Enhancing catalytic activity of pyridines via para-iminophosphorano substituents.

Four pyridines decorated with π-donating iminophosphorano substituents (R3PN-) in the 4-position were assessed as acylation catalysts. These catalysts display high sensitivity to the groups at phosphorus, with activities that are well correlated to the corresponding Hammett-type substituent constants (σp+), and can achieve superior activity over the most active dialkylamino-substituted pyridines. Iminophosphorano-substituted pyridines represent an easily accessible, tunable, and highly active class of nucleophilic organocatalysts.

Pre-existing anxiety, depression, and neurological disability are associated with long COVID: A prospective and longitudinal cohort study of the United Kingdom Multiple Sclerosis Register

ObjectivesTo assess the prevalence of long COVID among people with multiple sclerosis (MS) and its predictors, including their pre-COVID-19 functional status. DesignCommunity-based prospective and longitudinal cohort study SettingThe United Kingdom (UK) MS Register (UKMSR) COVID-19 study ParticipantsA national cohort of people with MS and COVID-19 Main outcome measuresParticipants used the online questionnaire-based platform of the UKMSR to update their COVID-19 symptoms, recovery status, and duration of symptoms for those who had fully recovered. Questionnaires were date-stamped for estimation of COVID-19 symptom duration for those who had not recovered at their last follow-up. The UKMSR holds demographic and up-to-date clinical data on participants as well as their web-based Expanded Disability Status Scale (a measure of physical disability in MS) and Hospital Anxiety and Depression Scale scores. The association between these factors and recovery from COVID-19 was assessed using multivariable Cox regression analysis. ResultsOut of 7,977 people with MS who participated in the UKMSR COVID-19 study, 599 had COVID-19 and updated their recovery status prospectively. At least 181 participants (31.1%) had long-standing COVID-19 symptoms for [≥]4 weeks and 76 (13.1 %) for [≥]12 weeks. Participants with higher levels of pre-COVID-19 physical disability, participants with anxiety and/or depression prior to COVID-19 onset, and women were less likely to report recovery from COVID-19. ConclusionsLong COVID appears to disproportionately affect people with pre-existing mental health problems or physical disabilities. As post-COVID-19 rehabilitation services are being developed, individualised pathways should be considered to accommodate the needs of these vulnerable populations. Trial RegistrationClinicalTrials.gov: NCT04354519

COVID-19 is associated with multiple sclerosis exacerbations that are prevented by disease modifying therapies

BackgroundInfections can trigger exacerbations of multiple sclerosis (MS). The effects of the coronavirus disease 2019 (COVID-19) on MS are not known. The aim of this study was to understand the impact of COVID-19 on new and pre-existing symptoms of MS. MethodsThe COVID-19 and MS study is an ongoing community-based, prospective cohort study conducted as part of the United Kingdom MS Register. People with MS and COVID-19 were invited by email to complete a questionnaire about their MS symptoms during the infection. An MS exacerbation was defined as developing new MS symptoms and/or worsening of pre-existing MS symptoms. ResultsFifty-seven percent (230/404) of participants had an MS exacerbation during their infection; 82 developed new MS symptoms, 207 experienced worsened pre-existing MS symptoms, and 59 reported both. Disease modifying therapies (DMTs) reduced the likelihood of developing new MS symptoms during the infection (OR 0.556, 95%CI 0.316-0.978). Participants with a higher pre-COVID-19 webEDSS (web-based Expanded Disability Status Scale) score (OR 1.251, 95%CI 1.060-1.478) and longer MS duration (OR 1.042, 95%CI 1.009-1.076) were more likely to experience worsening of their pre-existing MS symptoms during the infection. ConclusionCOVID-19 infection was associated with exacerbation of MS. DMTs reduced the chance of developing new MS symptoms during the infection.

Associations of DMT therapies with COVID-19 severity in multiple sclerosis

Background: People with multiple sclerosis (MS) are a vulnerable group for severe COVID-19, particularly those taking immunosuppressive disease-modifying therapies (DMTs). We examined the characteristics of COVID-19 severity in an international sample of people with MS. Methods: Data from 12 data-sources in 28 countries were aggregated. Demographic and clinical covariates were queried, alongside COVID-19 clinical severity outcomes, hospitalisation, admission to ICU, requiring artificial ventilation, and death. Characteristics of outcomes were assessed in patients with suspected/confirmed COVID-19 using multilevel mixed-effects logistic regression. Results: 657 (28.1%) with suspected and 1,683 (61.9%) with confirmed COVID-19 were analysed. Older age, progressive MS-phenotype, and higher disability were associated with worse COVID-19 outcomes. Compared to dimethyl fumarate, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.56,95%CI=1.01-2.41; aOR=2.43,95%CI=1.48-4.02) and ICU admission (aOR=2.30,95%CI=0.98-5.39; aOR=3.93,95%CI=1.56-9.89), though only rituximab was associated with higher risk of artificial ventilation (aOR=4.00,95%CI=1.54-10.39). Compared to pooled other DMTs, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.75,95%CI=1.29-2.38; aOR=2.76,95%CI=1.87-4.07) and ICU admission (aOR=2.55,95%CI=1.49-4.36; aOR=4.32,95%CI=2.27-8.23) but only rituximab with artificial ventilation (aOR=6.15,95%CI=3.09-12.27). Compared to natalizumab, ocrelizumab and rituximab were associated with hospitalisation (aOR=1.86,95%CI=1.13-3.07; aOR=2.88,95%CI=1.68-4.92) and ICU admission (aOR=2.13,95%CI=0.85-5.35; aOR=3.23,95%CI=1.17-8.91), but only rituximab with ventilation (aOR=5.52,95%CI=1.71-17.84). Importantly, associations persisted on restriction to confirmed COVID-19 cases. No associations were observed between DMTs and death. Conclusions: Using the largest cohort of people with MS and COVID-19 available, we demonstrated consistent associations of rituximab with increased risk of hospitalisation, ICU admission, and requiring artificial ventilation, and ocrelizumab with hospitalisation and ICU admission, suggesting their use may be a risk factor for more severe COVID-19.

Iminophosphorano-Substituted Bispyridinylidenes: Redox Potentials and Substituent Constants from Tolman Electronic Parameters.

Bispyridinylidenes (BPYs) have emerged as an important class of neutral organic electron donors, with redox potentials that vary widely with choice of substituent. Methods to predict the effect of substitution on the redox potential are therefore highly desirable. Here we show that the redox potential of BPYs featuring iminophosphorano substituents (R3 P=N-), which represent the most reducing class of BPYs, can be predicted based on the well-known Tolman electronic parameter (TEP) for the respective phosphine fragment (R3 P). Moreover, building on earlier work relating redox potentials to Hammett-type substituent constants, it is now possible to quantitatively predict σp + values for iminophosphorano substituents from TEP values. These results provide a path for precisely tailoring redox potentials of iminophosphorano-substituted BPYs, but also give quantitative descriptors for how these highly versatile iminophosphorano substituents can impact the properties of any molecular scaffold.

Prevalence, associated factors and treatment of post spinal shivering in a Sub-Saharan tertiary hospital: a prospective observational study.

BACKGROUND: Surgery and anaesthesia cause shivering due to thermal dysregulation as a compensatory mechanism and is worsened by vasodilatation from spinal anaesthesia that redistributes core body heat. Due to paucity of data Mulago Hospital's post spinal shivering burden is unknown yet it causes discomfort and morbidity. METHODS: Ethical approval was obtained to perform the study among consenting mothers due for elective caesarean section from March to May 2011. We recruited ASA class I & II parturients and excluded non-consenting or spinal contra-indication patients. A standard spinal anaesthetic of 2mls of 0.5 % bupivacaine was given, intraoperative vitals were recorded every 5 min and we monitored for perioperative shivering till PACU discharge. RESULTS: We recruited 270 patients with majority being emergency caesarean deliveries (90.74 %), mainly due to failed progress from cephalopelvic disproportion. We noted 8.15 % shivering occuring mostly at 20 min, with hypotension plus hypothermia as associated factors. Intravenous pethidine (Meperidine) 25 mg effectively treated shivering and we had drowsiness, nausea and vomiting as PACU side effects that resolved on discharge to the ward. CONCLUSION: Post spinal shivering had a prevalence of 8.15 %, commonly occurred at 20 min postoperatively with hypotension plus hypothermia as main associated factors and intravenous Pethidine controlled it.

Microbial communities reflect temporal changes in cyanobacterial composition in a shallow ephemeral freshwater lake.

The frequency of freshwater cyanobacterial blooms is at risk of increasing as a consequence of climate change and eutrophication of waterways. It is increasingly apparent that abiotic data are insufficient to explain variability within the cyanobacterial community, with biotic factors such as heterotrophic bacterioplankton, viruses and protists emerging as critical drivers. During the Australian summer of 2012-2013, a bloom that occurred in a shallow ephemeral lake over a 6-month period was comprised of 22 distinct cyanobacteria, including Microcystis, Dolichospermum, Oscillatoria and Sphaerospermopsis. Cyanobacterial cell densities, bacterial community composition and abiotic parameters were assessed over this period. Alpha-diversity indices and multivariate analysis were successful at differentiating three distinct bloom phases and the contribution of abiotic parameters to each. Network analysis, assessing correlations between biotic and abiotic variables, reproduced these phases and assessed the relative importance of both abiotic and biotic factors. Variables possessing elevated betweeness centrality included temperature, sodium and operational taxonomic units belonging to the phyla Verrucomicrobia, Planctomyces, Bacteroidetes and Actinobacteria. Species-specific associations between cyanobacteria and bacterioplankton, including the free-living Actinobacteria acI, Bacteroidetes, Betaproteobacteria and Verrucomicrobia, were also identified. We concluded that changes in the abundance and nature of freshwater cyanobacteria are associated with changes in the diversity and composition of lake bacterioplankton. Given this, an increase in the frequency of cyanobacteria blooms has the potential to alter nutrient cycling and contribute to long-term functional perturbation of freshwater systems.

Powerful Bispyridinylidene Organic Reducing Agents with Iminophosphorano π-Donor Substituents.

Four members of a new family of powerful bispyridinylidene organic reducing agents have been prepared, which exploit iminophosphorano (-N=PR3; R = Ph, Cy) π-donor substituents. Electrochemical studies show exceptionally high oxidation potentials, ranging from 1.30 to 1.51 V versus SCE. These new reductants were shown to effectively convert 1-bromonaphthalene to naphthalene under mild reaction conditions. From the redox potentials, substituent constants (σp(+)) for the iminophosphorano groups Ph3P=N- (-1.82) and Cy3P=N- (-2.21) were determined, demonstrating their superior π-donating properties compared to traditional amino substituents.

Efficacy of a Botanical Supplement with Concentrated Echinacea purpurea for Increasing Aerobic Capacity.

The present investigation evaluated the efficacy of a botanical supplement that delivered a concentrated dose of Echinacea purpurea (8 grams day(-1)). The participants were 13 apparently healthy, recreationally active college students (VO2 max: 51 mL O2/kg∗min). The participants were provided with a 30-day supplementation regime. Data regarding maximum aerobic capacity was collected through pre- and posttesting surrounding the 30-day supplementation regime. The participants were instructed to maintain normal levels of physical activity and exercise during the experimental period. The levels of physical activity and exercise were monitored via the Leisure and Physical Activity Survey. The participants did not report any significant increases in aerobic physical activity or exercise during the supplementation period. Paired samples t-test analysis did not reveal a significant difference in maximum aerobic capacity, t(12) = 0.67, P = .516. Presupplementation maximum aerobic capacity (M = 51.0, SD = 6.8) was similar to postsupplementation values (M = 51.8, SD = 6.5). This study suggests that botanical supplements containing a concentrated dose of Echinacea purpurea is not an effective intervention to increase aerobic capacity of recreationally active individuals.