Metaplasticity A Promising Tool to Disentangle Chronic Disorders of Consciousness Differential Diagnosis

The extent of cortical reorganization after brain injury in patients with Vegetative State/Unresponsive Wakefulness Syndrome (UWS) and Minimally Conscious State (MCS) depends on the residual capability of modulating synaptic plasticity. Neuroplasticity is largely abnormal in patients with UWS, although the fragments of cortical activity may exist, while patients MCS show a better cortical organization. The aim of this study was to evaluate cortical excitability in patients with disorders of consciousness (DoC) using a transcranial direct current stimulation (TDCS) metaplasticity protocol. To this end, we tested motor-evoked potential (MEP) amplitude, short intracortical inhibition (SICI), and intracortical facilitation (ICF). These measures were correlated with the level of consciousness (by the Coma Recovery Scale-Revised, CRS-R). MEP amplitude, SICI, and ICF strength were significantly modulated following different metaplasticity TDCS protocols only in the patients with MCS. SICI modulations showed a significant correlation with the CRS-R score. Our findings demonstrate, for the first time, a partial preservation of metaplasticity properties in some patients with DoC, which correlates with the level of awareness. Thus, metaplasticity assessment may help the clinician in differentiating the patients with DoC, besides the clinical evaluation. Moreover, the responsiveness to metaplasticity protocols may identify the subjects who could benefit from neuromodulation protocols

Interleukin-1 Receptor Antagonist Modulates the Early Phase of Liver Regeneration after Partial Hepatectomy in Mice

Cytokine administration is a potential therapy for acute liver failure by reducing inflammatory responses and favour hepatocyte regeneration. The aim of this study was to evaluate the role of interleukin-1 receptor antagonist (IL-1ra) during liver regeneration and to study the effect of a recombinant human IL-1ra on liver regeneration

Clinical Study Sativex in the Management of Multiple Sclerosis-Related Spasticity: Role of the Corticospinal Modulation

Sativex is an emergent treatment option for spasticity in patients affected by multiple sclerosis (MS). This oromucosal spray, acting as a partial agonist at cannabinoid receptors, may modulate the balance between excitatory and inhibitory neurotransmitters, leading to muscle relaxation that is in turn responsible for spasticity improvement. Nevertheless, since the clinical assessment may not be sensitive enough to detect spasticity changes, other more objective tools should be tested to better define the real drug effect. The aim of our study was to investigate the role of Sativex in improving spasticity and related symptomatology in MS patients by means of an extensive neurophysiological assessment of sensory-motor circuits. To this end, 30 MS patients underwent a complete clinical and neurophysiological examination, including the following electrophysiological parameters: motor threshold, motor evoked potentials amplitude, intracortical excitability, sensory-motor integration, and H max /M max ratio. The same assessment was applied before and after one month of continuous treatment. Our data showed an increase of intracortical inhibition, a significant reduction of spinal excitability, and an improvement in spasticity and associated symptoms. Thus, we can speculate that Sativex could be effective in reducing spasticity by means of a double effect on intracortical and spinal excitability

Peeling the Otolith of Fish: Optimal Parameterization for Micro-CT Scanning

In this paper, we aim to provide optimal parameters for micro-computed tomography scans of fish otoliths. We tested fifteen different combinations to sagittae. The images were scaled to Hounsfield units, and segmented in two distinct volumes-of-interest (external and internal). The strategy we applied, for identifying optimum scan settings for otoliths, included analyses of the sinogram, the distribution of the Hounsfield units and the signal-to-noise ratio. Based on these tests, the optimum sets of parameters for the acquisition of tomographic images of sagittal otoilths were 80 kV, 220 μA, and 0.5 mm aluminum filter. The method allowed 3D shape analysis, internal and external density distribution, layer-by-layer density segmentation, and a potential objective method to count growth rings in otoliths. It was possible to compare mean densities between species, and we observed a significant difference among them. In addition, there are ontogenic changes, which could be increasing or decreasing the density. In this study, we applied tomography for several otolith analysis, that could be of great interest for future studies in diverse areas that use otoliths as the basic structure of analysis, or represents a new research line called eco-densitometry of otoliths, where tomography could be applied to explore the density within an ecological perspective.Fil: Vasconcelos Filho, Jonas. Universidad Federal Rural Pernambuco; BrasilFil: Thomsen, Felix Sebastian Leo. Universidad Nacional del Sur. Departamento de Ingeniería Eléctrica y de Computadoras; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca; ArgentinaFil: Stosic, Borko. Universidad Federal Rural Pernambuco; BrasilFil: Antonino, Antonio C. D.. Universidad Federal Rural Pernambuco; BrasilFil: Duarte, Daniel A.. Universidad Federal Rural Pernambuco; BrasilFil: Heck, Richard J.. University of Guelph; CanadáFil: Lessa, Rosangela P. T.. Universidad Federal Rural Pernambuco; BrasilFil: Santana, Francisco M.. Universidad Federal Rural Pernambuco; BrasilFil: Ferreira, Beatrice P.. Universidad Federal Rural Pernambuco; BrasilFil: Duarte Neto, Paulo J.. Universidad Federal Rural Pernambuco; Brasi

Biliverdin Protects against Liver Ischemia Reperfusion Injury in Swine

Ischemia reperfusion injury (IRI) in organ transplantation remains a serious and unsolved problem. Organs that undergo significant damage during IRI, function less well immediately after reperfusion and tend to have more problems at later times when rejection can occur. Biliverdin has emerged as an agent that potently suppress IRI in rodent models. Since the use of biliverdin is being developed as a potential therapeutic modality for humans, we tested the efficacy for its effects on IRI of the liver in swine, an accepted and relevant pre-clinical animal model. Administration of biliverdin resulted in rapid appearance of bilirubin in the serum and significantly suppressed IRI-induced liver dysfunction as measured by multiple parameters including urea and ammonia clearance, neutrophil infiltration and tissue histopathology including hepatocyte cell death. Taken together, our findings, in a large animal model, provide strong support for the continued evaluation of biliverdin as a potential therapeutic in the clinical setting of transplantation of the liver and perhaps other organs

A Plague of Magnetic Spots Among the Hot Stars of Globular Clusters

Six decades and counting, the formation of hot ~20,000-30,000 K Extreme Horizontal Branch (EHB) stars in Galactic Globular Clusters remains one of the most elusive quests in stellar evolutionary theory. Here we report on two discoveries shattering their currently alleged stable luminosity. The first EHB variability is periodic and cannot be ascribed to binary evolution nor pulsation. Instead, we here attribute it to the presence of magnetic spots: superficial chemical inhomogeneities whose projected rotation induces the variability. The second EHB variability is aperiodic and manifests itself on time-scales of years. In two cases, the six-year light curves display superflare events a mammoth several million times more energetic than solar analogs. We advocate a scenario where the two spectacular EHB variability phenomena are different manifestations of diffuse, dynamo-generated, weak magnetic fields. Ubiquitous magnetic fields, therefore, force an admittance into the intricate matrix governing the formation of all EHBs, and traverse to their Galactic field counterparts. The bigger picture is one where our conclusions bridge similar variability/magnetism phenomena in all radiative-enveloped stars: young main-sequence stars, old EHBs and defunct white dwarfs.Comment: Author's version of the main article (23 pages) and Supplementary Information (22 pages) combined into a single pdf (45 pages). Readers invited to read the Nature Astronomy Published version available at this url: https://www.nature.com/articles/s41550-020-1113-

Bone Health in Adults With Prader-Willi Syndrome : Clinical Recommendations Based on a Multicenter Cohort Study

Prader-Willi syndrome (PWS) is a rare complex genetic syndrome, characterized by delayed psychomotor development, hypotonia, and hyperphagia. Hormone deficiencies such as hypogonadism, hypothyroidism, and growth hormone deficiency are common. The combination of hypotonia, low physical activity, and hypogonadism might lead to a decrease in bone mass and increase in fracture risk. Moreover, one would expect an increased risk of scoliosis due to hypotonia and low physical activity. To study the prevalence and risk factors for skeletal problems (reduced bone mineral density, fractures, and scoliosis) in adults with PWS. We retrospectively collected patient characteristics, medical history, medication, biochemical measurements, dual-energy X-ray absorptiometry scans, and spinal X-rays and reviewed the current literature. We included 354 adults with PWS (median age 31 years; 43% males), of whom 51 (14%) had osteoporosis (T-score below −2.5) and 143 (54%) had osteopenia (T-score −1 to −2.5). The most prevalent modifiable risk factors for osteoporosis were hypogonadism, insufficient dairy intake, sedentary lifestyle, and corticosteroid use. Male sex was associated with osteoporosis (P =.005). Growth hormone treatment was not associated with osteoporosis. A history of vertebral fractures was present in 10 (3%) and nonvertebral fractures in 59 (17%). Scoliosis was present in 263 (80%), but no modifiable risk factors were identified. Besides scoliosis, osteoporosis is common in adults with PWS. Based on the literature and the risk factors for osteoporosis found in our cohort, we provide practical clinical recommendations to avoid skeletal complications in these vulnerable patients

Minimally invasive vs. open segmental resection of the splenic flexure for cancer: a nationwide study of the Italian Society of Surgical Oncology-Colorectal Cancer Network (SICO-CNN)

Background Evidence on the efficacy of minimally invasive (MI) segmental resection of splenic flexure cancer (SFC) is not available, mostly due to the rarity of this tumor. This study aimed to determine the survival outcomes of MI and open treatment, and to investigate whether MI is noninferior to open procedure regarding short-term outcomes. Methods This nationwide retrospective cohort study included all consecutive SFC segmental resections performed in 30 referral centers between 2006 and 2016. The primary endpoint assessing efficacy was the overall survival (OS). The secondary endpoints included cancer-specific mortality (CSM), recurrence rate (RR), short-term clinical outcomes (a composite of Clavien-Dindo > 2 complications and 30-day mortality), and pathological outcomes (a composite of lymph nodes removed >= 12, and proximal and distal free resection margins length >= 5 cm). For these composites, a 6% noninferiority margin was chosen based on clinical relevance estimate. Results A total of 606 patients underwent either an open (208, 34.3%) or a MI (398, 65.7%) SFC segmental resection. At univariable analysis, OS and CSM were improved in the MI group (log-rank test p = 0.004 and Gray's tests p = 0.004, respectively), while recurrences were comparable (Gray's tests p = 0.434). Cox multivariable analysis did not support that OS and CSM were better in the MI group (p = 0.109 and p = 0.163, respectively). Successful pathological outcome, observed in 53.2% of open and 58.3% of MI resections, supported noninferiority (difference 5.1%; 1-sided 95%CI - 4.7% to infinity). Successful short-term clinical outcome was documented in 93.3% of Open and 93.0% of MI procedures, and supported noninferiority as well (difference - 0.3%; 1-sided 95%CI - 5.0% to infinity). Conclusions Among patients with SFC, the minimally invasive approach met the criterion for noninferiority for postoperative complications and pathological outcomes, and was found to provide results of OS, CSM, and RR comparable to those of open resection

Diversity and ethics in trauma and acute care surgery teams: results from an international survey

Background Investigating the context of trauma and acute care surgery, the article aims at understanding the factors that can enhance some ethical aspects, namely the importance of patient consent, the perceptiveness of the ethical role of the trauma leader, and the perceived importance of ethics as an educational subject. Methods The article employs an international questionnaire promoted by the World Society of Emergency Surgery. Results Through the analysis of 402 fully filled questionnaires by surgeons from 72 different countries, the three main ethical topics are investigated through the lens of gender, membership of an academic or non-academic institution, an official trauma team, and a diverse group. In general terms, results highlight greater attention paid by surgeons belonging to academic institutions, official trauma teams, and diverse groups. Conclusions Our results underline that some organizational factors (e.g., the fact that the team belongs to a university context or is more diverse) might lead to the development of a higher sensibility on ethical matters. Embracing cultural diversity forces trauma teams to deal with different mindsets. Organizations should, therefore, consider those elements in defining their organizational procedures. Level of evidence Trauma and acute care teams work under tremendous pressure and complex circumstances, with their members needing to make ethical decisions quickly. The international survey allowed to shed light on how team assembly decisions might represent an opportunity to coordinate team member actions and increase performance