Diabetic foot infections: current concept review

The purpose of this manuscript is to provide a current concept review on the diagnosis and management of diabetic foot infections which are among the most serious and frequent complications encountered in patients with diabetes mellitus. A literature review on diabetic foot infections with emphasis on pathophysiology, identifiable risk factors, evaluation including physical examination, laboratory values, treatment strategies and assessing the severity of infection has been performed in detail. Diabetic foot infections are associated with high morbidity and risk factors for failure of treatment and classification systems are also described. Most diabetic foot infections begin with a wound and once an infection occurs, the risk of hospitalization and amputation increases dramatically. Early identification of infection and prompt treatment may optimize the patient's outcome and provide limb salvage

Differential expression analysis with global network adjustment

<p>Background: Large-scale chromosomal deletions or other non-specific perturbations of the transcriptome can alter the expression of hundreds or thousands of genes, and it is of biological interest to understand which genes are most profoundly affected. We present a method for predicting a gene’s expression as a function of other genes thereby accounting for the effect of transcriptional regulation that confounds the identification of genes differentially expressed relative to a regulatory network. The challenge in constructing such models is that the number of possible regulator transcripts within a global network is on the order of thousands, and the number of biological samples is typically on the order of 10. Nevertheless, there are large gene expression databases that can be used to construct networks that could be helpful in modeling transcriptional regulation in smaller experiments.</p> <p>Results: We demonstrate a type of penalized regression model that can be estimated from large gene expression databases, and then applied to smaller experiments. The ridge parameter is selected by minimizing the cross-validation error of the predictions in the independent out-sample. This tends to increase the model stability and leads to a much greater degree of parameter shrinkage, but the resulting biased estimation is mitigated by a second round of regression. Nevertheless, the proposed computationally efficient “over-shrinkage” method outperforms previously used LASSO-based techniques. In two independent datasets, we find that the median proportion of explained variability in expression is approximately 25%, and this results in a substantial increase in the signal-to-noise ratio allowing more powerful inferences on differential gene expression leading to biologically intuitive findings. We also show that a large proportion of gene dependencies are conditional on the biological state, which would be impossible with standard differential expression methods.</p> <p>Conclusions: By adjusting for the effects of the global network on individual genes, both the sensitivity and reliability of differential expression measures are greatly improved.</p&gt

An ATP and Oxalate Generating Variant Tricarboxylic Acid Cycle Counters Aluminum Toxicity in Pseudomonas fluorescens

Although the tricarboxylic acid (TCA) cycle is essential in almost all aerobic organisms, its precise modulation and integration in global cellular metabolism is not fully understood. Here, we report on an alternative TCA cycle uniquely aimed at generating ATP and oxalate, two metabolites critical for the survival of Pseudomonas fluorescens. The upregulation of isocitrate lyase (ICL) and acylating glyoxylate dehydrogenase (AGODH) led to the enhanced synthesis of oxalate, a dicarboxylic acid involved in the immobilization of aluminum (Al). The increased activity of succinyl-CoA synthetase (SCS) and oxalate CoA-transferase (OCT) in the Al-stressed cells afforded an effective route to ATP synthesis from oxalyl-CoA via substrate level phosphorylation. This modified TCA cycle with diminished efficacy in NADH production and decreased CO2-evolving capacity, orchestrates the synthesis of oxalate, NADPH, and ATP, ingredients pivotal to the survival of P. fluorescens in an Al environment. The channeling of succinyl-CoA towards ATP formation may be an important function of the TCA cycle during anaerobiosis, Fe starvation and O2-limited conditions

The impact of an intervention to introduce malaria rapid diagnostic tests on fever case management in a high transmission setting in Uganda: A mixed-methods cluster-randomized trial (PRIME).

Rapid diagnostic tests for malaria (mRDTs) have been scaled-up widely across Africa. The PRIME study evaluated an intervention aiming to improve fever case management using mRDTs at public health centers in Uganda. A cluster-randomized trial was conducted from 2010-13 in Tororo, a high malaria transmission setting. Twenty public health centers were randomized in a 1:1 ratio to intervention or control. The intervention included training in health center management, fever case management with mRDTs, and patient-centered services; plus provision of mRDTs and artemether-lumefantrine (AL) when stocks ran low. Three rounds of Interviews were conducted with caregivers of children under five years of age as they exited health centers (N = 1400); reference mRDTs were done in children with fever (N = 1336). Health worker perspectives on mRDTs were elicited through semi-structured questionnaires (N = 49) and in-depth interviews (N = 10). The primary outcome was inappropriate treatment of malaria, defined as the proportion of febrile children who were not treated according to guidelines based on the reference mRDT. There was no difference in inappropriate treatment of malaria between the intervention and control arms (24.0% versus 29.7%, adjusted risk ratio 0.81 95\% CI: 0.56, 1.17 p = 0.24). Most children (76.0\%) tested positive by reference mRDT, but many were not prescribed AL (22.5\% intervention versus 25.9\% control, p = 0.53). Inappropriate treatment of children testing negative by reference mRDT with AL was also common (31.3\% invention vs 42.4\% control, p = 0.29). Health workers appreciated mRDTs but felt that integrating testing into practice was challenging given constraints on time and infrastructure. The PRIME intervention did not have the desired impact on inappropriate treatment of malaria for children under five. In this high transmission setting, use of mRDTs did not lead to the reductions in antimalarial prescribing seen elsewhere. Broader investment in health systems, including infrastructure and staffing, will be required to improve fever case management

Balanced Schnyder woods for planar triangulations: an experimental study with applications to graph drawing and graph separators

In this work we consider balanced Schnyder woods for planar graphs, which are Schnyder woods where the number of incoming edges of each color at each vertex is balanced as much as possible. We provide a simple linear-time heuristic leading to obtain well balanced Schnyder woods in practice. As test applications we consider two important algorithmic problems: the computation of Schnyder drawings and of small cycle separators. While not being able to provide theoretical guarantees, our experimental results (on a wide collection of planar graphs) suggest that the use of balanced Schnyder woods leads to an improvement of the quality of the layout of Schnyder drawings, and provides an efficient tool for computing short and balanced cycle separators.Comment: Appears in the Proceedings of the 27th International Symposium on Graph Drawing and Network Visualization (GD 2019

Reduction of mitomycin C is catalysed by human recombinant NRH:quinone oxidoreductase 2 using reduced nicotinamide adenine dinucleotide as an electron donating co-factor

NRH:Quinone Oxidoreductase 2 (NQO2) has been described as having no enzymatic activity with nicotinamide adenine dinucleotide (NADH) or NADPH as electron donating cosubstrates. Mitomycin C (MMC) is both a substrate for and a mechanistic inhibitor of the NQO2 homologue NQO1. NRH:quinone oxidoreductase 2 catalysed the reduction of MMC at pH 5.8 with NADH as a co-factor. This reaction results in species that inhibit the NQO2-mediated metabolism of CB1954. In addition, MMC caused an increase in DNA cross-links in a cell line transfected to overexpress NQO2 to an extent comparable to that observed with an isogenic NQO1-expressing cell line. These data indicate that NQO2 may contribute to the metabolism of MMC to cytotoxic species

Religious Participation and DSM IV Major Depressive Disorder Among Black Caribbeans in the United States

This study examines the relationship between religious involvement and 12-month and lifetime DSM-IV major depressive disorder (MDD) within a nationally rep- resentative sample of Black Caribbean adults. MDD was assessed using the DSM-IV World Mental Health Com- posite International Diagnostic Interview (WMH-CIDI). Religious involvement included measures of religious coping, organizational and nonorganizational involvement, and subjective religiosity. Study findings indicate that religious involvement is associated with 12-month and lifetime prevalence of MDD. Multivariate relationships between religious involvement and MDD indicate lower prevalence of 12-month and lifetime MDD among persons who use religious coping and characterize themselves as being religious (for lifetime prevalence only); persons who frequently listen to religious radio programs report higher lifetime MDD. Lower rates of 12-month and lifetime MDD are noted for persons who attend religious services at least once a week (as compared to both higher and lower levels of attendance), indicating a curvilinear relationship. The findings are discussed in relation to previous research on religion and mental health concerns, conceptual models of the role of religion in mental health (e.g., prevention, resource mobilization) that specify multiple and often divergent pathways and mechanisms of religious effects on health outcomes, and the role of religion among Caribbean Blacks.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107411/1/Religious Participation and DSM IV Major Depressive Disorder Among Black Caribbeans in the United States.pdfDescription of Religious Participation and DSM IV Major Depressive Disorder Among Black Caribbeans in the United States.pdf : Main articl

How market standards affect building design: the case of low energy design in commercial offices

This paper develops existing work on building design through a focus on one important yet understudied form of regulation: market standards. Market standards are agreed upon definitions of ‘necessary’ provision in buildings and are fundamental in ‘formatting’ markets and determining the value of a building in the market. The paper presents a case study of the design of ten commercial offices in London, UK, the effects of market standards on the designs and on the potential for the development of lower energy buildings. Theoretically, the paper integrates literatures on standards, institutions and markets to argue that market standards do important ‘work’ in design processes that requires closer scrutiny. In particular, we show that market standards: are an important form of normative and cultural regulation in the field of commercial office design; format and act as calculative devices in property markets; and result in forms of knowledge diminution that break the relationship between building design and occupiers’ practices. Together, these effects result in particular designs being legitimised and valued, and lower energy designs being delegitimised, devalued and pushed to the periphery of the attention of commercial office designers

Defining language impairments in a subgroup of children with autism spectrum disorder

Autism spectrum disorder (ASD) is diagnosed on the basis of core impairments in pragmatic language skills, which are found across all ages and subtypes. In contrast, there is significant heterogeneity in language phenotypes, ranging from nonverbal to superior linguistic abilities, as defined on standardized tests of vocabulary and grammatical knowledge. The majority of children are verbal but impaired in language, relative to age-matched peers. One hypothesis is that this subgroup has ASD and co-morbid specific language impairment (SLI). An experiment was conducted comparing children with ASD to children with SLI and typically developing controls on aspects of language processing that have been shown to be impaired in children with SLI: repetition of nonsense words. Patterns of performance among the children with ASD and language impairment were similar to those with SLI, and contrasted with the children with ASD and no language impairment and typical controls, providing further evidence for the hypothesis that a subgroup of children with ASD has co-morbid SLI. The findings are discussed in the context of brain imaging studies that have explored the neural bases of language impairment in ASD and SLI, and overlap in the genes associated with elevated risk for these disorders.M01 RR00533 - NCRR NIH HHS; R01 DC10290 - NIDCD NIH HHS; U19 DC03610 - NIDCD NIH HH