Hydrogen Activation by Benzene-Ruthenium Complexes in Aqueous Solution: Synthesis, Molecular Structure, and Intercalation of the Cluster Cation [{C₆H₆)₄Ru₄H₄]²⁺

The hydrogenation of the aqua complex [(C6H6)Ru(H2O)3]2+, prepared in situ by hydrolysis of (C6H6)2Ru2Cl4 in water, was found to lead to the tetranuclear cluster dication [(C6H6)4Ru4H4]2+ (1) which crystallizes as the dichloride from the aqueous solution. In the presence of acetate ions, however, the reaction yields the dinuclear cations [(C6H6)2Ru2H(OOCCH3)X]+ (X=OH: 2, X=Cl: 3) which crystallize as the hexafluorophosphate salts. The X-ray crystal-structure analysis of [(C6H6)4Ru4H4]Cl2 reveals the cluster dication 1 to consist of a tetrahedral ruthenium framework; the four hydrido ligands are presumably coordinated to three faces and to one edge of the Ru4 tetrahedron. The cationic complexes 1 and 2 have been found to intercalate in sodium hectorite

Ruthenium Nanoparticles Intercalated in Hectorite: A Reusable Hydrogenation Catalyst for Benzene and Toluene

The cationic organometallic aqua complexes formed by hydrolysis of [(C6H6)RuCl2]2 in water, mainly [(C6H6)Ru(H2O)3]2+, intercalate into sodium hectorite by ion exchange, replacing the sodium cations between the anionic silicate layers. The yellow hectorite thus obtained reacts in ethanol with molecular hydrogen (50 bar, 100°C) with decomposition of the organometallic aqua complexes to give a black material, in which ruthenium(0) nanoparticles (9-18nm) are intercalated between the anionic silicate layers, the charges of which being balanced by hydronium cations. The black ruthenium-modified hectorite efficiently catalyses the hydrogenation of benzene and toluene in ethanol (50 bar H2, 50°C), the turnover frequencies attaining 7000 catalytic cycles per hou

My migraine voice survey. aA global study of disease burden among individuals with migraine for whom preventive treatments have failed

Background: Migraine is associated with many debilitating symptoms that affect daily functioning. My Migraine Voice is a large global cross-sectional study aimed at understanding the full burden and impact of migraine directly from patients suffering from ≥4 monthly migraine days (MMDs) with a history of prophylactic treatment failure. Methods: This study was conducted worldwide (31 countries across North and South Americas, Europe, the Middle East and Northern Africa, and the Asia-Pacific region) using an online survey administered to adults with migraine who reported ≥4 MMDs in the 3 months preceding survey administration, with pre-specified criteria of 90% having used preventive migraine treatment (80% with history of ≥1 treatment failure). Prophylactic treatment failure was defined as a reported change in preventive medication by individuals with migraine for any reason, at least once. Results: In total, 11,266 individuals participated in the survey. Seventy-four percent of the participants reported spending time in darkness/isolation due to migraine (average: 19 h/month). While 85% of all respondents reported negative aspects of living with migraine (feeling helpless, depressed, not understood), sleeping difficulties (83%), and fear of the next attack (55%), 57% shared ≥1 positive aspect (learning to cope, becoming a stronger person). Forty-nine percent reported feeling limited in daily activities throughout all migraine phases. Migraine impact on professional, private, or social domains was reported by 87% of respondents (51% in all domains). In the previous 12 months, 38% of respondents had visited the emergency department (average: 3.3 visits), whereas 23% stayed in hospital overnight (average: 3.2 nights) due to migraine. Conclusions: The burden of migraine is substantial among this cohort of individuals with at least 4 migraine days per month and for whom at least 1 preventive migraine treatment had failed. Interestingly, respondents reported some positive aspects in their migraine journey; the greater resilience and strength brought on by coping with migraine suggests that if future treatments could address existing unmet needs, these individuals with migraine will be able to maximize their contribution to society

Pathology of a mouse mutation in peripheral myelin protein P0 is characteristic of a severe and early onset form of human Charcot-Marie-Tooth type 1B disorder

Mutations in the gene of the peripheral myelin protein zero (P0) give rise to the peripheral neuropathies Charcot-Marie-Tooth type 1B disease (CMT1B), Déjérine-Sottas syndrome, and congenital hypomyelinating neuropathy. To investigate the pathomechanisms of a specific point mutation in the P0 gene, we generated two independent transgenic mouse lines expressing the pathogenic CMT1B missense mutation Ile106Leu (P0sub) under the control of the P0 promoter on a wild-type background. Both P0sub-transgenic mouse lines showed shivering and ultrastructural abnormalities including retarded myelination, onion bulb formation, and dysmyelination seen as aberrantly folded myelin sheaths and tomacula in all nerve fibers. Functionally, the mutation leads to dispersed compound muscle action potentials and severely reduced conduction velocities. Our observations support the view that the Ile106Leu mutation acts by a dominant-negative gain of function and that the P0sub-transgenic mouse represents an animal model for a severe, tomaculous form of CMT1B

The Contribution of High Levels of Somatic Symptom Severity to Sickness Absence Duration, Disability and Discharge

Introduction: The primary objectives were to compare the duration of sickness absence in employees with high levels of somatic symptom severity (HLSSS) with employees with lower levels of somatic symptom severity, and to establish the long-term outcomes concerning return to work (RTW), disability and discharge. Secondary objective was to evaluate determinants of the duration of sickness absence in employees with HLSSS. Methods: 489 sick-listed employees registered with five Occupational Health Physician (OHP) group practices were included in this study. We measured their baseline scores for somatic symptoms severity, depressive disorders, anxiety disorders, health anxiety, distress and functional impairment. The OHPs filled in a questionnaire on their diagnosis. A prospective 2-year follow-up was carried out to assess the long-term outcomes concerning sickness absence, and retrospective information was gathered with regard to sickness absence during the 12 months before the employees were sick-listed. Results: The median duration of sickness absence was 78 days longer for employees with HLSSS. They more often remained disabled and were discharged more often, especially due to problems in the relationship between the employer and the employee. HLSSS, health anxiety and older age contributed to a longer duration of sickness absence of employees. Conclusion: High levels of somatic symptom severity are a determinant of prolonged sickness absence, enduring disabilities and health-related job loss. Occupational health physicians should identify employees who are at risk and adhere to guidelines for medically unexplained somatic symptoms

Diagnosis and Therapy of Female Pelvic Organ Prolapse. Guideline of the DGGG, SGGG and OEGGG (S2e-Level, AWMF Registry Number 015/006, April 2016).

Aims: The aim was to establish an official interdisciplinary guideline, published and coordinated by the German Society of Gynecology and Obstetrics (DGGG). The guideline was developed for use in German-speaking countries. In addition to the Germany Society of Gynecology and Obstetrics, the guideline has also been approved by the Swiss Society of Gynecology and Obstetrics (SGGG) and the Austrian Society of Gynecology and Obstetrics (OEGGG). This is a guideline published and coordinated by the DGGG. The aim is to provide evidence-based recommendations obtained by evaluating the relevant literature for the diagnostic, conservative and surgical treatment of women with female pelvic organ prolapse with or without stress incontinence. Methods: We conducted a systematic review together with a synthesis of data and meta-analyses, where feasible. MEDLINE, Embase, Cinahl, Pedro and the Cochrane Register were searched for relevant articles. Reference lists were hand-searched, as were the abstracts of the Annual Meetings of the International Continence Society and the International Urogynecological Association. We included only abstracts of randomized controlled trials that were presented and discussed in podium sessions. We assessed original data on surgical procedures published since 2008 with a minimum follow-up time of at least 12 months. If the studies included descriptions of perioperative complications, this minimum follow-up period did not apply. Recommendations: The guideline encompasses recommendations for the diagnosis and treatment of female pelvic organ prolapse. Recommendations for anterior, posterior and apical pelvic organ prolapse with or without concomitant stress urinary incontinence, uterine preservation options, and the pros and cons of mesh placements during surgery for pelvic organ prolapse are presented. The recommendations are based on an extensive and systematic review and evaluation of the current literature and include the experiences and specific conditions in Germany, Austria and Switzerland

Exposure to Apoptotic Activated CD4+ T Cells Induces Maturation and APOBEC3G- Mediated Inhibition of HIV-1 Infection in Dendritic Cells

Dendritic cells (DCs) are activated by signaling via pathogen-specific receptors or exposure to inflammatory mediators. Here we show that co-culturing DCs with apoptotic HIV-infected activated CD4+ T cells (ApoInf) or apoptotic uninfected activated CD4+ T cells (ApoAct) induced expression of co-stimulatory molecules and cytokine release. In addition, we measured a reduced HIV infection rate in DCs after co-culture with ApoAct. A prerequisite for reduced HIV infection in DCs was activation of CD4+ T cells before apoptosis induction. DCs exposed to ApoAct or ApoInf secreted MIP-1α, MIP-1β, MCP-1, and TNF-α; this effect was retained in the presence of exogenous HIV. The ApoAct-mediated induction of co-stimulatory CD86 molecules and reduction of HIV infection in DCs were partially abrogated after blocking TNF-α using monoclonal antibodies. APOBEC3G expression in DCs was increased in co-cultures of DCs and ApoAct but not by apoptotic resting CD4+ T cells (ApoRest). Silencing of APOBEC3G in DC abrogated the HIV inhibitory effect mediated by ApoAct. Sequence analyses of an env region revealed significant induction of G-to-A hypermutations in the context of GG or GA dinucleotides in DNA isolated from DCs exposed to HIV and ApoAct. Thus, ApoAct-mediated DC maturation resulted in induction of APOBEC3G that was important for inhibition of HIV-infection in DCs. These findings underscore the complexity of differential DC responses evoked upon interaction with resting as compared with activated dying cells during HIV infection

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity