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Cancer: More of polygenic disease and less of multiple mutations? A quantitative viewpoint.

The focus of cancer research is on cancer-specific mutations, with most clinical trials involving targeted drugs. Huge numbers of DNA lesions and tumor resistance events, in each of the >10(13) cells of a human individual, form a striking contrast to the low, and also very narrow, cancer incidence window (10(-1)-10(0)). A detailed consideration of these quantitative observations seems to question

Cognitive manic symptoms associated with the P2RX7 gene in bipolar disorder.

Objective: Several genetic loci have been suggested to be associated with bipolar disorder but results have been inconsistent. Studying associations between bipolar symptoms and candidate genes may better expose this relationship. Here we investigate the association between bipolar key symptoms and the P2RX7 gene. Methods: Key symptoms of mania were rated in two sets of medicated bipolar disorder

Staphylococcus aureus induced clotting of plasma is an immune evasion mechanism to persist within the fibrin network.

Recent work has shown that coagulation and innate immunity are tightly interwoven host responses that help eradicate an invading pathogen. Some bacterial species including Staphylococcus aureus secrete pro-coagulant factors that in turn can modulate these immune reactions. Such mechanisms may not only protect the microorganism from a lethal attack, but also promote bacterial proliferation and the

Photodynamic therapy: superficial and interstitial illumination.

Photodynamic therapy (PDT) is reviewed using the treatment of skin tumors as an example of superficial lesions and prostate cancer as an example of deep-lying lesions requiring interstitial intervention. These two applications are among the most commonly studied in oncological PDT, and illustrate well the different challenges facing the two modalities of PDT-superficial and interstitial. They thus

A longitudinal study of the perimenopausal transition: altered profiles of steroid and pituitary hormones, SHBG and bone mineral density.

From a longitudinal prospective study, 160 women with spontaneous menopause and without steroid medication were followed during the transition from pre- to postmenopause. After 12 years 152 women were still participating in the study. Blood samples were drawn every 6 months until 1 year after the menopause and every 12 months thereafter. Measurements of bone mineral density (BMD) on the forearm we

Biofilm formation by Propionibacterium acnes is a characteristic of invasive isolates.

Clin Microbiol InfectAbstract Propionibacterium acnes is a common and probably underestimated cause of delayed joint prosthesis infection. Bacterial biofilm formation is central in the pathogenesis of infections related to foreign material, and P. acnes has been shown to form biofilm both in vitro and in vivo. Here, biofilm formation by 93 P. acnes isolates, either from invasive infections (n = 45

Doing Ambivalence: Embracing Innovation – at Arm’s Length

This article considers the social organization of responses among human service staff to changes in public policy, using a study of a Swedish treatment center for juveniles as an illustration. The stance towards a new treatment ideology, “family-work,” was not one of either accepting or rejecting the new policy; the staff conveyed both embracing and distancing. Policy innovations, it is argued, cr

Comparison and evaluation of a Point-of-care device (CoaguChek XS) to Owren-type prothrombin time assay for monitoring of oral anticoagulant therapy with warfarin.

BACKGROUND: The standardized test used for evaluating the effect of warfarin is the prothrombin time (PT) which is measured and expressed in international normalized ratio (INR). Regular control of treatment intensity is required since inappropriate dosage increases the risk for complications. Portable point-of-care analytical instruments for measurement of capillary whole blood PT have been avail

Early changes in bone mineral density measured by digital X-ray radiogrammetry predict up to 20 years radiological outcome in rheumatoid arthritis.

ABSTRACT: INTRODUCTION: Change in bone mineral density (BMD) in the hand, as evaluated by digital X-ray radiogrammetry (DXR) of the II-IV metacarpal bones, has been suggested to predict future joint damage in rheumatoid arthritis (RA). This study's objective was to investigate if DXR-BMD loss early in the disease predicts development of joint damage in RA patients followed for up to 20 years. METH

Survival of pancreatic beta cells is partly controlled by a TCF7L2-p53-p53INP1-dependent pathway.

The transcription factor T-cell factor 7-like 2 (TCF7L2) confers type 2 diabetes risk mainly through impaired insulin secretion, perturbed incretin effect and reduced beta-cell survival. The aim of this study was to identify the molecular mechanism through which TCF7L2 influences beta-cell survival. TCF7L2 target genes in INS-1 cells were identified using Chromatin Immunoprecipitation. Validation

Host and pathogen hyaluronan signal through human siglec-9 to suppress neutrophil activation.

Inhibitory CD33-related Siglec receptors regulate immune cell activation upon engaging ubiquitous sialic acids (Sias) on host cell surface glycans. Through molecular mimicry, Sia-expressing pathogen group B Streptococcus binds inhibitory human Siglec-9 (hSiglec-9) to blunt neutrophil activation and promote bacterial survival. We unexpectedly discovered that hSiglec-9 also specifically binds high m

The anti-tumour effect of cisplatin and ifosfamide on xenografted squamous cell carcinoma of the head and neck is schedule-dependent.

The role of chemotherapy (CHX) in squamous cell carcinoma of the head and neck (SCCHN) has been expanding. Although combination chemotherapy regimens regularly produce significantly high response rates, meta-analyses show little benefit regarding final outcome. One way to improve induction CHX is to improve drug combinations and schedules for CHX. Cisplatin (CDDP) is one of the most active drugs i

Effectiveness of ciprofloxacin or linezolid in combination with rifampicin against Enterococcus faecalis in biofilms.

ObjectivesTo assess the in vitro antibiotic susceptibility of Enterococcus faecalis in biofilms.MethodsE. faecalis isolates were from infections of prosthetic hip and knee joints. Minimal biofilm eradication concentrations (MBECs) for ampicillin, vancomycin, linezolid, ciprofloxacin and rifampicin, alone and in combinations, were determined. E. faecalis biofilms in microtitre plate wells or on bea

The value of tomographic ventilation/perfusion scintigraphy (V/PSPECT) for follow-up and prediction of recurrence in pulmonary embolism.

BACKGROUND: Pulmonary embolism (PE) is diagnosed with imaging techniques such as ventilation/perfusion (V/P) lung scintigraphy or multidetector computed tomography of the pulmonary arteries (MDCT). Lung scintigraphy can be performed with planar (V/P PLANAR) and tomographic (V/P SPECT) techniques. V/P SPECT has higher sensitivity and specificity than V/P PLANAR. As nephrotoxic contrast media are no

Apparent exchange rate mapping with diffusion MRI.

Water exchange through the cell membranes is an important feature of cells and tissues. The rate of exchange is determined by factors such as membrane lipid composition and organization, as well as the type and activity of aquaporins. A method for noninvasively estimating the rate of water exchange would be useful for characterizing pathological conditions, e.g., tumors, multiple sclerosis, and is

Effects of green foam, black foam and gauze on contraction, blood flow and pressure delivery to the wound bed in negative pressure wound therapy.

BACKGROUND: Negative pressure wound therapy (NPWT) contracts the wound and alters the microvascular blood flow in the wound edge, which may be crucial in promoting wound healing. The aim of the present study was to examine these biological effects in the wound edge using different types of wound fillers. METHODS: Wounds were created on the backs of pigs and filled with green foam, black foam or g

Endoplasmic reticulum dynamics in hippocampal dendritic spines induced by agonists of type I metabotropic glutamate but not by muscarinic acetylcholine receptors.

Neurons in the hippocampus exhibit subpopulations of dendritic spines that contain endoplasmic reticulum (ER). ER in spines is important for synaptic activity and its associated Ca(2+) signaling. The dynamic distribution of ER to spines is regulated by diacylglycerol and partly mediated by protein kinase C, metalloproteinases and γ-secretase. In this study, we explored whether pharmacological acti

Optimal Coordination and Control of Posture and Movements

This paper presents a theoretical model of stability and coordination of posture and locomotion, together with algorithms for continuous-time quadratic optimization of motion control. Explicit solutions to the Hamilton-Jacobi equation for optimal control of rigid-body motion are obtained by solving an algebraic matrix equation. The stability is investigated with Lyapunov function theory and it is