Timing of default from tuberculosis treatment: a systematic review

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73281/1/j.1365-3156.2008.02042.x.pd

Assessing New York City's COVID-19 Vaccine Rollout Strategy: A Case for Risk-Informed Distribution.

From PubMed via Jisc Publications RouterHistory: accepted 2024-03-08Publication status: aheadofprintDaniel Reidpath - ORCID: 0000-0002-8796-0420 https://orcid.org/0000-0002-8796-0420This study reviews the impact of eligibility policies in the early rollout of the COVID-19 vaccine on coverage and probable outcomes, with a focus on New York City. We conducted a retrospective ecological study assessing age  65+, area-level income, vaccination coverage, and COVID-19 mortality rates, using linked Census Bureau data and New York City Health administrative data aggregated at the level of modified zip code tabulation areas (MODZCTA). The population for this study was all individuals in 177 MODZCTA in New York City. Population data were obtained from Census Bureau and New York City Health administrative data. The total mortality rate was examined through an ordinary least squares (OLS) regression model, using area-level wealth, the proportion of the population aged 65 and above, and the vaccination rate among this age group as predictors. Low-income areas with high proportions of older people demonstrated lower coverage rates (mean vaccination rate 52.8%; maximum coverage 67.9%) than wealthier areas (mean vaccination rate 74.6%; maximum coverage 99% in the wealthiest quintile) in the first 3 months of vaccine rollout and higher mortality over the year. Despite vaccine shortages, many younger people accessed vaccines ahead of schedule, particularly in high-income areas (mean coverage rate 60% among those 45-64 years in the wealthiest quintile). A vaccine program that prioritized those at greatest risk of COVID-19-associated morbidity and mortality would have prevented more deaths than the strategy that was implemented. When rolling out a new vaccine, policymakers must account for local contexts and conditions of high-risk population groups. If New York had focused limited vaccine supply on low-income areas with high proportions of residents 65 or older, overall mortality might have been lower. [Abstract copyright: © 2024. The Author(s).]pubpu

A Global Health Partnership's Use of Time-Limited Support to Catalyze Health Practice Change: The Case of GAVI's Injection Safety Support

This paper presents the findings of a study to assess the effectiveness and sustainability of a GAVI (Global Alliance of Vaccines and Immunization) sponsored, time-limited Injection Safety (INS) support. The support came in two forms: 1) in-kind, in the form of AD syringes and safety boxes, and 2) in cash, for those countries that already had a secure, multi-year source of AD syringes and safety boxes, but proposed to use INS support to strengthen their injection safety activities. In total, GAVI gave INS support for a three-year period to 58 countries: 46 with commodities and 12 with cash support. To identify variables that might be associated with financial sustainability, frequencies and cross-tabulations were run against various programmatic and socio-economic variables in the 58 countries. All but two of the 46 commodity-recipient countries were able to replace and sustain the use of AD syringes and safety boxes after the end of their GAVI INS support despite the fact that standard disposable syringes are less costly than ADs (10–15 percent differential). In addition, all 12 cash-recipient countries continued to use AD syringes and safety boxes in their immunization programs in the years following GAVI INS assistance. At the same time, countries were often not prepared for the increased waste management requirements associated with the use of the syringes, suggesting the importance of anticipating challenges with the introduction of new technologies. The sustained use of AD syringes in countries receiving injection safety support from GAVI, in a majority of cases through government financing, following the completion of three years of time-limited support, represents an early indication of how GHPs can contribute to improved health outcomes in immunization safety in the world's poorest countries in a sustainable way

Metabolic plasticity is an essential requirement of acquired tyrosine kinase inhibitor resistance in Chronic myeloid leukemia

Tyrosine kinase inhibitors (TKIs) are currently the standard chemotherapeutic agents for the treatment of chronic myeloid leukemia (CML). However, due to TKI resistance acquisition in CML patients, identification of new vulnerabilities is urgently required for a sustained response to therapy. In this study, we have investigated metabolic reprogramming induced by TKIs independent of BCR-ABL1 alterations. Proteomics and metabolomics profiling of imatinib-resistant CML cells (ImaR) was performed. KU812 ImaR cells enhanced pentose phosphate pathway, glycogen synthesis, serine-glycine-one-carbon metabolism, proline synthesis and mitochondrial respiration compared with their respective syngeneic parental counterparts. Moreover, the fact that only 36% of the main carbon sources were utilized for mitochondrial respiration pointed to glycerol-phosphate shuttle as mainly contributors to mitochondrial respiration. In conclusion, CML cells that acquire TKIs resistance present a severe metabolic reprogramming associated with an increase in metabolic plasticity needed to overcome TKI-induced cell death. Moreover, this study unveils that KU812 Parental and ImaR cells viability can be targeted with metabolic inhibitors paving the way to propose novel and promising therapeutic opportunities to overcome TKI resistance in CML

NMR and MD studies of the temperature-dependent dynamics of RNA YNMG-tetraloops

In a combined NMR/MD study, the temperature-dependent changes in the conformation of two members of the RNA YNMG-tetraloop motif (cUUCGg and uCACGg) have been investigated at temperatures of 298, 317 and 325 K. The two members have considerable different thermal stability and biological functions. In order to address these differences, the combined NMR/MD study was performed. The large temperature range represents a challenge for both, NMR relaxation analysis (consistent choice of effective bond length and CSA parameter) and all-atom MD simulation with explicit solvent (necessity to rescale the temperature). A convincing agreement of experiment and theory is found. Employing a principle component analysis of the MD trajectories, the conformational distribution of both hairpins at various temperatures is investigated. The ground state conformation and dynamics of the two tetraloops are indeed found to be very similar. Furthermore, both systems are initially destabilized by a loss of the stacking interactions between the first and the third nucleobase in the loop region. While the global fold is still preserved, this initiation of unfolding is already observed at 317 K for the uCACGg hairpin but at a significantly higher temperature for the cUUCGg hairpin