Background

Acidithiobacillus ferrooxidans is a major participant in consortia of microorganisms used for the industrial recovery of copper (bioleaching or biomining). It is a chemolithoautrophic, gamma-proteobacterium using energy from the oxidation of iron- and sulfur-containing minerals for growth. It thrives at extremely low pH (pH 1-2) and fixes both carbon and nitrogen from the atmosphere. It solubilizes copper and other metals from rocks and plays an important role in nutrient and metal biogeochemical cycling in acid environments. The lack of a well-developed system for genetic manipulation has prevented thorough exploration of its physiology. Also, confusion has been caused by prior metabolic models constructed based upon the examination of multiple, and sometimes distantly related, strains of the microorganism.

Results

The genome of the type strain A. ferrooxidans ATCC 23270 was sequenced and annotated to identify general features and provide a framework for in silico metabolic reconstruction. Earlier models of iron and sulfur oxidation, biofilm formation, quorum sensing, inorganic ion uptake, and amino acid metabolism are confirmed and extended. Initial models are presented for central carbon metabolism, anaerobic metabolism (including sulfur reduction, hydrogen metabolism and nitrogen fixation), stress responses, DNA repair, and metal and toxic compound fluxes.

Conclusion

Bioinformatics analysis provides a valuable platform for gene discovery and functional prediction that helps explain the activity of A. ferrooxidans in industrial bioleaching and its role as a primary producer in acidic environments. An analysis of the genome of the type strain provides a coherent view of its gene content and metabolic potential.

Diabetic patients undergoing coronary interventions have worse clinical and angiographic outcomes than do patients without diabetes. Metformin, an insulin sensitizer, may decrease the occurrence of these outcomes. Diabetic patients in the Prevention of Restenosis with Tranilast and its Outcomes Trial were identified through their medical records (n = 2,772). In this trial, 1,110 diabetic patients received nonsensitizer therapy (insulin and/or sulfonylureas) and 887 received sensitizer therapy (metformin with or without additional therapy). Logistic regression was used to obtain odds ratios (ORs) (sensitizer vs nonsensitizer therapy) of any clinical event (death, myocardial infarction, or ischemia-driven target vessel revascularization) and adjusted for multiple risk factors. Multivariate analysis showed no effect of lesion characteristics on clinical outcomes. Compared with patients on nonsensitizer therapy, those on sensitizer therapy showed an adjusted OR of 0.72 (95% confidence interval [CI] 0.57 to 0.91, p = 0.005) for any clinical event. The differences between the nonsensitizer therapy group and the sensitizer group were attributable mainly to decreased rates of death (OR 0.39, 95% CI 0.19 to 0.77, p = 0.007) and myocardial infarction (OR 0.31, 95% CI 0.15 to 0.66, p = 0.002). In our retrospective analysis, use of metformin in diabetics undergoing coronary interventions appeared to decrease adverse clinical events, especially death and myocardial infarction, compared with diabetic patients treated with nonsensitizer therapy.

BACKGROUND: Oral anticoagulation (OAC) has been considered the standard of care for stroke prophylaxis for patients with nonvalvular atrial fibrillation; however, many individuals are unable or unwilling to take long-term OAC. The safety and efficacy of percutaneous left atrial appendage closure (LAAC) have been controversial, and new trial data have recently emerged. We therefore sought to perform an updated meta-analysis of randomized clinical trials (RCTs) comparing OAC to percutaneous LAAC, focusing on individual clinical endpoints. METHODS: We performed a systematic search of the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from January 2000 through December 2021 for all RCTs comparing percutaneous LAAC to OAC in patients with nonvalvular atrial fibrillation. Fixed and random effects meta-analyses of hazard ratios (HRs) were performed using the longest follow-up duration available by intention-to-treat. The prespecified primary endpoint was all-cause mortality. RESULTS: Three RCTs enrolling 1516 patients were identified. The weighted mean follow-up was 54.7 months. LAAC was associated with a reduced risk of all-cause mortality (HR 0.76; 95% confidence interval [CI], 0.59-0.96; p = 0.023), hemorrhagic stroke (HR 0.24; 95% CI, 0.09-0.61; p = 0.003), and major nonprocedural bleeding (HR 0.52; 95% CI, 0.37-0.74; p < 0.001). There was no significant difference between LAAC and OAC for any other endpoints. CONCLUSIONS: The available evidence from RCTs suggests LAAC therapy is associated with reduced long-term risk of death compared with OAC. This may be driven by reductions in hemorrhagic stroke and major nonprocedural bleeding. There were no significant differences in the risk of all stroke. Further large-scale clinical trials are needed to validate these findings.

Background

Patient-reported outcome measures provide an essential perspective on the quality of health care provided. However, how data are collected, how providers value and make sense of the data, and, ultimately, use the data to create meaningful impact all influence the success of using patient-reported outcomes.

Objectives

The primary objective is to assess post-operative pain experiences by dental procedure type through 21 days post-procedure as reported by patients following dental procedures and assess patients' satisfaction with pain management following dental surgical procedures. Secondary objectives are to: 1) assess post-operative pain management strategies 1 week following dental surgical procedures, as recommended by practitioners and reported by patients, and 2) evaluate practitioner and patient acceptance of the FollowApp.Care post visit patient monitoring technology (FollowApp.Care). We will evaluate FollowApp.Care usage, perceived usefulness, ease of use, and impact on clinical workload.

Design and methods

We describe the protocol for an observational study involving the use of the FollowApp.Care platform, an innovative mobile application that collects dental patients' assessments of their post-operative symptoms (e.g., pain). The study will be conducted in collaboration with the National Dental Practice-based Research Network, a collective Network of dental practices that include private and group practices, public health clinics, community health centers and Federal Qualified Health Centers, academic institutional settings, and special patient populations. We will recruit a minimum of 150 and up to 215 dental providers and up to 3147 patients who will receive push notifications through text messages FollowApp.Care on their mobile phones at designated time intervals following dental procedures. This innovative approach of implementing an existing and tested mobile health system technology into the real-world dental office setting will actively track pain and other complications following dental procedures. Through patients' use of their mobile phones, we expect to promptly and precisely identify specific pain levels and other issues after surgical dental procedures. The study's primary outcome will be the patients' reported pain experiences. Secondary outcomes include pain management strategies and medications implemented by the patient and provider and perceptions of usefulness and ease of use by patients and providers.

BACKGROUND: Dental Patient Reported Outcomes (PROs) relate to a dental patients subjective experience of their oral health. How practitioners and patients value PROs influences their successful use in practice. METHODS: Semi-structured interviews were conducted with 22 practitioners and 32 patients who provided feedback on using a mobile health (mHealth) platform to collect the pain experience after dental procedures. A themes analysis was conducted to identify implementation barriers and facilitators. RESULTS: Five themes were uncovered: (1) Sense of Better Care. (2) Tailored Follow-up based on the dental procedure and patients pain experience. (3) Effective Messaging and Alerts. (4) Usable Digital Platform. (5) Routine mHealth Integration. CONCLUSION: Frequent automated and preferably tailored follow-up messages using an mHealth platform provided a positive care experience for patients, while providers felt it saved them time and effort. Patients thought that the mHealth questionnaires were well-developed and of appropriate length. The mHealth platform itself was perceived as user-friendly by users, and most would like to continue using it. PRACTICAL IMPLICATIONS: Patients are prepared to use mobile phones to report their pain experience after dental procedures. Practitioners will be able to close the post-operative communication gap with their patients, with little interruption of their workflow.

Background

Acidithiobacillus caldus is a sulfur oxidizing extreme acidophile and the only known mesothermophile within the Acidithiobacillales. As such, it is one of the preferred microbes for mineral bioprocessing at moderately high temperatures. In this study, we explore the genomic diversity of A. caldus strains using a combination of bioinformatic and experimental techniques, thus contributing first insights into the elucidation of the species pangenome.

Principal findings

Comparative sequence analysis of A. caldus ATCC 51756 and SM-1 indicate that, despite sharing a conserved and highly syntenic genomic core, both strains have unique gene complements encompassing nearly 20% of their respective genomes. The differential gene complement of each strain is distributed between the chromosomal compartment, one megaplasmid and a variable number of smaller plasmids, and is directly associated to a diverse pool of mobile genetic elements (MGE). These include integrative conjugative and mobilizable elements, genomic islands and insertion sequences. Some of the accessory functions associated to these MGEs have been linked previously to the flexible gene pool in microorganisms inhabiting completely different econiches. Yet, others had not been unambiguously mapped to the flexible gene pool prior to this report and clearly reflect strain-specific adaption to local environmental conditions.

Significance

For many years, and because of DNA instability at low pH and recurrent failure to genetically transform acidophilic bacteria, gene transfer in acidic environments was considered negligible. Findings presented herein imply that a more or less conserved pool of actively excising MGEs occurs in the A. caldus population and point to a greater frequency of gene exchange in this econiche than previously recognized. Also, the data suggest that these elements endow the species with capacities to withstand the diverse abiotic and biotic stresses of natural environments, in particular those associated with its extreme econiche.

Background

Few studies have examined the efficacy of drug-eluting stents (DES) for reducing aortocoronary saphenous vein bypass graft (SVG) failure compared with bare-metal stents (BMS) in patients undergoing stenting of de-novo SVG lesions. We assessed the risks and benefits of the use of DES versus BMS in de-novo SVG lesions.

Methods

Patients were recruited to our double-blind, randomised controlled trial from 25 US Department of Veterans Affairs centres. Eligible participants were aged at least 18 years and had at least one significant de-novo SVG lesion (50-99% stenosis of a 2·25-4·5 mm diameter SVG) requiring percutaneous coronary intervention with intent to use embolic protection devices. Enrolled patients were randomly assigned, in a 1:1 ratio, by phone randomisation system to receive a DES or BMS. Randomisation was stratified by presence or absence of diabetes and number of target SVG lesions requiring percutaneous coronary intervention (one or two or more) within each participating site by use of an adaptive scheme intended to balance the two stent type groups on marginal totals for the stratification factors. Patients, referring physicians, study coordinators, and outcome assessors were masked to group allocation. The primary endpoint was the 12-month incidence of target vessel failure, defined as the composite of cardiac death, target vessel myocardial infarction, or target vessel revascularisation. The DIVA trial is registered with ClinicalTrials.gov, number NCT01121224.

Findings

Between Jan 1, 2012, and Dec 31, 2015, 599 patients were randomly assigned to the stent groups, and the data for 597 patients were used. The patients' mean age was 68·6 (SD 7·6) years, and 595 (>99%) patients were men. The two stent groups were similar for most baseline characteristics. At 12 months, the incidence of target vessel failure was 17% (51 of 292) in the DES group versus 19% (58 of 305) in the BMS group (adjusted hazard ratio 0·92, 95% CI 0·63-1·34, p=0·70). Between-group differences in the components of the primary endpoint, serious adverse events, or stent thrombosis were not significant. Enrolment was stopped before the revised target sample size of 762 patients was reached.

Interpretation

In patients undergoing stenting of de-novo SVG lesions, no significant differences in outcomes between those receiving DES and BMS during 12 months of follow-up were found. The study results have important economic implications in countries with high DES prices such as the USA, because they suggest that the lower-cost BMS can be used in SVG lesions without compromising either safety or efficacy.

Funding

US Department of Veterans Affairs Cooperative Studies Program.