The Broad Concept of "Spasticity-Plus Syndrome" in Multiple Sclerosis: A Possible New Concept in the Management of Multiple Sclerosis Symptoms

Multiple sclerosis (MS) pathology progressively affects multiple central nervous system (CNS) areas. Due to this fact, MS produces a wide array of symptoms. Symptomatic therapy of one MS symptom can cause or worsen other unwanted symptoms (anticholinergics used for bladder dysfunction produce impairment of cognition, many MS drugs produce erectile dysfunction, etc.). Appropriate symptomatic therapy is an unmet need. Several important functions/symptoms (muscle tone, sleep, bladder, pain) are mediated, in great part, in the brainstem. Cannabinoid receptors are distributed throughout the CNS irregularly: There is an accumulation of CB1 and CB2 receptors in the brainstem. Nabiximols (a combination of THC and CBD oromucosal spray) interact with both CB1 and CB2 receptors. In several clinical trials with Nabiximols for MS spasticity, the investigators report improvement not only in spasticity itself, but also in several functions/symptoms mentioned before (spasms, cramps, pain, gait, sleep, bladder function, fatigue, and possibly tremor). We can conceptualize and, therefore, hypothesize, through this indirect information, that it could be considered the existence of a broad "Spasticity-Plus Syndrome" that involves, a cluster of symptoms apart from spasticity itself, the rest of the mentioned functions/symptoms, probably because they are interlinked after the increase of muscle tone and mediated, at least in part, in the same or close areas of the brainstem. If this holds true, there exists the possibility to treat several spasticity-related symptoms induced by MS pathology with a single therapy, which would permit to avoid the unnecessary adverse effects produced by polytherapy. This would result in an important advance in the symptomatic management of MS

Aversive memory formation in humans involves an amygdala-hippocampus phase code

Memory for aversive events is central to survival but can become maladaptive in psychiatric disorders. Memory enhancement for emotional events is thought to depend on amygdala modulation of hippocampal activity. However, the neural dynamics of amygdala-hippocampal communication during emotional memory encoding remain unknown. Using simultaneous intracranial recordings from both structures in human patients, here we show that successful emotional memory encoding depends on the amygdala theta phase to which hippocampal gamma activity and neuronal firing couple. The phase difference between subsequently remembered vs. not-remembered emotional stimuli translates to a time period that enables lagged coherence between amygdala and downstream hippocampal gamma. These results reveal a mechanism whereby amygdala theta phase coordinates transient amygdala -hippocampal gamma coherence to facilitate aversive memory encoding. Pacing of lagged gamma coherence via amygdala theta phase may represent a general mechanism through which the amygdala relays emotional content to distant brain regions to modulate other aspects of cognition, such as attention and decision-making

Un monestir a la cruïlla. Els inventaris de sagristia del monestir de Sant Antoni i Santa Clara de Barcelona (1389-1461)

The Monastery of Santa Clara and San Antonio in Barcelona was the first community of the Order of St. Clare in Catalonia. The present article reveals the wealth of its sacristy inventories as first-class historical sources. The study illustrates the special characteristics of the series of documents in the monastery’s archives: its authorship (by female sacristans) as well as the main types of items inventoried and described (liturgical clothing and ornaments, jewelry, works of art, books ...). The ensemble provides a rich perspective on female monastic culture with regard to its involvement in liturgy, sacred imagery and written culture. One of the outstanding results is an appreciation of the careful and detailed functional design applied by the community of nuns to each item, to keep track of time and the liturgical calendar, as well as to manage and live their relationship with the outside world.[ca] En el present article es posa al descobert la riquesa com a font històrica de primer ordre dels inventaris de sagristia del monestir de Sant Antoni i Santa Clara de Barcelona, primera comunitat de l’orde de Santa Clara en terres catalanes. L’estudi ens acosta a les particularitats d’aquesta sèrie documental en el seu fons arxivístic, la seva autoria (el càrrec de sagristana), així com a les principals tipologies de béns inventariats i descrits (parament i vestimenta litúrgica, orfebreria, obres d’art, llibres...). El conjunt permet donar una imatge rica de la cultura monàstica femenina, en l’acompanyament de la litúrgia, en la imatgeria sagrada, en la cultura escrita. Entre els resultats, sobresurt, la concepció funcional, curosa i detallada que la comunitat de germanes féu de cada peça, a l’hora de marcar el temps i el calendari litúrgic, com també a l’hora de gestionar i viure el dins/fora, la relació amb l’exterior

Accuracy of transcutaneous bilirubin on covered skin in preterm and term newborns receiving phototherapy using a JM-105 bilirubinometer

OBJECTIVE: Determine the suitability of transcutaneous bilirubin (TCB) as a tool to assess the effectiveness of phototherapy on patched skin. STUDY DESIGN: A prospective observational study was conducted. We covered a fragment of skin (sternum) with a photo-opaque patch. Several simultaneous TCB and TSB measurements were performed with the JM-105 bilirubinometer. Bland and Altman test evaluated the agreement between bilirubin levels. RESULT: A total of 217 patients were studied, 48.8% were preterm. The mean difference between TSB and TCB before the start of treatment was 1.07 mg/dL. During phototherapy, differences on covered skin were 0.52, 0.27, and 0.39 mg/dL at 24, 48, and 72 h of therapy respectively. The best correlation was observed at 48 h in preterm infants. CONCLUSION: The measurement of TCB on patched skin (PTCB) is useful for monitoring the response to phototherapy in term and preterm infants. We use a patch with a removable flap that eases successive measures without disturbing the patients

Influence of contaminant-spiked polyethylene-type microplastics on the growth and primary production of the freshwater phytoplankton species Scenedesmus armatus and Microcystis aeruginosa

Microplastic pollution and its ecological impact on the aquatic environment are a current focus of research in the scientific community. These microplastics may adsorb contaminants discharged into the aquatic environment, thereby serving as a sink and source for the dissemination of these associated chemical contaminants. However, knowledge about the potential risks of microplastics and associated chemical contaminants on aquatic biota, especially on primary freshwater producers, remains to be explored. In this study, the impact of a polyethylene microplastic type (MP) associated with amoxicillin, ibuprofen, sertraline and simazine (OCs) on the cell growth and photosynthetic activity of the green algae Scenedesmus armatus and the cyanobacteria Microcystis aeruginosa was evaluated after 28 days of exposure. The results show that all the organic contaminants and their respective MP-OC complexes induced stress on cell growth after 28 days of exposure, except when the cyanobacterial strain was exposed to amoxicillin and ibuprofen. Similarly, photosynthetic activity was affected by exposure to MP-OC complexes, with the most evident effect on cellular respiration in the cyanobacterial strain and on net photosynthesis in the green algae strain. Additionally, the ability of the M. aeruginosa strain to synthesize microcystin was significantly reduced. These results show that the formation of MP-OC complexes could reduce their adverse effects, although there is wide variability depending on both the type of organic contaminant and the photosynthetic organisms involved, so further studies are needed to better understand the interactions between these aquatic contaminants

A New Sugarcane Cystatin Strongly Binds to Dental Enamel and Reduces Erosion.

Cystatin B was recently identified as an acid-resistant protein in acquired enamel pellicle; it could therefore be included in oral products to protect against caries and erosion. However, human recombinant cystatin is very expensive, and alternatives to its use are necessary. Phytocystatins are reversible inhibitors of cysteine peptidases that are found naturally in plants. In plants, they have several biological and physiological functions, such as the regulation of endogenous processes, defense against pathogens, and response to abiotic stress. Previous studies performed by our research group have reported high inhibitory activity and potential agricultural and medical applications of several sugarcane cystatins, including CaneCPI-1, CaneCPI-2, CaneCPI-3, and CaneCPI-4. In the present study, we report the characterization of a novel sugarcane cystatin, named CaneCPI-5. This cystatin was efficiently expressed in Escherichia coli, and inhibitory assays demonstrated that it was a potent inhibitor of human cathepsins B, K, and L ( Ki = 6.87, 0.49, and 0.34 nM, respectively). The ability of CaneCPI-5 to bind to dental enamel was evaluated using atomic force microscopy. Its capacity to protect against initial enamel erosion was also tested in vitro via changes in surface hardness. CaneCPI-5 showed a very large force of interaction with enamel (e.g., compared with mucin and casein) and significantly reduced initial enamel erosion. These results suggest that the inclusion of CaneCPIs in dental products might confer protection against enamel erosion.This research was supported by the São Paulo Research Foundation (FAPESP) (CEPID-CBME #98/14138-2) and by the Royal Society (Newton Advanced Fellowship #NA140459). A.C.S. is a recipient of a scholarship from the National Council for Scientific and Technological Development (CNPq). M.C.M. received a grant from the Coordination for the Improvement of Higher Education Personnel (CAPES). V.T.P. received a grant from the FAPESP. F.H.-S. and M.A.R.B. were recipients of a productivity scholarship from the CNPq

Effect of central nervous system (CNS) metastases in a real-world multicenter cohort study of Spanish ALK-positive non-small cell lung cancer (NSCLC) patients (p)

Background: CNS is a common site of metastases in patients with ALK-positive NSCLC. CNS metastases are associated with a number of deleterious effects, such as reduction in quality of life. However, the relationship between brain metastases and prognosis remains unclear. We aimed to evaluate the effect of CNS metastases on overall survival (OS) in a multicenter cohort of Spanish ALK-positive NSCLC patients diagnosed between 2008 and 2017. Methods: We included patients with stage IV at diagnoses, followed up to April 2018; OS (months [m]) was estimated with the Kaplan-Meier method. Survival curves were compared between groups of patients using the log-rank test. Hazard risk (HR) to death was estimated with multivariable Cox model. Results: Out of 163 patients in the cohort, a total of 116 were evaluated, with a median of follow-up of 29.2 m and 59 deaths reported. Characteristics at diagnosis were a median age of 58 years, 50% female, 58.6% never-smokers, 54.3% with comorbidities, PS by ECOG 0-1 93.1%. CNS metastases (median number of lesions 6) were present in 43.1% of patients and 34% of patients with CNS metastases were treated with local therapy (11.8 % local radiotherapy and 76.5% holocraneal radiotherapy). ALK inhibitors as first line and second line treatment were administered to 45.5% and 78.6% of patients, respectively. The median OS was 39 months; OS in patients with CNS metastases at diagnosis was 34.4 m and 39.0 m in those without CNS metastases at diagnosis (p=.9). In patients without CNS metastases at baseline (n=60), 22 developed CNS, with a median OS greater than in those without CNS metastases during follow-up, although the difference is not significant (45.5 m vs 33.3 m; p=.9). There were 81 patients who presented with metastases in more than one organ and 33 patients with metastases in a single organ. The risk of death increased as the number of metastatic organs at diagnoses increased (HR=1.26, p=.0305), with worse OS in those presenting with liver metastases at diagnoses (21.1%, OS: 20 m), compared to those without tumor involvement (OS: 45.4 m; p =.008). Conclusions: OS was similar for ALK-positive NSCLC patients with and without CNS metastases at diagnoses. OS was worse as the number of metastatic organs at diagnosis increased, with liver metastases being associated with the highest risk of mortality

Particle-yield modification in jet-like azimuthal di-hadron correlations in Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

The yield of charged particles associated with high-$p_{\rm T}$ trigger particles ($8 < p_{\rm T} < 15$ GeV/$c$) is measured with the ALICE detector in Pb-Pb collisions at $\sqrt{s_{\rm NN}}$ = 2.76 TeV relative to proton-proton collisions at the same energy. The conditional per-trigger yields are extracted from the narrow jet-like correlation peaks in azimuthal di-hadron correlations. In the 5% most central collisions, we observe that the yield of associated charged particles with transverse momenta $p_{\rm T}> 3$ GeV/$c$ on the away-side drops to about 60% of that observed in pp collisions, while on the near-side a moderate enhancement of 20-30% is found.Comment: 15 pages, 2 captioned figures, 1 table, authors from page 10, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/350