the possibility of using this method in the routine screening of the Spanish population.

Accuracy of CT colonography in the preoperative staging of colon cancer: a prospective study of 217 patients.

AIM: The purpose of the present study was to evaluate the accuracy of computed tomography colonography (CTC) in the preoperative localization and TN staging of colon cancer. CTC can be an effective technique for preoperative evaluation of colon cancer and could facilitate the selection of high-risk patients who may benefit from neoadjuvant chemotherapy. METHOD: This was a prospective observational study conducted at a single tertiary-care centre. It involved 217 patients (225 tumours) who had colon cancer and underwent preoperative CTC and elective colectomy. The radiologist determined the TNM stage using postprocessing software with multiplanar images and virtual colonoscopy. The following criteria were analysed for every colon tumour: location, size and signs of direct colon wall invasion. The histopathological findings of the surgical colectomy specimens served as the reference standard for local staging. RESULTS: CTC detected all tumours and achieved an exact location in 208 cases (92.4%). CTC findings changed the surgical plan in 31 patients (14.3%) following colonoscopy. The accuracy in differentiating T3/T4 vs T1/T2 tumours was 87.1%, with a sensitivity and specificity of 88.5% and 84.1%, respectively (kappa = 0.71). For high-risk tumours (T3 ≥ 5 mm and T4), CTC showed an accuracy, sensitivity and specificity of 82.7%, 86% and 80%, respectively (kappa = 0.65). The accuracy of N-stage evaluation was 69.3%, the sensitivity 74% and the specificity 67.1% (kappa = 0.37). CONCLUSION: CTC provides accurate information for the assessment of tumour localization and T staging, allowing better surgical planning and also allows the selection of locally advanced tumours that may benefit from new treatments such as neoadjuvant chemotherapy.

Barriers to health care services for migrants living with HIV in Spain.

Background: In Spain, migrants are disproportionately affected by HIV and experience high rates of late diagnosis. We investigated barriers to health care access among migrants living with HIV (MLWH) in Spain. Methods: Cross sectional electronic survey of 765 adult HIV-positive migrants recruited within 18 health care settings between July 2013 and July 2015. We collected epidemiological, demographic, behavioral and clinical data. We estimated the prevalence and risk factors of self-reported barriers to health care using multivariable logistic regression. Results: Of those surveyed, 672 (88%) had information on health care access barriers: 23% were women, 63% from Latin America and Caribbean, 14% from Sub-Saharan Africa and 15% had an irregular immigration status. Men were more likely to report barriers than women (24% vs. 14%, P = 0.009). The main barriers were: lengthy waiting times for an appointment (9%) or in the clinic (7%) and lack of a health card (7%). Having an irregular immigration status was a risk factor for experiencing barriers for both men (OR: (4.0 [95%CI: 2.2-7.2]) and women (OR: 10.5 [95%CI: 3.1-34.8]). Men who experienced racial stigma (OR: 3.1 [95%CI: 1.9-5.1]) or food insecurity (OR: 2.1 [95%CI: 1.2-3.4]) were more likely to report barriers. Women who delayed treatment due to medication costs (6.3 [95%CI: 1.3-30.8]) or had a university degree (OR: 5.8 [95%CI: 1.3-25.1]) were more likely to report barriers. Conclusion: Health care barriers were present in one in five5 MLWH, were more common in men and were associated to legal entitlement to access care, perceived stigma and financial constraints.

Adaptive hybrid robotic system for rehabilitation of reaching movement after a brain injury: a usability study.

BACKGROUND: Brain injury survivors often present upper-limb motor impairment affecting the execution of functional activities such as reaching. A currently active research line seeking to maximize upper-limb motor recovery after a brain injury, deals with the combined use of functional electrical stimulation (FES) and mechanical supporting devices, in what has been previously termed hybrid robotic systems. This study evaluates from the technical and clinical perspectives the usability of an integrated hybrid robotic system for the rehabilitation of upper-limb reaching movements after a brain lesion affecting the motor function. METHODS: The presented system is comprised of four main components. The hybrid assistance is given by a passive exoskeleton to support the arm weight against gravity and a functional electrical stimulation device to assist the execution of the reaching task. The feedback error learning (FEL) controller was implemented to adjust the intensity of the electrical stimuli delivered on target muscles according to the performance of the users. This control strategy is based on a proportional-integral-derivative feedback controller and an artificial neural network as the feedforward controller. Two experiments were carried out in this evaluation. First, the technical viability and the performance of the implemented FEL controller was evaluated in healthy subjects (N = 12). Second, a small cohort of patients with a brain injury (N = 4) participated in two experimental session to evaluate the system performance. Also, the overall satisfaction and emotional response of the users after they used the system was assessed. RESULTS: In the experiment with healthy subjects, a significant reduction of the tracking error was found during the execution of reaching movements. In the experiment with patients, a decreasing trend of the error trajectory was found together with an increasing trend in the task performance as the movement was repeated. Brain injury patients expressed a great acceptance in using the system as a rehabilitation tool. CONCLUSIONS: The study demonstrates the technical feasibility of using the hybrid robotic system for reaching rehabilitation. Patients' reports on the received intervention reveal a great satisfaction and acceptance of the hybrid robotic system. TRIAL REGISTRATION: Retrospective trial registration in ISRCTN Register with study ID ISRCTN12843006 .

Electroencephalography as a post-stroke assessment method: An updated review. / Electroencefalografía como método de evaluación tras un ictus. Una revisión actualizada.

Given that stroke is currently a serious problem in the population, employing more reliable and objective techniques for determining diagnosis and prognosis is necessary in order to enable effective clinical decision-making. EEG is a simple, low-cost, non-invasive tool that can provide information about the changes occurring in the cerebral cortex during the recovery process after stroke. EEG provides data on the evolution of cortical activation patterns which can be used to establish a prognosis geared toward harnessing each patient's full potential. This strategy can be used to prevent compensation and maladaptive plasticity, redirect treatments, and develop new interventions that will let stroke patients reach their new maximum motor levels.

In vivo reflectance confocal microscopy characterization of silver deposits in localized cutaneous argyria.

Localized cutaneous argyria is a rare condition secondary to skin deposition of silver following exposure to substances containing this metal. The clinical appearance and dermoscopy findings require deep melanocytic lesions and particularly melanoma metastasis to be ruled out. Silver deposits are usually confirmed by scanning electron microscopy and/or energy-dispersive X-ray spectroscopy. Herein we describe the in vivo reflectance confocal microscopy (RCM) features observed in one case of localized cutaneous argyria. These features include the presence of a hyperrefractile network in the papillary dermis and a periadnexal dotted bright pattern. In vivo RCM might be a useful tool for an early diagnosis of this uncommon entity.

Long-Term Mortality After Pneumonia in Cardiac Surgery Patients: A Propensity-Matched Analysis.

BACKGROUND: The role that intensive care unit (ICU)-acquired pneumonia plays in the long-term outcomes of cardiac surgery patients is not well known. This study examined the association of pneumonia with in-hospital mortality and long-term mortality after adult cardiac surgery. METHODS: A total of 2750 patients admitted to our ICU after cardiac surgery from January 2003 to December 2009 are the basis for this observational study. Patients who developed ICU-acquired pneumonia were matched with patients without it in a 1:2 ratio. The matching criteria were age, urgent or scheduled surgery, surgical procedure, and the propensity score for pneumonia. Multiple regression analysis was used to find predictors of hospital mortality. The relationship between pneumonia and long-term survival was analyzed with Kaplan-Meier survival estimates and a risk-adjusted Cox proportional regression model for patients discharged alive from hospital. RESULTS: Pneumonia was diagnosed in 32 (1.2%) patients and there were 19 cases per 1000 days of mechanical ventilation. Patients with pneumonia had a significantly higher hospital mortality rate (28% vs 6.2%, P = .003) and a higher mortality at the end of follow-up (53% vs 19%, P < .0001) than those without it. Regression analysis showed that pneumonia was a strong predictor of hospital mortality. Five-year survival was as follows: pneumonia, 62%; control, 81%; and cohort patients, 91%. The Cox model showed that, after adjusting for confounding factors, patients with pneumonia (hazard ratio = 3.96, 95% confidence interval [CI]: 1.41-11.14) had poorer long-term survival. CONCLUSION: Pneumonia remains a serious complication in patients operated for cardiac surgery and is associated with increased hospital mortality and reduced long-term survival.

Estimation of the Maximal Lactate Steady State in Junior Soccer Players.

This study aimed to predict the velocity corresponding to the maximal lactate steady state (MLSS(V)) from non-invasive variables obtained during an incremental maximal running test (University of Montreal Track Test, UMTT) and to determine whether a single constant velocity test (CVT), performed several days after the UMTT, could estimate the MLSS(V). During a period of 3 weeks, 20 male junior soccer players performed: (1) a UMTT, and (2) several 20-min CVTs to determine MLSS(V) to a precision of 0.35 km·h(-1). Maximal aerobic velocity (MAV) and velocity at 80% of maximum heart rate (V80%HRmax) were strong predictors of MLSS(V). A regression equation was obtained: MLSS(V)=(1.106·MAV) - (0.309·V(80%HRmax)) - 3.024; R2=0.60. Running velocity during CVT (V(CVT)) and blood lactate at 10 (La10) and 20 (La20) minutes further improved the MLSS(V) prediction: MLSS(V)=V(CVT)+0.26 - (0.812·ΔLa(20-10)); R2=0.66. MLSS(V) can be estimated from MAV and V(80%HRmax) during a single incremental maximal running test among a homogeneous group of soccer players. This estimation can be improved by performing an additional CVT. In terms of accuracy, simplicity and cost-effectiveness, the reported regression equations can be used for the assessment and training prescription of endurance in team sport players.

Clinical results after ultrasound-guided intratissue percutaneous electrolysis (EPI®) and eccentric exercise in the treatment of patellar tendinopathy.

PURPOSE: To investigate the outcome of ultrasound (US)-guided intratissue percutaneous electrolysis (EPI(®)) and eccentric exercise in the treatment of patellar tendinopathy during a long-term follow-up. METHODS: Forty patients with patellar tendinopathy were prospectively evaluated over a 10-year follow-up period. Pain and function were evaluated before treatment, at 3 months and at 2, 5 and 10 years using the Victorian Institute of Sport Assessment-Patella (VISA-P) score, the Tegner score and Blazina's classification. According to VISA-P score at baseline, patients were also dichotomized into Group 1 (<50 points) and Group 2 (≥50 points). There were 21 patients in Group 1 and 19 in Group 2. Patient satisfaction was measured according to the Roles and Maudsley score. RESULTS: The VISA-P score improved globally by 41.2 points (p < 0.01) after a mean 4.1 procedures. In Group 1, VISA-P score improved from 33.1 ± 13 to 78.9 ± 14.4 at 3-month and to 88.8 ± 10.1 at 10-year follow-up (p < 0.001). In Group 2, VISA-P score improved from 69.3 ± 10.5 to 84.9 ± 9 at 3-month and to 96.0 ± 4.3 at 10-year follow-up (p < 0.001). After 10 years, 91.2 % of the patients had a VISA-P score >80 points. The same level (80 % of patients) or the Tegner score at no more than one level lower (20 % of patients) was restored, and 97.5 % of the patients were satisfied with the procedure. CONCLUSION: Treatment with the US-guided EPI(®) technique and eccentric exercises in patellar tendinopathy resulted in a great improvement in knee function and a rapid return to the previous level of activity after few sessions. The procedure has proved to be safe with no recurrences on a long-term basis. LEVEL OF EVIDENCE: Therapeutic study, Level IV.

Peptide aptamers that bind to geminivirus replication proteins confer a resistance phenotype to tomato yellow leaf curl virus and tomato mottle virus infection in tomato.

Geminiviruses constitute a large family of single-stranded DNA viruses that cause serious losses in important crops worldwide. They often exist in disease complexes and have high recombination and mutation rates, allowing them to adapt rapidly to new hosts and environments. Thus, an effective resistance strategy must be general in character and able to target multiple viruses. The geminivirus replication protein (Rep) is a good target for broad-based disease control because it is highly conserved and required for viral replication. In an earlier study, we identified a set of peptide aptamers that bind to Rep and reduce viral replication in cultured plant cells. In this study, we selected 16 of the peptide aptamers for further analysis in yeast two-hybrid assays. The results of these experiments showed that all 16 peptide aptamers interact with all or most of the Rep proteins from nine viruses representing the three major Geminiviridae genera and identified two peptide aptamers (A22 and A64) that interact strongly with different regions in the Rep N terminus. Transgenic tomato lines expressing A22 or A64 and inoculated with Tomato yellow leaf curl virus or Tomato mottle virus exhibited delayed viral DNA accumulation and often contained lower levels of viral DNA. Strikingly, the effect on symptoms was stronger, with many of the plants showing no symptoms or strongly attenuated symptoms. Together, these results established the efficacy of using Rep-binding peptide aptamers to develop crops that are resistant to diverse geminiviruses.

Respiratory CO2 response in acute cervical spinal cord injury (CO2 response in spinal cord injury).

STUDY DESIGN: Retrospective study. OBJECTIVES: The objective of this study was to compare the CO2 response of acute tetraplegic cervical spinal cord injury (SCI) patients undergoing mechanical ventilation with a control group of critically ill patients ready for weaning of mechanical ventilation and successfully extubated. SETTING: This study was conducted at the intensive care unit of a University Hospital in Mallorca, Spain. METHODS: CO2 response was studied in 12 acute tetraplegic cervical SCI patients at the C4-C7 level and 22 control patients. The control group patients were consecutively selected from a database of patients with mechanical ventilation and who were successfully extubated after a CO2 response test. To increase the CO2 , we used the method of re-inhalation of expired air, and we evaluated the hypercapnic ventilatory response, the change in minute ventilation induced by the increase of partial pressure of arterial carbon dioxide (PaCO2 ), which measures the whole respiratory system (metabolic control, neuromuscular or ventilatory apparatus), and the hypercapnic drive response, the change in the airway occlusion pressure at 100 ms induced by the increase in PaCO2, which measures the chemosensitivity of the respiratory center. RESULTS: Cervical SCI patients were younger than the control group patients (26±7 and 62±12 years, respectively; P<0.001). Mean values of the hypercapnic ventilatory response in cervical SCI and control groups were 0.52±0.31 and 0.64±0.33 l min(-1) per mm Hg (P=0.40), respectively, and the hypercapnic drive response was 0.24±0.16 and 0.48±0.23 cm H2O per mm Hg (P=0.001), respectively. CONCLUSION: Acute tetraplegic cervical SCI patients had reduced hypercapnic drive response that may contribute to the difficult weaning, without reduction in hypercapnic ventilatory response.

Respiratory CO2 response depends on plasma bicarbonate concentration in mechanically ventilated patients.

OBJECTIVE: There is controversy about the effects of high plasma bicarbonate concentration ([HCO3(-)]) and the CO2 response test. We analyzed the relationship between [HCO3(-)] and the variation in hydrogen ion concentration (pH) for a given change in PaCO2, and its effects upon CO2 response. DESIGN: A retrospective study was carried out. SETTING: Two intensive care units. PATIENTS: Subjects with and without chronic obstructive pulmonary disease (COPD), at the beginning of weaning from mechanical ventilation. INTERVENTIONS: The CO2 response was evaluated by the re-inhalation of expired air method, measuring the hypercapnic ventilatory response (ΔVE/ΔPaCO2) and hypercapnic drive response (ΔP01/ΔPaCO2), where VE is minute volume and P0.1 is airway occlusion pressure 0.1s after the initiation of inspiration. MAIN OUTCOME MEASURES: [HCO3(-)] and CO2 response. RESULTS: A total of 120 patients in the non-COPD group and 48 in the COPD group were studied. COPD patients had higher mean [HCO3(-)] than non-COPD patients (33.2 ± 5.4 vs. 25.7 ± 3.7 mmol/l, p<0.001). In both non-COPD and COPD patients we observed a significant inverse linear relationship between [HCO3(-)] and pH change per mmHg of PaCO2 (p<0.001), ΔVE/ΔPaCO2 (p<0.001) and ΔP0.1/ΔPaCO2 (p<0.001). CONCLUSIONS: There is an inverse linear relationship between [HCO3(-)] and the variation of pH for a given change in PaCO2 and the CO2 response.

[Red cell transfusion and long-term survival in non-complicated heart surgery]. / Transfusión de hematíes y supervivencia a largo plazo en la cirugía cardíaca no complicada.

OBJECTIVE: A study was made to explore the possible association between the perioperative transfusion of 1 - 2 red blood cell units and in-hospital morbidity, 30-day mortality, and long-term survival in patients undergoing heart surgery. DESIGN: A prospective observational study was carried out. SETTING: The ICU of a university hospital. PATIENTS: All patients over 17 years of age that underwent heart surgery and were admitted to the ICU between November 2002 and December 2009 were included. Those patients who did not (n=703) and those who did (n=959) receive the perioperative transfusion of 1 - 2 red blood cell units were assessed. STUDY ENDPOINTS: The endpoints were the effect of transfusion on both hospital morbidity and on 30-day mortality. In addition, all patients discharged alive from hospital until 31 December 2011 were subjected to follow-up. The association between transfusion and survival was assessed by means of the Kaplan-Meier method. Cox proportional hazards models were used to assess factors associated with long-term survival. RESULTS: The frequency of both cardiac and non-cardiac perioperative complications was higher in patients receiving transfusion. The 30-day mortality rate was higher in those who received transfusion (1% vs 0.1%, P=.02). Preoperative anemia was associated with a more intensive use of transfusion. Red blood cell transfusion was not found to be a risk factor for long-term mortality (hazar ratio=1.4, 95%CI 0.9-2.1). CONCLUSIONS: The perioperative transfusion of 1 - 2 red blood cell units in patients undergoing heart surgery increases both hospital morbidity and the 30-day mortality rate, but does not increase long-term mortality.

Impact of N-Acetylcysteine in the mortality of patients hospitalized with COVID-19: a retrospective cohort study.

INTRODUCTION AND AIM: N-Acetylcysteine has been proposed for the treatment of COVID-19 thanks to its mucolytic, antioxidant and anti-inflammatory effects. Our aim is to evaluate its effect on patients admitted with COVID-19 in mortality terms. MATERIAL AND METHODS: Retrospective single-center cohort study. All patients admitted to our hospital for COVID-19 from March to April 2020 have been considered. RESULTS: A total of 378 patients were included, being 196 (51.9%) men, with an average age of 73.3±14.5 years. 52.6% (199) received treatment with N-Acetylcysteine. More than 70% presented coughs, fever, and/or dyspnea. The global hospital mortality was 26.7%. A multivariate analysis through logistic regression identified the age of patients [older than 80; OR: 8.4 (CI95%:3-23.4)], a moderate or severe radiologic affectation measured by the RALE score [OR:7.3 (CI95%:3.2-16.9)], the tobacco consumption [OR:2.8 (CI95%:1.3-6.1)] and previous arrhythmia [OR 2.8 (CI95%: 1.3-6.2)] as risk factor that were independently associated with mortality during the admission. The treatment with N-Acetylcysteine was identified as a protective factor [OR: 0.57 (CI95%: 0.31-0.99)]. Asthma also seems to have a certain protective factor although it was not statistically significant in our study [OR: 0.19 (CI95%: 0.03-1.06)]. CONCLUSIONS: Patients with COVID-19 treated with N-acetylcysteine have presented a lower mortality and a better evolution in this study. Future prospective studies or randomized clinical trials must confirm the impact of N-Acetylcysteine on COVID-19 patients.

Fluoxetine increased adult neurogenesis is mediated by 5-HT3 receptor.

Adult neurogenesis is an aspect of structural plasticity that remains active during adulthood in some brain regions. One of them is the subgranular zone (SGZ) of the dentate gyrus of the hippocampus. Adult neurogenesis is reduced by different factors and in disorders of the CNS, including major depression. Antidepressant treatments, such as chronic fluoxetine administration, recover the normal level of adult neurogenesis. Fluoxetine treatment increases the free concentration of the neurotransmitter serotonin and this monoamine is implicated in the regulation of the neurogenic process; however, the target of the action of this neurotransmitter has not been fully elucidated. In this study, we have tried to determine the relevance of the serotonin receptor 3 (5-HT3) in the hippocampal neurogenesis of adult rats. We have used fluorescent immunohistochemistry to study the expression of the 5-HT3 receptor in different neurogenesis stages in the SGZ, identifying its expression in stem cells, amplifying neural progenitors and immature neurons. Moreover, we have studied the impact of a 5-HT3 antagonist (ondansetron) in the fluoxetine-induced adult neurogenesis. We observed that fluoxetine alone increases the number of both proliferating cells (ki67 positive) and immature neurons (DCX positive) in the SGZ. By contrast, co-treatment with ondansetron blocked the increase in proliferation and neurogenesis. This study demonstrates that the activation of 5-HT3 receptors is necessary for the increase of adult neurogenesis induced by fluoxetine.

REALMS: Resilient exploration and lunar mapping system.

Space resource utilisation is opening a new space era. The scientific proof of the presence of water ice on the south pole of the Moon, the recent advances in oxygen extraction from lunar regolith, and its use as a material to build shelters are positioning the Moon, again, at the centre of important space programs. These worldwide programs, led by ARTEMIS, expect robotics to be the disrupting technology enabling humankind's next giant leap. However, Moon robots require a high level of autonomy to perform lunar exploration tasks more efficiently without being constantly controlled from Earth. Furthermore, having more than one robotic system will increase the resilience and robustness of the global system, improving its success rate, as well as providing additional redundancy. This paper introduces the Resilient Exploration and Lunar Mapping System, developed with a scalable architecture for semi-autonomous lunar mapping. It leverages Visual Simultaneous Localization and Mapping techniques on multiple rovers to map large lunar environments. Several resilience mechanisms are implemented, such as two-agent redundancy, delay invariant communications, a multi-master architecture different control modes. This study presents the experimental results of REALMS with two robots and its potential to be scaled to a larger number of robots, increasing the map coverage and system redundancy. The system's performance is verified and validated in a lunar analogue facility, and a larger lunar environment during the European Space Agency (ESA)-European Space Resources Innovation Centre Space Resources Challenge. The results of the different experiments show the efficiency of REALMS and the benefits of using semi-autonomous systems.