Mechanistic versatility at Ir(PSiP) pincer catalysts: triflate proton shuttling from 2-Butyne to Diene and [3]Dendralene motifs

The five-coordinate hydrido complex [IrH(OTf)(PSiP)] (1) catalytically transforms 2-butyne into a mixture of its isomer 1,3-butadiene, and [3]dendralene and linear hexatriene dimerization products: (E)-4-methyl-3-methylene-1,4-hexadiene and (3Z)-3,4-dimethyl-1,3,5-hexatriene, respectively. Under the conditions of the catalytic reaction, benzene, and 363 K, the hexatriene further undergoes thermal electrocyclization into 2,3-dimethyl-1,3-cyclohexadiene. The reactions between 1 and the alkyne substrate allow isolation or nuclear magnetic resonance (NMR) observation of catalyst resting states and possible reaction intermediates, including complexes with the former PSiP pincer ligands disassembled into PSi and PC chelates, and species coordinating allyl or carbene fragments en route to products. The density functional theory (DFT) calculations guided by these experimental observations disclose competing mechanisms for C–H bond elaboration that move H atoms either classically, as hydrides, or as protons transported by the triflate. This latter role of triflate, previously recognized only for more basic anions such as carboxylates, is discussed to result from combining the unfavorable charge separation in the nonpolar solvent and the low electronic demand from the metal to the anion at coordination positions trans to silicon. Triflate deprotonation of methyl groups is key to release highly coordinating diene products from stable allyl intermediates, thus enabling catalytic cycling

Differences between plasma and cerebrospinal fluid glial fibrillary acidic protein levels across the Alzheimer Disease continuum

Importance: Glial fibrillary acidic protein (GFAP) is a marker of reactive astrogliosis that increases in the cerebrospinal fluid (CSF) and blood of individuals with Alzheimer disease (AD). However, it is not known whether there are differences in blood GFAP levels across the entire AD continuum and whether its performance is similar to that of CSF GFAP. Objective: To evaluate plasma GFAP levels throughout the entire AD continuum, from preclinical AD to AD dementia, compared with CSF GFAP. Design, Setting, and Participants: This observational, cross-sectional study collected data from July 29, 2014, to January 31, 2020, from 3 centers. The Translational Biomarkers in Aging and Dementia (TRIAD) cohort (Montreal, Canada) included individuals in the entire AD continuum. Results were confirmed in the Alzheimer’s and Families (ALFA+) study (Barcelona, Spain), which included individuals with preclinical AD, and the BioCogBank Paris Lariboisière cohort (Paris, France), which included individuals with symptomatic AD. Main Outcomes and Measures: Plasma and CSF GFAP levels measured with a Simoa assay were the main outcome. Other measurements included levels of CSF amyloid-β 42/40 (Aβ42/40), phosphorylated tau181 (p-tau181), neurofilament light (NfL), Chitinase-3-like protein 1 (YKL40), and soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and levels of plasma p-tau181 and NfL. Results of amyloid positron emission tomography (PET) were available in TRIAD and ALFA+, and results of tau PET were available in TRIAD. Results: A total of 300 TRIAD participants (177 women [59.0%]; mean [SD] age, 64.6 [17.6] years), 384 ALFA+ participants (234 women [60.9%]; mean [SD] age, 61.1 [4.7] years), and 187 BioCogBank Paris Lariboisière participants (116 women [62.0%]; mean [SD] age, 69.9 [9.2] years) were included. Plasma GFAP levels were significantly higher in individuals with preclinical AD in comparison with cognitively unimpaired (CU) Aβ-negative individuals (TRIAD: Aβ-negative mean [SD], 185.1 [93.5] pg/mL, Aβ-positive mean [SD], 285.0 [142.6] pg/mL; ALFA+: Aβ-negative mean [SD], 121.9 [42.4] pg/mL, Aβ-positive mean [SD], 169.9 [78.5] pg/mL). Plasma GFAP levels were also higher among individuals in symptomatic stages of the AD continuum (TRIAD: CU Aβ-positive mean [SD], 285.0 [142.6] pg/mL, mild cognitive impairment [MCI] Aβ-positive mean [SD], 332.5 [153.6] pg/mL; AD mean [SD], 388.1 [152.8] pg/mL vs CU Aβ-negative mean [SD], 185.1 [93.5] pg/mL; Paris: MCI Aβ-positive, mean [SD], 368.6 [158.5] pg/mL; AD dementia, mean [SD], 376.4 [179.6] pg/mL vs CU Aβ-negative mean [SD], 161.2 [67.1] pg/mL). Plasma GFAP magnitude changes were consistently higher than those of CSF GFAP. Plasma GFAP more accurately discriminated Aβ-positive from Aβ-negative individuals than CSF GFAP (area under the curve for plasma GFAP, 0.69-0.86; area under the curve for CSF GFAP, 0.59-0.76). Moreover, plasma GFAP levels were positively associated with tau pathology only among individuals with concomitant Aβ pathology. Conclusions and Relevance: This study suggests that plasma GFAP is a sensitive biomarker for detecting and tracking reactive astrogliosis and Aβ pathology even among individuals in the early stages of AD

Organizational climate in Spanish Public Health Services: Administration and Services Staff

The main goal of this research is to explore the organizational climate perceived by administrative and healthcare personnel working in Spanish healthcare services, analyzing the differences according to their health specialization, sex, age and professional status. The sample was made up of 3,787 individuals working in the administrative and healthcare services of the Public Health System of the Principality of Asturias, 88.7 % were working in specialist care and 11.3 % in primary care. Mean age was 51.88 (standard deviation of 6.28); 79.9 % were women and 20.1 % men. The organizational climate was assessed with the CLIOR scale. The organizational climate perceived is moderately positive, with a global mean of 3.03 on a scale of 1 to 5 points. The differences are statistically significant (p < .01) according to specialty, age and profession. A better working climate is perceived in primary care than in specialist care, and among older as compared to younger workers. The results indicate that the working climate perceived by administration and services staff employees in the Spanish healthcare context is moderately positive, with a better perceived climate in primary care than in specialist care

Maximum entropy niche-based modelling of seasonal changes in little bustard (Tetrax tetrax) distribution

P. 17-29The effects of habitat fragmentation on species may change seasonally mainly due to variations in resource availability and biotic interactions. In critical periods, such as winter, when the importance of intraspecific competition diminish, species may relax their environmental requirements widening their ecological niche to exploit the scarcer trophic resources more efficiently in comparison with spring. Those variations in niche width may implicate seasonal expansions/retractions in species distribution. In this sense, an integrated knowledge on the spatial arrangement of breeding and wintering suitable patches is essential to infer seasonal movements (migratory connectivity). This paper shows that little bustard environmental preferences were more predictable and complex (controlled by a larger number of environmental factors) in spring than in winter, when potential distribution and ecological niche width were slightly larger. In spring, habitat variables (i.e. percentage of dry crops and pasturelands and altitude) ruled species’ distribution; while, winter pattern was driven by mixed criteria, based on both habitat and climate (i.e. percentage of dry crops and wastelands and winter rainfall). Suitable patches were more connected across spatial scales in winter than in spring, i.e. landscape was perceived as less fragmented. The overlap between potential breeding and wintering distribution areas was high. In fact, most of the predicted wintering areas coincided or showed high connectedness with predicted breeding patches. Conversely, there were significant breeding patches that were predicted with low suitability, showing little connectedness with potential winter areas. Spring habitat was a better predictor of little bustard’s wintering range than vice versa, which has clear management implications (preserving breeding sites closer to wintering areas ensures the conservation of a larger proportion of the total distribution range). This is an example of how predictive large-scale modeling procedures can contribute to the optimization of land management aimed at species conservation.S

Transcranial static magnetic stimulation reduces seizures in a mouse model of Dravet syndrome

[Abstract] Dravet syndrome is a rare form of severe genetic epilepsy characterized by recurrent and long-lasting seizures. It appears around the first year of life, with a quick evolution toward an increase in the frequency of the seizures, accompanied by a delay in motor and cognitive development, and does not respond well to antiepileptic medication. Most patients carry a mutation in the gene SCN1A encoding the α subunit of the voltage-gated sodium channel Nav1.1, resulting in hyperexcitability of neural circuits and seizure onset. In this work, we applied transcranial static magnetic stimulation (tSMS), a non-invasive, safe, easy-to-use and affordable neuromodulatory tool that reduces neural excitability in a mouse model of Dravet syndrome. We demonstrate that tSMS dramatically reduced the number of crises. Furthermore, crises recorded in the presence of the tSMS were shorter and less intense than in the sham condition. Since tSMS has demonstrated its efficacy at reducing cortical excitability in humans without showing unwanted side effects, in an attempt to anticipate a possible use of tSMS for Dravet Syndrome patients, we performed a numerical simulation in which the magnetic field generated by the magnet was modeled to estimate the magnetic field intensity reached in the cerebral cortex, which could help to design stimulation strategies in these patients. Our results provide a proof of concept for nonpharmacological treatment of Dravet syndrome, which opens the door to the design of new protocols for treatment.Instituto de salud Carlos III; PI21/00151Xunta de Galicia; ED431C 2022/05 (CR)Ministerio de Ciencia e Innovacion (España); PID2019-108250RJ-10

Outbreak of persistent cutaneous abscesses due to Mycobacterium chelonae after mesotherapy sessions, Lima, Peru

Surtos de micobactérias de crescimento rápido têm sido relatados ocasionalmente. O estudo relata um surto de abscessos cutâneos por Mycobacterium chelonae após sessões de mesoterapia em Lima, Peru. De dezembro de 2004 a janeiro de 2005, 35 pessoas que haviam passado por sessões de mesoterapia apresentaram esses abscessos cutâneos. Treze (37%) desses casos suspeitos concordaram em realizar exames clínicos. Foram realizadas biópsias de punção de pele de lesões suspeitas e examinadas substâncias injetadas durante a mesoterapia. Os casos suspeitos eram predominantemente mulheres jovens e as lesões incluíram nódulos subcutâneos, abscessos e úlceras. Mycobacterium chelonae foi isolada de quatro pacientes e de um frasco de procaína. Em conclusão, é importante considerar a mesoterapia como fonte potencial de infecções de micobactérias de crescimento rápido.Outbreaks of rapidly growing mycobacteria have been occasionally described. The article reports an outbreak of cutaneous abscesses due to Mycobacterium chelonae following mesotherapy in Lima, Peru. From December 2004 through January 2005, 35 subjects who had participated in mesotherapy training sessions presented with persistent cutaneous abscesses. Thirteen (37%) of these suspected cases consented to underwent clinical examination. Skin punch-biopsies were collected from suspicious lesions and substances injected during mesotherapy were analyzed. Suspected cases were mainly young women and lesions included subcutaneous nodules, abscesses and ulcers. Mycobacterium chelonae was isolated from four patients and from a procaine vial. In conclusion, it is important to consider mesotherapy as a potential source of rapidly growing mycobacteria infections

Taxonomic and functional metagenomic profiling of the microbial community in the anoxic sediment of a sub-saline Shallow Lake (Laguna de Carrizo, Central Spain)

The phylogenetic and functional structure of the microbial community residing in a Ca2+-rich anoxic sediment of a sub-saline shallow lake (Laguna de Carrizo, initially operated as a gypsum (CaSO4 × 2 H2O) mine) was estimated by analyzing the diversity of 16S rRNA amplicons and a 3.1 Mb of consensus metagenome sequence. The lake has about half the salinity of seawater and possesses an unusual relative concentration of ions, with Ca2+ and SO 4 2- being dominant. The 16S rRNA sequences revealed a diverse community with about 22% of the bacterial rRNAs being less than 94.5% similar to any rRNA currently deposited in GenBank. In addition to this, about 79% of the archaeal rRNA genes were mostly related to uncultured Euryarchaeota of the CCA47 group, which are often associated with marine and oxygen-depleted sites. Sequence analysis of assembled genes revealed that 23% of the open reading frames of the metagenome library had no hits in the database. Among annotated genes, functions related to (thio) sulfate and (thio) sulfonate-reduction and iron-oxidation, sulfur-oxidation, denitrification, synthrophism, and phototrophic sulfur metabolism were found as predominant. Phylogenetic and biochemical analyses indicate that the inherent physical–chemical characteristics of this habitat coupled with adaptation to anthropogenic activities have resulted in a highly efficient community for the assimilation of polysulfides, sulfoxides, and organosulfonates together with nitro-, nitrile-, and cyanide-substituted compounds. We discuss that the relevant microbial composition and metabolic capacities at Laguna de Carrizo, likely developed as an adaptation to thrive in the presence of moderate salinity conditions and potential toxic bio-molecules, in contrast with the properties of previously known anoxic sediments of shallow lakes.This research was supported by the Spanish CSD2007-00005 project and FEDER funds. M-E.G. thanks the CSIC for a JAE fellowship.Peer Reviewe

Relationship between alcoholism addiction and periodontitis. An in vivo study using drinking-in-darkness protocol in rats.

Periodontal disease (PD) has been considered a probable risk factor for several systemic diseases. Among them, PD is presumed to be one of the possible etiologies of chronic illness of the central nervous system. In this context, poor oral health and PD is associated with substance abuse in humans. However, if periodontal lesions can produce addiction is unknown. This paper aims to evaluate the possibility that chronic periodontal injury (CPL) can cause ethanol binge intake in drink-in-darkness (DID) protocol in rats. In CPL group (n=10) experimental damage was done to the periodontal tissue of the second maxillary molar, the control group (n=9) received sham injury. Forty-three days after CPL the intake of ethanol was assessed using several concentrations in DID experiment. During the DID experiment, we observed significant differences between the binge-type consumption of ethanol at the lowest concentration of 10% (p=0.01). Differences in consumption of 20% ethanol are observed during a few days (p=0.04), and there are no differences in consumption at 40% concentration of ethanol (p=0.2). It is concluded that chronic periodontal lesion leads to alcoholism in Wistar rats