Intramolecular epoxide ring opening cyclisation reactions involving guanidines

The cyclisation of N-allyl- and N-homoallylguanidines using DMDO leading to the formation of novel 5- and 6-membered guanidine heterocycles is reported. Several of the products formed displayed weak inhibition of glycosidase enzymes

Interaction of Xenopus Cdc2 x cyclin A1 with the origin recognition complex

The initiation of DNA replication in eukaryotes is regulated in a minimum of at least two ways. First, several proteins, including origin recognition complex (ORC), Cdc6 protein, and the minichromosome maintenance (MCM) protein complex, need to be assembled on chromatin before initiation. Second, cyclin-dependent kinases regulate DNA replication in both a positive and a negative way by inducing the initiation of DNA replication at G(1)/S transition and preventing further rounds of origin firing within the same cell cycle. Here we characterize a link between the two levels. Immunoprecipitation of Xenopus origin recognition complex with anti-XOrc1 or anti-XOrc2 antibodies specifically co-immunoprecipitates a histone H1 kinase activity. The kinase activity is sensitive to several inhibitors of cyclin-dependent kinases including 6-dimethylaminopurine (6-DMAP), olomoucine, and p21(Cip1). This kinase activity also copurifies with ORC over several fractionation steps and was identified as a complex of the Cdc2 catalytic subunit and cyclin A1. Neither Cdk2 nor cyclin E could be detected in ORC immunoprecipitations. Reciprocal immunoprecipitations with anti-Xenopus Cdc2 or anti-Xenopus cyclin A1 antibodies specifically co-precipitate XOrc1 and XOrc2. Our results indicate that Xenopus ORC and Cdc2 x cyclin A1 physically interact and demonstrate a physical link between an active cyclin-dependent kinase and proteins involved in the initiation of DNA replication

The Global Anesthesia Workforce Survey: Updates and trends in the anesthesia workforce

Background: There is a large global deficit of anesthesia providers. In 2016, the World Federation of Societies of Anaesthesiologists (WFSA) conducted a survey to count the number of anesthesia providers worldwide. Much work has taken place since then to strengthen the anesthesia health workforce. This study updates the global count of anesthesia providers.Methods: Between 2021 and 2023, an electronic survey was sent to national professional societies of physician anesthesia providers (PAPs), nurse anesthetists, and other nonphysician anesthesia providers (NPAPs). Data included number of providers and trainees, proportion of females, and limited intensive care unit (ICU) capacity data. Descriptive statistics were calculated by country, World Bank income group, and World Health Organization (WHO) region. Provider density is reported as the number of providers per 100,000 population.Results: Responses were obtained for 172 of 193 United Nations (UN) member countries. The global provider density was 8.8 (PAP 6.6 NPAP 2.3). Seventy-six countries had a PAP density \u3c5, whereas 66 countries had a total provider density \u3c5. PAP density increased everywhere except for high- and low-income countries and the African region.Conclusions: The overall size of the global anesthesia workforce has increased over time, although some countries have experienced a decrease. Population growth and differences in which provider types that are counted can have an important impact on provider density. More work is needed to define appropriate metrics for measuring changes in density, to describe anesthesia cadres, and to improve workforce data collection processes. Effort to scale up anesthesia provider training must urgently continue

Anesthesia Provider Training and Practice Models: A Survey of Africa.

BACKGROUND:In Africa, most countries have fewer than 1 physician anesthesiologist (PA) per 100,000 population. Nonphysician anesthesia providers (NPAPs) play a large role in the workforce of many low- and middle-income countries (LMICs), but little information has been systematically collected to describe existing human resources for anesthesia care models. An understanding of existing PA and NPAP training pathways and roles is needed to inform anesthesia workforce planning, especially for critically underresourced countries. METHODS:Between 2016 and 2018, we conducted electronic, phone, and in-person surveys of anesthesia providers in Africa. The surveys focused on the presence of anesthesia training programs, training program characteristics, and clinical scope of practice after graduation. RESULTS:One hundred thirty-one respondents completed surveys representing data for 51 of 55 countries in Africa. Most countries had both PA and NPAP training programs (57%; mean, 1.6 pathways per country). Thirty distinct training pathways to become an anesthesia provider could be discriminated on the basis of entry qualification, duration, and qualification gained. Of these 30 distinct pathways, 22 (73%) were for NPAPs. Physician and NPAP program durations were a median of 48 and 24 months (ranges: 36-72, 9-48), respectively. Sixty percent of NPAP pathways required a nursing background for entry, and 60% conferred a technical (eg, diploma/license) qualification after training. Physicians and NPAPs were trained to perform most anesthesia tasks independently, though few had subspecialty training (such as regional or cardiac anesthesia). CONCLUSIONS:Despite profound anesthesia provider shortages throughout Africa, most countries have both NPAP and PA training programs. NPAP training pathways, in particular, show significant heterogeneity despite relatively similar scopes of clinical practice for NPAPs after graduation. Such heterogeneity may reflect the varied needs and resources for different settings, though may also suggest lack of consensus on how to train the anesthesia workforce. Lack of consistent terminology to describe the anesthesia workforce is a significant challenge that must be addressed to accelerate workforce research and planning efforts