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Introduction The Emergency Department (ED) of Mbarara Regional Referral Hospital serves a largely rural population of 4 million people in western Uganda. Here, ED patients with incurable illness often have prolonged stays. Palliative care (PC) is a low-cost intervention that focuses on alleviating pain and suffering for patients with incurable disease, while improving satisfaction with care and optimizing healthcare utilization. This is especially important in low resource settings. A prior needs assessment in our ED revealed that 50% of patients have PC needs. The ED is an optimal location to initiate PC, yet this rarely happens. There is a great need to identify factors affecting initiation of ED PC in our resource-limited setting. Methods A semi-structured questionnaire and chart review was conducted from March to August 2020. Patients admitted from the ED were assessed for PC needs. Those who met criteria were approached for inclusion and flagged for initiation of PC. The follow-up period was 7 days. Results Sixty two percent of those subjects flagged for initiation of PC received it. By day seven, 36.1 of the study population had died. ED initiation of PC varied significantly by diagnosis, with cancer patients more likely to receive PC (p = 0.0097). Conclusion Important barriers to PC initiation were identified in our Ugandan ED, related to diagnosis. These barriers could be overcome by improving awareness of PC amongst patients and providers alike and implementing a PC screening tool for all admissions. Future research is needed to identify other barriers, as well as strategies for improved hospital-wide uptake of PC in this resource-limited setting.

Seven readily synthesized 8-quinoline-4-R-3-thiosemicarbazone ligands [where R = phenyl (L1H), 4-fluorophenyl (L2H), 4-iodophenyl (L3H), 4-nitrophenyl (L4H), 4-carboxyphenyl (L5H), 3-picolyl (L6H), and octadecyl (L7H)], and their corresponding Co(III) coordination complexes, [Co(L)2]BF4, have been synthesized and characterized. Crystallographic analysis of the complexes revealed that the substituents significantly alter solid-state supramolecular network topologies. The solution processability of these complexes was confirmed by incorporating a long carbon alkyl-chain into the ligand (L7H) and immobilizing the complex onto quartz slides using Langmuir-Blodgett deposition. The facile and modular synthesis of these thiosemicarbazone-based ligands coupled with the potential to exploit multiple applications makes these compounds excellent candidates for functional supramolecular materials.

The inherently rapid ligand substitution kinetics associated with the novel and chemically compatible precursors, [MCl3(EnBu2)3] (M = Sb, Bi; E = Se, Te), enable CVD growth of ternary Bi2(Se1-xTex)3 and (Bi1-ySby)2Te3 thin films with very good compositional, structural and morphological control, for the first time. X-ray diffraction data follow Vegard’s law and Raman bands shift linearly with the atom substitutions, indicating very well-distributed solid solutions.

BACKGROUND: Organizations have a key role to play in supporting healthcare workers (HCWs) and mitigating stress during COVID-19. We aimed to understand whether perceptions of support and communication by local leadership were associated with reduced reports of stress and burnout among frontline HCWs. METHODS: We conducted cross-sectional surveys embedded within emergency department (ED) workflow during the first wave of COVID-19 from April 9, 2020 to June 15th, 2020 within three EDs of a multisite health system in the Northeast United States. All ED HCWs were administered electronic surveys during shift via text message. We simultaneously conducted 64 qualitative interviews to better characterize and validate survey responses. Primary survey outcomes were levels of work stress and burnout. RESULTS: Over 10 week study, 327 of 431 (76%) frontline HCWs responded to at least one round of the survey. More useful communication mediated through higher perception of support was significantly associated with lower work stress (B = -0.33, p

BackgroundThe COVID-19 pandemic has exposed front-line healthcare workers to unprecedented risks and stressors threatening both physical and mental health. Prior work in the military has found that team identification, or the sense that one was a part of a team, can help reduce stress and prevent burnout during prolonged stress.MethodsWe conducted repeated cross-sectional surveys embedded within emergency department workflow to understand whether team identification was associated with reduced reports of stress and burnout among front-line workers.ResultsDuring the 10-week study which spanned the first wave of COVID-19, 327 of 431 (76%) front-line healthcare workers responded to at least one round of the survey. Higher team identification was associated with significantly less work stress (B=−0.60, 95% CI −0.84 to to -0.40, pB=−12.87, 95% CI −17.73 to -8.02, pB=−0.36, 95% CI −0.76 to 0.05, p=0.09) and burnout (B=−13.25, 95% CI −17.77 to -8.73, pConclusionThis work suggests work team identification is a key buffering factor against feelings of stress and burnout. Efforts to promote team identification may offer a promising way for leaders to support front-line healthcare workers’ well-being during the COVID-19 pandemic. These results can inform ongoing COVID-19 operational and quality improvement initiatives.

Patient-reported outcomes and economic aspects of Palliative Care (PC) provision in low-income countries (LIC) are under-studied. Demonstrating the economic value of PC is key to sustainability and guiding health care policy. Our preliminary data in Ethiopia demonstrated a widespread need for PC, poor access to it, and high out of pocket payments (OOP). We suspect that in this and other LIC, PC may function not only to reduce suffering but also as a poverty reduction strategy. We are conducting a randomized controlled trial of standard Oncology care versus standard Oncology care plus PC in newly diagnosed cancer patients in Addis Ababa. Ninety-seven adults presenting to Oncology Clinic will be randomized in a 1:1 ratio. Subjects receiving PC will meet with a PC provider at time of enrollment and at follow up visits in their homes. All subjects will be assessed via questionnaire at enrollment and follow-up Oncology visits at 8 ± 4 and 12 ± 4 weeks. A cost-consequence analysis will be performed, to include: patient-reported OOP and healthcare utilization, the latter to be assessed through chart adjudication. Outcomes will include change in African Palliative Care Association Palliative Outcome Score, changes in OOP and healthcare utilization. We hypothesize that the cost of home-based PC will be offset by improvements in patient-reported outcomes, decreased OOP and healthcare utilization, rendering PC cost-effective in this LIC. These findings may lead to widespread dissemination of an effective, sustainable and cost-saving public PC delivery strategy that would improve the quality of life and death for millions of people. Trial registration Clinicaltrials.gov NCT03712436 .

Palliative care aims to reduce physical suffering and the emotional, spiritual, and psychosocial distress of life-limiting illness. Palliative care is a human right, yet there are vast disparities in its provision: of the 40 million people globally in need of palliative care, less than 10% receive it, largely in high-income countries. There is a particular paucity of data on palliative care needs across the spectrum of incurable disease in Ethiopia.The aims of this research were to assess the overall burden of life-limiting illness, the costs associated with life-limiting illness, and barriers to accessing palliative care in Ethiopia.Mixed-methods case-series.One hundred adults (mean age: 43.7 ± 14 years, 64% female) were recruited at three outpatient clinics (oncology, HIV, noncommunicable disease) and hospice patient homes in Ethiopia.Four internationally validated questionnaires were used to assess physical symptoms, psychosocial distress, and disability. In-depth interviews gauged poverty level, costs of care, and end-of-life preferences. Qualitative data were analyzed by thematic content, quantitative data by standard descriptive, frequency and regression analyses.In oncology, 95.5% of the population endorsed moderate or severe pain, while 24% were not prescribed analgesia. Importantly, 80% of the noncommunicable disease population reported moderate or severe pain. The mean psychosocial distress score was 6.4/10. Severe disability was reported in 26% of the population, with mobility most affected. Statistically significant relationships were found between pain and costs, and pain and lack of well-being. Very high costs were reported by oncology patients. Oncology withstanding, the majority of subjects wished to die at home. Oncology patients cited pain control as the top reason they preferred a hospital death.There are extensive unmet palliative care needs in Ethiopia. Untreated pain and high costs of illness are the major contributors to psychosocial distress and financial crisis in this Ethiopian population.

IntroductionOf the 40 million people globally in need of palliative care (PC), just 14% receive it, predominantly in high-income countries. Within fragile health systems that lack PC, incurable illness is often marked by pain and suffering, as well as burdensome costs. In high-income settings, PC decreases healthcare utilisation, thus enhancing value. Similar cost-effectiveness models are lacking in low-income and middle-income countries and with them, the impetus and funding to expand PC delivery.MethodsWe conducted a systematic search of seven databases to gather evidence of the cost-effectiveness of PC in low-income and middle-income countries. We extracted and synthesised palliative outcomes and economic data from original research studies occurring in low-income and middle-income countries. This review adheres to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and includes a quality appraisal.ResultsOur search identified 10 eligible papers that included palliative and economic outcomes in low-income and middle-income countries. Four provided true cost-effectiveness analyses in comparing the costs of PC versus alternative care, with PC offering cost savings, favourable palliative outcomes and positive patient-reported and family-reported outcomes.ConclusionsDespite the small number of included studies, wide variety of study types and lack of high-quality studies, several patterns emerged: (1) low-cost PC delivery in low-income and middle-income countries is possible, (2) patient-reported outcomes are favourable and (3) PC is less costly than the alternative. This review highlights the extraordinary need for robust cost-effectiveness analysis of PC in low-income and middle-income countries in order to develop health economic models for the delivery of PC, direct resource allocation and guide healthcare policy for PC delivery in low-income and middle-income countries.

The Neisseria gonorrhoeae genome encodes a homologue of the Escherichia coli FNR protein (the fumarate and nitrate reductase regulator). Despite its similarity to E. coli FNR, the gonococcal FNR only partially complemented an E. coli fnr mutation. After error-prone PCR mutagenesis of the gonococcal fnr gene, we identified four mutant fnr derivatives carrying the same S18F substitution, and we showed that the mutant FNR could activate transcription from a range of class I and class II FNR-dependent promoters in E. coli . Prompted by the similarities between gonococcal and E. coli FNR, we made changes in gonococcal fnr that created substitutions that are equivalent to previously characterized substitutions in E. coli FNR. First, our experiments showed that cysteine, C116, in the gonococcal FNR, equivalent to C122 in E. coli FNR, is essential, presumably because, as in E. coli FNR, it binds to an iron-sulfur center. Second, the L22H and D148A substitutions in gonococcal FNR were made. These changes are equivalent to the L28H and D154A changes in E. coli FNR, which had been shown to increase FNR activity in the presence of oxygen. We show that the effects of these substitutions in gonococcal FNR are distinct from those of the S18F substitution. Similarly, substitutions in the putative activating regions of gonococcal FNR were made. We show that the activity of gonococcal FNR in E. coli can be increased by transplanting certain activating regions from E. coli FNR. The effects of these substitutions are additive to those due to S18F. From these data, we conclude that the effects of the S18F substitution in gonococcal FNR are distinct from the effects of the other substitutions. S18 is immediately adjacent to one of three N-terminal cysteine residues that coordinate the iron-sulfur center, and thus the S18F substitution is most likely to stabilize this center. Support for this came from complementary experiments in which we created the S24F substitution in E. coli FNR, which is equivalent to the S18F substitution in gonococcal FNR. Our results show that the S24F substitution changes the activity of E. coli FNR and that the changes are distinct from those due to previously characterized substitutions.

In Escherichia coli K-12, c-type cytochromes are synthesized only during anaerobic growth with trimethylamine-N-oxide, nitrite or low concentrations of nitrate as the terminal electron acceptor. A thioredoxin-like protein, CcmG, is one of 12 proteins required for their assembly in the periplasm. Its postulated function is to reduce disulphide bonds formed between correctly paired cysteine residues in the cytochrome c apoproteins prior to haem attachment by CcmF and CcmH. We report that loss of CcmG synthesis by mutation was not compensated by a second mutation in disulphide-bond-forming proteins, DsbA or DsbB, or by the chemical reductant, 2-mercaptoethanesulphonic acid. An anti-CcmG polyclonal antibody was used in Western-blot analysis to probe the redox state of CcmG in mutants defective in the synthesis of other proteins essential for cytochrome c assembly. The oxidized form of CcmG accumulated not only in trxA or dipZ mutants defective in the transfer of electrons from the cytoplasm for disulphide isomerization and reduction reactions in the periplasm, but also in ccmF and ccmH mutants. The requirement of both CcmF and CcmH for the reduction of the disulphide bond in CcmG indicates that CcmG functions later than CcmF and CcmH in cytochrome c assembly, rather than in electron transfer from the membrane-associated DipZ (also known as DsbD) to CcmH. The data support a model proposed by others in which CcmG catalyses one of the last reactions specific to cytochrome c assembly.

The eight ccm genes located at minute 47 on the Escherichia coli chromosome, in the order ccmABCDEFGH, encode homologues of proteins which are essential for cytochrome c assembly in other bacteria. The ccm genes are immediately downstream from the napFDAGHBC genes encoding a periplasmic nitrate reductase. CcmH was previously shown to be essential for cytochrome c assembly. Deletion analysis and a two-plasmid strategy have now been used to demonstrate that CcmA, B, D, E, F and G are also essential for cytochrome c assembly, and hence for cytochrome-c-dependent nitrite reduction. The ccm genes are transcribed from a ccmA promoter located within the adjacent gene, napC, which is the structural gene for a 24 kDa membrane-bound c-type cytochrome, NapC. Transcription from this ccmA promoter is induced approximately 5-fold during anaerobic growth, independently of a functional Fnr protein: it is also not regulated by the ArcB–ArcA two-component regulatory system. The ccmA promoter is an example of the ‘extended -10 sequence ’ group of promoters with a TGX motif immediately upstream of the -10 sequence. Mutagenesis of the TG motif to TC, CT or CC resulted in loss of about 50% of the promoter activity. A weak second promoter is suggested to permit transcription of the downstream ccmEFGH genes in the absence of transcription readthrough from the upstream napF and ccmA promoters. The results are consistent with, but do not prove, the current view that CcmA, B, C and D are part of an essential haem transport mechanism, that CcmE, F and H are required for covalent haem attachment to cysteine-histidine motifs in cytochrome c apoproteins in the periplasm, and that CcmG is required for the reduction of cysteine residues on apocytochromes c in preparation for haem ligation.

A cytochrome c peroxidase (CCP) produced by Neisseria gonorrhoeae has been shown to have novel characteristics by investigating its location, expression and role in Neisseria gonorrhoeae and by expression in Escherichia coli. Analysis of the N-terminus of CCP indicated that it is a lipoprotein with a signal peptide for cleavage by signal peptidase II. Expression of the gonococcal CCP in E. coli revealed that it is first synthesized as a pro-apo-cytochrome that is translocated across the cytoplasmic membrane. The signal peptide is cleaved and haem is attached in the periplasm. The gonococcal CCP was associated with the membrane of both E. coli and N. gonorrhoeae. The expression of a MalE–CCP fusion protein has allowed characterization of CCP in vitro. Evidence is presented that CCP protects gonococci from hydrogen peroxide, presumably in the periplasmic compartment of the cell. The expression of CCP is dependent on the transcription factor FNR, but is repressed by nitrite, indicating that it could be most important in the stationary-phase response. These data support the hypothesis that the gonococcal lipoprotein CCP is anchored to the membrane in the periplasm, where it might be responsible for the reduction of hydrogen peroxide. Other putative CCP lipoproteins have been identified, representing a new subclass of bacterial CCP proteins.

We previously reported that a 17.5-kDa haem-binding polypeptide accumulates in Escherichia coli K-12 mutants defective in an essential gene for cytochrome c assembly, ccmF, and speculated that this polypeptide is either CcmE or CcmG. The haem-containing polypeptide, which is associated with the cytoplasmic membrane, has now been identified by N-terminal sequencing to be CcmE. The haem-dependent peroxidase activity of CcmE is clearly visible not only in a ccmF mutant, but also in ccmG and ccmH mutants, implying that CcmE functions either before or in the same step as CcmF, CcmG and CcmH in cytochrome c maturation. A trxA mutant, like the dipZ mutant, was unable to assemble c-type cytochromes or catalyse formate-dependent nitrite reduction: both activities were restored in the trxA and dipZ, but not ccmG, mutants by the reducing agent, 2-mercaptoethanesulphonic acid. Our data suggest that haem transferred across the cytoplasmic membrane by the CcmABCD complex becomes associated with CcmE, possibly by a labile covalent bond, before it is transferred to the cytochrome c apoproteins by the periplasmic haem lyase encoded by ccmF and ccmH. We further propose that CcmG is essential to reduce the disulphide bonds formed in cytochrome c apoproteins by DsbA, before haem is attached by the haem lyase. Electrons for disulphide bond reduction are supplied from thioredoxin in the cytoplasm via DipZ in the membrane, but can be replaced by the chemical reductant, 2-mercaptoethanesulphonic acid. According to this model, CcmG is the last protein in the reducing pathway which interacts stereospecifically with the apoprotein.

This report documents a study of commodity bid offers made to the Defense National Stockpile Center (DNSC). The purpose of the study was to provide DNSC with better information about potential changes in market commodity prices. This report provides the project findings of the new PC based price forecasting model, "market basket" decision support package, and "optimal" price methodology.