Predicted hexameric structure of the Agrobacterium VirB4 C terminus suggests VirB4 acts as a docking site during type IV secretion

The Agrobacterium T-DNA transporter belongs to a growing class of evolutionarily conserved transporters, called type IV secretion systems (T4SSs). VirB4, 789 aa, is the largest T4SS component, providing a rich source of possible structural domains. Here, we use a variety of bioinformatics methods to predict that the C-terminal domain of VirB4 (including the Walker A and B nucleotide-binding motifs) is related by divergent evolution to the cytoplasmic domain of TrwB, the coupling protein required for conjugative transfer of plasmid R388 from Escherichia coli. This prediction is supported by detailed sequence and structure analyses showing conservation of functionally and structurally important residues between VirB4 and TrwB. The availability of a solved crystal structure for TrwB enables the construction of a comparative model for VirB4 and the prediction that, like TrwB, VirB4 forms a hexamer. These results lead to a model in which VirB4 acts as a docking site at the entrance of the T4SS channel and acts in concert with VirD4 and VirB11 to transport substrates (T-strand linked to VirD2 or proteins such as VirE2, VirE3, or VirF) through the T4SS.     

Association between a prolonged corrected QT interval and outcomes in patients in a medical Intensive Care Unit

Introduction:

Patients admitted into a medical Intensive Care Unit (ICU) have varying illnesses and risk factors. An electrocardiogram (ECG) is a useful tool to assess the cardiac status. The aim of the study was to determine the prevalence of QT prolongation of the ECG in patients admitted to a medical ICU in a tertiary hospital, to assess outcomes in terms of mortality, cardiovascular events, and duration of ICU stay.

Materials and Methods:

Prospective observational study, 6 months duration, assessing the prevalence of prolonged corrected QT interval (QTc) at admission into a medical ICU. A QTc calculated by Bazett''s formula, of >440 ms for males and >460 ms for females was considered prolonged. Details of illness, clinical and lab parameters were monitored.

Results:

The total number of patients screened was 182. There was a high prevalence of prolonged QTc (30%) on admission to the ICU. This reduced to 19% on day 3 (P = 0.011). In patients with a prolonged QTc the odds ratio of adverse outcome from ICU was 3.17 (confidence interval [CI]: 1.52–6.63) (P = 0.001) and of adverse outcome for hospital stay was 2.27 (CI: 1.11–4.66) (P = 0.014). In the study, 35% of all patients received drugs with QT prolonging action. Of patients with a prolonged QTc at admission 18 (35%) received a QT prolonging drug.

Conclusions:

We found that prolonged QTc is common (30%) in our medical ICU at admission and a large proportion (35%) received drugs capable of prolonging QT interval. These patients with QTc prolongation have a higher odds ratio for adverse outcomes.     

Non-pharmacological management of phantom limb pain in lower limb amputation: a systematic review

Background: The incidence and severity of phantom limb pain (PLP) does not differ much between the extremities of amputation. However, its impact on functional ability and quality of life in lower limb amputation may be different, as prosthetic weight bearing is a key component in the movement and functional rehabilitation of individuals with a lower limb amputation.

Objective: To evaluate the evidence for effectiveness or efficacy of non-pharmacological interventions in the management of PLP in adults with lower limb amputation.

Methods: A comprehensive literature search conducted on 11 electronic databases, from their inception to 25 March 2016 identified 626 potentially relevant articles. Full-text randomised controlled trials in English which examined any form of non-pharmacologic intervention for managing PLP in lower limb amputees were included. The data with regard to characteristics of the studies, participants, intervention and outcome measures and overall statistical result were extracted. The Cochrane ‘Risk of bias assessment tool’ was used to assess the bias of all included articles.

Results: Four studies met the final criteria to be included in the review. Four treatment techniques had been used in the treatment of 204 patients with lower limb amputation. Two trials showed a positive impact of intervention on PLP compared to control group. Risk of bias varied across studies, and only one included study was assessed as having a low risk of bias.

Conclusion: The review identified lack of evidence to support non-pharmacological interventions in the management of PLP. Adequately powered high-quality trials are needed in this area to inform rehabilitation.     

Genoprotection and Cytotoxicity of Cassia surattensis Seed Extract on Vero Cell Evaluated by Comet and Cytotoxicity Assays

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Cassia (C.) surattensis Burm. f. (Leguminosae) is a flowering plant that has been traditionally used in many...     

Importance of measurement site on assessment of lesion-specific ischemia and diagnostic performance by coronary computed tomography Angiography-Derived Fractional Flow Reserve

BackgroundValues of fractional flow reserve (FFR_CT) by coronary computed tomography angiography (CTA) decline from the ostium to the terminal vessel, irrespective of stenosis severity. The purpose of this study is to determine if the site of measurement of FFR_CT impacts assessment of ischemia and its diagnostic performance relative to invasive FFR (FFR_INV).Methods1484 patients underwent FFR_CT; 1910 vessels were stratified by stenosis severity (normal; <25%, 25–50%, 50–70%, and >70% stenosis). The rates of positive FFR_CT (≤0.8) were determined by measuring FFR_CT from the terminal vessel and from distal-to-the-lesion. Reclassification rates from positive to negative FFR_CT were calculated. Diagnostic performance of FFR_CT relative to FFR_INV was evaluated in 182 vessels using linear regression, Bland Altman analysis, and receiver operating characteristic (ROC) curves.ResultsPositive FFR_CT was identified in 24.9% of vessels using terminal vessel FFR_CT and 10.1% using FFR_CT distal-to-the-lesion (p ?< ?0.001). FFR_CT obtained distal-to-the-lesion resulted in reclassification of 59.6% of positive terminal FFR_CT to negative FFR_CT. Relative to FFR_INV, there were improvements in specificity (50% to 86%, p ?< ?0.001), diagnostic accuracy (65% to 88%, p ?< ?0.001), positive predictive value (50% to 78%, p ?< ?0.001), and area-under-the-curve (AUC, 0.83 to 0.91, p ?< ?0.001) when FFR_CT was measured distal-to-the-lesion.ConclusionFFR_CT values from the terminal vessel should not be used to assess lesion-specific ischemia due to high rates of false positive results. FFR_CT measured distal-to-the-lesion improves the diagnostic performance of FFR_CT relative to FFR_INV, ensures that FFR_CT values are due to lesion-specific ischemia, and could reduce the rate of unnecessary invasive procedures.     

Impact of age on coronary artery plaque progression and clinical outcome: A PARADIGM substudy

BackgroundThe association of age with coronary plaque dynamics is not well characterized by coronary computed tomography angiography (CCTA).MethodsFrom a multinational registry of patients who underwent serial CCTA, 1153 subjects (61 ± 5 years old, 61.1% male) were analyzed. Annualized volume changes of total, fibrous, fibrofatty, necrotic core, and dense calcification plaque components of the whole heart were compared by age quartile groups. Clinical events, a composite of all-cause death, acute coronary syndrome, and any revascularization after 30 days of the initial CCTA, were also analyzed. Random forest analysis was used to define the relative importance of age on plaque progression.ResultsWith a 3.3-years’ median interval between the two CCTA, the median annual volume changes of total plaque in each age quartile group was 7.8, 10.5, 10.8, and 12.1 mm³/year and for dense calcification, 2.5, 4.6, 5.4, and 7.1 mm³/year, both of which demonstrated a tendency to increase by age (p-for-trend = 0.001 and < 0.001, respectively). However, this tendency was not observed in any other plaque components. The annual volume changes of total plaque and dense calcification were also significantly different in the propensity score-matched lowest age quartile group versus the other age groups as was the composite clinical event (log-rank p = 0.003). In random forest analysis, age had comparable importance in the total plaque volume progression as other traditional factors.ConclusionsThe rate of whole-heart plaque progression and dense calcification increases depending on age. Age is a significant factor in plaque growth, the importance of which is comparable to other traditional risk factors.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifiers: NCT02803411.     

Clinical profile of acute kidney injury in a pediatric intensive care unit from Southern India: A prospective observational study

Background:

Although the term acute renal failure was replaced by acute kidney injury (AKI) recently, there is a paucity of data on the incidence and profile of AKI in critically ill children from the developing world.

Objectives:

The objective of this study is to determine the incidence, etiology, short term outcome and predictors of fatality in critically ill children admitted to the pediatric intensive care unit (PICU) with AKI, aged 1 month to 13 years.

Materials and Methods:

In this prospective observational study, from June 2010 to March 2011, 215 children admitted to the PICU were screened for AKI, defined according to the AKI Network criteria. The patients with AKI were followed-up until discharge/death. Their clinical and biochemical data were recorded.

Results:

The incidence of AKI among 215 patients screened was 54 (25.1%). The common etiologies were infections, [34 (62.9%)], acute glomerulonephritis (7.6%), snake envenomation (5.7%), hemolytic uremic syndrome (3.8%) and congestive cardiac failures (3.8%). Among infections, pneumonia and septicemia constituted 26.5% each, meningoencephalitis accounted for 23.5%, and dengue, scrub typhus, tuberculosis and malaria constituted 9.3% of children with AKI. 27.8% of patients required dialysis. Overall mortality was 46.3%. On logistic regression analysis, requirement of mechanical ventilation was an independent predictor of fatality in AKI.

Conclusions:

Besides the high incidence of AKI in critically ill-children admitted to the PICU (25.1%), the condition was associated with adverse outcomes, including high mortality (46.3%) and need for dialysis (27.8%). Infections dominated the etiological profile. Requirement of mechanical ventilation predicted an adverse outcome in our patient population.     

Circumspect descent prevails in solving random constraint satisfaction problems

We study the performance of stochastic local search algorithms for random instances of the K-satisfiability (K-SAT) problem. We present a stochastic local search algorithm, ChainSAT, which moves in the energy landscape of a problem instance by never going upwards in energy. ChainSAT is a focused algorithm in the sense that it focuses on variables occurring in unsatisfied clauses. We show by extensive numerical investigations that ChainSAT and other focused algorithms solve large K-SAT instances almost surely in linear time, up to high clause-to-variable ratios alpha; for example, for K = 4 we observe linear-time performance well beyond the recently postulated clustering and condensation transitions in the solution space. The performance of ChainSAT is a surprise given that by design the algorithm gets trapped into the first local energy minimum it encounters, yet no such minima are encountered. We also study the geometry of the solution space as accessed by stochastic local search algorithms.