Single-molecule dynamics of DNA gyrase in evolutionarily distant bacteria Mycobacterium tuberculosis and Escherichia coli.

DNA gyrase is an essential nucleoprotein motor present in all bacteria and is a major target for antibiotic treatment of Mycobacterium tuberculosis (MTB) infection. Gyrase hydrolyzes ATP to add negative supercoils to DNA using a strand passage mechanism that has been investigated using biophysical and biochemical approaches. To analyze the dynamics of substeps leading to strand passage, single-molecule rotor bead tracking (RBT) has been used previously to follow real-time supercoiling and conformational transitions in Escherichia coli (EC) gyrase. However, RBT has not yet been applied to gyrase from other pathogenically relevant bacteria, and it is not known whether substeps are conserved across evolutionarily distant species. Here, we compare gyrase supercoiling dynamics between two evolutionarily distant bacterial species, MTB and EC. We used RBT to measure supercoiling rates, processivities, and the geometries and transition kinetics of conformational states of purified gyrase proteins in complex with DNA. Our results show that E. coli and MTB gyrases are both processive, with the MTB enzyme displaying velocities ∼5.5× slower than the EC enzyme. Compared with EC gyrase, MTB gyrase also more readily populates an intermediate state with DNA chirally wrapped around the enzyme, in both the presence and absence of ATP. Our substep measurements reveal common features in conformational states of EC and MTB gyrases interacting with DNA but also suggest differences in populations and transition rates that may reflect distinct cellular needs between these two species.

Accelerating the global response against the exponentially growing COVID-19 outbreak through decent data sharing.

The novel coronavirus disease 2019 (COVID-19) is a novel and exponentially growing disease, and consequently, the accelerated development of knowledge from good data is possible quickly and globally. In order to combat the global pandemic of COVID-19, all humans on earth need to make difficult strategic decisions on three very different scales, all fueled by Analytical and Artificial Intelligence-based predictive Models.

Effects of Virtual Reality Sessions on the Quality of Life, Happiness, and Functional Fitness among the Older People: A Randomized Controlled Trial from Taiwan.

BACKGROUND AND OBJECTIVE: Ageing is a complex process with physical, psychological, and social changes, which can lead to diseases and disability, and further reduce happiness levels. Virtual reality (VR) is an emerging technology with the potential to improve overall well-being, quality of life (QoL), muscle activity and balance. Our study aimed to determine the influence of VR sessions on the QoL, happiness, and functional fitness components of an elderly cohort. METHODS: A non-blinded randomized controlled trial was conducted. Sixty participants, who visited the active ageing center at the university were randomized into two groups- intervention and control. The intervention group received VR experience sessions for 15 min twice a week for a duration of 6 weeks, while the control group received no sessions. Participants filled out a questionnaire for QoL assessment and happiness assessment. They were also tested for several functional fitness components. Both questionnaires and fitness tests were conducted at the beginning and at the end of study. RESULTS: QoL improved by some metrics assessed (Pain/Discomfort and Anxiety/Depression). Happiness significantly improved in the intervention group relative to the control group. Among the functional fitness tests, the back scratch test 1st and back scratch test 2nd were measured to be significantly improved in the intervention group in comparison to control group. CONCLUSIONS: VR sessions have potential to influence the well-being and functional fitness of older adults and further support the process of healthy and active ageing. Future considerations could focus on supporting more physical and psychological aspects of the older people through VR content. TRIAL REGISTRATION: NCT04166747.

COVID-19 preventive measures showing an unintended decline in infectious diseases in Taiwan.

Most of the communicable diseases have contact, airborne and/or droplet mode of transsmission. Following the outbreak of COVID-19, the Taiwan government implemented the use of masks and sanitizer, as well as other preventive measures like social distancing for prevention. This public response likely contributed significantly to the decline in the outbreak of other infectious diseases.

Meta-analysis of proton pump inhibitors induced risk of community-acquired pneumonia.

PURPOSE: Proton pump inhibitors (PPIs), one of the most widely used medications, are commonly used to suppress several acid-related upper gastrointestinal disorders. Acid-suppressing medication use could be associated with increased risk of community-acquired pneumonia (CAP), although the results of clinical studies have been conflicting. DATA SOURCES: A comprehensive search of MEDLINE, EMBASE and Cochrane library and Database of Systematic Reviews from the earliest available online year of indexing up to October 2018. STUDY SELECTION: We performed a systematic review and meta-analysis of observational studies to evaluate the risk of PPI use on CAP outcomes. DATA EXTRACTION: Included study location, design, population, the prevalence of CAP, comparison group and other confounders. We calculated pooled odds ratio (OR) using a random-effects meta-analysis. RESULTS OF DATA SYNTHESIS: Of the 2577 studies screening, 11 papers were included in the systematic review and 7 studies with 65 590 CAP cases were included in the random-effects meta-analysis. In current PPI users, pooled OR for CAP was 1.86 (95% confidence interval (CI), 1.30-2.66), and in the case of recent users, OR for CAP was 1.66 (95% CI, 1.22-2.25). In the subgroup analysis of CAP, significance association is also observed in both high-dose and low-dose PPI therapy. When stratified by duration of exposure, 3-6 months PPIs users group was associated with increased risk of developing CAP (OR, 2.05; 95% CI, 1.22-3.45). There was a statistically significant association between the PPI users and the rate of hospitalization (OR, 2.59; 95% CI, 1.83-3.66). CONCLUSION: We found possible evidence linking PPI use to an increased risk of CAP. More randomized controlled studies are warranted to clarify an understanding of the association between PPI use and risk of CAP because observational studies cannot clarify whether the observed epidemiologic association is a causal effect or a result of unmeasured/residual confounding.

Statins use and its impact in EGFR-TKIs resistance to prolong the survival of lung cancer patients: A Cancer registry cohort study in Taiwan.

Statins have been shown to be a beneficial treatment as chemotherapy and target therapy for lung cancer. This study aimed to investigate the effectiveness of statins in combination with epidermal growth factor receptor-tyrosine kinase inhibitor therapy for the resistance and mortality of lung cancer patients. A population-based cohort study was conducted using the Taiwan Cancer Registry database. From January 1, 2007, to December 31, 2012, in total 792 non-statins and 41 statins users who had undergone EGFR-TKIs treatment were included in this study. All patients were monitored until the event of death or when changed to another therapy. Kaplan-Meier estimators and Cox proportional hazards regression models were used to calculate overall survival. We found that the mortality was significantly lower in patients in the statins group compared with patients in the non-statins group (4-y cumulative mortality, 77.3%; 95% confidence interval (CI), 36.6%-81.4% vs. 85.5%; 95% CI, 78.5%-98%; P = .004). Statin use was associated with a reduced risk of death in patients the group who had tumor sizes <3 cm (hazard ratio [HR], 0.51, 95% CI, 0.29-0.89) and for patients in the group who had CCI scores <3 (HR, 0.6; 95% CI, 0.41-0.88; P = .009). In our study, statins were found to be associated with prolonged survival time in patients with lung cancer who were treated with EGFR-TKIs and played a synergistic anticancer role.

Use of mobile applications to improve nutrition behaviour: A systematic review.

BACKGROUND AND OBJECTIVE: Mobile applications could be effectively used for dietary intake assessment, physical activity monitoring, behavior improvement, and nutrition education. The aim of this review is to determine the effectiveness of mobile applications in improving nutrition behaviors through a systematic review of literature. METHODS: The review protocol was registered with PROSPERO: registration number CRD42018118809, and followed PRISMA guidelines. We involved original articles including mobile electronic devices for improving dietary intake, physical activity, and weight management in adult populations in this review. Data were retrieved from January 2010 to December 2018 with PubMed, Web of Science, Excerpta Medica Database (Embase), and Cumulative Index to Nursing and Allied Health Literature (CINAHL) as data sources. Authors individually screened the titles and abstracts, then full articles in order to obtain papers that met inclusion criteria. RESULTS: The database search yielded 2962 records. After removing the duplicates and analyzing the full text papers a total of 8 original articles were reviewed. Two articles showed obvious bias and were not included in our results or discussion. The remaining six articles with low to moderate bias risk were included in this systematic review. Three selected studies were randomized control trials (RCTs) with over 180 participants each. The other three studies were a nested trial, a case-control trial, and a pilot RCT with 36, 162, and 24 participants respectively. All larger RCTs and the small case control trail showed significant improvements in some nutritional-health objectives measured. The other two trials showed insignificant improvements in outcomes measured between groups. CONCLUSION: This study highlights the potential significant health benefits acquirable through mobile health application-assisted nutrition interventions. Some of these studies required significant financial and time input from providers for the application's utilization. Further studies, perhaps with multiple intervention arms, are required to compare across programs the elements that are essential for health benefits observed.

The cost of illness attributable to diabetic foot and cost-effectiveness of secondary prevention in Peru.

BACKGROUND: Diabetes mellitus is a public health challenge worldwide, and roughly 25% of patients with diabetes in developing countries will develop at least one foot ulcer during their lifetime. The gravest outcome of an ulcerated foot is amputation, leading to premature death and larger economic costs. METHODS: This study aimed to estimate the economic costs of diabetic foot in high-risk patients in Peru in 2012 and to model the cost-effectiveness of a year-long preventive strategy for foot ulceration including: sub-optimal care (baseline), standard care as recommended by the International Diabetes Federation, and standard care plus daily self-monitoring of foot temperature. A decision tree model using a population prevalence-based approach was used to calculate the costs and the incremental cost-effectiveness ratio (ICER). Outcome measures were deaths and major amputations, uncertainty was tested with a one-way sensitivity analysis. RESULTS: The direct costs for prevention and management with sub-optimal care for high-risk diabetics is around US$74.5 million dollars in a single year, which decreases to US$71.8 million for standard care and increases to US$96.8 million for standard care plus temperature monitoring. The implementation of a standard care strategy would avert 791 deaths and is cost-saving in comparison to sub-optimal care. For standard care plus temperature monitoring compared to sub-optimal care the ICER rises to US$16,124 per death averted and averts 1,385 deaths. CONCLUSION: Diabetic foot complications are highly costly and largely preventable in Peru. The implementation of a standard care strategy would lead to net savings and avert deaths over a one-year period. More intensive prevention strategies such as incorporating temperature monitoring may also be cost-effective.

A metal-free organic-inorganic aqueous flow battery.

As the fraction of electricity generation from intermittent renewable sources--such as solar or wind--grows, the ability to store large amounts of electrical energy is of increasing importance. Solid-electrode batteries maintain discharge at peak power for far too short a time to fully regulate wind or solar power output. In contrast, flow batteries can independently scale the power (electrode area) and energy (arbitrarily large storage volume) components of the system by maintaining all of the electro-active species in fluid form. Wide-scale utilization of flow batteries is, however, limited by the abundance and cost of these materials, particularly those using redox-active metals and precious-metal electrocatalysts. Here we describe a class of energy storage materials that exploits the favourable chemical and electrochemical properties of a family of molecules known as quinones. The example we demonstrate is a metal-free flow battery based on the redox chemistry of 9,10-anthraquinone-2,7-disulphonic acid (AQDS). AQDS undergoes extremely rapid and reversible two-electron two-proton reduction on a glassy carbon electrode in sulphuric acid. An aqueous flow battery with inexpensive carbon electrodes, combining the quinone/hydroquinone couple with the Br2/Br(-) redox couple, yields a peak galvanic power density exceeding 0.6 W cm(-2) at 1.3 A cm(-2). Cycling of this quinone-bromide flow battery showed >99 per cent storage capacity retention per cycle. The organic anthraquinone species can be synthesized from inexpensive commodity chemicals. This organic approach permits tuning of important properties such as the reduction potential and solubility by adding functional groups: for example, we demonstrate that the addition of two hydroxy groups to AQDS increases the open circuit potential of the cell by 11% and we describe a pathway for further increases in cell voltage. The use of π-aromatic redox-active organic molecules instead of redox-active metals represents a new and promising direction for realizing massive electrical energy storage at greatly reduced cost.

Complex Chemical Reaction Networks from Heuristics-Aided Quantum Chemistry.

While structures and reactivities of many small molecules can be computed efficiently and accurately using quantum chemical methods, heuristic approaches remain essential for modeling complex structures and large-scale chemical systems. Here, we present a heuristics-aided quantum chemical methodology applicable to complex chemical reaction networks such as those arising in cell metabolism and prebiotic chemistry. Chemical heuristics offer an expedient way of traversing high-dimensional reactive potential energy surfaces and are combined here with quantum chemical structure optimizations, which yield the structures and energies of the reaction intermediates and products. Application of heuristics-aided quantum chemical methodology to the formose reaction reproduces the experimentally observed reaction products, major reaction pathways, and autocatalytic cycles.