Modified Rapid Emergency Medicine Score-Lactate (mREMS-L) performance to screen non-anticipated 30-day-related-mortality in emergency department.

BACKGROUND: The aim of this study was to compare the ability to predict 30-day in-hospital mortality of lactate versus the modified Rapid Emergency Medicine Score (mREMS) versus the arithmetic sum of the mREMS plus the numerical value of lactate (mREMS-L). METHODS: A prospective, multicentric, emergency department delivery, pragmatic study was conducted. To determine the predictive capacity of the scales, lactate was measured and the mREMS and mREMS-L were calculated in adult patients (aged>18 years) transferred with high priority by ambulance to the emergency department in five hospitals of Castilla y Leon between 1 January 2020 and 31 December 2021. The area under the receiver operating characteristic (ROC) curve of each of the scales was calculated in terms of mortality for 30 days. RESULTS: A total of 5371 participants were included, and the in-hospital mortality rate at 30 days was of 11.4% (615 cases). The best cut-off point determined in the mREMS was 7.0 points (sensitivity of 67% and specificity of 84%), and for lactate, the cut-off point was 1.4 mmol/L (sensitivity of 88% and specificity of 67%). Finally, the combined mREMS-L showed a cut-off point of 7.9 (sensitivity of 83% and a specificity of 83%). The area under the ROC curve of the mREMS, lactate and mREMS-L for 30-day mortality was 0.851, 0.853, and 0.903, respectively (p < 0.001 in all cases). CONCLUSIONS: The new score generated, mREMS-L, obtained better statistical results than its components (mREMS and lactate) separately.

Prehospital seizures: Short-term outcomes and risk stratification based in point-of-care testing.

BACKGROUND: Information for treatment or hospital derivation of prehospital seizures is limited, impairing patient condition and hindering patients risk assessment by the emergency medical services (EMS). This study aimed to determine the associated factors to clinical impairment, and secondarily, to determine risk factors associated to cumulative in-hospital mortality at 2, 7 and 30 days, in patients presenting prehospital seizures. METHODS: Prospective, multicentre, EMS-delivery study involving adult subjects with prehospital seizures, including five advanced life support units, 27 basic life support units and four emergency departments in Spain. All bedside variables: including demographic, standard vital signs, prehospital laboratory tests and presence of intoxication or traumatic brain injury (TBI), were analysed to construct a risk model using binary logistic regression and internal validation methods. RESULTS: A total of 517 patients were considered. Clinical impairment was present in 14.9%, and cumulative in-hospital mortality at 2, 7 and 30-days was 3.4%, 4.6% and 7.7%, respectively. The model for the clinical impairment indicated that respiratory rate, partial pressure of carbon dioxide, blood urea nitrogen, associated TBI or stroke were risk factors; higher Glasgow Coma Scale (GCS) scores mean a lower risk of impairment. Age, potassium, glucose, prehospital use of mechanical ventilation and concomitant stroke were risk factors associated to mortality; and oxygen saturation, a high score in GCS and haemoglobin were protective factors. CONCLUSION: Our study shows that prehospital variables could reflect the clinical impairment and mortality of patients suffering from seizures. The incorporation of such variables in the prehospital decision-making process could improve patient outcomes.

"Nurses and health professionals facing female genital mutilation: a qualitative study ".

BACKGROUND: Transnational migratory movements make Spain a country with a very diverse population, including women and girls from countries where Female Genital Mutilation (FGM) is practiced. Given this reality, we set out to carry out a qualitative study to identify the knowledge, attitudes and skills of health professionals regarding FGM. METHOD: Qualitative study with a content analysis approach. Forty-seven health professionals with the profiles of Nursing, Family Medicine, Pediatrics, Midwifery and Gynecology and Obstetrics were purposively selected. Data were collected through semi-structured in-depth interviews and focus groups. The qualitative content analysis approach was used for data analysis. The study was conducted in the years 2019 and 2022. RESULTS: Although most professionals are aware of the current legislation on FGM in Spain, only a few of them are aware of the existence of the FGM prevention protocol in Castilla-La Mancha. This lack of knowledge together with the perception that FGM belongs to the private sphere of women, contributes to the loss of opportunities to identify and prevent FGM. CONCLUSION: Health professionals' training, especially midwives and pediatricians, is essential to the identification and action against Female Genital Mutilation.

Lactate improves the predictive ability of the National Early Warning Score 2 in the emergency department.

AIMS: The aim of this study was to compare the ability to predict 2-, 7-, 14-, and 30-day in-hospital mortality of lactate vs the National Early Warning Score 2 (NEWS2) vs the arithmetic sum of the NEWS2 plus the numerical value of lactate (NEWS2-L). METHODS: This was a prospective, multicentric, emergency department delivery, pragmatic cohort study. To determine the predictive capacity of lactate, we calculated the NEWS2 and NEWS2-L in adult patients (aged >18 years) transferred with high priority by ambulance to the emergency department in five hospitals of Castilla y Leon (Spain) between November 1, 2019, and September 30, 2020. The area under the receiver operating characteristic curve of each of the scales was calculated in terms of mortality for every time frame (2, 7, 14, and 30 days). We determined the cut-off point of each scale that offered highest sensitivity and specificity using the Youden index. RESULTS: A total of 1716 participants were included, and the in-hospital mortality rates at 2, 7, 14, and 30 days were of 7.8% (134 cases), 11.6% (200 cases), 14.2% (243 cases), and 17.2% (295 cases), respectively. The best cut-off point determined in the NEWS2 was 6.5 points (sensitivity of 97% and specificity of 59%), and for lactate, the cut-off point was 3.3 mmol/L (sensitivity of 79% and specificity of 72%). Finally, the combined NEWS2-L showed a cut-off point of 11.7 (sensitivity of 86% and a specificity of 85%). The area under the receiver operating characteristic curve of the NEWS2, lactate, and NEWS2-L in the validation cohort for 2-day mortality was 0.889, 0.856, and 0.923, respectively (p<0.001 in all cases). CONCLUSIONS: The new score generated, NEWS2-L, obtained better statistical results than its components (NEWS2 and lactate) separately.

Development of chronic pain in males with traumatic spinal cord injury: role of circulating levels of the chemokines CCL2 and CXCL10 in subacute stage.

STUDY DESIGN: Longitudinal study. OBJECTIVES: To assess the impact of spinal cord injury (SCI) on circulating levels of chemokines (CCL2 and CXCL10) and its relation with pain development. SETTING: National Hospital for SCI patients. METHODS: We longitudinally studied changes in the circulating levels of CCL2 and CXCL10 in 27 male patients with complete SCI who were evaluated in the early subacute phase and indeed 3 and 6 months after injury measuring at each time-point serum levels of CCL2 and CXCL10. Patients were telephonically interviewed about pain 1 year after SCI. RESULTS: In the early subacute phase, patients with pain showed higher CXCL10 and similar CCL2 levels as opposed to those without pain. Moreover, CCL2 concentrations were positively associated with pain intensity. The results obtained by analysing the temporal profile of the chemokines suggested that CXCL10 was inclined to decrease over time, while CCL2 increased over time. CONCLUSION: The results of this preliminary study, the first performed in humans with traumatic SCI, suggest a link between changes in the circulating chemokine profile and pain development in subacute SCI stage as well as with severity in a more chronic stage. Large series studies will evaluate whether the circulating chemokine status can be useful as a biomarker for assessing the patients' risk for pain development.

Angiotensin II type-2 receptor stimulation induces neuronal VEGF synthesis after cerebral ischemia.

Intense efforts are being undertaken to understand the pathobiology of ischemia and to develop novel and effective treatments. Angiotensin II type 2 receptor (AT2R) is related with a beneficial role in neurodegenerative disorders, including ischemia. However, the underlying molecular mechanism remains elusive. In this study, we have established that AT2R stimulation by C21 compound, a specific AT2R agonist, caused a VEGF upregulation. Using mouse primary cortical neurons exposed to oxygen-glucose deprivation (OGD), we established that this effect was mediated by a mechanism dependent of mTORC1 signaling since mTOR inhibition abolished the C21-induced VEGF upregulation. Also, we have temporally characterized the changes on VEGF levels after ischemia induction in rats using two different approaches: transient and permanent middle cerebral artery occlusion (tMCAO and pMCAO). VEGF levels were permanently augmented after reperfusion (tMCAO) whereas lower levels of VEGF were found after pMCAO, remarkably at 21days. Therefore, C21 compound accelerated the recovery of the neurological status of pMCAO rats, reduced the ischemic damage area and abolished pMCAO-induced VEGF downregulation at 21days. This effect of C21 compound was mainly observed in neurons of the peri-infarct area. Our results suggest that a C21-induced VEGF upregulation may be crucial after an ischemic neuronal insult in both of our experimental approaches. This upregulation was mediated by a mechanism dependent of Akt/mTOR signaling pathway, since mTOR inhibition abolished the VEGF upregulation induced by C21. Considering that VEGF is involved in regenerative processes, we propose that AT2R activation could be used as a potential pharmacological strategy after ischemic stroke.

The effects of expectancy on corticospinal excitability: passively preparing to observe a movement.

The corticospinal tract excitability is modulated when preparing movements. Earlier to movement execution, the excitability of the spinal cord increases waiting for supraspinal commands to release the movement. Movement execution and movement observation share processes within the motor system, although movement observation research has focused on processes later to movement onset. We used single and paired pulse transcranial magnetic stimulation on M1 (n = 12), and electrical cervicomedullary stimulation (n = 7), to understand the modulation of the corticospinal system during the "preparation" to observe a third person's movement. Subjects passively observed a hand that would remain still or make an index finger extension. The observer's corticospinal excitability rose when "expecting to see a movement" vs. when "expecting to see a still hand." The modulation took origin at a spinal level and not at the corticocortical networks explored. We conclude that expectancy of seeing movements increases the excitability of the spinal cord.

Combining transcranial direct current stimulation with hand robotic rehabilitation in chronic stroke patients: a double blind randomized clinical trial.

OBJECTIVE: This study aimed to assess the impact of combining transcranial direct current stimulation (tDCS) with end-effector robot-assisted treatment (RAT) on upper limb function, spasticity, and hand dexterity in chronic stroke patients. DESIGN: This was a prospective, double-blind randomized trial with 20 equally allocated stroke patients. The experimental group received dual-tDCS (anode over affected M1, cathode over contralateral M1) alongside RAT, while the control group received sham tDCS with the same electrode placement + RAT. Each patient underwent 20 combined tDCS and RAT sessions. The primary outcome measure was the Fugl Meyer Upper Limb motor score (mFM-UL), with secondary outcomes including AMADEO® kinematic measures, Action Research Arm Test (ARAT), and Functional Independence Measure (FIM). Assessments were conducted at baseline, post-rehabilitation, and three months later. RESULTS: Combining bilateral tDCS with RAT did not yield additional improvements in mFM-UL, FIM, or ARAT scores among stroke patients. However, the real tDCS group showed enhanced finger flexion in the affected hand based on AMADEO® kinematic measures. CONCLUSION: The addition of tDCS to RAT did not result in significant overall functional improvements in chronic stroke patients. However, a benefit was observed in finger flexion of the affected hand.

Is the Combination of Robot-Assisted Therapy and Transcranial Direct Current Stimulation Useful for Upper Limb Motor Recovery? A Systematic Review with Meta-Analysis.

Stroke is the third leading cause of disability in the world, and effective rehabilitation is needed to improve lost functionality post-stroke. In this regard, robot-assisted therapy (RAT) and transcranial direct current stimulation (tDCS) are promising rehabilitative approaches that have been shown to be effective in motor recovery. In the past decade, they have been combined to study whether their combination produces adjuvant and greater effects on stroke recovery. The aim of this study was to estimate the effectiveness of the combined use of RATs and tDCS in the motor recovery of the upper extremities after stroke. After reviewing 227 studies, we included nine randomised clinical trials (RCTs) in this study. We analysed the methodological quality of all nine RCTs in the meta-analysis. The analysed outcomes were deficit severity, hand dexterity, spasticity, and activity. The addition of tDCS to RAT produced a negligible additional benefit on the effects of upper limb function (SMD -0.09, 95% CI -0.31 to 0.12), hand dexterity (SMD 0.12, 95% CI -0.22 to 0.46), spasticity (SMD 0.04, 95% CI -0.24 to 0.32), and activity (SMD 0.66, 95% CI -1.82 to 3.14). There is no evidence of an additional effect when adding tDCS to RAT for upper limb recovery after stroke. Combining tDCS with RAT does not improve upper limb motor function, spasticity, and/or hand dexterity. Future research should focus on the use of RAT protocols in which the patient is given an active role, focusing on the intensity and dosage, and determining how certain variables influence the success of RAT.

A Prospective Observational Study of Frailty in Geriatric Revitalization Aimed at Community-Dwelling Elderly.

(1) Background: The increasing life expectancy brings an increase in geriatric syndromes, specifically frailty. The literature shows that exercise is a key to preventing, or even reversing, frailty in community-dwelling populations. The main objective is to demonstrate how an intervention based on multicomponent exercise produces an improvement in frailty and pre-frailty in a community-dwelling population. (2) Methods: a prospective observational study of a multicomponent exercise program for geriatric revitalization with people aged over 65 holding Barthel Index scores equal to, or beyond, 90. The program was developed over 30 weeks, three times a week, in sessions lasting 45-50 min each. Frailty levels were registered by the Short Physical Performance Battery, FRAIL Questionnaire Screening Tool, and Timed "Up & Go" at the beginning of the program, 30 weeks later (at the end of the program), and following 13 weeks without training; (3) Results: 360 participants completed the program; a greater risk of frailty was found before the program started among older women living in urban areas, with a more elevated fat percentage, more baseline pathologies, and wider baseline medication use. Furthermore, heterogeneous results were observed both in training periods and in periods without physical activity. However, they are consistent over time and show improvement after training. They show a good correlation between TUG and SPPB; (4) Conclusions: A thirty-week multicomponent exercise program improves frailty and pre-frailty status in a community-dwelling population with no functional decline. Nevertheless, a lack of homogeneity is evident among the various tools used for measuring frailty over training periods and inactivity periods.

Serum Ferritin in Obese Dogs: Changes and Comparison with Other Analytes.

Canine obesity is the most common nutritional disorder and is associated with decreased quality of life and longevity as well as comorbidities including cardiorespiratory, endocrine, oncologic, or orthopaedic disorders. Ferritin is a major acute-phase protein in dogs, increasing during inflammation; however, it could also be affected by other conditions, including trauma, iron metabolism dysregulations, neoplasia, or hypoxia. Higher ferritin levels have been reported in obese humans, but ferritin has not been explored in canine obesity. To evaluate the possible changes in serum ferritin in canine obesity, ferritin levels from lean/normal weight (CG, n = 55) and overweight/obese dogs (OG, n = 37) were measured, together with complete hemogram and biochemical analyses. Statistically significant higher ferritin levels (1.2-fold) were found in OG (median, (interquartile range), 204 (166-227.5) µg/L) in comparison to CG animals (172 (137-210) µg/L)), with median levels of ferritin in OG dogs above the reference range for healthy animals in our laboratory (60-190 µg/L). In addition, statistically significant higher mean corpuscular volume (MCV), mean cell haemoglobin concentration (MCHC), total proteins, globulins, haptoglobin, total ferric fixation capacity (TIBC), alkaline phosphatase (ALP), butyrylcholinesterase (BChE), triglycerides, and calcium were observed in OG in comparison to CG. The higher levels in ferritin, together with higher TBIC, haematocrit, and MCV, could indicate tissue hypoxia in obese dogs.

Clinical outcome prediction of acute neurological patients admitted to the emergency department: Sequential Organ Failure Assessment score and modified SOFA score.

Background: The aim of this study was to determine the ability of the Sequential Organ Failure Assessment score (SOFA) and modified SOFA score (mSOFA) as predictive tools for 2-day and 28-day mortality and ICU admission in patients with acute neurological pathology treated in hospital emergency departments (EDs). Methods: An observational, prospective cohort study in adults with acute neurological disease transferred by ambulance to an ED was conducted from 1 January 2019 to 31 August 2022 in five hospitals in Castilla-León (Spain). Score discrimination was assessed by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve of the score. Results: A total of 640 adult patients with neurological disease were included. For the prediction of 2-day mortality (all-cause), mSOFA presented a higher AUC than SOFA (mSOFA = 0.925 vs. SOFA = 0.902). This was not the case for 28-day mortality, for which SOFA was higher than mSOFA (mSOFA = 0.852 vs. SOFA = 0.875). Finally, ICU admission showed that SOFA was higher than mSOFA (mSOFA = 0.834 vs. SOFA = 0.845). Conclusion: Both mSOFA and SOFA presented similar predictive ability, with mSOFA being the best predictor for short-term mortality and SOFA being the best predictor for medium-term mortality, as well as for ICU admission. These results in a cohort of patients with acute neurological pathology pave the way for the use of both predictive tools in the ED. The inclusion of these tools could improve the clinical assessment and further treatment of neurological patients, who commonly present the worst outcomes.

Side chain-oxidized oxysterols regulate the brain renin-angiotensin system through a liver X receptor-dependent mechanism.

Disturbances in cholesterol metabolism have been associated with hypertension and neurodegenerative disorders. Because cholesterol metabolism in the brain is efficiently separated from plasma cholesterol by the blood-brain barrier (BBB), it is an unsolved paradox how high blood cholesterol can cause an effect in the brain. Here, we discuss the possibility that cholesterol metabolites permeable to the BBB might account for these effects. We show that 27-hydroxycholesterol (27-OH) and 24S-hydroxycholesterol (24S-OH) up-regulate the renin-angiotensin system (RAS) in the brain. Brains of mice on a cholesterol-enriched diet showed up-regulated angiotensin converting enzyme (ACE), angiotensinogen (AGT), and increased JAK/STAT activity. These effects were confirmed in in vitro studies with primary neurons and astrocytes exposed to 27-OH or 24S-OH, and were partially mediated by liver X receptors. In contrast, brain RAS activity was decreased in Cyp27a1-deficient mice, a model exhibiting reduced 27-OH production from cholesterol. Moreover, in humans, normocholesterolemic patients with elevated 27-OH levels, due to a CYP7B1 mutation, had markers of activated RAS in their cerebrospinal fluid. Our results demonstrate that side chain-oxidized oxysterols are modulators of brain RAS. Considering that levels of cholesterol and 27-OH correlate in the circulation and 27-OH can pass the BBB into the brain, we suggest that this cholesterol metabolite could be a link between high plasma cholesterol levels, hypertension, and neurodegeneration.

side-chain-oxidized oxysterols upregulate ACE2 and Mas receptor in rat primary neurons.

BACKGROUND: Disturbances in cholesterol metabolism have been associated with hypertension and Alzheimer's disease (AD). We recently reported increased angiotensin-converting enzyme (ACE) activity and angiotensinogen (AGT) levels in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment and AD. ACE activity positively correlated with plasma and CSF 27-hydroxycholesterol (27-OH) levels, an oxysterol that passes to the brain from the blood. Additionally, we showed that 27-OH and 24(S)-hydroxycholesterol (24S-OH) enhance AGT synthesis and modulate renin and ACE activities in brain cells. OBJECTIVES: To gain insight into how oxysterols affect the brain renin-angiotensin system (RAS), we analyzed the effects of 24S-OH and 27-OH on two other proteins in this system: ACE2 and Mas receptor (MasR). METHODS: RT-PCR and Western blot analysis in rat primary neurons treated with either 24S-OH or 27-OH. RESULTS: The levels of ACE2 and MasR were increased by a physiological concentration (1 µM) of these oxysterols after 24 h. CONCLUSIONS: 24S-OH and 27-OH enhance the brain RAS by acting on different levels, from the precursor to several downstream enzymes. Our results support the idea that disturbances in cholesterol metabolism would contribute to alterations in the brain RAS, which further suggest mechanistic links between two well-known risk factors for AD: hypercholesterolemia and hypertension.

Hand Motor Fatigability Induced by a Simple Isometric Task in Spinal Cord Injury.

This study aimed: (1) to evaluate the hand motor fatigability in people with spinal cord injury (SCI) and compare it with measurements obtained form an able-bodied population; (2) to compare the hand motor fatigability in people with tetraplegia and in people with paraplegia; and (3) to analyse if motor fatigability is different in people with SCI with and without clinical significant perceived fatigability. MATERIALS AND METHODS: 96 participants with SCI (40 cervical and 56 thoracolumbar) and 63 able-bodied controls performed a simple hand isometric task to assess motor fatigability. The Fatigue Severity Scale was used for perceived fatigability evaluation. RESULTS: The main results of this study can be summarized as follows: (1) the waning in muscle force (motor fatigability) during a fatiguing task is similar in controls and participants with SCI; (2) the motor fatigability is influenced by the maximal muscle force (measured at the beginning of the task); and (3) the perceived fatigability and the motor fatigability are largely independent in the individuals with SCI. CONCLUSION: Our findings suggest that the capability to maintain a prolonged effort is preserved in SCI, and this capacity depends on the residual maximal muscle force in people with SCI.

Static magnetic field stimulation over motor cortex modulates resting functional connectivity in humans.

Focal application of transcranial static magnetic field stimulation (tSMS) over the human motor cortex induces local changes in cortical excitability. Whether tSMS can also induce distant network effects, and how these local and distant effects may vary over time, is currently unknown. In this study, we applied 10 min tSMS over the left motor cortex of healthy subjects using a real/sham parallel design. To measure tSMS effects at the sensori-motor network level, we used resting-state fMRI. Real tSMS, but not sham, reduced functional connectivity within the stimulated sensori-motor network. This effect of tSMS showed time-dependency, returning to sham levels after the first 5 min of fMRI scanning. With 10 min real tSMS over the motor cortex we did not observe effects in other functional networks examined (default mode and visual system networks). In conclusion, 10 min of tSMS over a location within the sensori-motor network reduces functional connectivity within the same functional network.

Comparison of Nine Early Warning Scores for Identification of Short-Term Mortality in Acute Neurological Disease in Emergency Department.

(1) Background: The aim was screening the performance of nine Early Warning Scores (EWS), to identify patients at high-risk of premature impairment and to detect intensive care unit (ICU) admissions, as well as to track the 2-, 7-, 14-, and 28-day mortality in a cohort of patients diagnosed with an acute neurological condition. (2) Methods: We conducted a prospective, longitudinal, observational study, calculating the EWS [Modified Early Warning Score (MEWS), National Early Warning Score (NEWS), VitalPAC Early Warning Score (ViEWS), Modified Rapid Emergency Medicine Score (MREMS), Early Warning Score (EWS), Hamilton Early Warning Score (HEWS), Standardised Early Warning Score (SEWS), WHO Prognostic Scored System (WPSS), and Rapid Acute Physiology Score (RAPS)] upon the arrival of patients to the emergency department. (3) Results: In all, 1160 patients were included: 808 patients were hospitalized, 199 cases (17%) required ICU care, and 6% of patients died (64 cases) within 2 days, which rose to 16% (183 cases) within 28 days. The highest area under the curve for predicting the need for ICU admissions was obtained by RAPS and MEWS. For predicting mortality, MREMS obtained the best scores for 2- and 28-day mortality. (4) Conclusions: This is the first study to explore whether several EWS accurately identify the risk of ICU admissions and mortality, at different time points, in patients with acute neurological disorders. Every score analyzed obtained good results, but it is suggested that the use of RAPS, MEWS, and MREMS should be preferred in the acute setting, for patients with neurological impairment.

COVID-19 as a risk factor for long-term mortality in patients managed by the emergency medical system: A prospective, multicenter, ambulance-based cohort study.

Introduction: COVID-19 has initially been studied in terms of an acute-phase disease, although recently more attention has been given to the long-term consequences. In this study, we examined COVID-19 as an independent risk factor for long-term mortality in patients with acute illness treated by EMS (emergency medical services) who have previously had the disease against those who have not had the disease. Methods: A prospective, multicenter, ambulance-based, ongoing study was performed with adult patients with acute disease managed by EMS and transferred with high priority to the emergency department (ED) as study subjects. The study involved six advanced life support units, 38 basic life support units, and five emergency departments from Spain. Sociodemographic inputs, baseline vital signs, pre-hospital blood tests, and comorbidities, including COVID-19, were collected. The main outcome was long-term mortality, which was classified into 1-year all-cause mortality and 1-year in- and out-of-hospital mortality. To compare both the patients with COVID-19 vs. patients without COVID-19 and to compare survival vs non-survival, two main statistical analyses were performed, namely, a longitudinal analysis (Cox regression) and a logistic regression analysis. Results: Between 12 March 2020 and 30 September 2021, a total of 3,107 patients were included in the study, with 2,594 patients without COVID-19 and 513 patients previously suffering from COVID-19. The mortality rate was higher in patients with COVID-19 than in patients without COVID-19 (31.8 vs. 17.9%). A logistic regression showed that patients previously diagnosed with COVID-19 presented higher rates of nursing home residency, a higher number of breaths per minute, and suffering from connective disease, dementia, and congestive heart failure. The longitudinal analysis showed that COVID-19 was a risk factor for mortality [hazard ratio 1.33 (1.10-1.61); p < 0.001]. Conclusion: The COVID-19 group presented an almost double mortality rate compared with the non-COVID-19 group. The final model adjusted for confusion factors suggested that COVID-19 was a risk factor for long-term mortality.

Transcranial static magnetic field stimulation of the human motor cortex.

The aim of the present study was to investigate in healthy humans the possibility of a non-invasive modulation of motor cortex excitability by the application of static magnetic fields through the scalp. Static magnetic fields were obtained by using cylindrical NdFeB magnets. We performed four sets of experiments. In Experiment 1, we recorded motor potentials evoked by single-pulse transcranial magnetic stimulation (TMS) of the motor cortex before and after 10 min of transcranial static magnetic field stimulation (tSMS) in conscious subjects. We observed an average reduction of motor cortex excitability of up to 25%, as revealed by TMS, which lasted for several minutes after the end of tSMS, and was dose dependent (intensity of the magnetic field) but not polarity dependent. In Experiment 2, we confirmed the reduction of motor cortex excitability induced by tSMS using a double-blind sham-controlled design. In Experiment 3, we investigated the duration of tSMS that was necessary to modulate motor cortex excitability. We found that 10 min of tSMS (compared to 1 min and 5 min) were necessary to induce significant effects. In Experiment 4, we used transcranial electric stimulation (TES) to establish that the tSMS-induced reduction of motor cortex excitability was not due to corticospinal axon and/or spinal excitability, but specifically involved intracortical networks. These results suggest that tSMS using small static magnets may be a promising tool to modulate cerebral excitability in a non-invasive, painless, and reversible way.

Cholinergic hypofunction impairs memory acquisition possibly through hippocampal Arc and BDNF downregulation.

Recent evidence suggests that activity-regulated cytoskeleton associated protein (Arc) and brain-derived neurotrophic factor (BDNF) are key players in the cellular mechanisms that trigger synaptic changes and memory consolidation. Cholinergic deafferentiation of hippocampus has been largely shown to induce memory impairments in different behavioral tasks. However, the mechanisms underlying cholinergic-induced memory formation remain unclear. The role of hippocampal cholinergic denervation on synaptic consolidation and further acquisition of spatial memory was hereby examined by analyzing Arc and BDNF in standard environment and after behavioral training in Morris water maze (MWM). In standard environment, a cholinergic hypofunction induced by the toxin (192) IgG-saporin led to significant decreases in Arc protein and mRNA as well as in BDNF. Lesioned rats subjected to MWM showed a worse acquisition performance that was reversed after galantamine treatment. Recovery of memory acquisition was accompanied by normalization of Arc and BDNF levels in hippocampus. Stimulation of muscarinic, but not nicotinic receptors, in hippocampal primary neurons caused a rapid induction of Arc production. These data suggest that cholinergic denervation of hippocampus leads to deficits in muscarinic-dependent induction of Arc and a subsequent impairment of spatial memory acquisition.