Research data supporting "A fragment profiling approach to inhibitors of the orphan M. tuberculosis P450 CYP144A1"

Fragment-based approaches to targeting CYP144 from Mycobacterium tuberculosi

Objective and subjective sleep disorders in automated peritoneal dialysis

Background: Automated peritoneal dialysis (APD) is one of the fastest growing dialysis modalities. It is unknown whether sleep and mood are disturbed while performing repeated overnight exchanges. Objectives: In this report, we aim to describe and compare the prevalence of sleep-disordered breathing (SDB), periodic limb movements (PLMS), poor sleep quality (SQ), and depression among APD patients compared with stages 3b-5 (estimated glomerular filtration rate ≤44 ml/min/1.73 m2) chronic kidney disease (CKD) and hemodialysis (HD) patients. Design: This is a cross-sectional, descriptive study. Setting: Study participants were recruited from outpatient nephrology clinics, local dialysis centers, and the Thomas E. Starzl Transplant Institute in Western Pennsylvania between April 2004 and July 2009. Patients: There were 186 participants in this study including 22 APD patients, 89 CKD patients, and 75 HD patients. Measurements: In-home polysomnography was performed and two questionnaires were completed, the Pittsburgh Sleep Quality Index (PSQI) and the Patient Health Questionnaire-9 (PHQ-9). Methods: SDB and PLMS were quantified by in-home unattended polysomnography; poor SQ was defined by a score >5 on the PSQI, and the presence of moderate to severe depression was defined by a score >5 on the PHQ-9. Results: The APD patients had a median age of 37.5 years, were predominantly female (72.7 %), and had a median body mass index (BMI) of 23.8 kg/m2. In univariate analyses, APD patients had significantly lower apnea-hypopnea index compared to HD patients by 12.2 points (likelihood ratio test p = 0.008) and revealed the least percent of TST with nocturnal hypoxemia compared to CKD patients by 2.7 points, respectively (likelihood ratio test p = 0.01). The APD group had also significantly greater stages 3 to 4 sleep compared to the CKD patients by 8.6 points (likelihood ratio test p = 0.009). In multivariate analyses and after adjustment for age, gender, race, and BMI, both APD and HD patients had higher average PSQI scores than CKD patients by 2.54 and 2.22 points, respectively (likelihood ratio test p = 0.005). No other comparisons of sleep parameters among groups reached statistical significance. Limitations: The limitations of this study are the small sample size of the APD population and the demographic and clinical differences among the three study groups. Conclusions: Despite differences in univariate analyses, after multivariate adjustment, APD patients had similar sleep parameters and sleep architecture and as poor SQ and symptoms of depression as HD patients. Future studies with larger APD cohorts are needed

Evidence-based hydro- and balneotherapy in Hungary-a systematic review and meta-analysis

Balneotherapy is appreciated as a traditional treatment modality in medicine. Hungary is rich in thermal mineral waters. Balneotherapy has been in extensive use for centuries and its effects have been studied in detail. Here, we present a systematic review and meta-analysis of clinical trials conducted with Hungarian thermal mineral waters, the findings of which have been published by Hungarian authors in English. The 122 studies identified in different databases include 18 clinical trials. Five of these evaluated the effect of hydro- and balneotherapy on chronic low back pain, four on osteoarthritis of the knee, and two on osteoarthritis of the hand. One of the remaining seven trials evaluated balneotherapy in chronic inflammatory pelvic diseases, while six studies explored its effect on various laboratory parameters. Out of the 18 studies, 9 met the predefined criteria for meta-analysis. The results confirmed the beneficial effect of balneotherapy on pain with weight bearing and at rest in patients with degenerative joint and spinal diseases. A similar effect has been found in chronic pelvic inflammatory disease. The review also revealed that balneotherapy has some beneficial effects on antioxidant status, and on metabolic and inflammatory parameters. Based on the results, we conclude that balneotherapy with Hungarian thermal-mineral waters is an effective remedy for lower back pain, as well as for knee and hand osteoarthritis. © 2013 The Author(s)

Lorentzian and Euclidean Quantum Gravity - Analytical and Numerical Results

We review some recent attempts to extract information about the nature of quantum gravity, with and without matter, by quantum field theoretical methods. More specifically, we work within a covariant lattice approach where the individual space-time geometries are constructed from fundamental simplicial building blocks, and the path integral over geometries is approximated by summing over a class of piece-wise linear geometries. This method of ``dynamical triangulations'' is very powerful in 2d, where the regularized theory can be solved explicitly, and gives us more insights into the quantum nature of 2d space-time than continuum methods are presently able to provide. It also allows us to establish an explicit relation between the Lorentzian- and Euclidean-signature quantum theories. Analogous regularized gravitational models can be set up in higher dimensions. Some analytic tools exist to study their state sums, but, unlike in 2d, no complete analytic solutions have yet been constructed. However, a great advantage of our approach is the fact that it is well-suited for numerical simulations. In the second part of this review we describe the relevant Monte Carlo techniques, as well as some of the physical results that have been obtained from the simulations of Euclidean gravity. We also explain why the Lorentzian version of dynamical triangulations is a promising candidate for a non-perturbative theory of quantum gravity.Comment: 69 pages, 16 figures, references adde

Introduction to the functional RG and applications to gauge theories

These lectures contain an introduction to modern renormalization group (RG) methods as well as functional RG approaches to gauge theories. In the first lecture, the functional renormalization group is introduced with a focus on the flow equation for the effective average action. The second lecture is devoted to a discussion of flow equations and symmetries in general, and flow equations and gauge symmetries in particular. The third lecture deals with the flow equation in the background formalism which is particularly convenient for analytical computations of truncated flows. The fourth lecture concentrates on the transition from microscopic to macroscopic degrees of freedom; even though this is discussed here in the language and the context of QCD, the developed formalism is much more general and will be useful also for other systems.Comment: 60 pages, 14 figures, Lectures held at the 2006 ECT* School "Renormalization Group and Effective Field Theory Approaches to Many-Body Systems", Trento, Ital

Metallothionein genes: no association with Crohn's disease in a New Zealand population

Metallothioneins (MTs) are excellent candidate genes for Inflammatory Bowel Disease (IBD) and have previously been shown to have altered expression in both animal and human studies of IBD. This is the first study to examine genetic variants within the MT genes and aims to determine whether such genetic variants have an important role in this disease. 28 tag SNPs in genes MT1 (subtypes A, B, E, F, G, H, M, X), MT2, MT3 and MT4 were selected for genotyping in a well-characterized New Zealand dataset consisting of 406 patients with Crohn's Disease and 638 controls. We did not find any evidence of association for MT genetic variation with CD. The lack of association indicates that genetic variants in the MT genes do not play a significant role in predisposing to CD in the New Zealand population

Networked buffering: a basic mechanism for distributed robustness in complex adaptive systems

A generic mechanism - networked buffering - is proposed for the generation of robust traits in complex systems. It requires two basic conditions to be satisfied: 1) agents are versatile enough to perform more than one single functional role within a system and 2) agents are degenerate, i.e. there exists partial overlap in the functional capabilities of agents. Given these prerequisites, degenerate systems can readily produce a distributed systemic response to local perturbations. Reciprocally, excess resources related to a single function can indirectly support multiple unrelated functions within a degenerate system. In models of genome:proteome mappings for which localized decision-making and modularity of genetic functions are assumed, we verify that such distributed compensatory effects cause enhanced robustness of system traits. The conditions needed for networked buffering to occur are neither demanding nor rare, supporting the conjecture that degeneracy may fundamentally underpin distributed robustness within several biotic and abiotic systems. For instance, networked buffering offers new insights into systems engineering and planning activities that occur under high uncertainty. It may also help explain recent developments in understanding the origins of resilience within complex ecosystems. \ud \u

Sexuality of Young Adults with Cerebral Palsy: Experienced Limitations and Needs

Objective of this study is to describe the problems young adults with Cerebral Palsy (CP) experience in the various stages of the sexual response cycle, and the physical and emotional obstacles they experience with sexuality. In this prospective cohort study 74 young adults (46 men; 28 women) with CP and average intelligence participated, aged 20–24 years. Twenty percent of these young adults with CP experienced anorgasmia, 80% reported physical problems with sex related to CP and 45% emotional inhibition to initiate sexual contact. In 90% of the participants, sexuality had not been discussed during the rehabilitation treatment. Many adolescents reported wanting information about the impact of CP on sexuality and reproduction (35%), about interventions (26%), tools and medicines (16%) and about problems with their partner (14%). Young adults with CP can experience various problems or challenges with sexuality. For preventing sexual difficulties and treating sexual problems, health care professionals need to proactively take the initiative to inform young people with CP about sexuality

A Sensitive and Quantitative Polymerase Chain Reaction-Based Cell Free In Vitro Non-Homologous End Joining Assay for Hematopoietic Stem Cells

Hematopoietic stem cells (HSCs) are responsible for sustaining hematopoietic homeostasis and regeneration after injury for the entire lifespan of an organism. Maintenance of genomic stability is crucial for the preservation of HSCs, which depends on their efficient repair of DNA damage, particularly DNA double strand breaks (DSBs). Because of the paucity of HSCs and lack of sensitive assays, directly measuring the ability of HSCs to repair DSBs has been difficult. Therefore, we developed a sensitive and quantitative cell free in vitro non-homologous end joining (NHEJ) assay using linearized plasmids as the substrates and quantitative polymerase chain reaction (qPCR) technique. This assay can sensitively detect DSB repair via NHEJ in less than 1 µg 293T cell nuclear proteins or nuclear extracts from about 5,000 to 10,000 human BM CD34+ hematopoietic cells. Using this assay, we confirmed that human bone marrow HSCs (CD34+CD38− cells) are less proficient in the repair of DSBs by NHEJ than HPCs (CD34+CD38+ cells). In contrast, mouse quiescent HSCs (Pyronin-Ylow LKS+ cells) and cycling HSCs (Pyronin-Yhi LKS+ cells) repaired the damage more efficiently than HPCs (LKS− cells). The difference in the abilities of human and mouse HSCs and HPCs to repair DSBs through NHEJ is likely attributed to their differential expression of key NHEJ DNA damage repair genes such as LIG4. These findings suggest that the qPCR-based cell free in vitro NHEJ assay can be used to sensitively measure the ability of human and mouse HSCs to repair DSBs