Personal omics profiling reveals dynamic molecular and medical phenotypes.

Personalized medicine is expected to benefit from combining genomic information with regular monitoring of physiological states by multiple high-throughput methods. Here, we present an integrative personal omics profile (iPOP), an analysis that combines genomic, transcriptomic, proteomic, metabolomic, and autoantibody profiles from a single individual over a 14 month period. Our iPOP analysis revealed various medical risks, including type 2 diabetes. It also uncovered extensive, dynamic changes in diverse molecular components and biological pathways across healthy and diseased conditions. Extremely high-coverage genomic and transcriptomic data, which provide the basis of our iPOP, revealed extensive heteroallelic changes during healthy and diseased states and an unexpected RNA editing mechanism. This study demonstrates that longitudinal iPOP can be used to interpret healthy and diseased states by connecting genomic information with additional dynamic omics activity.

Involvement of ArlI, ArlJ, and CirA in archaeal type IV pilin-mediated motility regulation.

Many prokaryotes use swimming motility to move toward favorable conditions and escape adverse surroundings. Regulatory mechanisms governing bacterial flagella-driven motility are well-established; however, little is yet known about the regulation underlying swimming motility propelled by the archaeal cell surface structure, the archaella. Previous research showed that the deletion of the adhesion pilins (PilA1-6), subunits of the type IV pili cell surface structure, renders the model archaeon Haloferax volcanii non-motile. In this study, we used ethyl methanesulfonate mutagenesis and a motility assay to identify motile suppressors of the ∆pilA[1-6] strain. Of the eight suppressors identified, six contain missense mutations in archaella biosynthesis genes, arlI and arlJ. In trans expression of arlI and arlJ mutant constructs in the respective multi-deletion strains ∆pilA[1-6]∆arlI and ∆pilA[1-6]∆arlJ confirmed their role in suppressing the ∆pilA[1-6] motility defect. Additionally, three suppressors harbor co-occurring disruptive missense and nonsense mutations in cirA, a gene encoding a proposed regulatory protein. A deletion of cirA resulted in hypermotility, while cirA expression in trans in wild-type cells led to decreased motility. Moreover, quantitative real-time PCR analysis revealed that in wild-type cells, higher expression levels of arlI, arlJ, and the archaellin gene arlA1 were observed in motile early-log phase rod-shaped cells compared to non-motile mid-log phase disk-shaped cells. Conversely, ∆cirA cells, which form rods during both early- and mid-log phases, exhibited similar expression levels of arl genes in both growth phases. Our findings contribute to a deeper understanding of the mechanisms governing archaeal motility, highlighting the involvement of ArlI, ArlJ, and CirA in pilin-mediated motility regulation.IMPORTANCEArchaea are close relatives of eukaryotes and play crucial ecological roles. Certain behaviors, such as swimming motility, are thought to be important for archaeal environmental adaptation. Archaella, the archaeal motility appendages, are evolutionarily distinct from bacterial flagella, and the regulatory mechanisms driving archaeal motility are largely unknown. Previous research has linked the loss of type IV pili subunits to archaeal motility suppression. This study reveals three Haloferax volcanii proteins involved in pilin-mediated motility regulation, offering a deeper understanding of motility regulation in this understudied domain while also paving the way for uncovering novel mechanisms that govern archaeal motility. Understanding archaeal cellular processes will help elucidate the ecological roles of archaea as well as the evolution of these processes across domains.

IL-10 indirectly modulates functional activity of CD4+CD28null T-lymphocytes through LFA-3 and HLA class II inhibition.

Expansion of CD4+CD28null T-lymphocytes is common in chronic heart failure (CHF) patients. Its ability to produce high levels of proinflammatory cytokines is probably the key role of these cells in CHF. IL-10 is a candidate for limiting CD4+CD28null T-lymphocyte responses, whereas tumour necrosis factor (TNF) is the cytokine most closely involved in the loss of CD28 expression. Serum levels of TNF and IL-10 were measured in 65 CHF patients (mean age, 65.2 ± 13.84 years). Patients with an IL-10/TNF ratio ≥1 had significantly lower levels of CD4+CD28null T-lymphocytes than those with a ratio <1. In vitro, IL-10 reduced the frequency of proliferative CD4+CD28null T-lymphocytes stimulated with anti-CD3. Pre-treatment with IL-10 before anti-CD3 stimulation was required for the cytokine to inhibit TNF production by CD4+CD28null T-lymphocytes. In addition to the previously described effect of IL-10 on HLA-DR and ICAM-1 expression, LFA-3 protein and mRNA levels were reduced in the presence of the cytokine in monocytes. IL-10 inhibition on CD4+CD28null T-lymphocytes may be mediated by a reduction in HLA class II and LFA-3 expression because blocking interactions with these costimulators has similar effects to those of IL-10 treatment. Moreover, costimulation through CD2/LFA-3 interaction is enough to induce proliferation and cytokine production in CD4+CD28null T-lymphocytes.

Social approach and avoidance in language: N400-like ERP negativity indexes congruency and theta rhythms the conflict.

Motivational congruency has been examined using tasks where participants perform approach or avoidance movements towards socially positive or negative faces. Language is tightly intertwined with interpersonal cognition. Thus, similar situations could be represented by means of language in interpersonal contexts: adjectives furnish valence to people (e.g. someone is cordial or arrogant), and attitudinal verbs define direction to relationship-actions: approach-avoidance (e.g. accept vs. reject). In an Electroencephalography (EEG) study, 40 participants were presented with sentences where a character was valenced (e.g. "Arthur is cordial/arrogant") before being the target of a relationship-actions ("Grisela welcomed/ignored Arthur at the party"). We analyzed both Event-related potential (ERP) amplitude and time-frequency power in response to the attitudinal verb. For ERP amplitudes, we found a significant cluster between 280 and 370 ms, covering part of the development of a N400-like ERP component. This cluster reflects an interaction driven by congruency between motivational direction and target valence. Likewise, time-frequency power analysis revealed an enhancement of theta rhythms under incongruent conditions, most likely indexing conflict processing. Results support that relationship-actions are represented as approach and avoidance and thus involve conflict processing and resolution of incongruent situations. Implications for the interweaving of affective language and social cognition within Embodiment Simulation Theory are discussed.

Randomised, double-blind, placebo-controlled, parallel-group, multicentric, phase IIA clinical trial for evaluating the safety, tolerability, and therapeutic efficacy of daily oral administration of NFX88 to treat neuropathic pain in individuals with spinal cord injury.

STUDY DESIGN: Double-blind, randomized, placebo-controlled, parallel-group multicentric phase IIA clinical trial. OBJECTIVE: To assess the safety and tolerability of oral administration of NFX-88 in subjects with chronic spinal cord injury (SCI) and explore its efficacy in pain control. SETTING: A total of 7 spinal cord injury rehabilitation units in Spain. METHODS: A total of 61 adult with traumatic complete or incomplete spinal cord injury (C4-T12 level), were randomised 1:1:1:1 to a placebo, NFX88 1.05 g, 2.1 g, 4.2 g/day for up to 12 weeks. The placebo or NFX-88 was administered as add-on therapy to pre-existing pregabalin (150-300 mg per day). Safety and tolerability were evaluated, and the Visual Analogue Scale (VAS) was the primary measure to explore the efficacy of NFX-88 in pain control. RESULTS: No severe treatment-related adverse effects were reported for any of the four study groups. 44 SCI individuals completed the study and were analysed. The data obtained from the VAS analysis and the PainDETECT Questionnaire (PD-Q) suggested that the combination of NFX88 with pregabalin is more effective than pregabalin with placebo at reducing neuropathic pain (NP) in individuals with SCI and that the dose 2.10 g/day causes the most dramatic pain relief. CONCLUSIONS: NFX88 treatment was found to be highly safe and well tolerated, with the dose of 2.10 g/day being the most effective at causing pain relief. Thus, the promising efficacy of this first-in-class lipid mediator deserves further consideration in future clinical trials.

Forearm Posture Affects the Corticospinal Excitability of Intrinsic and Extrinsic Hand Muscles in Dominant and Nondominant Sides.

Different forearm postures can modulate corticospinal excitability. However, there is no consensus on whether handedness plays a role in such a mechanism. This study investigated the effects of 3 forearm postures (pronation, neutral, and supination) on the corticospinal excitability of muscles from the dominant and nondominant upper limbs. Surface electromyography was recorded from the abductor digiti minimi, flexor pollicis brevis, and flexor carpi radialis from both sides of 12 right-handed volunteers. Transcranial magnetic stimulation pulses were applied to each muscle's hotspot in both cerebral hemispheres. Motor-evoked potential peak-to-peak amplitude and latency and resting motor threshold were measured. The data were evaluated by analysis of variance. The level of significance was set at 5%. The resting motor threshold was similar for the 3 muscles and both sides. Motor-evoked potential peak-to-peak amplitude from flexor pollicis brevis was lower during supination, and the dominant upper limb latency was longer. The flexor carpi radialis presented lower motor-evoked potential peak-to-peak amplitudes for neutral and shorter latencies during supination. Abductor digiti minimi seemed not to be affected by posture or side. Different muscles from dominant and nondominant sides may undergo corticospinal modulation, even distally localized from a particular joint and under rest.

Repeated Administration of 2-Hydroxypropyl-ß-Cyclodextrin (HPßCD) Attenuates the Chronic Inflammatory Response to Experimental Stroke.

Globally, more than 67 million people are living with the effects of ischemic stroke. Importantly, many stroke survivors develop a chronic inflammatory response that may contribute to cognitive impairment, a common and debilitating sequela of stroke that is insufficiently studied and currently untreatable. 2-Hydroxypropyl-ß-cyclodextrin (HPßCD) is an FDA-approved cyclic oligosaccharide that can solubilize and entrap lipophilic substances. The goal of the present study was to determine whether the repeated administration of HPßCD curtails the chronic inflammatory response to stroke by reducing lipid accumulation within stroke infarcts in a distal middle cerebral artery occlusion mouse model of stroke. To achieve this goal, we subcutaneously injected young adult and aged male mice with vehicle or HPßCD 3 times per week, with treatment beginning 1 week after stroke. We evaluated mice at 7 weeks following stroke using immunostaining, RNA sequencing, lipidomic, and behavioral analyses. Chronic stroke infarct and peri-infarct regions of HPßCD-treated mice were characterized by an upregulation of genes involved in lipid metabolism and a downregulation of genes involved in innate and adaptive immunity, reactive astrogliosis, and chemotaxis. Correspondingly, HPßCD reduced the accumulation of lipid droplets, T lymphocytes, B lymphocytes, and plasma cells in stroke infarcts. Repeated administration of HPßCD also preserved NeuN immunoreactivity in the striatum and thalamus and c-Fos immunoreactivity in hippocampal regions. Additionally, HPßCD improved recovery through the protection of hippocampal-dependent spatial working memory and reduction of impulsivity. These results indicate that systemic HPßCD treatment following stroke attenuates chronic inflammation and secondary neurodegeneration and prevents poststroke cognitive decline.SIGNIFICANCE STATEMENT Dementia is a common and debilitating sequela of stroke. Currently, there are no available treatments for poststroke dementia. Our study shows that lipid metabolism is disrupted in chronic stroke infarcts, which causes an accumulation of uncleared lipid debris and correlates with a chronic inflammatory response. To our knowledge, these substantial changes in lipid homeostasis have not been previously recognized or investigated in the context of ischemic stroke. We also provide a proof of principle that solubilizing and entrapping lipophilic substances using HPßCD could be an effective strategy for treating chronic inflammation after stroke and other CNS injuries. We propose that using HPßCD for the prevention of poststroke dementia could improve recovery and increase long-term quality of life in stroke sufferers.

The evolving landscape of COVID-19 and post-COVID condition in patients with chronic lymphocytic leukemia: A study by ERIC, the European research initiative on CLL.

In this retrospective international multicenter study, we describe the clinical characteristics and outcomes of patients with chronic lymphocytic leukemia (CLL) and related disorders (small lymphocytic lymphoma and high-count monoclonal B lymphocytosis) infected by SARS-CoV-2, including the development of post-COVID condition. Data from 1540 patients with CLL infected by SARS-CoV-2 from January 2020 to May 2022 were included in the analysis and assigned to four phases based on cases disposition and SARS-CoV-2 variants emergence. Post-COVID condition was defined according to the WHO criteria. Patients infected during the most recent phases of the pandemic, though carrying a higher comorbidity burden, were less often hospitalized, rarely needed intensive care unit admission, or died compared to patients infected during the initial phases. The 4-month overall survival (OS) improved through the phases, from 68% to 83%, p = .0015. Age, comorbidity, CLL-directed treatment, but not vaccination status, emerged as risk factors for mortality. Among survivors, 6.65% patients had a reinfection, usually milder than the initial one, and 16.5% developed post-COVID condition. The latter was characterized by fatigue, dyspnea, lasting cough, and impaired concentration. Infection severity was the only risk factor for developing post-COVID. The median time to resolution of the post-COVID condition was 4.7 months. OS in patients with CLL improved during the different phases of the pandemic, likely due to the improvement of prophylactic and therapeutic measures against SARS-CoV-2 as well as the emergence of milder variants. However, mortality remained relevant and a significant number of patients developed post-COVID conditions, warranting further investigations.

Effect of muscle length in a handgrip task on corticomotor excitability of extrinsic and intrinsic hand muscles under resting and submaximal contraction conditions.

The neurophysiological mechanisms underlying muscle force control for different wrist postures still need to be better understood. To further elucidate these mechanisms, the present study aimed to investigate the effects of wrist posture on the corticospinal excitability by transcranial magnetic stimulation (TMS) of extrinsic (flexor [FCR] and extensor carpi radialis [ECR]) and intrinsic (flexor pollicis brevis (FPB)) muscles at rest and during a submaximal handgrip strength task. Fourteen subjects (24.06 ± 2.28 years) without neurological or motor disorders were included. We assessed how the wrist posture (neutral: 0°; flexed: +45°; extended: -45°) affects maximal handgrip strength (HGSmax ) and the motor evoked potentials (MEP) amplitudes during rest and active muscle contractions. HGSmax was higher at 0° (133%) than at -45° (93.6%; p < 0.001) and +45° (73.9%; p < 0.001). MEP amplitudes were higher for the FCR at +45° (83.6%) than at -45° (45.2%; p = 0.019) and at +45° (156%; p < 0.001) and 0° (146%; p = 0.014) than at -45° (106%) at rest and active condition, respectively. Regarding the ECR, the MEP amplitudes were higher at -45° (113%) than at +45° (60.8%; p < 0.001) and 0° (72.6%; p = 0.008), and at -45° (138%) than +45° (96.7%; p = 0.007) also at rest and active conditions, respectively. In contrast, the FPB did not reveal any difference among wrist postures and conditions. Although extrinsic and intrinsic hand muscles exhibit overlapping cortical representations and partially share the same innervation, they can be modulated differently depending on the biomechanical constraints.

Automated diagnosis of 7 canine skin tumors using machine learning on H&E-stained whole slide images.

Microscopic evaluation of hematoxylin and eosin-stained slides is still the diagnostic gold standard for a variety of diseases, including neoplasms. Nevertheless, intra- and interrater variability are well documented among pathologists. So far, computer assistance via automated image analysis has shown potential to support pathologists in improving accuracy and reproducibility of quantitative tasks. In this proof of principle study, we describe a machine-learning-based algorithm for the automated diagnosis of 7 of the most common canine skin tumors: trichoblastoma, squamous cell carcinoma, peripheral nerve sheath tumor, melanoma, histiocytoma, mast cell tumor, and plasmacytoma. We selected, digitized, and annotated 350 hematoxylin and eosin-stained slides (50 per tumor type) to create a database divided into training, n = 245 whole-slide images (WSIs), validation (n = 35 WSIs), and test sets (n = 70 WSIs). Full annotations included the 7 tumor classes and 6 normal skin structures. The data set was used to train a convolutional neural network (CNN) for the automatic segmentation of tumor and nontumor classes. Subsequently, the detected tumor regions were classified patch-wise into 1 of the 7 tumor classes. A majority of patches-approach led to a tumor classification accuracy of the network on the slide-level of 95% (133/140 WSIs), with a patch-level precision of 85%. The same 140 WSIs were provided to 6 experienced pathologists for diagnosis, who achieved a similar slide-level accuracy of 98% (137/140 correct majority votes). Our results highlight the feasibility of artificial intelligence-based methods as a support tool in diagnostic oncologic pathology with future applications in other species and tumor types.

Association Between Protocols of the Sit-to-Stand Test and Lower Limb Muscle Force Output in Patients on Hemodialysis and Subjects Without Chronic Kidney Disease.

OBJECTIVE: To evaluate the association of three protocols of the sit-to-stand (STS) test with muscle force output of knee extension (KE) and knee flexion (KF) in patients on hemodialysis and subjects without chronic kidney disease. METHODS: This cross-sectional study included a hemodialysis group [n = 60, 59.5 (16.8) years, 55% female] and a control group [n = 60, 43.0 (11.8) years, 50% female]. The assessments were performed in 2 days, and the participants were submitted to three protocols of STS test (5-repetition STS, 10-repetition STS and 30-s STS) or muscle force output of the KE and KF evaluation by handheld dynamometer based on randomization. RESULTS: The hemodialysis group presented reduced muscle force output of the KE and KF, a longer time to perform the 5 STS and 10 STS tests, and a lower number of repetitions in the 30-s STS test. The three STS tests were associated with muscle force output of the KE in the hemodialysis group, in which the 10-repetition STS test showed the best association (R2 = 0.47; adjusted R2 = 0.42). However, the only association between the STS test and muscle force output of the KE in the control group was found in the 10-repetition STS test (R2 = 0.20; adjusted R2 = 0.13). CONCLUSIONS: The three protocols of STS tests were associated with muscle force output of the KE in patients on hemodialysis. However, the 10-repetition STS test was the best protocol to estimate the quadriceps muscle torque in these patients.

Sustainable Cellulose Nanofibers-Mediated Synthesis of Uniform Spinel Zn-Ferrites Nanocorals for High Performances in Supercapacitors.

Spinel ferrites are versatile, low-cost, and abundant metal oxides with remarkable electronic and magnetic properties, which find several applications. Among them, they have been considered part of the next generation of electrochemical energy storage materials due to their variable oxidation states, low environmental toxicity, and possible synthesis through simple green chemical processing. However, most traditional procedures lead to the formation of poorly controlled materials (in terms of size, shape, composition, and/or crystalline structure). Thus, we report herein a cellulose nanofibers-mediated green procedure to prepare controlled highly porous nanocorals comprised of spinel Zn-ferrites. Then, they presented remarkable applications as electrodes in supercapacitors, which were thoroughly and critically discussed. The spinel Zn-ferrites nanocorals supercapacitor showed a much higher maximum specific capacitance (2031.81 F g-1 at a current density of 1 A g-1) than Fe2O3 and ZnO counterparts prepared by a similar approach (189.74 and 24.39 F g-1 at a current density of 1 A g-1). Its cyclic stability was also scrutinized via galvanostatic charging/discharging and electrochemical impedance spectroscopy, indicating excellent long-term stability. In addition, we manufactured an asymmetric supercapacitor device, which offered a high energy density value of 18.1 Wh kg-1 at a power density of 2609.2 W kg-1 (at 1 A g-1 in 2.0 mol L-1 KOH electrolyte). Based on our findings, we believe that higher performances observed for spinel Zn-ferrites nanocorals could be explained by their unique crystal structure and electronic configuration based on crystal field stabilization energy, which provides an electrostatic repulsion between the d electrons and the p orbitals of the surrounding oxygen anions, creating a level of energy that determines their final supercapacitance then evidenced, which is a very interesting property that could be explored for the production of clean energy storage devices.

Boosting Mitochondrial Biogenesis Diminishes Foam Cell Formation in the Post-Stroke Brain.

Following ischemic stroke, the degradation of myelin and other cellular membranes surpasses the lipid-processing capabilities of resident microglia and infiltrating macrophages. This imbalance leads to foam cell formation in the infarct and areas of secondary neurodegeneration, instigating sustained inflammation and furthering neurological damage. Given that mitochondria are the primary sites of fatty acid metabolism, augmenting mitochondrial biogenesis (MB) may enhance lipid processing, curtailing foam cell formation and post-stroke chronic inflammation. Previous studies have shown that the pharmacological activation of the ß2-adrenergic receptor (ß2-AR) stimulates MB. Consequently, our study sought to discern the effects of intensified ß2-AR signaling on MB, the processing of brain lipid debris, and neurological outcome using a mouse stroke model. To achieve this goal, aged mice were treated with formoterol, a long-acting ß2-AR agonist, daily for two and eight weeks following stroke. Formoterol increased MB in the infarct region, modified fatty acid metabolism, and reduced foam cell formation. However, it did not reduce markers of post-stroke neurodegeneration or improve recovery. Although our findings indicate that enhancing MB in myeloid cells can aid in the processing of brain lipid debris after stroke, it is important to note that boosting MB alone may not be sufficient to significantly impact stroke recovery.

Post-Stroke Administration of the p75 Neurotrophin Receptor Modulator, LM11A-31, Attenuates Chronic Changes in Brain Metabolism, Increases Neurotransmitter Levels, and Improves Recovery.

The aim of this study was to test whether poststroke oral administration of a small molecule p75 neurotrophin receptor (p75NTR) modulator (LM11A-31) can augment neuronal survival and improve recovery in a mouse model of stroke. Mice were administered LM11A-31 for up to 12 weeks, beginning 1 week after stroke. Metabolomic analysis revealed that after 2 weeks of daily treatment, mice that received LM11A-31 were distinct from vehicle-treated mice by principal component analysis and had higher levels of serotonin, acetylcholine, and dopamine in their ipsilateral hemisphere. LM11A-31 treatment also improved redox homeostasis by restoring reduced glutathione. It also offset a stroke-induced reduction in glycolysis by increasing acetyl-CoA. There was no effect on cytokine levels in the infarct. At 13 weeks after stroke, adaptive immune cell infiltration in the infarct was unchanged in LM11A-31-treated mice, indicating that LM11A-31 does not alter the chronic inflammatory response to stroke at the site of the infarct. However, LM11A-31-treated mice had less brain atrophy, neurodegeneration, tau pathology, and microglial activation in other regions of the ipsilateral hemisphere. These findings correlated with improved recovery of motor function on a ladder test, improved sensorimotor and cognitive abilities on a nest construction test, and less impulsivity in an open field test. These data support small molecule modulation of the p75NTR for preserving neuronal health and function during stroke recovery. SIGNIFICANCE STATEMENT: The findings from this study introduce the p75 neurotrophin receptor as a novel small molecule target for promotion of stroke recovery. Given that LM11A-31 is in clinical trials as a potential therapy for Alzheimer's disease, it could be considered as a candidate for assessment in stroke or vascular dementia studies.

International Population Study in Spain, Cuba, and the United States of Attitudes Toward Organ Donation Among the Cuban Population.

Cuban immigrants constitute an important group in both the United States and Spain, with different behaviors toward organ donation having been described among the different Latin American nationalities. We analyzed the attitude toward organ donation among the Cuban populations in Cuba, Spain, and Florida. The study population was Cuban immigrants over 15 years of age residing in Cuba, Spain, and Florida, with samples randomly stratified by age and sex. A validated questionnaire on psychosocial aspects of organ donation (PCID-DTO Rios) was used. Census was used as the sampling base in all 3 countries; however, additionally, in Spain and the United States (Florida), we sought the support of immigration support associations to determine the Cuban population without legal documentation. The questionnaire was completed anonymously and self-administered. The completion rate of the study was 74% (4123/5574) among 424 surveyed in Spain, 1224 in Florida, and 2475 in Cuba. The attitude in favor of donating their own organs upon death was 60.6% of those surveyed in Spain, 37.6% in Florida, and 68.9% in Cuba, or 58% of the global sample. Multivariate analysis showed that country of residence was an independent factor associated with attitude toward organ donation (odds ratio, 1.929). Other factors associated with attitude were sex, educational level, performance of prosocial activities, knowledge of the brain death concept, religion, the couple's opinion toward donation, fear of mutilation after donation, and attitude toward manipulation of the body after death. The attitude toward organ donation among Cubans in their country of origin and immigrants in Spain was similar, being significantly different from those who emigrate to Florida, where the attitude is much less favorable.

Forearm and Hand Muscles Exhibit High Coactivation and Overlapping of Cortical Motor Representations.

Most of the motor mapping procedures using navigated transcranial magnetic stimulation (nTMS) follow the conventional somatotopic organization of the primary motor cortex (M1) by assessing the representation of a particular target muscle, disregarding the possible coactivation of synergistic muscles. In turn, multiple reports describe a functional organization of the M1 with an overlapping among motor representations acting together to execute movements. In this context, the overlap degree among cortical representations of synergistic hand and forearm muscles remains an open question. This study aimed to evaluate the muscle coactivation and representation overlapping common to the grasping movement and its dependence on the stimulation parameters. The nTMS motor maps were obtained from one carpal muscle and two intrinsic hand muscles during rest. We quantified the overlapping motor maps in size (area and volume overlap degree) and topography (similarity and centroid Euclidean distance) parameters. We demonstrated that these muscle representations are highly overlapped and similar in shape. The overlap degrees involving the forearm muscle were significantly higher than only among the intrinsic hand muscles. Moreover, the stimulation intensity had a stronger effect on the size compared to the topography parameters. Our study contributes to a more detailed cortical motor representation towards a synergistic, functional arrangement of M1. Understanding the muscle group coactivation may provide more accurate motor maps when delineating the eloquent brain tissue during pre-surgical planning.

Regional accents modulate perspective in geographical space.

In this study, participants listened to first-person statements that mentioned a character who was approaching a geographical location close to (Tenerife, Canary Islands) or distant from the participant (Madrid, Spanish peninsula), pronounced with either the participants' local or a distal regional accent. Participants more often judged approaching statements as coherent when they refer to a close place pronounced with local accent or refer to a distant place with distal accent, rather than when they refer to a close place with distal accent or to a distant place with local accent. These results strongly suggest that the local accent induces listeners to keep their own geographical perspective, whereas the distal accent determines shifting to another's perspective. In sum, a subtle paralinguistic cue, the speaker's regional accent, modulates the participants' geographic perspective when they listen to identical first-person sentences with approaching deictic verbs.

Preventive treatment with alendronate of loss of bone mineral density in acute traumatic spinal cord injury. Randomized controlled clinical trial.

STUDY DESIGN: Randomized controlled clinical trial of two parallel groups. OBJECTIVES: Analyse the efficacy of primary prevention with alendronate on the loss of bone mass which occurs during the first year of traumatic SCI, measured by double-energy X-ray bone densitometry (DXA). SETTING: National Hospital for Paraplegics (HNP), Toledo, Spain. METHODS: We included 52 people admitted to the HNP with traumatic SCI Grade A and B on the ASIA Impairment Scale and less than 8 weeks of progression, which were randomized to one of the two treatment groups. Both groups received calcifediol and a calcium-enriched diet for 52 weeks. Only one group was administered alendronate 70 mg weekly. The dose of alendronate was adjusted according to changes in serum ß-CTX. RESULTS: 52 Participants were randomized. Of the 26 assigned to each group, 4 patients were lost in the alendronate group and 3 in the control group. The random distribution of women was asymmetrical, so we analysed the effect of treatment on men. In the total left hip, the mean (SD) decrease in bone mass was -22.791% (10.768) in the control group compared to the mean (SD) decrease of -2.693% (6.283) in the same location in the alendronate group (p < 0.0001). No patient presented related adverse events. CONCLUSION: Alendronate administered for one year in the first 8 weeks after traumatic SCI decreases bone loss in the hip in men. This treatment is well tolerated.

Building a network of TP53 and IGHV testing reference centers across Spain: the Red53 initiative.

Among the different biomarkers predicting response in chronic lymphocytic leukemia (CLL), the most influential parameters are the mutational status of the IGHV genes and the presence of TP53 gene disruptions. Nevertheless, these important assessments are not readily available in most centers dealing with CLL patients. To provide this molecular testing across the country, the Spanish Cooperative Group on CLL (GELLC) established a network of four analytical reference centers. A total of 2153 samples from 256 centers were analyzed over a period of 30 months. In 9% of the patients, we found pathological mutations in the TP53 gene, whereas 48.96% were classified as IGHV unmutated. Results of the satisfaction survey of the program showed a Net Promoter Score of 85.15. Building a national network for molecular testing in CLL allowed the CLL population a broad access to complex biomarkers analysis that should translate into a more accurate and informed therapeutic decision-making.

Usefulness of an organ donation opinion survey as a tool to promote organ donation among the adolescent population.

Opinion surveys on health issues are considered health promotion tools. However, no studies have confirmed this in deceased organ donation for transplantation. This study aimed to analyse the impact of completing an opinion questionnaire about deceased organ donation on the attitude towards organ donation among the adolescent population. This longitudinal study with repeated measurements of attitude towards deceased organ donation was conducted with an adolescent population. The measurement instrument was a validated questionnaire of the attitude towards organ donation (PCID-DTO-Ríos). The study process involved the application of the questionnaire at an initial time, 1 month later, and 6 months later. A total of 1374 adolescents participated in this study. The favourable attitude towards donation was 43.1%, which fell to 41.4% at 1 month (P = 0.145), and to 39.7% at 6 months (P = 0.019). Changes in the attitude were observed in all groups, both 1 and 6 months after the questionnaire was completed. There was no objective relationship between the adolescent's socio-family environment and the effect of completing the questionnaire on their attitude towards deceased organ donation. In conclusion, the opinion questionnaire was not useful for promoting organ donation and did not have a positive effect on adolescents' attitudes towards organ donation in the medium or long term.