Core strength: A new model for injury prediction and prevention

OBJECTIVE: Many work in injury prone awkward positions that require adequate flexibility and strength in trunk stabilizer muscle groups. Performance on a functional movement screen (FMS) that assessed those factors was conducted and an intervention was designed. METHODS: A battery of FMS tests were performed on 433 firefighters. We analyzed the correlation between FMS performance and injuries and other selected parameters. An intervention to improve flexibility and strength in trunk stabilizer or core muscle groups through a training program was evaluated. RESULTS: The intervention reduced lost time due to injuries by 62% and the number of injuries by 42% over a twelve month period as compared to a historical control group. CONCLUSION: These findings suggest that core strength and functional movement enhancement programs to prevent injuries in workers whose work involves awkward positions is warranted

Capital account regulations and the trading system: a compatibility review

This repository item contains a single issue of the Pardee Center Task Force Reports, a publication series that began publishing in 2009 by the Boston University Frederick S. Pardee Center for the Study of the Longer-Range Future. Spanish version produced by the Center for the Study of State and Society, Buenos Aires. Portuguese version coordinated by Daniela Magalhaes Prates, a contributing author of the report, in collaboration with Ana Trivellato (translator), and Maria Inês Amorozo (graphic designer).This report is the product of the Pardee Center Task Force on Regulating Capital Flows for Long-Run Development and builds on the Task Force´s first report published in March 2012. The Pardee Center Task Force was convened initially in September 2011 as consensus was emerging that the global financial crisis has re-confirmed the need to regulate cross-border finance. The March 2012 report argues that international financial institutions – and in particular the International Monetary Fund – need to support measures that would allow capital account regulations (CARs) to become a standard and effective part of the macroeconomic policy toolkit. Yet some policymakers and academics expressed concern that many nations — and especially developing countries — may not have the flexibility to adequately deploy such regulations because of trade and investment treaties they are party to. In June 2012, the Pardee Center, with the Center for the Study of State and Society (CEDES) in Argentina and Global Development and Environment Institute (GDAE) at Tufts University, convened a second Task Force workshop in Buenos Aires specifically to review agreements at the WTO and various Free Trade Agreements (FTAs) and Bilateral Investment Treaties (BITs) for the extent to which the trading regime is compatible with the ability to deploy effective capital account regulations. This report presents the findings of that review, and highlights a number of potential incompatibilities found between the trade and investment treaties and the ability to deploy CARs. It also highlights an alarming lack of policy space to use CARs under a variety of FTAs and BITs—especially those involving the United States. Like the first report, it was written by an international group of experts whose goal is to help inform discussions and decisions by policymakers at the IMF and elsewhere that will have implications for the economic health and development trajectories for countries around the world

Solution Structure of a CUE-Ubiquitin Complex Reveals a Conserved Mode of Ubiquitin Binding

AbstractMonoubiquitination serves as a regulatory signal in a variety of cellular processes. Monoubiquitin signals are transmitted by binding to a small but rapidly expanding class of ubiquitin binding motifs. Several of these motifs, including the CUE domain, also promote intramolecular monoubiquitination. The solution structure of a CUE domain of the yeast Cue2 protein in complex with ubiquitin reveals intermolecular interactions involving conserved hydrophobic surfaces, including the Leu8-Ile44-Val70 patch on ubiquitin. The contact surface extends beyond this patch and encompasses Lys48, a site of polyubiquitin chain formation. This suggests an occlusion mechanism for inhibiting polyubiquitin chain formation during monoubiquitin signaling. The CUE domain shares a similar overall architecture with the UBA domain, which also contains a conserved hydrophobic patch. Comparative modeling suggests that the UBA domain interacts analogously with ubiquitin. The structure of the CUE-ubiquitin complex may thus serve as a paradigm for ubiquitin recognition and signaling by ubiquitin binding proteins

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

Provision of clinical pharmacy education and services by RAK college of pharmaceutical sciences, Ras Al Khaimah, UAE

Objectives: Internationally, the role of pharmacist has now been extended from the provision of traditional services to patient specific care services. Unlike other developed countries, clinical pharmacy services are very rare in the health care settings of United Arab Emirates (UAE). Hence, clinical pharmacy based education and training is the need of the hour. Materials and Methods: RAK College of Pharmaceutical Sciences (RAKCOPS) through its innovative undergraduate pharmacy curriculum with a practice-oriented training, is enabling the students to acquire knowledge, skills, and practice to apply in a healthcare set up. RAKCOPS established a clinical pharmacy department in the year 2009 at Ibrahim Bin Hamad Obaidallah Hospital of Ras Al Khaimah, UAE, which is a 330 bedded tertiary care medical specialty hospital. In the year 2007, RAKCOPS initiated undergraduate pharmacy program of 4.6 years (B. Pharm) with a one semester of practice school training in the last semester. Results: Practice school training as a part of B. Pharm program is mainly designed to help the students to gain confidence in their ability to be an active and useful participant in the healthcare. Clinical pharmacy related services such as drug and poison related information, adverse drug reaction (ADR) monitoring, and reporting are also provided by the department of clinical pharmacy. Conclusion: Pharmacy practice related education and practice-based training provided for the undergraduate pharmacy students will be definitely a major contribution towards bringing up quality clinical pharmacists in UAE, who will be a major asset for the healthcare team

Deubiquitinase USP1 influences the dedifferentiation of mouse pancreatic β-cells

Summary: Loss of insulin-secreting β-cells in diabetes may be either due to apoptosis or dedifferentiation of β-cell mass. The ubiquitin-proteasome system comprising E3 ligase and deubiquitinases (DUBs) controls several aspects of β-cell functions. In this study, screening for key DUBs identified USP1 to be specifically involved in dedifferentiation process. Inhibition of USP1 either by genetic intervention or small-molecule inhibitor ML323 restored epithelial phenotype of β-cells, but not with inhibition of other DUBs. In absence of dedifferentiation cues, overexpression of USP1 was sufficient to induce dedifferentiation in β-cells; mechanistic insight showed USP1 to mediate its effect via modulating the expression of inhibitor of differentiation (ID) 2. In an in vivo streptozotocin (STZ)-induced dedifferentiation mouse model system, administering ML323 alleviated hyperglycemic state. Overall, this study identifies USP1 to be involved in dedifferentiation of β-cells and its inhibition may have a therapeutic application of reducing β-cell loss during diabetes

A ubiquitin-binding motif required for intramolecular monoubiquitylation, the CUE domain

Monoubiquitylation is a regulatory signal, like phosphorylation, that can alter the activity, location or structure of a protein. Monoubiquitin signals are likely to be recognized by ubiquitin-binding proteins that transmit the regulatory information conferred by monoubiquitylation. To identify monoubiquitin-binding proteins, we used a mutant ubiquitin that lacks the primary site of polyubiquitin chain formation as bait in a two-hybrid screen. The C-terminus of Vps9, a protein required in the yeast endocytic pathway, interacted specifically with monoubiquitin. The region required for monoubiquitin binding mapped to the Vps9 CUE domain, a sequence previously identified by database searches as similar to parts of the yeast Cue1 and mammalian Tollip proteins. We demonstrate that CUE domains bind directly to monoubiquitin and we have defined crucial interaction surfaces on both binding partners. The Vps9 CUE domain is required to promote monoubiquitylation of Vps9 by the Rsp5 hect domain ubiquitin ligase. Thus, we conclude that the CUE motif is an evolutionarily conserved monoubiquitin-binding domain that mediates intramolecular monoubiquitylation